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2025

nach oben zur Jahresübersicht

V. Mohan, N. Strepis, K. Mitsakakis, K. Becker, L. Chindelevitch, N. Shivaperumal, K. Swe Swe-Han, J.P. Hays
Antimicrobial resistance in Campylobacter spp. focussing on C. jejuni and C. coli – A Narrative Review
2025 J. Glob. Antimicrob. Resist., Band: 43, Seiten: 372 - 389
D. Kainz, B. Breiner, A. Klebes, N. Borst, R. Zengerle, F. von Stetten, T. Hutzenlaub, N. Paust, S. Früh
Centrifugal Microfluidic Lateral Flow Assay Enables High Sensitivity Interleukin-6 Detection and Ultrafast Readout of Elevated Analyte Levels
2025 Anal. Chem., Band: 97, Nummer: 16, Seiten: 8984 - 8991
L. Heinius, M. Klingenhof, G. Weiser, P. Schröer, L. Metzler, S. Koch, S. Selve, S. Vierrath, P. Strasser
Design and Analysis of Carbon-Supported NiMo HER Catalysts and Electrodes for High Performance All PGM-Free AEM Electrolysers
2025 Electrochem. Sci. Adv, Seite: 0:e2024000
L. Bohn, J. Häberlein, F. Brendel, L. Metzler, L. Helfen, A. Tengattini, C. Klose, S. Vierrath, J. Disch
High-Resolution Neutron Imaging of Water Transport in CO2 Electrolysis during Pulsed Operation
2025 ACS Energy Letters, Band: 10, Nummer: 2, Seiten: 975 - 981
K. Seteiz, H. Grammel, J.N. Häberlein, P. A. Heizmann, L. Metzler, D. Rusitov, M. Günthel, M. Knäbbeler-Buß, S. Vierrath, J. Disch
Highly active and selective Ag/C catalysts for CO2 electrolysis to CO using 4-aminothiophenol as anchoring agent
2025 Nano Energy, Band: 134, Seite: 110597
M. Knapp, S. Kadić, A. Lux, N. Paust, R. Zengerle, J. Hoffmann
Highly efficient isolation and multistep analysis of tumor cells from whole blood
2025 Lab Chip, Band: 25, Seiten: 1938 - 1946
T. Gross, T. Hundertmark, V. Csiszár, A. A. Sulyok, N. Gross, M. Breiden, N. Kitschen, U. von Groll, C. Niemöller, P. Sánchez-Martín, A. Heine, J. Göpfert, T. Szórádi, P. Lübbert, P. Koltay, P. Porschewski, R. Zengerle, C. Jeney
Lossless single-molecule counting to absolute quantify proteoforms
2025 Scientific Reports, Band: 15, Seite: 7356
D. Straubinger, P. Koltay, R. Zengerle, S. Kartmann, Z. Shu
Versatile Selective Soldering via Molten Metal Printing for Heat-Sensitive 3D Electronics and Smart Wearables
2025 Adv. Funct. Mater., Seite: 2419653

2024

nach oben zur Jahresübersicht

R. Qelibari, E. Cruz Ortiz, N. van Treel, F. Lombeck, C. Schare, A. Münchinger, N. Dumbadze, G. Titvinidze, C. Klose, S. Vierrath
74 µm PEEK-Reinforced Sulfonated Poly(phenylene sulfone)-Membrane for Stable Water Electrolysis with Lower Gas Crossover and Lower Resistance than Nafion N115
2024 Adv. Energy Mater., Seite: 2303271
M.U. Iturritza, P. Mlotshwa, J. Gantelius, T. Alfvén, E. Loh, J. Karlsson, C. Hadjineophytou, K. Langer, K. Mitsakakis, A. Russom, H.N. Jönsson, G. Gaudenzi
An Automated Versatile Diagnostic Workflow for Infectious Disease Detection in Low-Resource Settings
2024 Micromachines, Band: 15, Nummer: 6, Seite: 708
V. Zieger, E. Woehr, S. Zimmermann, D. Frejek, P. Koltay, R. Zengerle, S. Kartmann
Automated Nanodroplet Dispensing for Large-Scale Spheroid Generation via Hanging Drop and Parallelized Lossless Spheroid Harvesting
2024 Micromachines, Band: 15, Seite: 231
D. Straubinger, P. Koltay, R. Zengerle, S. Kartmann, Z. Shu
Bulge-Free and Homogeneous Metal Line Jet Printing with StarJet Technology
2024 Micromachines, Band: 15, Seite: 743
R. Kronstein-Wiedemann, J. Thiel, D. Sürün, M. Teichert, S. R. Künzel, S. Zimmermann, L. Wagenführ, F. Buchholz, T. Tonn
Characterization of immortalized bone marrow erythroid progenitor adult (imBMEP-A)—The first inducible immortalized red blood cell progenitor cell line derived from bone marrow CD71-positive cells
2024 Cytotherapy, Band: 26, Nummer: 11, Seiten: 1362 - 1373
K. Seteiz, J. N. Häberlein, P. A. Heizmann, L. Bohn, S. Vierrath, J. Disch
Effect of Ionomer Content and Ag/C Catalyst Surface Area on the Performance of CO2 Electrolysis to CO
2024 ACS Appl. Eng. Mater, Band: 2, Nummer: 6, Seite: 1654
A. Klebes, H. Ceren Ates, Rene D. Verboket, G. A. Urban, F. von Stetten, C. Dincer, S. M. Früh
Emerging multianalyte biosensors for the simultaneous detection of protein and nucleic acid biomarkers
2024 Biosensors and Bioelectronics, Band: 244, Seite: 115800
L. Niebling, R. Nitzsch, T. Sieksmeyer, V. Haskamp, J. Kissenkötter, A. Abd El Wahed, T. Teufel, H. Hermann, N. Paust, A. R. Homann
Fast and on-site animal species identification in processed meat via centrifugal microfluidics and isothermal amplification
2024 LabChip, Band: 24, Seite: 975
H. Liepold, H. Nguyen, P. A. Heizmann, C. Klose, S. Vierrath, A. Münchinger
Gas Transport Resistance of Hydrocarbon-Based Catalyst Layers in Proton-Exchange Membrane Fuel Cells
2024 Journal of The Electrochemical Society, Band: 171, Seite: 054509
H. Liepold, A. Bird, P. A. Heizmann, H. Fadlullah, H. Nguyen, C. Klose, S. Holdcroft, A. Kusoglu, S. Vierrath, A. Münchinger
High protonic resistance of hydrocarbon-based cathodes in PEM fuel cells under low humidity conditions: Origin, implication, and mitigation
2024 Journal of Power Sources, Band: 624, Seite: 235537
M. Klingenhof, H. Trzesniowski, S. Koch, J. Zhu, Z. Zeng, L. Metzler, A. Klinger, M. Elshamy, F. Lehmann, P. W. Buchheister, A. Weisser, G. Schmid, S. Vierrath, F. Dionigi, P. Strasser
High-performance anion-exchange membrane water electrolysers using NiX (X = Fe,Co,Mn) catalyst-coated membranes with redox-active Ni–O ligands
2024 Nature Catalysis
O. Rajabnia, A. Ernst, N. Lass, L. Riegger, R. Zengerle
Highly Parallel Droplet Dispensing Approach to Provide Homogeneous and Controllable Droplet Arrays for Diagnostic Test Manufacturing
2024 micromachines, Band: 15, Seite: 824
Z. Khan, D. Gururajan, P. Koltay, S. Kartmann, R. Zengerle, Z. Shu
Hybrid 3D Printing of Molten Metal Microdroplets and Polymers for Prototyping of Printed Circuit Boards Featuring Interdigitated 3D Capacitors
2024 EEJ TRANSACTIONS ON ELECTRICAL AND ELECTRONIC ENGINEERING, IEEJ Trans 2024
Z. Khan, A. Saphala, S. Kartmann, P. Koltay, R. Zengerle, O. Amft, Z. Shu
Hybrid Printing of Conductive Traces from Bulk Metal for Digital Signals in Intelligent Device
2024 Micromachines, Band: 15, Seite: 750
J. Stiegeler, T. Mittermeier, L. Tsikonis, T. Lehre, S. Vierrath
Influence Factors of Platinum Dissolution in Proton Exchange Membrane Fuel Cells: A Sensitivity Study
2024 J. Electrochem. Soc, Band: 171, Seite: 054517
B. Johannsen, D. Baumgartner, M. Karpíšek, D. Stejskal, N. Paust, R. Zengerle, K. Mitsakakis
Integration of a bead-based immunoassay on a commercial PCR-performing POC device
2024 Proceedings, Band: 97, Seite: 166
Z. Khan, D. Gururajan, S. Kartmann, P. Koltay, R. Zengerle, Z. Shu
Iterative printing of bulk metal and polymer for additive manufacturing of multi-layer electronic circuits
2024 npj Adv. Manuf., Band: 1, Nummer: 1
R. Weber, M. Klingenhof, S. Koch, L. Metzler, T. Merzdorf, J. Meier-Haack, P. Strasser, S. Vierrath, M. Sommer
Meta-kinks are key to binder performance of poly(arylene piperidinium) ionomers for alkaline membrane water electrolysis using non-noble metal catalysts
2024 J. Mater. Chem. A, Band: 12, Seite: 7826
M. Trotter, A. Schreiber, D. Kleinknecht, Z. Bagherian, F. von Stetten, N. Borst
Pathogen-Specific Electrochemical Real-Time LAMP Detection Using Universal Solid-Phase Probes on Carbon Electrodes
2024 ACS Sensors
F. Pescher, J. Stiegeler, P. A. Heizmann, C. Klose, S. Vierrath, M. Breitwieser
Pt/C catalysts synthesized in a commercial particle atomic layer deposition system enabling improved durability in fuel cells
2024 RSC Advances, Band: 44
L. Bohn, J. Kieninger, S. J. Rupitsch, C. Klose, S. Vierrath, J. Disch
Reference Electrode Types for Zero-Gap CO2 Electrolyzers: Benefits and Limitations
2024 Advanced Science, Band: 11, Seite: 32
E. Cruz Ortiz, N. van Treel, S. Koch, S. Vierrath, M. Bühler
The effect of compression on PEM Electrolyzer membrane electrode Assemblies
2024 J. of Power Sources, Band: 614, Seite: 235018
V. Zieger, D. Frejek, S. Zimmermann, G. A. A. Miotto, P. Koltay, R. Zengerle, S. Kartmann
Towards Automation in 3D Cell Culture: Selective and Gentle High-Throughput Handling of Spheroids and Organoids via Novel Pick-Flow-Drop Principle
2024 Adv Healthc Mater, Seite: e2303350
J. Schlanderer, H. Hoffmann, J. Lüddecke, A. Golubov, W. Grasse, E. V. Kindler, T. A. Kohl, M. Merker, C. Metzger, V. Mohr, S. Niemann, C. Pilloni, S. Plesnik, B. Raya, B. Shresta, C. Utpatel, R. Zengerle, M. Beutlerd, N. Paust
Two-stage tuberculosis diagnostics: combining centrifugal microfluidics to detect TB infection and Inh and Rif resistance at the point of care with subsequent antibiotic resistance profiling by targeted NGS
2024 LabChip, Band: 24, Seite: 74

2023

nach oben zur Jahresübersicht

K. Yildirim, H. Fadlullah, C. Schwarz, F. Lombeck, C. Klose, S. Vierrath, M. Breitwieser
30μm Thin Anode Gas Diffusion Layers for OptimizedPEM Fuel Cell Operation at 120 °C and Low Relative Humidity
2023 Adv. Energy Sustainability Res, Seite: 2300179
F. Fischer, A. Doll, D. Uereyener, S. Roenneberg, C. Hillig, L. Weber, V. Hackert, P. Seiringer, J. Thomas, P. Anand, L. Graner, F. Schlenker, R. Zengerle, M. Jargosch, F. J. Theis, C. B. Schmidt-Weber, T. Biedermann, M. Howell, K. Reich, M. Menden, N. Garzorz-Stark, F. Lauffer, S. Eyerich
394 Gene expression based molecular test proves clinical validity as diagnostic aid for the differential diagnosis of psoriasis and eczema in formalin fixed and paraffin embedded tissue
2023 British Journal of Dermatology, Band: 188, Nummer: 3
H. Nguyen, J. Stiegeler, H. Liepold, C. Schwarz, S. Vierrath, M. Breitwieser
A Comparative Study of Conditioning Methods for Hydrocarbon-Based Proton-Exchange Membrane Fuel Cells for Improved Performance
2023 Energy Technol., Seite: 2300202
J. Weygant, F. Koch, K. Adam, K. Tröndle, R. Zengerle, G. Finkenzeller, S. Kartmann, P. Koltay, S. Zimmermann
A Drop-on-Demand Bioprinting Approach to Spatial Arrangement of Multiple Cell Types and Monitoring Their Cell–Cell Interactions towards Vascularization Based on Endothelial Cells and Mesenchymal Stem Cells
2023 Cells, Band: 12, Nummer: 4, Seite: 646
P. A. Heizmann, H. Nguyen, M. von Holst, A. Fischbach, M. Kostelec, F. J. Gonzalez Lopez, M. Bele, L. Pavko, T. Đukić, M. Šala, F. Ruiz-Zepeda, C. Klose, M. Gatalo, N. Hodnik, S. Vierrath, M. Breitwieser
Alternative and facile production pathway towards obtaining high surface area PtCo/C intermetallic catalysts for improved PEM fuel cell performance
2023 RSC Adv, Band: 13, Seiten: 4601 - 4611
J. Disch, S. Ingenhoven, S. Vierrath
Bipolar Membrane with Porous Anion Exchange Layer for Efficient and Long-Term Stable Electrochemical Reduction of CO2 to CO
2023 Adv. Energy Mater., Seite: 2301614
K. Seteiz, J. N. Häberlein, P. A. Heizmann, J. Disch, S. Vierrath
Carbon black supported Ag nanoparticles in zero-gap CO2 electrolysis to CO enabling high mass activity
2023 RSC Advances, Band: 27
P. Sardana, M. Zolfaghari, G. Miotto, R. Zengerle, T. Brox, P. Koltay, S. Kartmann
DropletAI: Deep Learning-Based Classification of Fluids with Different Ohnesorge Numbers during Non-Contact Dispensing
2023 Fluids, Band: 8, Seite: 183
A. Klebes, H. C. Ates, R. D. Verboket, G. Urban, F. von Stetten, C. Dincer, S. M. Früh
Emerging multianalyte biosensors for the simultaneous detection of protein and nucleic acid biomarkers
2023 Biosensors and Bioelectronics, Seite: 115800
T. T. Bachmann, K. Mitsakakis, J. P. Hays, A. van Belkum, A. Russom, G. Luedke, G. Skov Simonsen, G. Abel, H. Peter, H. Goossens, J. Moran-Gilad, J. Vila, K. Becker, P. Moons, R. Sampath, R. W Peeling, S. Luz, T. van Staa, V. Di Gregori, JPIAMR AMR-RDT Working Group
Expert guidance on target product profile development for AMR diagnostic tests
2023 BMJ Glob Health, Band: 18, Nummer: 8, Seite: e012319
F. Fischer, A. Doll, D. Uereyener, S. Roenneberg, C. Hillig, L. Weber, V. Hackert, M. Meinel, A. Farnoud, P. Seiringer, J. Thomas, P. Anand, L. Graner, F. Schlenker, R. Zengerle, P. Jonsson, M. Jargosch, FJ Theis, CB Schmidt-Weber, T. Biedermann, M. Howell, K. Reich, K. Eyerich, M. Menden, N. Garzorz-Stark, F. Lauffer, S. Eyerich
Gene expression based molecular test as diagnostic aid for the differential diagnosis of psoriasis and eczema in formalin fixed and paraffin embedded tissue, microbiopsies and tape strips
2023 The Journal of Investigative Dermatology
G. Miotto, K. Thiemann, M. Rombach, R. Zengerle, S. Kartmann
Holographic PIV/PTV for nano flow rates - a study in the 70 to 200 nL/min range
2023 Biomedical engineering, Band: 68, Nummer: 1, Seiten: 97 - 107
Y.-K. Lai, Y.-T. Kao, J. Hess, S. Calabrese, F. von Stetten, N. Paust
Interfacing centrifugal microfluidics with linear-oriented 8-tube strips and multichannel pipettes for increased throughput of digital assays
2023 Lab on a Chip, Band: 23, Seiten: 2623 - 2632
F. Schlenker, P. Juelg, J. Lüddecke, N. Paust, R. Zengerle, T. Hutzenlaub
Nanobead handling on a centrifugal microfluidic LabDisk for automated extraction of cell-free circulating DNA with high recovery rates
2023 Analyst
D. Grijalva Garces, S. Strauß, S. Gretzinger, B. Schmieg, T. Jüngst, J. Groll, L. Meinel, I. Schmidt, H. Hartmann, K. Schenke-Layland, N. Brandt, M. Selzer, S. Zimmermann, P. Koltay, A. Southan, G. E. M. Tovar, S. Schmidt, A. Weber, T. Ahlfeld, M. Gelinsky, T. Scheibel, R. Detsch, A. R. Boccaccini, T. Naolou, C. Lee-Thedieck, C. Willems, T. Groth, S. Allgeier, B. Köhler, T. Friedrich, H. Briesen, J. Buchholz, D. Paulus, A. von Gladiss, J. Hubbuch
On the reproducibility of extrusion-based bioprinting: round robin study on standardization in the field
2023 Biofabrication, Band: 16, Seite: 015002
Z. Khan, P. Koltay, R. Zengerle, S. Kartmann, Z. Shu
One-Stop Hybrid Printing of Bulk Metal and Polymer for 3D Electronics
2023 Advanced Engineering Materials, Seite: 2300922
B. Johannsen, D. Baumgartner, M. Karpíšek, D. Stejskal, N. Boillat-Blanco, J. Knüsli, M. Panning, N. Paust, R. Zengerle, K. Mitsakakis
Patient Stratification for Antibiotic Prescriptions Based on the Bound-Free Phase Detection Immunoassay of C-Reactive Protein in Serum Samples
2023 Biosensors, Band: 13, Seite: 1009
S. Calabrese, A. M. Markl, M. Neugebauer, S. J. Krauth, N. Borst, F. von Stetten, M. Lehnert
Reporter emission multiplexing in digital PCRs (REM-dPCRs): direct quantification of multiple target sequences per detection channel by population specific reporters
2023 Analyst, Band: 148, Seiten: 5243 - 5254
S. Koch, L. Metzler, S. Kilian, P. A. Heizmann, F. Lombeck, M. Breitwieser, S. Vierrath
Toward scalable production: catalyst‐coated membranes (CCMs) for anion‐exchange membrane water electrolysis via direct bar coating
2023 Advanced sustainable systems, Band: 7, Seite: 2200332
V. Zieger, D. Frejek, S. Zimmermann, G. A. A. Miotto, P. Koltay, R. Zengerle, S. Kartmann
Towards Label-Free Standardization in 3d Cell Culture: Automated, Selective and Gentle High-Throughput Handling of Spheroids and Organoids via Novel Pick-Flow-Drop Principle
2023 Adv Healthc Mater, Seite: e2303350

2022

nach oben zur Jahresübersicht

E. Kipf, F. Schlenker, N. Borst, M. Fillies, R. Kirschner-Schwabe, R. Zengerle, C. Eckert, F. von Stetten, M. Lehnert
Advanced minimal residual disease monitoring for acute lymphoblastic leukemia with multiplex mediator probe PCR
2022 J. Mol. Diag, Band: 24, Nummer: 1, Seiten: 57 - 68
M. Neugebauer, C. E. Grundmann, M. Lehnert, F. von Stetten, S. M. Früh, R. Süss
Analyzing siRNA Concentration, Complexation and Stability in Cationic Dendriplexes by Stem-Loop Reverse Transcription-qPCR
2022 Pharmaceutics, Band: 2022, Nummer: 14, Seite: 1348
Dornhof J, Zieger V, Kieninger J, Frejek D, Zengerle R, Urban GA, Kartmann S, Weltin A
Bioprinting-based automated deposition of single cancer cell spheroids into oxygen sensor microelectrode wells
2022 LabChip, Band: 8, Nummer: 22, Seiten: 4369 - 4381
C. Mills, E. Batista, H. Bissig, F. Ogheard, A. W. Boudaoud, O. Büker, K. Stolt, J. Morgan, S. Kartmann, K. Thiemann, G. Miotto, A. Niemann, S. Klein, G. Ratering, J. Lötters
Calibration methods for flow rates down to 5 nL/min and validation methodology
2022 Biomed. Eng.-Biomed. Tech.
E. Balogun, P. Mardle, H. Nguyen, M. Breitwieser, S. Holdcroft
Catalyst layers for fluorine‐free hydrocarbon PEMFCs
2022 Electrochimica Acta, Band: 401, Seite: 139479
K. Tröndle, G. Miotto, L. Rizzo, R. Pichler, F. Koch, P. Koltay, R. Zengerle, S. S. Lienkamp, S. Kartmann, S. Zimmermann
Deep Learning-Assisted Nephrotoxicity Testing with Bioprinted Renal Spheroids
2022 Int. J. Bioprint, Band: 8, Nummer: 2, Seite: 528
V. Burchak, F. Koch, L. Siebler, S. Haase, V. K. Horner, X. Kempter, G. B. Stark, U. Schepers, A. Grimm, S. Zimmermann, P. Koltay, S. Strassburg, G. Finkenzeller, F. Simunovic, F. Lampert
Evaluation of a Novel Thiol–Norbornene-Functionalized Gelatin Hydrogel for Bioprinting of Mesenchymal Stem Cells
2022 Int. J. Mol. Sci., Band: 23, Seite: 7939
H. Nguyen, C. Klose, L. Metzler, S. Vierrath, M. Breitwieser
Fully Hydrocarbon Membrane Electrode Assemblies for Proton Exchange Membrane Fuel Cells and Electrolyzers: An Engineering Perspective
2022 Adv. Energy Mater., Band: 2022, Seite: 2103559
J. Disch, L. Bohn, S. Koch, M. Schulz, Y. Han, A. Tengattini, L. Helfen, M. Breitwieser, S. Vierrath
High-resolution neutron imaging of salt precipitation and water transport in zero-gap CO2 electrolysis
2022 nature communications, Band: 13, Seite: 6099
G. Miotto, K. Thiemann, M. Rombach, R. Zengerle, S. Kartmann
Holographic PIV/PTV for nano flow rates–A study in the 70 to 200 nL/min range
2022 Biomedical Engineering
B. Johannsen, D. Baumgartner, L. Karkossa, N. Paust, M. Karpíšek, N. Bostanci, R. Zengerle, K. Mitsakakis
ImmunoDisk - a fully automated bead-based immunoassay cartridge with all reagents pre-stored
2022 Biosensors, Band: 12, Nummer: 6, Seite: 413
H. Nguyen, D. Sultanova, P. A. Heizmann, S. Vierrath, M. Breitwieser
Improving the efficiency of fully hydrocarbon-based proton-exchange membrane fuel cells by ionomer content gradients in cathode catalyst layers
2022 Materials Advances, Band: 23
S. Hin, N. Paust, M. Rombach, J. Lüddecke, M. Specht, R. Zengerle, K. Mitsakakis
Magnetophoresis in Centrifugal Microfluidics at Continuous Rotation for Nucleic Acid Extraction
2022 Micromachines, Band: 13, Seite: 2112
F. Koch, O. Thaden, S. Conrad, K. Tröndle, G. Finkenzeller, R. Zengerle, S. Kartmann, S. Zimmermann, P. Koltay
Mechanical properties of polycaprolactone (PCL) scaffolds for hybrid 3D-bioprinting with alginate-gelatin hydrogel
2022 J. Mech. Behav. Biomed. Mat., Band: 130, Seite: 105219
L. Bohn, M. von Holst, E. Cruz Ortiz, M. Breitwieser, S. Vierrath, C. Klose
Methods— A Simple Method to Measure In-Plane Electrical Resistance of PEM Fuel Cell and Electrolyzer Catalyst Layers
2022 J.Electrochem. Soc., Band: 169, Nummer: 5, Seite: 054518
Y.-T. Kao, S. Calabrese, N. Borst, M. Lehnert, Y.-K. Lai, F. Schlenker, P. Juelg, R. Zengerle, P. Garstecki, F. von Stetten
Microfluidic One-Pot Digital Droplet FISH Using LNA/DNA Molecular Beacons for Bacteria Detection and Absolute Quantification
2022 Biosensors, Band: 12, Nummer: 4, Seite: 237
A. Klebes, A.-S. Kittel, R. D. Verboket, F. von Stetten, S. M. Früh
Multianalyte lateral flow immunoassay for simultaneous detection of protein-based inflammation biomarkers and pathogen DNA
2022 Sensors and Actuators B: Chemical, Band: 355, Seite: 131283
S. Hennig, Z. Shu, L. Gutzweiler, P. Koltay, F. von Stetten, R. Zengerle, S. M. Früh
Paper-based open microfluidic platform for protein electrophoresis and immunoprobing
2022 Electrophoresis, Band: 43, Nummer: 4, Seiten: 621 - 631
B. Afacan, V. Özgen Öztürk, G. Emingil, T. Köse, K. Mitsakakis, N. Bostanci
Salivary secretory leukocyte protease inhibitor levels in patients with stage 3 grade C periodontitis: a comparative cross-sectional study
2022 Scientific Reports, Band: 12, Nummer: 1, Seite: 21267
S. Koch, L. Metzler, S. K. Kilian, P. A. Heizmann, F. Lombeck, M. Breitwieser, S. Vierrath
Toward Scalable Production: Catalyst-Coated Membranes (CCMs) for Anion-Exchange Membrane Water Electrolysis via Direct Bar Coating
2022 Adv. Sustainable Syst., Seite: 2200332
S. Koch, J. Disch, S. K. Kilian, Y. Han, L. Metzler, A. Tengattini, L. Helfen, M. Schulz, M. Breitwieser, S. Vierrath
Water management in anion-exchange membrane water electrolyzers under dry cathode operation
2022 RSC Adv, Band: 12, Seiten: 20778 - 20784

2021

nach oben zur Jahresübersicht

A. Homann, L. Niebling, S. Zehnle, M. Beutler, L. Delamotte, M.C. Rothmund, D. Czurratis, K.-D. Beller, R. Zengerle, H. Hoffmann, N. Paust
A microfluidic cartridge for fast and accurate diagnosis of Mycobacterium tuberculosis infections on standard laboratory equipment
2021 Lab on a Chip, Band: 21, Nummer: 8, Seiten: 1540 - 1548
KurzfassungWe present a novel centrifugal microfluidic approach for fast and accurate tuberculosis (TB) diagnosis based on the use of standard laboratory equipment. The herein presented workflow can directly be integrated into laboratories with standard equipment and automates complex sample preparation. The system consists of a microfluidic cartridge, a laboratory centrifuge and a standard PCR cycler. The cartridge includes all required reagents and automates collection of bacteria on filter membranes, bacterial lysis, nucleic acid extraction and aliquoting of the DNA extract for PCR analysis. We show that storage of the reagents in aluminium-coated pouches is stable during accelerated storage and transport tests. When the limit of detection was assessed, we found that the cartridge-automated workflow consistently detected 10 CFU ml−1 of mycobacteria in spiked sputum samples. First tests with clinical samples showed a 100% specificity for non-TB specimens. In addition, Mycobacterium tuberculosis (MTB) was re-found in pre-characterized smear microscopy and culture positive sputum samples suggesting a high diagnostic sensitvity. In summary, the novel cartridge-automated workflow enables a flexible and sensitive TB diagnosis without the need to invest in specialized instrumentation.
J.F.Hess, M.E.Hess, R.Zengerle, N.Paust, M.Boerries, T.Hutzenlaub
Automated library preparation for whole genome sequencing by centrifugal microfluidic
2021 Analytica Chimica Acta, Seite: 338954
J.-N. Klatt, T.J. Dinh, O. Schilling, R. Zengerle, F. Schmidt, T. Hutzenlaub, N. Paust
Automation of peptide desalting for proteomic liquid chromatography–tandem mass spectrometry by centrifugal microfluidics
2021 Lab on a Chip, Band: 21, Nummer: 21, Seite: 2255
KurzfassungFor large-scale analysis of complex protein mixtures, liquid chromatography – tandem mass spectrometry (LC-MS/MS) has been proven to be one of the most versatile tools due to its high sensitivity and ability to both identify and quantify thousands of proteins in a single measurement. Sample preparation typically comprises site-specific cleavage of proteins into peptides, followed by desalting and concomitant peptide enrichment, which is commonly performed by solid phase extraction. Desalting workflows may include multiple liquid handling steps and are thus error prone and labour intensive. To improve the reproducibility of sample preparation for low amounts of protein, we present a centrifugal microfluidic disk that automates all liquid handling steps required for peptide desalting by solid phase extraction (DesaltingDisk). Microfluidic implementation was enabled by a novel centrifugal microfluidic dosing on demand structure that enabled mapping multiple washing steps onto a microfluidic disk. Evaluation of the microfluidic disk was performed by LC-MS/MS analysis of tryptic HEK-293 eukaryotic cell peptide mixtures desalted either using the microfluidic disk or a manual workflow. A comparable number of peptides were identified in the disk and manual set with 19 775 and 20 212 identifications, respectively. For a core set of 10 444 peptides that could be quantified in all injections, intensity coefficients of variation were calculated based on label-free quantitation intensities. The disk set featured smaller variability with a median CV of 9.3% compared to the median CV of 12.6% for the manual approach. Intensity CVs on protein level were lowered from 5.8% to 4.2% when using the LabDisk. Interday reproducibility for both workflows was assessed by LC-SRM/MS analysis of samples that were spiked with 11 synthetic peptides of varying hydrophobicity. Except for the most hydrophilic and hydrophobic peptides, the average CV was lowered to 3.6% for the samples processed with the disk compared to 7.2% for the manual workflow. The presented centrifugal microfluidic DesaltingDisk demonstrates the potential to improve reproducibility in the sample preparation workflow for proteomic mass spectrometry, especially for application with limited amount of sample material.
J.-N. Klatt, T. Hutzenlaub, T. Subkowski, T. Müller, S. Hennig, R. Zengerle, N. Paust
Blocking Protein Adsorption in Microfluidic Chips by a Hydrophobin Coating
2021 ACS Appl. Polym. Mater., Band: 3, Nummer: 7, Seiten: 3278 - 3286
KurzfassungMicrofluidics allows the miniaturization of biochemical analyses. Small dimensions reduce sample and reagent consumption and enhance reaction rates. A downside is that high surface-to-volume ratios increase the unspecific binding of proteins to the substrate material. The resulting sample loss and reagent depletion decrease the sensitivity and specificity of protein-based assays, especially if low concentrations are analyzed. Here, we introduce the hydrophobin coating of microfluidic chips made of cyclic olefin copolymers (COC). The recombinant hydrophobin H*Protein B self-assembles into stable monolayers on hydrophobic surfaces, making them hydrophilic and thus reducing hydrophobic interactions between the chip surfaces and proteins. The substrate and sealing layers of the microfluidic chip were simply dip-coated and subsequently assembled by thermodiffusion bonding, which renders our coating procedure compatible with mass fabrication. Contact angle measurements and atomic force microscopy were used to evaluate the effect of high temperatures (107 °C) on COC substrates coated with H*Protein B. The efficiency of the protein-repellent coating was evaluated by depletion experiments with bovine serum albumin, human serum, and cerebrospinal fluid in microfluidic chips. Protein recovery was investigated down to protein concentrations of 0.3 μg/mL. Recoveries of 90% were observed with total protein amounts of 10 ng, even for microfluidic channels up to 835 mm in length and with a cross section of 80 μm × 230 μm in a COC 6013/8007 foil. For comparison, only 30 and 60% of the protein was recovered in uncoated microfluidic channels with lengths of 835 and 128 mm, respectively. The long-term stability of the hydrophobin-coated chips for 8 weeks was demonstrated.
F. Schlenker, E. Kipf, N. Borst, N. Paust, R. Zengerle, F. von Stetten, P. Juelg, T. Hutzenlaub
Centrifugal Microfluidic Integration of 4-Plex ddPCR Demonstrated by the Quantification of Cancer-Associated Point Mutations
2021 Processes, Band: 2021, Nummer: 9, Ergänzungsband: 97
KurzfassungWe present the centrifugal microfluidic implementation of a four-plex digital droplet polymerase chain reaction (ddPCR). The platform features 12 identical ddPCR units on a LabDisk cartridge, each capable of generating droplets with a diameter of 82.7 +/- 9 µm. By investigating different oil–surfactant concentrations, we identified a robust process for droplet generation and stabilization. We observed high droplet stability during thermocycling and endpoint fluorescence imaging, as is required for ddPCRs. Furthermore, we introduce an automated process for fourcolor fluorescence imaging using a commercial cell analysis microscope, including a customized software pipeline for ddPCR image evaluation. The applicability of ddPCRs is demonstrated by the quantification of three cancer-associated KRAS point mutations (G12D, G12V and G12A) in a diagnostically relevant wild type DNA background. The four-plex assay showed high sensitivity (3.5–35 mutant DNA copies in 15,000 wild type DNA copies) and linear performance (R2 = 0.99) across all targets in the LabDisk.
T. Gross, C. Jeney, D. Halm, G. Finkenzeller, G. B. Stark, R. Zengerle, P. Koltay, S. Zimmermann
Characterization of CRISPR/Cas9 RANKL knockout mesenchymal stem cell clones based on single-cell printing technology and Emulsion Coupling assay as a low-cellularity workflow for single-cell cloning
2021 Plos One, Band: 16, Nummer: 3, Seite: e0238330
KurzfassungThe homogeneity of the genetically modified single-cells is a necessity for many applications such as cell line development, gene therapy, and tissue engineering and in particular for regenerative medical applications. The lack of tools to effectively isolate and characterize CRISPR/Cas9 engineered cells is considered as a significant bottleneck in these applications. Especially the incompatibility of protein detection technologies to confirm protein expression changes without a preconditional large-scale clonal expansion creates a gridlock in many applications. To ameliorate the characterization of engineered cells, we propose an improved workflow, including single-cell printing/isolation technology based on fluorescent properties with high yield, a genomic edit screen (Surveyor assay), mRNA RT-PCR assessing altered gene expression, and a versatile protein detection tool called emulsion-coupling to deliver a high-content, unified single-cell workflow. The workflow was exemplified by engineering and functionally validating RANKL knockout immortalized mesenchymal stem cells showing bone formation capacity of these cells. The resulting workflow is economical, without the requirement of large-scale clonal expansions of the cells with overall cloning efficiency above 30% of CRISPR/Cas9 edited cells. Nevertheless, as the single-cell clones are comprehensively characterized at an early, highly parallel phase of the development of cells including DNA, RNA, and protein levels, the workflow delivers a higher number of successfully edited cells for further characterization, lowering the chance of late failures in the development process.
D. Kainz, B. Breiner, S. M. Früh, T. Hutzenlaub, R. Zengerle, N. Paust
Eliminating viscosity bias in lateral flow tests
2021 Microsystems & Nanoengineering, Band: 7, Seite: 72
S. Hin, B. Lopez-Jimena, M. Bakheit, V. Klein, S. Stack, C. Fall, A. Sall, K. Enan, M. Mustafa, V. Rusu, S. Goethel, N. Paust, R. Zengerle, L. Gillies, S. Frischmann, M. Weidmann, K. Mitsakakis
Fully automated point-of-care differential diagnosis of acute febrile illness
2021 PLoS Negl. Trop. Dis., Band: 15, Nummer: 2, Seite: e0009177
KurzfassungIn this work, a platform was developed and tested to allow to detect a variety of candidate viral, bacterial and parasitic pathogens, for acute fever of unknown origin. The platform is based on a centrifugal microfluidic cartridge, the LabDisk (“FeverDisk” for the specific application), which integrates all necessary reagents for sample-to-answer analysis and is processed by a compact, point-of-care compatible device...
M. Schulz, J. Ruediger, E. Landmann, M. Bakheit, S. Frischmann, D. Rassler, A. Homann, F. von Stetten, R. Zengerle, N. Paust
High Dynamic Range Digital Assay Enabled by Dual-Volume Centrifugal Step Emulsification
2021 Analytical Chemistry, Band: 93, Nummer: 5, Seiten: 2854 - 2860
KurzfassungWe implement dual-volume centrifugal step emulsification on a single chip to extend the dynamic range of digital assays. Compared to published single-volume approaches, the range between the lower detection limit (LDL) and the upper limit of quantification (ULQ) increases by two orders of magnitude. In comparison to existing multivolume approaches, the dual-volume centrifugal step emulsification requires neither complex manufacturing nor specialized equipment. Sample metering into two subvolumes, droplet generation, and alignment of the droplets in two separate monolayers are performed automatically by microfluidic design. Digital quantification is demonstrated by exemplary droplet digital loop-mediated isothermal amplification (ddLAMP). Within 5 min, the reaction mix is split into subvolumes of 10.5 and 2.5 μL, and 2,5k and 176k droplets are generated with diameters of 31.6 ± 1.4 and 213.9 ± 7.5 μm, respectively. After 30 min of incubation, quantification over 5 log steps is demonstrated with a linearity of R2 ≥ 0.992.
H. Nguyen, F. Lombeck, C. Schwarz, P. A. Heizmann, M. Adamski, H-F. Lee, B. Britton, S. Holdcroft, S. Vierrath, M. Breitwieser
Hydrocarbon-based Pemion™ proton exchange membrane fuel cells with state-of-the-art performance
2021 Sustainable Energy and Fuels, Band: 5, Seiten: 3687 - 3699
KurzfassungNon-fluorinated hydrocarbon ionomers feature distinct technical, cost, and environmental advantages over incumbent perfluorinated sulfonic acid (PFSA)-based ionomers: they offer improved thermo-mechanical properties at temperatures beyond 90 °C, likelihood of lower material cost, lower gas cross-over, and facile recycling of platinum group metals. In addition, fluorine-free hydrocarbon ionomers are less hazardous to the environment owing to the lack of (per)fluorinated precursors. Yet, the performance of hydrogen fuel cells with hydrocarbon-based ionomers and membranes has been historically largely inferior to the PFSA-based state of the art. In this study, we present wholly hydrocarbon fuel cells exceeding previous literature landmarks by a factor of nearly two, with peak power densities of 2.1 W cm−2 under H2/O2 (atmospheric pressure and 95% relative humidity), and 1.1 W cm−2 under H2/air (250 kPaabs and 50% relative humidity). This improvement was achieved by the use of Pemion™ – a sulfo-phenylated polyphenylene-based cation exchange material – as ionomer in the catalyst layer and as proton exchange membrane with a low thickness of 7 μm, and an optimization of cathode catalyst layer based on PtCo/C. Based on an in-depth study of electrochemical performance under various conditions vs. a state-of-the-art PFSA reference cell, the performances of Pemion™-based cells were found to be more sensitive to changes in relative humidity of inlet gases, but the detrimental influence of high temperatures on performance was significantly reduced. At an operation temperature of 110 °C, 250 kPaabs, and 50% relative humidity, the peak power density (0.96 W cm−2) was 8% higher than the short-side chain PFSA-based reference cell (0.89 W cm−2), highlighting the potential of Pemion™ for next-generation fuel cells for heavy-duty or aeronautic applications.
J.-N. Klatt, I. Schwarz, T. Hutzenlaub, R. Zengerle, F. Schwemmer, D. Kosse, J. Vincent, M. Scaer, K. Franaszczuk, D. Wadsworth, N. Paust
Miniaturization, Parallelization, and Automation of Endotoxin Detection by Centrifugal Microfluidics
2021 Analytical Chemistry, Band: 93, Nummer: 24
KurzfassungWe demonstrate microfluidic automation and parallelization of Limulus amebocyte lysate (LAL)-based bacterial endotoxin testing using centrifugal microfluidics. LAL is the standard reagent to test for endotoxin contaminations in injectable pharmaceuticals. The main features of the introduced system are more than 90% reduction of LAL consumption, from 100 μL/reaction to 9.6 μL/reaction, automated liquid handling to reduce opportunities for contamination and manual handling errors, and microfluidic parallelization by integrating 104 reactions into a single centrifugal microplate. In a single Eclipse microplate, 21 samples and their positive product controls are tested in duplicate. In addition, a standard curve with up to five points is generated, resulting in a total of 104 reactions. Test samples with a defined concentration of 0.5 endotoxin units per milliliter were tested, resulting in a coefficient of variation below 0.75%. A key feature for achieving a small coefficient of variation is ensuring the same path length along the microfluidic channels to the final reaction chambers for each sample and the reagent, so that any unspecific adsorption to the polymer surfaces does not affect the accuracy and precision. Analysis of a sample containing naturally occurring endotoxin with the developed microfluidic microplate yielded comparable results to the conventional testing method. A test with eight commercially available pharmaceuticals was found to pass all requirements for bacterial endotoxin testing as specified in the United States Pharmacopeia. The automated endotoxin testing system reveals specific advantages of centrifugal microfluidics for analytical biochemistry applications. Small liquid volumes are handled (metered, mixed, and aliquoted) in a very precise, highly integrated, and highly parallel manner within mass-fabricated microplates.
K. Mitsakakis
Novel lab-on-a-disk platforms: a powerful tool for molecular fingerprinting of oral and respiratory tract infections
2021 Expert Rev. Mol. Diagn., Band: 21, Nummer: 6, Seiten: 523 - 526
B. Johannsen, M. Karpíšek, D. Baumgartner, V. Klein, N. Bostanci, N. Paust, S. M. Früh, R. Zengerle, K. Mitsakakis
One-step, wash-free, bead-based immunoassay employing bound-free phase detection
2021 Analytica Chimica Acta, Band: 1153, Seite: 338280
KurzfassungWe present a simple and fast one-step heterogeneous immunoassay, with performance characteristics that can enable easy and versatile adaptation to miniaturized, automated point-of-care systems. This novel analytical method uses magnetic and fluorescent beads as capture and detection agents respectively. Its main feature is the measurement of the fluorescent signal in the bound-free phase for (semi-)quantitative detection of analytes. Thus, no washing is required and the workflow consists only of sample and reagent supply, incubation, separation and detection. The immunoassay concept is demonstrated with C-reactive protein (CRP), a systemic inflammation marker. CRP in only 5 μL of undiluted serum was measured in the range 20-140 mg L-1 (includes clinically relevant cut-off values). The limit of detection (LOD) was 22.1 ± 6.3 mg L-1 (incubation 15 min). A CRP certified reference material was measured on five different days. Intra- and inter-assay coefficients of variation were 4.6 % ± 1.9 % and 5.6 % respectively. To demonstrate the compatibility of the assay concept with additional matrices and concentration ranges, three oral inflammation markers, namely matrix metalloproteinases 8 and 9 (MMP-8, MMP-9) and tissue inhibitor of metalloproteinases 1 (TIMP-1), were measured in saliva in the ranges 0.47-30 ng mL-1 for MMP-8 and MMP-9, and 0.69-44 ng mL-1 for TIMP-1. LODs were 0.24 ng mL-1, 0.38 ng mL-1 and 0.39 ng mL-1 respectively (incubation 20 min). Multiplexing capacity of the assay concept was also shown with these markers. The demonstrated excellent reproducibility of the results, combined with the versatility and low complexity of the introduced immunoassay concept, make it an attractive candidate for applied analytical chemistry and automated point-of-care testing.
F. Koch, O. Thaden, K. Tröndle, R. Zengerle, S. Zimmermann, P. Koltay
Open-source hybrid 3D-bioprinter for simultaneous printing of thermoplastics and hydrogels
2021 HardwareX, Band: 10, Seite: e00230
D. Baumgartner, B. Johannsen, M. Specht, J. Lüddecke, M. Rombach, S. Hin, N. Paust, F. von Stetten, R. Zengerle, C. Herz, J. R. Peham, P. N. Paqué, T. Attin, J. S. Jenzer, P. Körner, P. R. Schmidlin, T. Thurnheer, F. J. Wegehaupt, W. E. Kaman, A. Stubbs, J. P. Hays, V. Rusu, A. Michie, T. Binsl, D. Stejskal, M. Karpíšek, K. Bao, N. Bostanci, G. N. Belibasakis, K. Mitsakakis
OralDisk: A Chair-Side Compatible Molecular Platform Using Whole Saliva for Monitoring Oral Health at the Dental Practice
2021 Biosensors, Band: 11, Nummer: 11, Seite: 423
B. Shanahan, B. Britton, A. Belletti, S. Vierrath, M. Breitwieser
Performance and stability comparison of Aemion™ and Aemion+™ membranes for vanadium redox flow batteries
2021 RSC Advances, Band: 11, Nummer: 22, Seiten: 13077 - 13084
KurzfassungAnion exchange membranes (AEMs) have shown a significant rise in performance and durability within recent years for applications such as electrolysis and fuel cells. However, in vanadium redox-flow batteries, their use is of particular interest to lower costs and self-discharge rates compared to conventional perfluorinated sulfonic acid-based ionomers such as Nafion. In this work we evaluate the properties of two commercial AEMs, Aemion™ and Aemion+™, based on ex situ characterizations, an accelerated stress test degradation study (>1000 hours storage in highly oxidizing VO2+ electrolyte at 35 °C) and electrochemical battery cycle tests. All membranes feature low ionic resistances of below 320 mΩ cm2, enabling battery cycling at 100 mA cm−2. Aemion shows considerable VO2+ formation within a VO2+ stress test, whereas Aemion+ remains almost unaffected in the 1058 h stress test. Evaluating self-discharge data, cycling performance and durability data, Aemion+™ (50 μm thickness) features the best properties for vanadium redox-flow battery operation.
L. Becherer, J. F. Hess, S. Frischmann, M. Bakheit, H. Nitschko, S. Stinco, F. Zitz, H. Hofer, G. Porro, F. Hausladen, K. Stock, D. Drossart, H. Wurm, H. Kuhn, D. Huber, T. Hutzenlaub, N. Paust, M. Keller, O. Strohmeier, S. Wadle, N. Borst, R. Zengerle, F. von Stetten
Point-of-Care System for HTLV-1 Proviral Load Quantification by Digital Mediator Displacement LAMP
2021 Micromachines, Band: 12, Nummer: 2, Seite: 159
KurzfassungThis paper presents a universal point-of-care system for fully automated quantification of human T-cell lymphotropic virus type 1 (HTLV-1) proviral load, including genomic RNA, based on digital reverse RNA transcription and c-DNA amplification by MD LAMP (mediator displacement loop-mediated isothermal amplification). A disposable microfluidic LabDisk with pre-stored reagents performs automated nucleic acid extraction, reaction setup, emulsification, reverse transcription, digital DNA amplification, and quantitative fluorogenic endpoint detection with universal reporter molecules. Automated nucleic acid extraction from a suspension of HTLV-1-infected CD4+ Tlymphocytes (MT-2 cells) yielded 8 +/- 7 viral nucleic acid copies per MT-2 cell, very similar to the manual reference extraction (7 +/- 2 nucleic acid copies). Fully automated sample processing from whole blood spiked with MT-2 cells showed a comparable result of 7 +/- 3 copies per MT-2 cell after a run time of two hours and 10 min.
A. Brunauer, R. D. Verboket, D. M. Kainz, F. von Stetten, S. M. Früh
Rapid Detection of Pathogens in Wound Exudate via Nucleic Acid Lateral Flow Immunoassay
2021 Biosensors, Band: 11, Nummer: 3, Seite: 74
KurzfassungThe rapid detection of pathogens in infected wounds can significantly improve the clinical outcome. Wound exudate, which can be collected in a non-invasive way, offers an attractive sample material for the detection of pathogens at the point-of-care (POC). Here, we report the development of a nucleic acid lateral flow immunoassay for direct detection of isothermally amplified DNA combined with fast sample preparation. The streamlined protocol was evaluated using human wound exudate spiked with the opportunistic pathogen Pseudomonas aeruginosa that cause severe health issues upon wound colonization. A detection limit of 2.1 × 105 CFU per mL of wound fluid was achieved, and no cross-reaction with other pathogens was observed. Furthermore, we integrated an internal amplification control that excludes false negative results and, in combination with the flow control, ensures the validity of the test result. The paper-based approach with only three simple hands-on steps has a turn-around time of less than 30 min and covers the complete analytical process chain from sample to answer. This newly developed workflow for wound fluid diagnostics has tremendous potential for reliable pathogen POC testing and subsequent target-oriented therapy.
B. Shanahan, K. Seteiz, P. A. Heizmann, S. Koch, J. Büttner, S. Ouardi, S. Vierrath, A. Fischer, M. Breitwieser
Rapid wet-chemical oxidative activation of graphite felt electrodes for vanadium redox flow batteries
2021 RSC Advances, Band: 11, Nummer: 51, Seiten: 32095 - 32105
A. Lux, H. Bott, N. P. Malek, R. Zengerle, T. Maucher, J. Hoffmann, 1
Real-Time Detection of Tumor Cells during Capture on a Filter Element Significantly Enhancing Detection Rate
2021 Biosensors, Band: 11, Nummer: 9, Seite: 312
P.N. Paqué, C. Herz, D.B. Wiedemeier, K. Mitsakakis, T. Attin, K. Bao, G.N. Belibasakis, J.P. Hays, J.S. Jenzer, W.E Kaman, M. Karpíšek, P. Körner, J.R. Peham, P.R. Schmidlin, T. Thurnheer, F.J. Wegehaupt, N. Bostanci
Salivary Biomarkers for Dental Caries Detection and Personalized Monitoring
2021 J. Pers. Med., Band: 11, Nummer: 3, Seite: 235
KurzfassungThis study investigated the potential of salivary bacterial and protein markers for evaluating the disease status in healthy individuals or patients with gingivitis or caries. Saliva samples from caries- and gingivitis-free individuals (n = 18), patients with gingivitis (n = 17), or patients with deep caries lesions (n = 38) were collected and analyzed for 44 candidate biomarkers (cytokines, chemokines, growth factors, matrix metalloproteinases, a metallopeptidase inhibitor, proteolytic enzymes, and selected oral bacteria). The resulting data were subjected to principal component analysis and used as a training set for random forest (RF) modeling. This computational analysis revealed four biomarkers (IL-4, IL-13, IL-2-RA, and eotaxin/CCL11) to be of high importance for the correct depiction of caries in 37 of 38 patients. The RF model was then used to classify 10 subjects (five caries-/gingivitis-free and five with caries), who were followed over a period of six months. The results were compared to the clinical assessments of dental specialists, revealing a high correlation between the RF prediction and the clinical classification. Due to the superior sensitivity of the RF model, there was a divergence in the prediction of two caries and four caries-/gingivitis-free subjects. These findings suggest IL-4, IL-13, IL-2-RA, and eotaxin/CCL11 as potential salivary biomarkers for identifying noninvasive caries. Furthermore, we suggest a potential association between JAK/STAT signaling and dental caries onset and progression.
S. M. Früh, U. Matti, P. R. Spycher, M. Rubini, S. Lickert, T. Schlichthaerle, R. Jungmann, V. Vogel, J. Ries, I. Schoen
Site-Specifically-Labeled Antibodies for Super-Resolution Microscopy Reveal In Situ Linkage Errors
2021 ACS Nano, Band: 15, Nummer: 7, Seiten: 12161 - 12170
KurzfassungThe precise spatial localization of proteins in situ by super-resolution microscopy (SRM) demands their targeted labeling. Positioning reporter molecules as close as possible to the target remains a challenge in primary cells or tissues from patients that cannot be easily genetically modified. Indirect immunolabeling introduces relatively large linkage errors, whereas site-specific and stoichiometric labeling of primary antibodies relies on elaborate chemistries. In this study, we developed a simple two-step protocol to site-specifically attach reporters such as fluorophores or DNA handles to several immunoglobulin G (IgG) antibodies from different animal species and benchmarked the performance of these conjugates for 3D STORM (stochastic optical reconstruction microscopy) and DNA-PAINT (point accumulation in nanoscale topography). Glutamine labeling was restricted to two sites per IgG and saturable by exploiting microbial transglutaminase after removal of N-linked glycans. Precision measurements of 3D microtubule labeling shell dimensions in cell lines and human platelets showed that linkage errors from primary and secondary antibodies did not add up. Monte Carlo simulations of a geometric microtubule-IgG model were in quantitative agreement with STORM results. The simulations revealed that the flexible hinge between Fab and Fc segments effectively randomized the direction of the secondary antibody, while the restricted binding orientation of the primary antibody’s Fab fragment accounted for most of the systematic offset between the reporter and α-tubulin. DNA-PAINT surprisingly yielded larger linkage errors than STORM, indicating unphysiological conformations of DNA-labeled IgGs. In summary, our cost-effective protocol for generating well-characterized primary IgG conjugates offers an easy route to precise SRM measurements in arbitrary fixed samples.
M. Drews, J. Büttner, M. Bauer, J. Ahmed, R. Sahu, S. Vierrath, C. Scheu, A. Fischer, D. Biro
Spruce Hard Carbon Anodes for Lithium-Ion Batteries
2021 ChemElectroChem, Band: 8, Seiten: 4750 - 4761
F. Schlenker, E. Kipf, M. Deuter, I. Höffkes, M. Lehnert, R. Zengerle, F von Stetten, F. Scherer, J. Wehrle, N. von Bubnoff, P. Juelg, T. Hutzenlaub, N. Borst
Stringent Base Specific and Optimization-Free Multiplex Mediator Probe ddPCR for the Quantification of Point Mutations in Circulating Tumor DNA
2021 cancers, Band: 13, Nummer: 22, Seite: 5742
P. Juelg, E. Kipf, M. Specht, M. Fillies, C. Eckert, N. Paust, R. Zengerle, M. Lehnert, T. Hutzenlaub
The MRD disk: automated minimal residual disease monitoring by highly sensitive centrifugal microfluidic multiplex qPCR
2021 Lab Chip, Band: 21, Seiten: 558 - 570
KurzfassungWe present a proof-of-principle study on automated, highly sensitive and multiplexed qPCR quantification by centrifugal microfluidics. The MRD disk can be used for standardisation of repetitive, longitudinal assays with high requirements on reproducibility and sensitivity, such as cancer monitoring. In contrast to high-throughput qPCR automation by bulky and expensive robotic workstations we employ a small centrifugal microfluidic instrument, addressing the need of low- to mid-throughput applications. As a potential application we demonstrate automated minimum residual disease (MRD) monitoring of prognostic markers in patients with acute lymphoblastic leukaemia (ALL). The disk-workflow covers all aspects of clinical gold standard MRD quantification: generation of standard curves, specificity controls, no template controls and quantification of the ALL patient sample. We integrated a highly sensitive, colorimetric 2-plex analysis of MRD targets, as well as a 2-plex analysis of reference genes, both in parallel and in a single LabDisk cartridge. For this purpose, a systematic procedure for crosstalk- and signal-to-noise-optimisation is introduced, providing a guideline for efficient multiplex readout inside microfluidic platforms. The qPCR standard curves (n = 12/12) generated on-disk reach clinically required linearity (R2 = 98.1% to R2 = 99.8%). In three consecutive MRD disk runs with an ALL patient sample containing the two representative MRD targets VH3D3D5JH3 and VkIkde, we observe high accordance between the on-disk quantifications (48 ± 6 copies/reaction and 69 ± 6 copies/reaction) and the expected concentrations (57 copies/reaction for both targets). In comparison to the clinical gold standard of manually pipetted, singleplex assays, the MRD disk yields comparable limit of quantification (1 × 10−4) in n = 6/6 analyses (vs. n = 4/4 in gold standard) and a limit of detection (1 × 10−5) in n = 6/6 analysis (vs. n = 2/4 in gold standard). The automation reduces the risk of manual liquid handling errors, making the MRD disk an attractive solution to assure reproducibility in moderate-throughput, longitudinal gene quantification applications.
S. Koch, P. A. Heizmann, S. K. Kilian, B. Britton, S. Holdcroft, M. Breitwieser, S. Vierrath
The effect of ionomer content in catalyst layers in anion-exchange membrane water electrolyzers prepared with reinforced membranes (Aemion+™)
2021 J. Mater. Chem. A, Band: 9, Seiten: 15744 - 15754
M. Tsagiopoulou, M. C. Maniou, N. Pechlivanis, A. Togkousidis, M. Kotrová, T. Hutzenlaub, I. Kappas, A. Chatzidimitriou, F. Psomopoulos
UMIc: A Preprocessing Method for UMI Deduplication and Reads Correction
2021 Front. Genet., Band: May, 28
N. Bostanci, K. Mitsakakis, B. Afacan, K. Bao, B. Johannsen, D. Baumgartner, L. Müller, H. Kotolová, G. Emingil, M. Karpíšek
Validation and verification of predictive salivary biomarkers for oral health
2021 Scientific Reports, Band: 11, Seite: 6406
KurzfassungOral health is important not only due to the diseases emerging in the oral cavity but also due to the direct relation to systemic health. Thus, early and accurate characterization of the oral health status is of utmost importance. There are several salivary biomarkers as candidates for gingivitis and periodontitis, which are major oral health threats, affecting the gums. These need to be verified and validated for their potential use as differentiators of health, gingivitis and periodontitis status, before they are translated to chair-side for diagnostics and personalized monitoring. We aimed to measure 10 candidates using high sensitivity ELISAs in a well-controlled cohort of 127 individuals from three groups: periodontitis (60), gingivitis (31) and healthy (36). The statistical approaches included univariate statistical tests, receiver operating characteristic curves (ROC) with the corresponding Area Under the Curve (AUC) and Classification and Regression Tree (CART) analysis. The main outcomes were that the combination of multiple biomarker assays, rather than the use of single ones, can offer a predictive accuracy of > 90% for gingivitis versus health groups; and 100% for periodontitis versus health and periodontitis versus gingivitis groups. Furthermore, ratios of biomarkers MMP-8, MMP-9 and TIMP-1 were also proven to be powerful differentiating values compared to the single biomarkers
F. Schlenker, E. Kipf, N. Borst, T. Hutzenlaub, R. Zengerle, F. von Stetten, P. Juelg
Virtual Fluorescence Color Channels by Selective Photobleaching in Digital PCR Applied to the Quantification of KRAS Point Mutations
2021 Analytical Chemistry, Band: 93, Nummer: 30, Seiten: 10538 - 10545
KurzfassungMultiplexing of analyses is essential to reduce sample and reagent consumption in applications with large target panels. In applications such as cancer diagnostics, the required degree of multiplexing often exceeds the number of available fluorescence channels in polymerase chain reaction (PCR) devices. The combination of photobleaching-sensitive and photobleaching-resistant fluorophores of the same color can boost the degree of multiplexing by a factor of 2 per channel. The only additional hardware required to create virtual fluorescence color channels is a low-cost light-emitting diode (LED) setup for selective photobleaching. Here, we present an assay concept for fluorescence color multiplexing in up to 10 channels (five standard channels plus five virtual channels) using the mediator probe PCR with universal reporter (UR) fluorogenic oligonucleotides. We evaluate the photobleaching characteristic of 21 URs, which cover the whole spectral range from blue to crimson. This comprehensive UR data set is employed to demonstrate the use of three virtual channels in addition to the three standard channels of a commercial dPCR device (blue, green, and red) targeting cancer-associated point mutations (KRAS G12D and G12V). Moreover, a LOD (limit of detection) analysis of this assay confirms the high sensitivity of the multiplexing method (KRAS G12D: 16 DNA copies/reaction in the standard red channel and KRAS G12V: nine DNA copies/reaction in the virtual red channel). Based on the presented data set, optimal fluorogenic reporter combinations can be easily selected for the application-specific creation of virtual channels, enabling a high degree of multiplexing at low optical and technical effort.

2020

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C. Klose, T. Saatkamp, A. Münchinger, L. Bohn, G. Titvinidze, M. Breitwieser, K.-D. Kreuer, S. Vierrath
All-Hydrocarbon MEA for PEM Water Electrolysis Combining Low Hydrogen Crossover and High Efficiency
2020 Adv Energy Mater, Seite: 1903995
KurzfassungHydrocarbon ionomers bear the potential to significantly lower the material cost and increase the efficiency of proton-exchange membrane water electrolyzers (PEMWE). However, no fully hydrocarbon membrane electrode assembly (MEA) with a performance comparable to Nafion-MEAs has been reported. PEMWE-MEAs are presented comprising sPPS as membrane and electrode binder reaching 3.5 A cm−2 at 1.8 V and thus clearly outperforming state-of-the-art Nafion-MEAs (N115 as membrane, 1.5 A cm−2 at 1.8 V) due to a significantly lower high frequency resistance (57 ± 4 mΩ cm² vs 161 ± 7 mΩ cm²). Additionally, pure sPPS-membranes show a three times lower gas crossover (<0.3 mA cm−2) than Nafion N115-membranes (>1.1 mA cm−2) in a fully humidified surrogate test. Furthermore, more than 80 h of continuous operation is shown for sPPS-MEAs in a preliminary durability test (constant current hold at 1 A cm−2 at 80 °C). These results rely on the unique transport properties of sulfonated poly(phenylene sulfone) (sPPS) that combines high proton conductivity with low gas crossover.
D. Podbiel, R. Zengerle, J. Hoffmann
An analytical model for void-free priming of microcavities
2020 Microfluid Nanofluid, Band: 24, Nummer: 16
KurzfassungThe present work deals with the microfluidic evolution of capillary surfaces that are formed during the priming of microcavity structures with a non-wetting liquid. Due to the large contact angle of the priming liquid, a trapping of air within the microcavities poses a major impediment to a complete filling. We tackle this issue by developing a two-dimensional analytical model describing the geometrical shape of capillary surfaces formed in microcavity structures. In particular, the model is employed to derive two quantitative conditions for a void-free priming of a microcavity structure in terms of its aspect ratio, rounding parameters and the channel width. Microfluidic experiments are performed to verify the analytical results. Finally, we make use of the model to demonstrate a pressure-driven aliquoting of a non-wetting sample liquid in a flow chamber with an array of 55 microcavities by introducing a second immiscible liquid acting as a sealant. In this way, our work constitutes a basis for the design of microcavity-based liquid aliquoting structures that are used in various fields of application like PCR arrays, cell culture chips or digital reaction arrays.
J. F. Hess, M. Kotrová, S. Calabrese, N. Darzentas, T. Hutzenlaub, R. Zengerle, M. Brüggemann, N. Paust
Automation of amplicon-based library preparation for next generation sequencing by centrifugal microfluidics
2020 Anal Chem, Band: 92, Nummer: 19, Seiten: 12833 - 12841
KurzfassungNext generation sequencing has become a mainstream method in bioanalysis. Improvements in sequencing and bioinformatics turned the complex and cumbersome library preparation to the bottle neck in terms of reproducibility and costs in the complete NGS workflow. Here, we introduce an automated library preparation approach based on a generic centrifugal microfluidic car-tridge. Multiplex polymerase chain reaction amplification and subsequent clean-up were processed with all reagents pre-stored on disk, including cell line-based DNA as quality control. Exchange of pre-stored reagents allows to apply the cartridge to different target genes. Sequencing of automatically prepared libraries from T-cell receptor and immunoglobulin gene rearrangements in context of lymphoproliferative disorders demonstrated excellent clean-up performance between 91.9% and 99.9% of target DNA reads and successful amplification of all target regions by up to 15 forward combined with four reverse primers. The fully auto-mated library preparation by centrifugal microfluidics thus offers attractive automation options in diagnostic settings.
Z. Shu, M. Fechtig, F. Lombeck, M. Breitwieser, Roland Zengerle, Peter Koltay
Direct Drop-on-Demand Printing of Molten Solder Bumps on ENIG Finishing at Ambient Conditions through StarJet Technology
2020 IEEE Access, Band: 8, Seiten: 210225 - 210233
KurzfassungIn this paper, we report on a detailed experimental study carried out with the StarJet technology to investigate the mechanical adhesion properties of directly printed solder bumps on electroless nickel immersion gold (ENIG) plated PCB boards. The aim of this study is to determine the maximum bond strength achievable by this method and to find suitable printing parameters that allow for the production of reliable and consistent solder bumps by non-contact printing of molten solder (type SAC305). Molten solder droplets of about 250 μm diameter were printed at melt temperatures between 250 and 400 °C onto ENIG surfaces kept at temperatures in the range of 100 to 200 °C. Using shear force tests, the adhesion of the printed bumps was investigated as a function of the main process parameters: 1. printhead temperature, 2. substrate temperature, and 3. substrate preheating time. The formation of an intermetallic compound (IMC) between the solder and the ENIG was confirmed by scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX) measurements. As a result of the comprehensive experimental parameter study, suitable printing parameters for establishing bond strengths corresponding to maximum shear force values of 3000 to 4000 mN could be found, i.e. high printhead temperature of 400 °C, short preheating and time of < 2 min, and substrate heating at 180 °C The use of flux was found to slightly improve the bond strength and to improve the consistency of the printing results for extended operation times. The achieved high bond strength and the reasonable reproducibility of the printing results qualify the StarJet technology for further investigations regarding applications in the field of direct soldering of microelectronic chips and devices to PCB boards as well as other micro-assembly tasks in the future.
P. Holzapfel, M. Bühler, C. Van Pham, F. Hegge, T. Böhm, D. McLaughlin, M. Breitwieser, S. Thiele
Directly coated membrane electrode assemblies for proton exchange membrane water electrolysis
2020 Electrochemistry Communications, Band: 110, Seite: 106640
F. Hegge, F. Lombeck, E. Cruz Ortiz, L. Bohn, M. von Holst, M. Kroschel, J. Hübner, M. Breitwieser, P. Strasser, S. Vierrath
Efficient and Stable Low Iridium Loaded Anodes for PEM Water Electrolysis Made Possible by Nanofiber Interlayers
2020 ACS Appl. Energy Mater, Band: 3, Nummer: 9, Seiten: 8276 - 8284
KurzfassungSignificant reduction of the precious metal catalyst loading is one of the key challenges for the commercialization of proton-exchange membrane water electrolyzers. In this work we combine IrOx nanofibers with a conventional nanoparticle-based IrOx anode catalyst layer. With this hybrid design we can reduce the iridium loading by more than 80% while maintaining performance. In spite of an ultralow overall catalyst loading of 0.2 mgIr/cm2, a cell with a hybrid layer shows similar performance compared to a state-of-the-art cell with a catalyst loading of 1.2 mgIr/cm2 and clearly outperforms identically loaded reference cells with pure IrOx nanoparticle and pure nanofiber anodes. The improved performance is attributed to a combination of good electric contact and high porosity of the IrOx nanofibers with high surface area of the IrOx nanoparticles. Besides the improved performance, the hybrid layer also shows better stability in a potential cycling and a 150 h constant current test compared to an identically loaded nanoparticle reference.
R. Moroni, S. Thiele
FIB/SEM tomography segmentation by optical flow estimation
2020 Ultramicroscopy, Band: 219, Seite: 113090
KurzfassungFocused ion beam/scanning electron microscopy tomography (FIB/SEM tomography) is the method of choice for the tomographic reconstruction of mesoporous materials systems in various fields such as batteries, fuel cells, filter applications or composite materials. However, due to so called shine-through artifacts in FIB/SEM tomographies of porous materials, their segmentation into pore space and solid material is a nontrivial task. Here, an optical flow-based method that utilizes shine-through artifacts for segmentation is introduced. Subsequently, the performance of the method is discussed by means of tomographic datasets of a polymer electrolyte fuel cell catalyst layer and a lithium ion battery composite electrode. Previous, manual segmentations of these datasets allow the evaluation of the results – for the catalyst layer an accuracy of 86.6% and a precision of 84.0% is reached. In both cases, the optical flow-based approach gives significantly better results than comparable segmentations obtained from gray-value threshold binarization.
P. Holzapfel, M. Bühler, D. Escalera-López, M. Bierling, F. Speck, K. Mayrhofer, S. Cherevko, C. V. Pham, S. Thiele
Fabrication of a Robust PEM Water Electrolyzer Based on Non-Noble Metal Cathode Catalyst: [Mo3S13]2− Clusters Anchored to N-Doped Carbon Nanotubes
2020 Small, Seite: 2003161
KurzfassungHigh investment costs and a dependence on noble metal catalysts currently obstruct the large-scale implementation of proton exchange membrane water electrolyzers (PEMWEs) for converting fluctuating green electricity into chemical energy via water splitting. In this context, this work presents a high-performing and stable non-noble metal catalyst for the hydrogen evolution reaction (HER), consisting of [Mo3S13]2− clusters supported on nitrogen doped carbon nanotubes (NCNTs). Strikingly, a significant electrochemically induced activation of the Mo3S13-NCNT catalyst at high current densities is observed in full cell configuration, enabling a remarkable current density of 4 A cm−2 at a cell voltage of 2.36 V. To the authors’ knowledge, this is the highest reported value to date for a PEMWE full cell using a non-noble metal HER catalyst. Furthermore, only a minor degradation of 83 μV h−1 is observed during a stability test of 100 h constant current at 1 A cm−2, with a nearly unchanged polarization behavior after the current hold. Catalyst stability and activity are additionally analyzed via online dissolution measurements. X-ray photoelectron spectroscopy examination of the catalyst before and after electrochemical application reveals a correlation between the electrochemical activation occurring via electrodissolution with changes in the molecular structure of the Mo3S13-NCNT catalyst.
D. Podbiel, L. Boecking, H. Bott, J. Kassel, D. Czurratis, F. Laermer, R. Zengerle, J. Hoffmann
From CAD to microfluidic chip within one day: rapid prototyping of lab-on-chip cartridges using generic polymer parts
2020 J Micromech Microeng, Band: 30, Nummer: 11, Seite: 5012
KurzfassungWe report on a novel rapid prototyping approach for the manufacturing of highly individualized lab-on-chip (LoC) cartridges from generic polymer parts by laser micromachining and laser welding. The approach allows an immediate implementation of microfluidic networks, components, and functionalities into an existing LoC platform without the need for an expensive and time-consuming fabrication of production tools like molds or masks. We comprehensively describe the individual process steps of the rapid prototyping procedure including a wet-chemical treatment for an easy and effective surface polishing of laser micromachined polymer parts. For laying out, we introduce a generalized diagrammatic description of microfluidic functional units in order to design application-specific cartridges for molecular diagnostic workflows. We demonstrate the usability of our prototyped cartridges by performing microfluidic experiments within. Due to the use of generic polymer parts, our rapid prototyping approach combines a high degree of freedom with an intrinsic compatibility to an established and highly developed LoC system. By enabling an experimental testing within one day, the rapid prototyping procedure shortens development cycles and boosts the evolution of microfluidic networks as well as the implementation of novel microfluidic components and functionalities.
D. Podbiel, F. Laermer, R. Zengerle, J. Hoffmann
Fusing MEMS technology with lab-on-chip: nanoliter-scale silicon microcavity arrays for digital DNA quantification and multiplex testing
2020 Microsyst Nanoeng, Band: 6, Seite: 82
KurzfassungWe report on the development of a microfluidic multiplexing technology for highly parallelized sample analysis via quantitative polymerase chain reaction (PCR) in an array of 96 nanoliter-scale microcavities made from silicon. This PCR array technology features fully automatable aliquoting microfluidics, a robust sample compartmentalization up to temperatures of 95 °C, and an application-specific prestorage of reagents within the 25 nl microcavities. The here presented hybrid silicon–polymer microfluidic chip allows both a rapid thermal cycling of the liquid compartments and a real-time fluorescence read-out for a tracking of the individual amplification reactions taking place inside the microcavities. We demonstrate that the technology provides very low reagent carryover of prestored reagents < 6 × 10−2 and a cross talk rate < 1 × 10−3 per PCR cycle, which facilitate a multi-targeted sample analysis via geometric multiplexing. Furthermore, we apply this PCR array technology to introduce a novel digital PCR-based DNA quantification method: by taking the assay-specific amplification characteristics like the limit of detection into account, the method allows for an absolute gene target quantification by means of a statistical analysis of the amplification results.
F. Koch, K. Tröndle, G. Finkenzeller, R. Zengerle, S. Zimmermann, P. Koltay
Generic method of printing window adjustment for extrusion-based 3D-bioprinting to maintain high viability of mesenchymal stem cells in an alginate-gelatin hydrogel
2020 Bioprinting, Seite: e00094
KurzfassungOver the last decade, bioprinting of artificial tissues has been developed into a significant field of research. With an increasing number of printing technologies and bioinks used in bioprinting, its complexity increases as both the printing technology and the properties of the bioink influence the cell biological functionality and printing accuracy of the printed tissue. Therefore, optimization of bioprinting processes often remains a challenge, which could be solved by a smart fine-tuning of the process parameters. We present a novel method to adjust the printing window for extrusion-based bioprinting on the basis of a two-step assessment to determine process parameters such as nozzle size, extrusion flow rate, and printing temperature. First, a suitable printing temperature is deduced from the bioink properties and second nozzle size and extrusion flow rate is selected in a way that the immediate cell damage after printing is reduced. For both steps only basic rheological properties of the bioinks need to be known as well as detailed knowledge of the cell survival in the bioink for different shear stresses. This method is applied to an exemplary alginate-gelatin hydrogel to show how the printing temperature affects the achievable printing accuracy. For this bioink, viability of immortalized mesenchymal stem cells (iMSC) decreases with about 4% per thousand Pascal increase in maximum shear stress. For different combinations of flow rate, nozzle size and nozzle shape it is shown, that only the maximum shear stress experienced by the iMSCs influences average cell viability. Factors like flow rate, nozzle size and shape only play an indirect role by influencing the maximum shear stress and individually have no significant influence on cell viability. The experimental results allow a direct adjustment of printing parameters for the presented combination of hydrogel and cell type but are not limited to it. For other bioinks, the described generic method can be easily used to systematically adjust the printing parameters. For this purpose, only the basic rheological properties and the influence of shear stress on cell survival need to be known and process parameters can be set concerning the respective application.
Y.-T. Kao, T. S. Kaminski, W. Postek, J. Guzowski, K. Makuch, A. Ruszczak, F. von Stetten, R. Zengerle, P. Garstecki
Gravity-driven microfluidic assay for digital enumeration of bacteria and for antibiotic susceptibility testing
2020 Lab Chip, Band: 20, Seiten: 54 - 63
KurzfassungThe alarming dynamics of antibiotic-resistant infections calls for the development of rapid and point-of-care (POC) antibiotic susceptibility testing (AST) methods. Here, we demonstrated the first completely stand-alone microfluidic system that allowed the execution of digital enumeration of bacteria and digital antibiograms without any specialized microfluidic instrumentation. A four-chamber gravity-driven step emulsification device generated ∼2000 monodisperse 2 nanoliter droplets with a coefficient of variation of 8.9% of volumes for 95% of droplets within less than 10 minutes. The manual workload required for droplet generation was limited to the sample preparation, the deposition into the sample inlet of the chip and subsequent orientation of the chip vertically without an additional pumping system. The use of shallow chambers imposing a 2D droplet arrangement provided superior stability of the droplets against coalescence and minimized the leakage of the reporter viability dye between adjacent droplets during long-term culture. By using resazurin as an indicator of the growth of bacteria, we were also able to reduce the assay time to ∼5 hours compared to 20 hours using the standard culture-based test.
G.N. Belibasakis, B. Lund, C. Krüger Weiner, B. Johannsen, D. Baumgartner, D. Manoil, M. Hultin, K. Mitsakakis
Healthcare Challenges and Future Solutions in Dental Practice: Assessing Oral Antibiotic Resistances by Contemporary Point-of-Care Approaches
2020 Antibiotics, Band: 9, Seite: 810
KurzfassungAntibiotic resistance poses a global threat, which is being acknowledged at several levels, including research, clinical implementation, regulation, as well as by the World Health Organization. In the field of oral health, however, the issue of antibiotic resistances, as well as of accurate diagnosis, is underrepresented. Oral diseases in general were ranked third in terms of expenditures among the EU-28 member states in 2015. Yet, the diagnosis and patient management of oral infections, in particular, still depend primarily on empiric means. On the contrary, on the global scale, the field of medical infections has more readily adopted the integration of molecular-based systems in the diagnostic, patient management, and antibiotic stewardship workflows. In this perspective review, we emphasize the clinical significance of supporting in the future antibiotic resistance screening in dental practice with novel integrated and point-of-care operating tools that can greatly support the rapid, accurate, and efficient administration of oral antibiotics.

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L. Cojocaru, K. Wienands, U. Erdil, P. Schulze, L. Mundt, A. Bett, M. Breitwieser, F. Lombeck, M. Prescher, L. Kirste, S. Vierrath, J. Goldschmidt
Hybrid Evaporation/Spray-Coating Process for a Simplified and Controllable Production of Perovskite Solar Cells
2020 Journal of Photovoltaics, Band: 10, Nummer: 1, Seiten: 276 - 286
E.C. Ortiz, F. Hegge, M. Breitwieser, S. Vierrath
Improving the performance of proton exchange membrane water electrolyzers with low Ir-loaded anodes by adding PEDOT: PSS as electrically conductive binder
2020 Rsc Adv, Band: 10, Nummer: 62, Seiten: 37329 - 37927
KurzfassungReducing the iridium catalyst loading in the anode of polymer electrolyte membrane electrolyzers is a major goal to bring down the cost. However, anodes with low Ir-loading can suffer from poor electrical connectivity and hence lower the efficiency of the electrolyzer. In this work, we replace parts of the Nafion binder in the anode with an electrically conductive polymer (poly-3,4-ethylenedioxythiophene and polystyrene sulfonate acid complex, PEDOT:PSS) to counter this effect. At the optimal 50 : 50 blend we achieve a 120 mV lower overpotential (2.02 V) at 3 A cm−2 compared to a pure Nafion reference (2.14 V). This corresponds to a 6% better efficiency. Ex situ resistivity measurements and high frequency resistance measurements indicate that the major cause for this improvement lies in the reduced electrical in-plane resistance due to the electrical conductivity of PEDOT:PSS.
P. Veh, B. Britton, S. Holdcroft, R. Zengerle, S. Vierrath, M. Breitwieser
Improving the water management in anion-exchange membrane fuel cells via ultra-thin, directly deposited solid polymer electrolyte
2020 Rsc Adv, Band: 10, Seiten: 8645 - 8652
KurzfassungThin ionomer membranes are considered key to achieve high performances in anion exchange membrane fuel cells. However, the handling of unsupported anion exchange membranes with thicknesses below 15 μm is challenging. Typical pre-treatments of KOH-soaking, DI-water rinsing and/or wet assembly with sub-15 μm thin films are particularly problematic. In this work, we report configurations of membrane electrode assemblies with solid polymer electrolyte thicknesses equivalent to 3, 5 and 10 μm, made possible by direct coating of the ionomer onto gas diffusion electrodes (direct membrane deposition). The anion-conducting solid polymer electrolyte employed is hexamethyl-p-terphenyl poly(benzimidazolium) (HMT-PMBI), which is known for its high mechanical stability and low rate of gas crossover. By fabricating membrane-electrode-assemblies with PtRu/C anodes and Pt/C cathodes with a low precious metal loading of <0.3 mg cm−2, reproducible performances beyond 1 W cm−2 in H2/O2 atmosphere are achieved. The thin membranes enable excellent performance robustness towards changes in relative humidity, as well as low ionic resistances (<40 mOhm cm2).
P. Rukavina, F. Koch, M. Wehrle, K. Tröndle, G. B. Stark, P. Koltay, S. Zimmermann, R. Zengerle, F. Lampert, S. Strassburg, G. Finkenzeller, F. Simunovic
In vivo evaluation of bioprinted prevascularized bone tissue
2020 Biotechnol Bioeng, Seiten: 1 - 10
KurzfassungBioprinting can be considered as a progression of the classical tissue engineering approach, in which cells are randomly seeded into scaffolds. Bioprinting offers the advantage that cells can be placed with high spatial fidelity within three‐dimensional tissue constructs. A decisive factor to be addressed for bioprinting approaches of artificial tissues is that almost all tissues of the human body depend on a functioning vascular system for the supply of oxygen and nutrients. In this study, we have generated cuboid prevascularized bone tissue constructs by bioprinting human adipose‐derived mesenchymal stem cells (ASCs) and human umbilical vein endothelial cells (HUVECs) by extrusion‐based bioprinting and drop‐on‐demand (DoD) bioprinting, respectively. The computer‐generated print design could be verified in vitro after printing. After subcutaneous implantation of bioprinted constructs in immunodeficient mice, blood vessel formation with human microvessels of different calibers could be detected arising from bioprinted HUVECs and stabilization of human blood vessels by mouse pericytes was observed. In addition, bioprinted ASCs were able to synthesize a calcified bone matrix as an indicator of ectopic bone formation. These results indicate that the combined bioprinting of ASCs and HUVECs represents a promising strategy to produce prevascularized artificial bone tissue for prospective applications in the treatment of critical‐sized bone defects.
M. Trotter, D. Juric, Z. Bagherian, N. Borst, K. Gläser, T. Meissner, F. von Stetten, A. Zimmermann
Inkjet-Printing of Nanoparticle Gold and Silver Ink on Cyclic Olefin Copolymer for DNA-Sensing Applications
2020 Sensors, Band: 20, Nummer: 5, Seite: 1333
KurzfassungInkjet technology as a maskless, direct-writing technology offers the potential for structured deposition of functional materials for the realization of electrodes for, e.g., sensing applications. In this work, electrodes were realized by inkjet-printing of commercial nanoparticle gold ink on planar substrates and, for the first time, onto the 2.5D surfaces of a 0.5 mm-deep microfluidic chamber produced in cyclic olefin copolymer (COC). The challenges of a poor wetting behavior and a low process temperature of the COC used were solved by a pretreatment with oxygen plasma and the combination of thermal (130 °C for 1 h) and photonic (955 mJ/cm²) steps for sintering. By performing the photonic curing, the resistance could be reduced by about 50% to 22.7 μΩ cm. The printed gold structures were mechanically stable (optimal cross-cut value) and porous (roughness factors between 8.6 and 24.4 for 3 and 9 inkjet-printed layers, respectively). Thiolated DNA probes were immobilized throughout the porous structure without the necessity of a surface activation step. Hybridization of labeled DNA probes resulted in specific signals comparable to signals on commercial screen-printed electrodes and could be reproduced after regeneration. The process described may facilitate the integration of electrodes in 2.5D lab-on-a-chip systems.
C. Van Pham, M. Bühler, J. Knöppel, M. Bierling, D. Seeberger, D. Escalera-López, K. Mayrhofer, S. Cherevko, S. Thiele
IrO2 coated TiO2 core-shell microparticles advance performance of low loading proton exchange membrane water electrolyzers
2020 Applied Catalysis B: Environmental, Band: 269, Seite: 118762
KurzfassungHerein we present novel IrO2 coated TiO2 core-shell microparticles (IrO2@TiO2) as an oxygen evolution reaction catalyst. We compare the IrO2@TiO2 catalyst to commercial TiO2 supported IrO2 catalyst (IrO2/TiO2) and pure IrO2 catalyst powder. A stability analysis via on-line inductively coupled plasma mass spectrometry based on the S-number, a descriptor considering both energy efficiency and catalyst utilization efficiency, shows that the IrO2@TiO2 catalyst shows high potential for practical applications. This was further confirmed by full-cell tests showing superior performance of the IrO2@TiO2 catalyst with moderate and low loadings of 1.2 mgIr cm−2 and 0.4 mgIr cm−2, respectively. The core-shell catalyst is synthesized via facile route suitable for large quantities. Moreover, stable inks from the synthesized catalyst powder make this system appealing for large scale manufacturing of cells. Given the facile synthesis route, high activity, and good stability, the IrO2@TiO2 catalyst is potentially suitable for industry proton exchange membrane water electrolysis application.
L. Becherer, N. Borst, M. Bakheit, S. Frischmann, R. Zengerle, F. von Stetten
Loop-mediated isothermal amplification (LAMP) – review and classification of methods for sequence-specific detection
2020 Anal Methods-uk, Band: 12, Seiten: 717 - 746
KurzfassungIn the course of the last 20 years, isothermal nucleic acid amplification tests have emerged as an important diagnostic tool, not only for clinical applications, but also for food quality control and environmental monitoring. Loop-mediated isothermal amplification (LAMP) is well known for its robust and highly sensitive and specific amplification of target DNA, which is achieved by utilizing up to six primers. Moreover, LAMP excels through its isothermal and energy efficient amplification requirements, rendering it a prime candidate for low-cost diagnostics and analysis at the point of need. Recently, methods for sequence-specific detection have gained more importance because, unlike sequence-independent detection methods, they are highly specific towards the target DNA. In the last 13 years, a variety of sequence-specific methods have emerged, based on a very diverse range of sensing techniques, including optical, magnetic, piezoelectric, electrochemical and magnetoresistive sensing. To give structure to the diverse multitude of sequence-specific methods, we created a systematic classification and provide a critical comparative evaluation according to a catalogue of criteria (analytical performance, multiplexing, quantification and instrumental requirements). Fluorescence-based detection, making up half of the methods, can be processed on open platforms and satisfies all the criteria listed before. Instrumental requirements are discussed in terms of complexity, portability and fluidic cartridges. In addition, the technological readiness level and the kind of platform (open versus method-tailored) are evaluated, the latter playing an important role in the miniaturization and automation of operational process steps. We also observe an increase in the use of smartphone-integrated sensors to improve LAMP-based point-of-need testing. In summary, recent developments in methods for the sequence-specific detection of LAMP demonstrate high potential for many future applications.
P.N. Paqué, C. Herz, J.S. Jenzer, D.B. Wiedemeier, T. Attin, N. Bostanci, G.N. Belibasakis, K. Bao, P. Körner, T. Fritz, J. Prinz, P.R. Schmidlin, T. Thurnheer, F.J. Wegehaupt, K. Mitsakakis, J.R. Peham
Microbial Analysis of Saliva to Identify Oral Diseases Using a Point-of-Care Compatible qPCR Assay
2020 J Clin Med, Band: 9, Seite: 2945
KurzfassungOral health is maintained by a healthy microbiome, which can be monitored by state-of-the art diagnostics. Therefore, this study evaluated the presence and quantity of ten oral disease-associated taxa (P. gingivalis, T. forsythia, T. denticola, F. nucleatum, C. rectus, P. intermedia, A. actinomycetemcomitans, S. mutans, S. sobrinus, oral associated Lactobacilli) in saliva and their clinical status association in 214 individuals. Upon clinical examination, study subjects were grouped into healthy, caries and periodontitis and their saliva was collected. A highly specific point-of-care compatible dual color qPCR assay was developed and used to study the above-mentioned bacteria of interest in the collected saliva. Assay performance was compared to a commercially available microbial reference test. Eight out of ten taxa that were investigated during this study were strong discriminators between the periodontitis and healthy groups: C. rectus, T. forsythia, P. gingivalis, S. mutans, F. nucleatum, T. denticola, P. intermedia and oral Lactobacilli (p < 0.05). Significant differentiation between the periodontitis and caries group microbiome was only shown for S. mutans (p < 0.05). A clear distinction between oral health and disease was enabled by the analysis of quantitative qPCR data of target taxa levels in saliva.
L. Becherer, S. Knauf, M. Marks, S. Lueert, S. Frischmann, N. Borst, F. von Stetten, S. Bieb, Y. Adu-Sarkodie, K. Asiedu, O. Mitjà, M. Bakheit
Multiplex Mediator Displacement Loop-Mediated Isothermal Amplification for Detection of Treponema pallidum and Haemophilus ducreyi
2020 Emerg Infect Dis, Band: 26, Seiten: 282 - 288
M. Schulz, S. Calabrese, F. Hausladen, H. Wurm, D. Drossart, K. Stock, A. M. Sobieraj, F. Eichenseher, M. J. Loessner, M. Schmelcher, A. Gerhardts, U. Goetz, M. Handel, A. Serr, G. Haecker, J. Li, M. Specht, P. Koch, M. Meyer, P. Tepper, R. Rother, M. Jehle, S. Wadle, R. Zengerle, F. von Stetten, N. Paust, N. Borst
Point-of-care testing system for digital single cell detection of MRSA directly from nasal swabs
2020 Lab Chip, Band: 20, Seiten: 2549 - 2561
KurzfassungWe present an automated point-of-care testing (POCT) system for rapid detection of species- and resistance markers in methicillin-resistant Staphylococcus aureus (MRSA) at the level of single cells, directly from nasal swab samples. Our novel system allows clear differentiation between MRSA, methicillin-sensitive S. aureus (MSSA) and methicillin-resistant coagulase-negative staphylococci (MR-CoNS), which is not the case for currently used real-time quantitative PCR based systems. On top, the novel approach outcompetes the culture-based methods in terms of its short time-to-result (1 h vs. up to 60 h) and reduces manual labor. The walk-away test is fully automated on the centrifugal microfluidic LabDisk platform. The LabDisk cartridge comprises the unit operations swab-uptake, reagent pre-storage, distribution of the sample into 20 000 droplets, specific enzymatic lysis of Staphylococcus spp. and recombinase polymerase amplification (RPA) of species (vicK) – and resistance (mecA) -markers. LabDisk actuation, incubation and multi-channel fluorescence detection is demonstrated with a clinical isolate and spiked nasal swab samples down to a limit of detection (LOD) of 3 ± 0.3 CFU μl−1 for MRSA. The novel approach of the digital single cell detection is suggested to improve hospital admission screening, timely decision making, and goal-oriented antibiotic therapy. The implementation of a higher degree of multiplexing is required to translate the results into clinical practice.
B. Johannsen, D. Mark, N. Boillat-Blanco, A. Fresco, D. Baumgartner, R. Zengerle, K. Mitsakakis
Rapid diagnosis of respiratory tract infections using a point-of-care platform incorporating a clinical decision support algorithm
2020 Stud. in Health Technol. Inform, Band: 273, Seiten: 234 - 239
KurzfassungRespiratory Tract Infections (RTIs) are among the top reasons for visiting a General Practitioner (GP) and the main cause of unnecessary antibiotic prescriptions. Reducing inappropriate use is essential to decrease antibiotic resistance and adverse events. The goal of the Eurostars project “Respiotic” is to develop a new point-of-care (POC) platform based on the centrifugal microfluidic LabDisk that will detect the main responsible viruses and bacteria for community-acquired RTIs, including associated resistances and host biomarkers. The diagnostic platform will use a Polymerase Chain Reaction (PCR) and an immunoassay cartridge on the same instrument and provide the combined analysis within less than 1 h. An electronic clinical algorithm will co-assess the test results and act as a decision support tool for the GPs’ patient management and prescriptions.
M. Rombach, S. Hin, M. Specht, B. Johannsen, J. Lüddecke, N. Paust, R. Zengerle, L. Roux, T. Sutcliffe, J. Peham, C. Herz, M. Panning, O. Donoso Mantke, K. Mitsakakis
RespiDisk: a point-of-care platform for fully automated detection of respiratory tract infection pathogens in clinical samples
2020 Analyst, Band: 145, Seiten: 7040 - 7047
KurzfassungWe present the RespiDisk enabling the fully automated and multiplex point-of-care (POC) detection of (currently) up to 19 respiratory tract infection (RTI) pathogens from a single sample based on reverse transcriptase polymerase chain reaction (RT-PCR). RespiDisk comprises a RTI-specific implementation of the centrifugal microfluidic LabDisk platform and combines new and existing advanced unit operations for liquid control, thereby automating all assay steps only by a spinning frequency and temperature protocol in combination with the use of a permanent magnet for in situ bead handing. The capabilities of the system were demonstrated with 36 tested quality samples mimicking clinical conditions (clinical and/or cultured material suspended in transport medium or synthetic bronchoalveolar lavage (BAL)) from past external quality assessment (EQA) panels covering 13 of the 19 integrated RTI detection assays. In total, 36 samples × 19 assays/sample resulting in 684 assays were performed with the RespiDisk, and its analytical performance was in full agreement with the routine clinical workflow serving as reference. A strong feature of the platform is its universality since its components allow the simultaneous detection of a broad panel of bacteria and viruses in a single run, thereby enabling the differentiation between antibiotic-treatable diseases. Furthermore, the full integration of all necessary biochemical components enables a reduction of the hands-on time from manual to automated sample-to-answer analysis to about 5 min. The study was performed on an air-heated LabDisk Player instrument with a time-to-result of 200 min.
J. Riba, J. Schoendube, S. Zimmermann, P. Koltay, R. Zengerle
Single-cell dispensing and ‘realtime’cell classification using convolutional neural networks for higher efficiency in single-cell cloning
2020 nature scientific reports, Band: 10, Seite: 1193
KurzfassungSingle-cell dispensing for automated cell isolation of individual cells has gained increased attention in the biopharmaceutical industry, mainly for production of clonal cell lines. Here, machine learning for classification of cell images is applied for ‘real-time’ cell viability sorting on a single-cell printer. We show that an extremely shallow convolutional neural network (CNN) for classification of lowcomplexity cell images outperforms more complex architectures. Datasets with hundreds of cell images from four different samples were used for training and validation of the CNNs. The clone recovery, i.e. the fraction of single-cells that grow to clonal colonies, is predicted to increase for all the samples investigated. Finally, a trained CNN was deployed on a c.sight single-cell printer for ‘real-time’ sorting of a CHO-K1 cells. On a sample with artificially damaged cells the clone recovery could be increased from 27% to 73%, thereby resulting in a significantly faster and more efficient cloning. Depending on the classification threshold, the frequency at which viable cells are dispensed could be increased by up to 65%. This technology for image-based cell sorting is highly versatile and can be expected to enable cell sorting by computer vision with respect to different criteria in the future.
M. Drews, S. Tepner, P. Haberzettl, H. Gentischer, W. Beichel, M. Breitwieser, S. Vierrath, D. Biro
Towards 3D-lithium ion microbatteries based on silicon/graphite blend anodes using a dispenser printing technique
2020 RSC Adv., Band: 10, Seiten: 22440 - 22448
KurzfassungIn this work we present for the first time high capacity silicon/carbon–graphite blend slurries designed for application in 3D-printed lithium ion microbatteries (3D-MLIBs). The correlation between electrochemical and rheological properties of the corresponding slurries was systematically investigated with the prospect of production by an automated dispensing process. A variation of the binder content (carboxymethyl cellulose/styrene–butadiene rubber, CMC/SBR) between 6 wt%, 12 wt%, 18 wt% and 24 wt% in the anode slurry proved to be crucial for the printing process. Regarding the rheological properties increasing binder content leads to increased viscosity and yield stress values promising printed structures with high aspect ratios. Consequently, interdigital 3D-printed micro anode structures with increasing aspect ratios were printed with increasing binder content. For printed 6-layer structures aspect ratios of 6.5 were achieved with anode slurries containing 24 wt% binder. Electrochemical results from planar coin cell measurements showed that anodes containing 12 wt% CMC/SBR binder content exhibited stable cycling at the highest charge capacities of 484 mA h g−1 at a current rate of C/4. Furthermore, at 4C the cells showed high capacity retention of 89% compared to cycling at C/4. Based on this study and the given material formulation we recommend 18 wt% CMC/SBR as the best trade-off between electrochemical and rheological properties for future work with fully 3D-printed MLIBs.
J.-N. Klatt, M. Depke, N. Goswami, N. Paust, R. Zengerle, F. Schmidt, T. Hutzenlaub
Tryptic digestion of human serum for proteomic mass spectrometry automated by centrifugal microfluidics
2020 Lab Chip, Band: 20, Seite: 2937
KurzfassungMass spectrometry has become an important analytical tool for protein research studies to identify, characterise and quantify proteins with unmatched sensitivity in a highly parallel manner. When transferred into clinical routine, the cumbersome and error-prone sample preparation workflows present a major bottleneck. In this work, we demonstrate tryptic digestion of human serum that is fully automated by centrifugal microfluidics. The automated workflow comprises denaturation, digestion and acidification. The input sample volume is 1.3 μl only. A triplicate of human serum was digested with the developed microfluidic chip as well as with a manual reference workflow on three consecutive days to assess the performance of our system. After desalting and liquid chromatography tandem mass spectrometry, a total of 604 proteins were identified in the samples digested with the microfluidic chip and 602 proteins with the reference workflow. Protein quantitation was performed using the Hi3 method, yielding a 7.6% lower median intensity CV for automatically digested samples compared to samples digested with the reference workflow. Additionally, 17% more proteins were quantitated with less than 30% CV in the samples from the microfluidic chip, compared to the manual control samples. This improvement can be attributed to the accurate liquid metering with all volume CVs below 1.5% on the microfluidic chip. The presented automation solution is attractive for laboratories in need of robust automation of sample preparation from small volumes as well as for labs with a low or medium throughput that does not allow for large investments in robotic systems.
S. Hin, D. Baumgartner, M. Specht, J. Lüddecke, E. M. Arjmand, B. Johannsen, L. Schiedel, M. Rombach, N. Paust, F. von Stetten, R. Zengerle, N. Wipf, P. Müller, K. Mavridis, J. Vontas, K. Mitsakakis, * Indicates equally contributing authors
VectorDisk: A Microfluidic Platform Integrating Diagnostic Markers for Evidence-Based Mosquito Control
2020 Processes, Band: 8, Nummer: 12, Seite: 1677
KurzfassungEffective mosquito monitoring relies on the accurate identification and characterization of the target population. Since this process requires specialist knowledge and equipment that is not widely available, automated field-deployable systems are highly desirable. We present a centrifugal microfluidic cartridge, the VectorDisk, which integrates TaqMan PCR assays in two feasibility studies, aiming to assess multiplexing capability, specificity, and reproducibility in detecting disk-integrated vector-related assays. In the first study, pools of 10 mosquitoes were used as samples. We tested 18 disks with 27 DNA and RNA assays each, using a combination of multiple microfluidic chambers and detection wavelengths (geometric and color multiplexing) to identify mosquito and malaria parasite species as well as insecticide resistance mechanisms. In the second study, purified nucleic acids served as samples to test arboviral and malaria infective mosquito assays. Nine disks were tested with 14 assays each. No false positive results were detected on any of the disks. The coeffcient of variation in reproducibility tests was <10%. The modular nature of the platform, the easy adaptation of the primer/probe panels, the cold chain independence, the rapid (2–3 h) analysis, and the assay multiplexing capacity are key features, rendering the VectorDisk a potential candidate for automated vector analysis.
M. Schulz, S. Probst, S. Calabrese, A. Homann, N. Borst, M. Weiss, F. von Stetten, R. Zengerle, N. Paust
Versatile Tool for Droplet Generation in Standard Reaction Tubes by Centrifugal Step Emulsification
2020 Molecules, Band: 25, Nummer: 8, Seite: 1914
KurzfassungWe present a versatile tool for the generation of monodisperse water-in-fluorinated-oil droplets in standard reaction tubes by centrifugal step emulsification. The microfluidic cartridge is designed as an insert into a standard 2 mL reaction tube and can be processed in standard laboratory centrifuges. It allows for droplet generation and subsequent transfer for any downstream analysis or further use, does not need any specialized device, and manufacturing is simple because it consists of two parts only: A structured substrate and a sealing foil. The design of the structured substrate is compatible to injection molding to allow manufacturing at large scale. Droplets are generated in fluorinated oil and collected in the reaction tube for subsequent analysis. For sample sizes up to 100 µL with a viscosity range of 1 mPa·s–4 mPa·s, we demonstrate stable droplet generation and transfer of more than 6 × 105 monodisperse droplets (droplet diameter 66 µm ± 3 µm, CV ≤ 4%) in less than 10 min. With two application examples, a digital droplet polymerase chain reaction (ddPCR) and digital droplet loop mediated isothermal amplification (ddLAMP), we demonstrate the compatibility of the droplet production for two main amplification techniques. Both applications show a high degree of linearity (ddPCR: R2 ≥ 0.994; ddLAMP: R2 ≥ 0.998), which demonstrates that the cartridge and the droplet generation method do not compromise assay performance.
C. Klose, T. Saatkamp, A. Münchinger, L. Bohn, G. Titvinidze, M. Breitwieser, K.-D. Kreuer, S. Vierrath
Water Electrolyzers: All‐Hydrocarbon MEA for PEM Water Electrolysis Combining Low Hydrogen Crossover and High Efficiency
2020 Adv Energy Mater
KurzfassungHydrocarbon ionomers bear the potential to significantly lower the material cost and increase the efficiency of proton‐exchange membrane water electrolyzers (PEMWE). However, no fully hydrocarbon membrane electrode assembly (MEA) with a performance comparable to Nafion‐MEAs has been reported. PEMWE‐MEAs are presented comprising sPPS as membrane and electrode binder reaching 3.5 A cm−2 at 1.8 V and thus clearly outperforming state‐of‐the‐art Nafion‐MEAs (N115 as membrane, 1.5 A cm−2 at 1.8 V) due to a significantly lower high frequency resistance (57 ± 4 mΩ cm² vs 161 ± 7 mΩ cm²). Additionally, pure sPPS‐membranes show a three times lower gas crossover (<0.3 mA cm−2) than Nafion N115‐membranes (>1.1 mA cm−2) in a fully humidified surrogate test. Furthermore, more than 80 h of continuous operation is shown for sPPS‐MEAs in a preliminary durability test (constant current hold at 1 A cm−2 at 80 °C). These results rely on the unique transport properties of sulfonated poly(phenylene sulfone) (sPPS) that combines high proton conductivity with low gas crossover.

2019

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B. Shanahan, T. Böhm, B. Britton, S. Holdcroft, R. Zengerle, S. Vierrath, S. Thiele, M. Breitwieser
30 μm thin hexamethyl-p-terphenyl poly(benzimidazolium) anion exchange membrane for vanadium redox-flow batteries
2019 Electrochem Commun, Band: 102, Seiten: 37 - 40
KurzfassungWe present the first results of an anion exchange ionomer membrane, hexamethyl-p-terphenyl poly(benzimidazolium) (HMT-PMBI), in a vanadium redox flow battery. Anion exchange membranes exhibit superior vanadium crossover suppression compared to proton exchange membranes due to the Gibbs–Donnan effect. HMT-PMBI was benchmarked against a similarly thin Nafion XL membrane which allowed us to compare differences based solely on chemical properties of the ionomer materials. We report cycling data of 45 cycles at a current density of 150 mA/cm2 with excellent coulombic efficiency of >99.4%, energy efficiency of 80.6–74.2% and a low ohmic resistance of 0.219–0.255 Ω cm2. In addition, a three times lower self-discharge rate is obtained for the HMT-PMBI membrane compared to Nafion XL. HMT-PMBI is therefore a potential alternative for PFSA based ionomers in VRFB applications.
B. Johannsen, L. Müller, D. Baumgartner, L. Karkossa, S. M. Früh, N. Bostanci, M. Karpíšek, R. Zengerle, N. Paust, K. Mitsakakis
Automated Pre-Analytic Processing of Whole Saliva Using Magnet-Beating for Point-of-Care Protein Biomarker Analysis
2019 Micromachines, Band: 10, Nummer: 12, Seite: 833
KurzfassungSaliva offers many advantages for point-of-care (PoC) diagnostic applications due to non-invasive, easy, and cost-effective methods of collection. However, the complex matrix with its non-Newtonian behavior and high viscosity poses handling challenges. Several tedious and long pre-analytic steps, incompatible with PoC use, are required to liquefy and homogenize saliva samples before protein analysis can be performed. We apply magnet-beating to reduce hands-on time and to simplify sample preparation. A magnet in a chamber containing the whole saliva is actuated inside a centrifugal microfluidic cartridge by the interplay of centrifugal and magnetic forces. Rigorous mixing, which homogenizes the saliva sample, is then initiated. Consequently, fewer manual steps are required to introduce the whole saliva into the cartridge. After 4 min of magnet-beating, the processed sample can be used for protein analysis. The viscosity of whole saliva has been reduced from 10.4 to 2.3 mPa s. Immunoassay results after magnet-beating for three salivary periodontal markers (MMP-8, MMP-9, TIMP-1) showed a linear correlation with a slope of 0.99 when compared to results of reference method treated samples. Conclusively, magnet-beating has been shown to be a suitable method for the pre-analytic processing of whole saliva for fully automated PoC protein analysis.
P. Juelg, M. Specht, E. Kipf, M. Lehnert, C. Eckert, M. Keller, T. Hutzenlaub, F. von Stetten, R. Zengerle, N. Paust
Automated serial dilutions for high-dynamic-range assays enabled by fill-level-coupled valving in centrifugal microfluidics
2019 Lab Chip, Band: 19, Seiten: 2205 - 2219
KurzfassungWe introduce a new concept for centrifugal microfluidics that enables fully automated serial dilution generation without any additional means besides temperature control. Key feature is time-independent, serial valving of mixing chambers by fill-level-coupled temperature change rate (FLC-TCR) actuated valving. The automated dilution is realized under continuous rotation which enables reliable control of wetting liquids without the need of any additional fabrication steps such as hydrophobic coatings. All fluidic features are implemented in a monolithic fashion and disks are manufactured by foil thermoforming for scalable manufacturing. The new valving concept is demonstrated to reliably prevent valving if the diluted sample is not added to the mixing chamber (n = 30) and ensures valving if the dilution stage is completed (n = 15). Accuracy and precision of the automated serial dilution are verified by on-disk generation of qPCR standard curve dilutions and compared with manually generated reference dilutions. In a first step, the 5-log-stages standard curves are evaluated in a commercial qPCR thermocycler revealing a linearity of R² ≥ 99.92 % for the proposed LabDisk method vs. R² ≥ 99.67 % in manual reference dilutions. In a second step, the disk automated serial dilution is combined with on-disk qPCR thermocycling and readout, both inside a LabDisk Player. A 4-log-stages linearity of R² ≥ 99.81 % and a sensitivity of one leukemia associated ETV6-RUNX1 mutant DNA copy in a background of 100,000 wild-type DNA copies is achieved.
K. Tröndle, F. Koch, G. Finkenzeller, G. B. Stark, R. Zengerle, P. Koltay, S. Zimmermann
Bioprinting of high cell density constructs leads to controlled lumen formation with self‐assembly of endothelial cells
2019 Journal of Tissue Engineering and Regenerative Medicine, Band: 13, Nummer: 10, Seiten: 1883 - 1895
KurzfassungActive nutrient supply and waste product removal are key requirements for the fabrication of long term viable and functional tissue constructs of considerable size. This work aims to contribute to the fabrication of artificial perfusable networks with a bioprinting process, based on drop‐on‐demand (DoD) printing of primary endothelial cell (EC) suspension bioink (25 · 106 ± 3 · 106 cells/ml). The process results in prescribed lumen between two hydrogel layers, allowing its integration in common layering based bioprinting processes. Low volume bioink droplets (appr. 10 nl) as building blocks, were deposited between two fibrin or collagen I layers to realize shapeable, cell‐rich aggregates. Unattainable with manual positioning, DoD printing allowed precise fabrication of various designs, such as spheroidal‐, line‐shaped and Y‐branch cellular structures, with a mean lateral extension of 285 ± 81 μm. For basic characterization, the cell suspension building blocks were systematically compared to preformed spheroids of the same cell type, passage and number. Post printing investigations of initially loose cell arrangements showed self‐assembly and formation of central lumen with a mean cross‐sectional area of Ølumen = 6400 μm2 at day 3, lined by a single layer of CD31 positive ECs, as evaluated by confocal microscopy. Originating from this main lumen smaller, undirected side‐branches (Øbranches = 740 μm2) were formed by sprouting cells, inducing a first step towards a simplistic hierarchically organized network. These lumen could prospectively help for tissue construct perfusion in vitro or, potentially, as niche for angiogenesis of host vascularization in implants.
M. Schulz, F. von Stetten, R. Zengerle, N. Paust
Centrifugal Step Emulsification: How Buoyancy Enables High Generation Rates of Monodisperse Droplets
2019 Langmuir : the ACS Journal of Surfaces and Colloids, Band: 35, Nummer: 30, Seiten: 9809 - 9815
KurzfassungWe demonstrate that buoyancy in centrifugal step emulsification enables substantially higher generation rates of monodisperse droplets compared to pressure driven set-ups. Step emulsification in general can produce droplets in comparatively simple systems (only one moving liquid) with a low CV of <5% in droplet diameter and with a minimum dead volume. If operated below a critical capillary number, the droplet diameter is defined by geometry and surface forces only. Above that critical capillary number, however, jetting occurs, leading to an increased droplet diameter and CV. Consequently, generation rates of monodisperse droplets are limited in pressure-driven systems. In this paper, we show that centrifugal step emulsification can overcome this limitation by applying sufficient buoyancy to the system. The buoyancy, induced by the centrifugal field and a density difference of the continuous and disperse phase, supports droplet necking by pulling the forming droplet away from the nozzle. The influence of buoyancy is studied using specific microfluidic designs that allow for supplying different buoyancies to the same droplet generation rates. For a droplet diameter of 100 μm, droplet generation at rates above 2.8k droplets per second and nozzle were reached, which is an increase of more than a factor of 8 in comparison to pressure-driven systems.
M. Wehrle, F. Koch, S. Zimmermann, P. Koltay, R. Zengerle, G. B. Stark, S. Strassburg, G. Finkenzeller
Examination of Hydrogels and Mesenchymal Stem Cell Sources for Bioprinting of Artificial Osteogenic Tissues
2019 Cellular and Molecular Bioengineering, Seiten: 1 - 15
KurzfassungMesenchymal stem cells (MSCs) represent a very important cell source in the field of regenerative medicine and for bone and cartilage tissue engineering applications. Three-dimensional (3D) bioprinting has the potential to improve the classical tissue engineering concept as this technique allows the printing of cells with high spatial control of cell allocation within a 3D construct. In this study, we systematically compared different hydrogel blends for 3D bioprinting of MSCs by testing their cytocompatibility, ability to support osteogenic differentiation and their mechanical properties. In addition, we compared four different MSC populations isolated from different human tissues for their osteogenic differentiation capacity in combination with different hydrogels. The aim of this study was to identify the best MSC source and the most suitable hydrogel blend for extrusion-based bioprinting of 3D large-scaled osteogenic constructs.
D. Kainz, S. M. Früh, T. Hutzenlaub, R. Zengerle, N. Paust
Flow control for lateral flow strips with centrifugal microfluidics
2019 Lab Chip, Seiten: 2718 - 2727
KurzfassungLateral flow strips (LFSs) are widely used for clinical diagnostics. The restricted flow control of the current designs is one challenge to the development of quantitative and highly sensitive LFSs. Here, we present a flow control for LFSs using centrifugal microfluidics. In contrast to previously presented implementations of lateral flow membranes into centrifugal microfluidic cartridges, we direct the flow radially outwards through the membrane. We control the flow using only the centrifugal force, thus it is independent of membrane wetting properties and permeability. The flow rate can be decreased and increased, enabling control of incubation times for a wide variety of samples. We deduced a formula as a guideline for the integration of chromatographic membranes into centrifugal microfluidic disks to ensure that all the sample liquid flows through the membrane, hence safely avoiding bypass flow around the membrane. We verified the calculated operation conditions using different membranes, different flow rates, and different sample viscosities.
M. Bühler, P. Holzapfel, D. McLaughlin, S. Thiele
From catalyst coated membranes to porous transport electrode based configurations in PEM water electrolyzers
2019 J Electrochem Soc, Band: 166, Seite: F1070
KurzfassungSo far the superior cell polarization behavior of membrane electrode assemblies (MEAs) using catalyst coated membranes (CCMs) as compared to those using porous transport electrodes (PTEs) was a paradigm in proton exchange membrane water electrolyzers (PEMWEs). However, this paradigm was so far neither systematically investigated nor understood. In this study, we investigate the changes in PEMWE polarization behavior upon gradually changing the MEA from a full CCM toward a full PTE-type configuration. We explain all observed findings based on the idea for a structural model of discontinuous catalyst layers. Our results show, that for current densities above 750 mA cm−2, PTE-based MEAs can result in a better polarization behavior than CCMs. Therefore, the prevailing paradigm was disproved. CCMs showed better kinetics, while PTE-type configurations performed more reproducible than CCMs despite rougher surfaces. Due to the trend of a stabilizing HFR-free cell voltage, an improved mass transport behavior of the PTE-type configurations at high current densities is assumed. Within the error-tolerance, no clear differences between PTE and CCM-based configurations in ohmic resistance could be determined. We conclude that PTE-based configurations for PEMWE, as alternatives to standard CCM-configurations, could be highly important for future manufacturing techniques depending on the application's needs.
F. Hegge, J. Sharman, R. Moroni, S. Thiele, R. Zengerle, M. Breitwieser, S. Vierrath
Impact of Carbon Support Corrosion on Performance Losses in Polymer Electrolyte Membrane Fuel Cells
2019 J Electrochem Soc, Band: 166, Seiten: F956 - F962
KurzfassungCorrosion of the carbon support leads to a severe decay in the performance of PEM fuel cells, mainly due to an increase in the oxygen transport resistance. To investigate the effect of degradation on oxygen transport, we cycled MEAs between 1−1.5 V and analyzed the electrode structure with FIB-SEM tomography at various ageing states. The tomography results show that the electrode structure changes over 1000 cycles in terms of thickness (7.8 to 6.5 μm), porosity (44 to 38%) and diffusivity (9 to 8 105 m2s−1). Limiting current measurements in the wet (hydrogen/air) and dry state (hydrogen pumping) allowed the pressure dependent and pressure independent mass transport resistances to be distinguished and to quantify the impact of product water. The pressure independent resistance increased from 24 to 41 sm−1. Considering the marginal contribution of the catalyst pore space resistance (3 to 4 sm−1) it is concluded that the largest portion of the increase (50%) is caused by an increased local mass transport resistance. This is due to a decrease of the electrode roughness factor (282 to 169). The limiting current under wet conditions shows that another 44% could stem from a change in the wetting behavior, while 6% remains unexplained.
M. Solihul Mu’min, T. Böhm, R. Moroni, R. Zengerle, S. Thiele, S. Vierrath, M. Breitwieser
Local hydration in ionomer composite membranes determined with confocal Raman microscopy
2019 Journal of Membrane Science, Band: 585, Seiten: 126 - 135
KurzfassungWater management in electrochemical energy applications like fuel cells has a crucial impact on performance, in particular on the ionic conduction of ionomer membranes. To strengthen the understanding of water management in such devices, we report a novel method for non-destructive measurements of the hydration of composite membranes based on confocal Raman microscopy. Composite membranes were produced by spray-coating of Nafion into a mesh of electrospun poly(vinylidene fluoride-co-hexafluoropropylene)/polyvinylpyrrolidone (PVDF-HFP/PVP) blend nanofibers. Hydration levels of several pure nanofiber meshes and nanofiber/Nafion composites were evaluated by linear least squares fitting of reference Raman spectra to hyperspectral images. We found that spectral contribution of water to nanofiber spectra depends on the PVDF-HFP/PVP ratio and is independent from fiber diameter. Further, we were able to reliably determine nanofiber polymer composition of single fibers based on Raman spectroscopy. Raman imaging of composite membranes was performed at ambient air and fully hydrated conditions to study the local hydration in PVDF-HFP/PVP/Nafion composites as well as in a Nafion XL membrane. 2D through-plane mappings revealed that the nanofiber hydration positively correlated with PVP content. In the Nafion XL membrane, the polytetrafluoroethylene-based reinforcement was verified as a hydrophobic layer sandwiched between Nafion ionomer, which showed a more than 10% reduced hydration compared to the outer Nafion layers. These results motivate the use of confocal Raman microscopy as a novel method to investigate the local water distribution in ionomer composite membranes that are widely used in electrochemical energy conversion.
U. Karakus, T. Thamamongood, K. Ciminski, W. Ran, S. C. Günther, M. O. Pohl, D. Eletto, C. Jeney, D. Hoffmann, S. Reiche, J. Schinköthe, R. Ulrich, J. Wiener, M. G. B. Hayes, M. W. Chang, A. Hunziker, E. Yángüez, T. Aydillo, F. Krammer, J. Oderbolz, M. Meier, A. Oxenius, A. Halenius, G. Zimmer, C. Benner, B. G. Hale, A. García-Sastre, M. Beer, M. Schwemmle, S. Stertz
MHC class II proteins mediate cross-species entry of bat influenza viruses
2019 Nature, Band: 567, Seiten: 109 - 112
KurzfassungZoonotic influenza A viruses of avian origin can cause severe disease in individuals, or even global pandemics, and thus pose a threat to human populations. Waterfowl and shorebirds are believed to be the reservoir for all influenza A viruses, but this has recently been challenged by the identification of novel influenza A viruses in bats1,2. The major bat influenza A virus envelope glycoprotein, haemagglutinin, does not bind the canonical influenza A virus receptor, sialic acid or any other glycan1,3,4, despite its high sequence and structural homology with conventional haemagglutinins. This functionally uncharacterized plasticity of the bat influenza A virus haemagglutinin means the tropism and zoonotic potential of these viruses has not been fully determined. Here we show, using transcriptomic profiling of susceptible versus non-susceptible cells in combination with genome-wide CRISPR–Cas9 screening, that the major histocompatibility complex class II (MHC-II) human leukocyte antigen DR isotype (HLA-DR) is an essential entry determinant for bat influenza A viruses. Genetic ablation of the HLA-DR α-chain rendered cells resistant to infection by bat influenza A virus, whereas ectopic expression of the HLA-DR complex in non-susceptible cells conferred susceptibility. Expression of MHC-II from different bat species, pigs, mice or chickens also conferred susceptibility to infection. Notably, the infection of mice with bat influenza A virus resulted in robust virus replication in the upper respiratory tract, whereas mice deficient for MHC-II were resistant. Collectively, our data identify MHC-II as a crucial entry mediator for bat influenza A viruses in multiple species, which permits a broad vertebrate tropism.
M. Bühler, P. Holzapfel, F. Hegge, M. Bierling, S. Vierrath, S. Thiele
Optimization of porous transport electrodes for PEM water electrolysis
2019 J Mater Chem A, Band: 165, Seite: F305
KurzfassungIn this study we investigate the potential of porous transport electrode (PTE) based membrane electrode assemblies (MEAs) for proton exchange membrane water electrolysis. The focus is on the overpotential determining anodic PTE for the oxygen evolution reaction. The influences of catalyst loading, ionomer content and porous titanium substrate on the polarization behavior are analyzed. The comparison of a porous fiber-sintered substrate with a powder-sintered substrate shows no significant differences in the kinetic and mass transport regions. Ohmic losses, however, are lower for fiber PTEs above a catalyst loading of 1.0 mgIrO2 cm−2. Variations of the Nafion content in the catalyst layer reveal changes of mass transport and ohmic losses and have an influence on the reproducibility. Varying the noble metal loading and therefore the thickness of the applied catalyst layer influences the kinetic region and ohmic resistance of the MEAs. The best compromise between reproducibility and performance is found for a loading of 1.4 mgIrO2 cm−2 and 9 wt% Nafion. The stable operation of the aforementioned PTE is shown in a 200 h durability test at 2 A cm−2.
J. F. Cahill, J. Riba, V. Kertesz
Rapid, Untargeted Chemical Profiling of Single Cells in Their Native Environment
2019 Anal Chem, Band: 91, Seiten: 6118 - 6126
KurzfassungWe report a method that enables untargeted, high throughput, and quantitative mass spectrometric analysis of single cells from cell suspension without needing additional sample preparation procedures (e.g., molecular tagging) through the combination of single-cell printer technology and liquid vortex capture−mass spectrometry (SCP-LVC-MS). The operating principle behind the SCP-LVC-MS technology is single cell isolation via small droplet piezoelectric ejection followed by capture of the droplet into an LVC-MS sampling probe. Once exposed to an appropriate solvent, the cell is lysed, extracted, and analyzed by MS. The SCP-LVC-MS approach was validated by measuring the lipid composition of microalgae, Chlamydomonas reinhardtii (ChRe) and Euglena gracilis (EuGr), and HeLa cells in their native growth media. Numerous diacylglyceryltrimethylhomo-Ser (DGTS), phosphatidylcholine (PC), monogalactosyldiacylglycerol (MGDG), and digalactosyldiacylglycerol (DGDG) lipids were observed in single cells. Continuous solvent flow ensures that cells are analyzed rapidly, and no signal carryover between cells is observed. ChRe and EuGr microalgae mixed together in the same solution were differentiated cell-by-cell in real-time based on differences between levels of diacylglyceryltrimethylhomo-Ser (DGTS) and phosphatidylcholine (PC) lipids measured in each cell. Several DGTS lipids present in ChRe were quantified with single-cell resolution by normalizing to a DGTS(32:0) internal standard added to the LVC probe solvent during analysis. Quantitative peak areas were validated by comparing to bulk lipid extracts. Lastly, peak area distributions comprised of hundreds of cells were compared for ChRe after 5 days of nitrogen-limited and normal growth conditions, which show clear differences and the ability to resolve cellular population differences with single-cell resolution.
T. Boehm, R. Moroni, M. Breitwieser, S. Thiele, S. Vierrath
Spatially Resolved Quantification of Ionomer Degradation in Fuel Cells by Confocal Raman Microscopy
2019 J Electrochem Soc, Band: 166, Nummer: 7, Seiten: F3044 - F3051
KurzfassungIonomer membranes are crucial components of many electrochemical devices. In this work, confocal Raman microscopy is employed to characterize Nafion ionomers quantitatively in pristine status and after usage as a proton exchange membrane in a fuel cell. Confocal Raman microscopy allows non-destructive thickness and equivalent weight measurements of Nafion with a 95% confidence interval of ±13 g mol−1 at an equivalent weight of 1000 g mol−1, which is significantly more accurate than previously reported methods. Characterization can be performed at a spatial resolution better than 2 μm, providing insights into local membrane degradation after fuel cell operation. Membrane thinning to less than 40% of the initial thickness of Nafion NR-211 occurs after a 100 h open circuit voltage hold, accompanied by an anisotropic increase of the equivalent weight from 1035 g mol−1 to an average of 1200 g mol−1. Most pronounced increases are found close to the anode. Further, the characterization of a Nafion XL membrane shows that its microporous reinforcement is represented as increased equivalent weight with local heterogeneities within the membrane. These results show that confocal Raman microscopy is a valuable tool to investigate ionomers that are used as ion exchange membranes in electrochemical devices.
J.P. Hays, K. Mitsakakis, S. Luz, A. van Belkum, K. Becker, A. van den Brue, S. Harbarth, J. H. Rex, G. Skov Simonsen, G. Werner, V. Di Gregori, G. Lüdke, T. van Staa, J. Moran-Gilad, T. T. Bachmann, on behalf of the JPIAMR AMR-RDT
The successful uptake and sustainability of rapid infectious disease and antimicrobial resistance point-of-care testing requires a complex ‘mix-and-match’ implementation package
2019 Eur J Clin Microbiol, Band: 38, Seiten: 1015 - 1022
KurzfassungThe emergence and spread of antimicrobial resistance is one of the major global issues currently threatening the health and wealth of nations, with effective guidelines and intervention strategies urgently required. Such guidelines and interventions should ideally be targeted at individuals, communities, and nations, requiring international coordination for maximum effect. In this respect, the European Joint Programming Initiative on Antimicrobial Resistance Transnational Working Group ‘Antimicrobial Resistance - Rapid Diagnostic Tests’ (JPIAMR AMR-RDT) is proposing to consider a ‘mix-and-match’ package for the implementation of point-of-care testing (PoCT), which is described in this publication. The working group was established with the remit of identifying barriers and solutions to the development and implementation of rapid infectious disease PoCT for combatting the global spread of antimicrobial resistance. It constitutes a multi-sectoral collaboration between medical, technological, and industrial opinion leaders involved in in vitro diagnostics development, medical microbiology, and clinical infectious diseases. The mix-and-match implementation package is designed to encourage the implementation of rapid infectious disease and antimicrobial resistance PoCT in transnational medical environments for use in the fight against increasing antimicrobial resistance.

2018

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E. Kipf, S. Sané, D. Morse, T. Messinger, R. Zengerle, S. Kerzenmacher
An air-breathing enzymatic cathode with extended lifetime by continuous laccase supply
2018 Bioresource Technol, Band: 264, Seiten: 306 - 310
KurzfassungWe present a novel concept of an air-breathing enzymatic biofuel cell cathode combined with continuous supply of unpurified laccase-containing supernatant of the white-rot fungus Trametes versicolor for extended lifetime. The air-breathing cathode design obviates the need for energy-intensive active aeration. In a corresponding longterm experiment at a constant current density of 50 μA cm−2, we demonstrated an increased lifetime of 33 days (cathode potential above 0.430 V vs. SCE), independent of enzyme degradation. The obtained data suggest that theoretically a longer lifetime is feasible. However, further engineering efforts are required to prevent clogging and fouling of the supply tubes. These results represent an important step towards the realization of enzymatic biofuel cell cathodes with extended lifetime and enhanced performance.
B. Gerdes, M. Breitwieser, T. Kaltenbach, M. Jehle, J. Wilde, R. Zengerle, P. Koltay, L. Riegger
Analysis of the metallic structure of microspheres produced by printing of aluminum alloys from the liquid melt
2018 Mater Res Express, Band: 6, Seite: 036514
KurzfassungThis work presents an analysis of the metallic structure of microspheres produced by drop-on-demand printing of the aluminum alloy AlSi12 directly printed from the liquid melt via StarJet technology. AlSi alloys are commonly used in casting processes, but microdroplets from these materials could potentially be used for additive manufacturing of metal and composite parts. Recently, several printing technologies were presented that enable the drop-on-demand printing of Al-alloy microdroplets. However, the material distribution and metallic structure inside of printed droplets is expected to be significantly different from the bulk material properties, and hardly any data on the microscopic structure of small droplets that have undergone rapid solidification has been published so far. Therefore, a microscopic in-depth study of microdroplets printed directly from the metal melt has been carried out: By the means of energy-dispersive X-ray spectroscopy (EDX), scanning electron microscopy (SEM), Auger electron spectroscopy (AES) and optical microscopy the material properties as well as the droplet morphology are investigated for the first time. The analysis demonstrates that the Al alloy droplets printed via StarJet technology exhibit almost no oxidation during the printing process and can therefore potentially be used for additive manufacturing of metal parts. Moreover, the metallurgical structure inside the droplets is analyzed. It exhibits significant difference to the bulk material in terms of the average secondary dendrite arm spacing.
J. Streeck, C. Hank, M. Neuner, L. Gil-Carrera, M. Kokko, S. Pauliuk, A. Schaadt, S. Kerzenmacher, R. J. White
Bio-electrochemical conversion of industrial wastewater-COD combined with downstream methanol synthesis – an economic and life cycle assessment
2018 Green Chem, Band: 20, Seiten: 2742 - 2762
KurzfassungHerein, a techno-economic and environmental performance evaluation (i.e. Life Cycle Assessment (LCA)) of a 45 kW Microbial Electrolysis Cell (MEC) system is presented in the context of industrial wastewater remediation. This system produces H2 and CO2 – suitable for downstream CH3OH synthesis – based on the bio-electrochemical conversion of chemical industry wastewater with an organic content of 3.9 g(COD) L−1. A cost–benefit analysis indicates that the MEC system hardware costs, share of CO2 captured from the MEC and MEC operating current density (i.e. 1.0 mA cm−2) are crucial parameters influencing the total cost and represent areas for potential cost reductions. It was established based on the present study that MEC system operation with renewable electricity leads to H2 production costs of 4–5.7€ kg(H2) −1 (comparable to H2O electrolysis) and CH3OH production costs of 900€ t(CH3OH) −1. At the current CH3OH market prices, however, the production is currently not profitable. In turn, the cost-efficient construction of the MEC system and the use of less expensive materials could lead to improved CH3OH production economics based on this route. Our results indicate that the use of low-cost materials has greater potential with regard to cost reduction compared to reducing the internal resistance and polarization losses via the use of expensive high-performance materials in MEC construction. A complementary LCA of the proposed system, based on a “cradle-to-gate” definition, indicates that waste-based is superior to fossil-based CH3OH production with respect to global warming potential and cumulated fossil energy demand, provided the system is operated with 100% renewable electricity and CO2 sourced only from the MEC. However, with regard to the impact categories Metal Depletion and Freshwater Eutrophication Potential, the system was found to perform less satisfactorily (i.e. in comparison with fossil-based CH3OH production).
K. Mitsakakis, W.E. Kaman, G. Elshout, M. Specht, J.P. Hays
Challenges in identifying antibiotic resistance targets for point-of-care diagnostics in general practice
2018 Future Microbiol, Band: 13, Nummer: 10, Seiten: 1157 - 1164
KurzfassungGeneral practitioners stand at the front line of healthcare provision and have a pivotal role in the fight against increasing antibiotic resistance. In this respect, targeted antibiotic prescribing by general practitioners would help reduce the unnecessary use of antibiotics, leading to reduced treatment failures, fewer side-effects for patients and a reduction in the (global) spread of antibiotic resistances. Current ‘gold standard’ antibiotic resistance detection strategies tend to be slow, taking up to 48 h to obtain a result, although the implementation of point-of-care testing by general practitioners could help achieve the goal of targeted antibiotic prescribing practices. However, deciding on which antibiotic resistances to include in a point-of-care diagnostic is not a trivial task, as outlined in this publication.
S. H. Moosavi, M. Kroener, M. Frei, F. Frick, S. Kerzenmacher, P. Woias
Development of a TEM Compatible Nanowire Characterization Platform With Self-forming Contacts
2018 Ieee T Semiconduct M, Band: 31, Nummer: 1, Seiten: 1 - 10
KurzfassungA nanowire characterization platform is designed and fabricated in MEMS-technology for the thermoelectric and structural characterization of single nanowires. The latter is achieved by making the chip compatible to TEM holder, by restricting its thickness to less than 160μm and its diagonal dimensions to less than 3mm. Two different fabrication technologies are presented for the realization of such platform, based on a design reproducing the functional requirements. Our first fabrication technique is based on ICP etching, using (100)-silicon wafers, and a subsequent rear grinding. However, as the design includes a vertical wall trench structures, ICP etching of such deep recesses is time-consuming and expensive. Therefore, a second fabrication process is developed, making use of wet-etched (110)-silicon. With these substrates a challenge arises from the intersection of inclined {111} facets. To solve this natural limitation, we introduce a novel fabrication process. Our technique relies on damaging the intersecting {111} planes, to make them etchable again and to produce deeper trenches with vertical walls in a wet-chemical etching process. Additionally, the electrical contacts at the platform are made from porous metal to increase the surface-to-volume ratio, to increase the possibility of a spontaneous electrical contact between the electrodes and nanowires.
C.H. Tsai, X. Wu, D.H. Kuan, S. Zimmermann, R. Zengerle, P. Koltay
Digital hydraulic drive for microfluidics and miniaturized cell culture devices based on shape memory alloy actuators
2018 J Micromech Microeng, Band: 28, Seite: 084001
KurzfassungIn order to culture and analyze individual living cells, microfluidic cell culture and manipulation of cells becomes an increasingly important topic. Such microfluidic systems allow for exploring the phenotypic differences between thousands of genetically identical cells or pharmacological tests in parallel, which is impossible to achieve by traditional macroscopic cell culture methods. Therefore, plenty of microfluidic devices have been developed for cell biological studies like cell culture, cell sorting, and cell lysis in the past. However, these devices are still limited by the external pressure sources which most of the time are large in size and have to be connected by fluidic tubing leading to complex and delicate systems. In order to provide a miniaturized, more robust actuation system a novel, compact and low power consumption Digital Hydraulic Drive (DHD) has been developed that is intended for use in portable and automated systems for microfluidic applications. The DHD consists of a shape memory alloy (SMA) actuator and a pneumatic cylinder. The switching time of the digital modes (pressure ON vs. OFF) can be adjusted from 1 second to minutes. Thus, the DHDs might have many applications for driving microfluidic devices. In this work different implementations of DHDs are presented and their performance is characterized by experiments. In particular, it will be shown that DHDs can be used for microfluidic large-scale integration (mLSI) valve control (256 valves in parallel) as well as potentially for droplet-based microfluidic systems. As further application example high-throughput mixing of cell cultures (96 wells in parallel) are demonstrated employing the DHD and a so called "functional lid" (FL) approach, to enable a miniaturized microbioreactor in a regular 96-well micro well plate.
B. Gerdes, R. Zengerle, P. Koltay, L. Riegger
Direct printing of miniscule aluminum alloy droplets and 3D structures by StarJet technology
2018 J Micromech Microeng, Band: 28, Seite: 074003
KurzfassungDrop-on demand printing of molten metal droplets could be used for prototyping of 3D objects as promising alternative to laser melting technologies. However, up to date only few printheads were investigated for this purpose using only a limited range of materials. The pneumatically actuated StarJet technology presented previously enables the direct and non-contact printing of molten metal microdroplets from metal melts at high temperatures. Printheads according to the StarJet technology utilize nozzle chips featuring a star-shaped orifice geometry that leads to a formation of the droplets inside the nozzle with high precision. In this paper we present a novel StarJet printhead for printing aluminum alloys featuring a hybrid design with a ceramic reservoir for the molten metal and an outer shell fabricated from stainless steel. The micro machined nozzle chip is made from silicon carbide (SiC). This printhead can be operated at up to 950 °C and is capable of printing high melting metals like aluminum (Al) alloys in standard laboratory conditions. In this work, an aluminum-silicon alloy that features 12 % silicon (AlSi12) is printed. The printhead, the nozzle and the peripheral actuation system have been optimized for stable generation of AlSi12 droplets with high monodispersity, low angular deviation and miniaturized droplet diameters. As main result, a stable drop-on-demand printing of droplets exhibiting diameters of ddroplet = 702 µm +/- 1 % was demonstrated at 5 Hz with a low angular deviation of 0.3°, when a nozzle chip with 500 µm orifice diameter was used. Further, AlSi12 droplets featuring ddroplet = 176 µm ± 7 % were printed when using a nozzle chip with an orifice diameter of 130 µm. Moreover, we present directly printed objects from molten aluminum alloy droplets such as high aspect ratio, free-standing walls (aspect ratio 12:1) and directly printed, flexible springs to demonstrate the principle of 3D printing with molten metal droplets.
C. Van Pham, B. Britton, T. Böhm, S. Holdcroft, S. Thiele
Doped, Defect-Enriched Carbon Nanotubes as an Efﬁcient Oxygen Reduction Catalyst for Anion Exchange Membrane Fuel Cells
2018 Adv Mater Interfaces, Seite: 1800184
KurzfassungBond polarization of doped atoms and carbon and lattice defects are con- sidered important aspects in the catalytic mechanisms of oxygen reduction reaction (ORR) on heteroatom-doped carbon catalysts. Previous work on metal-free catalysts has focused either on bond polarization or lattice defects. Here multi-heteroatom doped defect-enriched carbon nanotubes (MH-DCNTs) that combine both effects to enhance ORR activity are designed. Lattice defects in MH-DCNTs are enriched by unzipping and length-shortening of carbon nanotubes, and also by creating carbon vacancies via decomposition of doped F atoms. Electrochemical analysis using rotating disc electrode voltam- metry shows that the ORR kinetic current density of MH-DCNT increases with lattice-defect density, the latter of which is veriﬁed by Raman spectroscopy, while the onset potential increases with annealing temperatures. An optimized MH-DCNT ORR catalyst exhibits a half-wave potential of 0.81 V versus revers- ible hydrogen electrode and limiting current density of 5.0 mA cm −2 at an electrode rotation speed of 1600 rpm in 0.1 M KOH. Further, it is demonstrated that MH-DCNT, as a cathode catalyst layer in an anion exchange membrane fuel cell (AEMFC), delivers a peak power density of 250 mW cm −2 , which is ≈70% the performance of an AEMFC using a conventional Pt/C catalyst.
M. Lehnert, E. Kipf, F. Schlenker, N. Borst, R. Zengerle, F. von Stetten
Fluorescence signal-to-noise optimisation for real-time PCR using universal reporter oligonucleotides
2018 Anal Methods-uk
KurzfassungIn this study we optimised the fluorescence signal generation of contact quenched universal reporter oligonucleotides. These are used as secondary probes in real-time Mediator Probe PCR to detect the sequence-specific cleavage of label-free primary mediator probes. Since the fluorescence signal generation of a universal reporter is not influenced by the target DNA sequence, optimisation of the fluorescence signal-to-noise ratio will improve the performance of all Mediator Probe PCRs that are based on this type of universal reporter. To determine the critical factors influencing signal-to-noise optimisation, we systematically analysed four parameters. These parameters were type of fluorophore, type of quencher molecule, intramolecular orientation of both residuals, and the number of quencher labels. In total, more than 30 different fluorogenic universal reporter structures were analysed, covering the whole fluorescence spectrum from green to crimson. From our results, we deduced a novel set of guidelines for signal-to-noise optimisation in the design of contact quenched, fluorogenic universal reporter oligonucleotides. We confirmed these guidelines in a different thermocycler, and by designing a second set of universal reporters, which were used for multiplex real-time PCR quantification of acute lymphoblastic leukaemia marker sequences. This optimised biplex Mediator Probe PCR showed an improved performance under clinical conditions, with a 10 times higher resolution regarding the limit of quantification. In addition to Mediator Probe PCR, these guidelines may also prove useful in signal-to-noise optimisation of other fluorescence-based assays where contact quenched oligonucleotides or secondary reporter molecules are used.
B. Gerdes, M. Jehle, N. Lass, L. Riegger, A. Spribille, M. Linse, F. Clement, R. Zengerle, P. Koltay
Front side metallization of silicon solar cells by direct printing of molten metal
2018 Solar Energy Materials and Solar Cells, Band: 180, Seiten: 83 - 90
KurzfassungIn this work, a new approach for the front side metallization of silicon solar cells is presented. Molten solder (Sn96Ag3Cu) is directly printed in a non-contact manner on solar cell precursors via StarJet technology. The StarJet technology features a pneumatically driven, heatable printhead with a reservoir of molten metal and a star-shaped silicon nozzle chip. Using this printhead, a jet of molten metal with 55 μm ± 5 μm diameter is generated and used to apply busbars as well as contact fingers on prefabricated electroplated seed layers. After deposition via StarJet, printed fingers have a minimum width of 70 μm and a mean aspect ratio of 0.94. The printed metallization is evaluated optically and electrically. Aluminum back surface field silicon solar cells with front side electroplated NiAg seed layers and StarJet metallization (busbars and fingers) show efficiencies of up to 18.1% after degradation. Solder is about 30–40 times cheaper than silver and therefore may allow costefficient solar cell metallization. The StarJet metallization on electroplated NiAg seed layers is fully functional and requires no additional post-processing steps. Only 6 mg of Ag per cell are consumed for the seed layer. As a proof-of-principle, a module is demonstrated, which consists of four solar cells that are metallized via StarJet.
K. Kraiczek, G. Rozing, R. Zengerle
G-Index: A New Metric to Describe Dynamic Refractive Index Effects in HPLC Absorbance Detection
2018 Talanta, Band: 187, Seiten: 200 - 206
KurzfassungHigh performance liquid chromatography (HPLC) with a solvent gradient and absorbance detection is one of the most widely used methods in analytical chemistry. The observed absorbance baseline is affected by the changes in the refractive index (RI) of the mobile phase. Near the limited of detection, this complicates peak quantitation. The general aspects of these RI-induced apparent absorbance effects are discussed. Two different detectors with fundamentally different optics and flow cell concepts, a variable-wavelength detector equipped with a conventional flow cell and a diode-array detector equipped with a liquid core waveguide flow cell, are compared with respect to their RI behavior. A simple method to separate static – partly unavoidable – RI effects from dynamic RI effects is presented. It is shown that the dynamic RI behavior of an absorbance detector can be well described using a single, relatively easy-to-determine metric called the G-index. The G-index is typically in the order of a few seconds and its sign depends on the optical flow cell concept.
J. M. Stosch, A. Heumüller, C. Niemöller, S. Bleul, M. Rothenberg-Thurley, J. Riba, N. Renz, K. Szarc vel Szic, D. Pfeifer, M. Follo, H. L. Pahl, S. Zimmermann, J. Duyster, J. Wehrle, M. Lübbert, K. H. Metzeler, R. Claus, H. Becker
Gene mutations and clonal architecture in myelodysplastic syndromes and changes upon progression to acute myeloid leukaemia and under treatment
2018 Brit J Haematol, Band: 182, Seiten: 830 - 842
KurzfassungKnowledge of the molecular and clonal characteristics in the myelodysplastic syndromes (MDS) and during progression to acute myeloid leukaemia (AML) is essential to understand the disease dynamics and optimize treatment. Sequencing serial bone marrow samples of eight patients, we observed that MDS featured a median of 3 mutations. Mutations in genes involved in RNA-splicing or epigenetic regulation were most frequent, and exclusively present in the major clone. Minor subclones were distinguishable in three patients. As the MDS progressed, a median of one mutation was gained, leading to clonal outgrowth. No AML developed genetically independent of a pre-existing clone. The gained mutation mostly affected genes encoding signalling proteins. Additional acquisition of genomic aberrations frequently occurred. Upon treatment, emergence of new clones could be observed. As confirmed by single-cell sequencing, multiple mutations in identical genes in different clones were present within individual patients. DNA-methylation profiling in patients without identification of novel mutations in AML revealed methylation changes in individual genes. In conclusion, our data complement previous observations on the mutational and clonal characteristics in MDS and at progression. Moreover, DNA-methylation changes may be associated with progression in single patients. Redundancy of mutated genes in different clones suggests fertile grounds promoting clonal selection or acquisition.
C. Klose, P. Trinke, T. Böhm, B. Bensmann, S. Vierrath, R. Hanke-Rauschenbach, S. Thiele
Membrane Interlayer with Pt Recombination Particles for Reduction of the Anodic Hydrogen Content in PEM Water Electrolysis
2018 J Electrochem Soc, Band: 165, Seiten: F1271 - F1277
KurzfassungPolymer electrolyte membrane (PEM) water electrolysis is a key technology for sustainable hydrogen based energy supply. Gaspermeation through the PEM leads to hydrogen in oxygen at the anode side posing a safety hazard and therefore restricting theoperation window of PEM water electrolysis, especially when operating under pressure. In this work the hydrogen in oxygen contentat the anode is significantly reduced when a recombination interlayer is integrated into the membrane electrode assemblies (MEAs)compared to reference MEAs without interlayer. The recombination interlayer with a platinum loading of 0.02 mg cm−2is sprayedbetween two membranes that are coated with anode and cathode catalysts on the outside. The permeating H2and O2forms waterat the recombination interlayer, leading to higher gas purity and resolving safety issues. In case of the MEAs with interlayer alsoa constant current hold at 1 A cm−2for 245 h revealed only a slight increase of the hydrogen in oxygen content (below 140·10−6vol.% h−1) whereas for the reference MEAs without interlayer a stronger increase was observed (above 1250·10−6vol.% h−1).Furthermore, the long-term experiments showed no increased degradation rates compared to the reference MEAs.
S. Hin, M. Loskyll, V. Klein, M. Keller, O. Strohmeier, F. von Stetten, R. Zengerle, K. Mitsakakis
Membrane-based sample inlet for centrifugal microfluidic cartridges
2018 Microelectron Eng, Band: 187-188, Seiten: 78 - 83
KurzfassungCentrifugal microfluidics enables the rapid execution of complex blood sample analyses in a fully automated manner at the point of care. However, during blood sample addition, the cartridge is at rest and centrifugal forces are not present to allocate the sample in a controlled way. We present a versatile approach for the user-friendly, well-controlled and safe sample addition into a centrifugal microfluidic cartridge for use in serology. It features a commercial (plasma separation) membrane stacked into the inlet chamber of the cartridge. This combination of sample inlet and plasma separation in one structural unit brings the advantage of reducing footprint in highly integrated point-of-care testing. By using a pipette the user may add a blood sample (90 μL) to the membrane holding the liquid by capillary forces. Flowing across the membrane, cells separate from blood plasma. The blood plasma releases into the downstream structure upon centrifugation. The mean plasma recovery rate was 57.3 (± 4.7) % and mean plasma purity 99.5 (± 0.6) % from samples of varying hematocrit (36%–59%). Furthermore, the analyte C-reactive protein (CRP) did not significantly adsorb to the membrane. This was concluded, since CRP immunoassay results with plasma from spiked whole blood, obtained from membrane-based plasma separation and from plasma separation on a standard laboratory centrifuge, did not significantly differ. Thus, the suggested approach is promising for simultaneous application as sample inlet holding the sample by capillary forces and as a plasma separation module for centrifugal microfluidics. Potential future applications may include other sample matrices. The use with further blood transfer devices (capillary, directly from fingertip) seems possible, yet requiring further evaluation.
M. Frei, J. Martin, S. Kindler, G. Cristiano, R. Zengerle, S. Kerzenmacher
Power supply for electronic contact lenses: Abiotic glucose fuel cells vs. Mg/air batteries
2018 J Power Sources, Band: 401, Seiten: 403 - 414
KurzfassungElectronic contact lenses are a promising platform for medical sensors. With these devices a variety of vital signs and medical parameters can be monitored noninvasively and without the risk of foreign body response. However, one current limitation of this technology is the need for an external power supply, resulting in bulky, multi component devices. In this paper, we for the first time investigate and compare the application of abiotic glucose fuel cells and Mg/air batteries as alternative power supply technologies for electronic contact lenses. While abiotic glucose fuel cells harvest energy from metabolites present in tear fluid, Mg/air batteries provide electricity by the oxidation of a sacrificial anode. Considering the space available on standard contact lenses, our results indicate that approx. 40 μW and 2 μW can be generated by Mg/air batteries and glucose fuel cells for a period of at least 24 h, respectively. However, coating galvanic cells with the commonly used contact lens material pHEMA, results in drastically reduced performance, presumably due to hindered mass transport. Nevertheless, even under those circumstances a Mg/air battery can still provide about 7 μW for 24 h, which would already be sufficient for many electronic contact lens applications.
M. Frei, C. Köhler, L. Dietel, J. Martin, F. Wiedenmann, R. Zengerle, S. Kerzenmacher
Pulsed electro-deposition of highly porous Pt-alloys for the use in methanol, formic acid, and glucose fuel cells
2018 Chemelectrochem, Seiten: 1013 - 1023
KurzfassungWe demonstrate an electro-deposition process for the fabrication of highly porous PtCu-alloy anodes. In the fabrication process, Pt and different amounts of a second noble metal (Pd, Ru, Au) are repeatedly co-deposited with Cu from an aqueous electrolyte, followed by selective dealloying of Cu. This way, highly porous PtCu alloys with roughness factors ranging from 400 to 4000 can be obtained. In all cases both noble metal partners are present on the electrode surface, whereas the majority of copper is likely buried underneath. In addition, we can show that H-desorption and COstripping yield substantially different roughness factors, even when applied to PtCu anodes. Hence, when using or comparing results from different stripping methods a calibration is required. Compared to PtCu anodes, small additions of Ru (~3 at% Ru) lead to significantly enhanced catalytic activity for the electro-oxidation of formic acid and methanol, whereas Au-rich PtCu-Au alloys (~75 at% Au) exhibit significantly improved electro-catalytic activity for glucose oxidation. In some cases, large variations impede the identification of significant differences in electro-catalytic activity. To reduce process variability and to increase the specific surface area further optimization of the fabrication process is required. Similarly, the deposition of defined alloy compositions will require further investigation since the composition of electrolyte and deposited alloy do not directly correspond.
L. Becherer, M. Bakheit, S. Frischmann, S. Stinco, N. Borst, R. Zengerle, F. von Stetten
Simplified real-time multiplex detection of loop-mediated isothermal amplification (LAMP) using novel mediator displacement probes with universal reporters
2018 Anal Chem, Band: 90, Seiten: 4741 - 4748
KurzfassungA variety of real-time detection techniques for LAMP based on the change in fluorescence intensity during DNA amplification enable simultaneous detection of multiple targets. However these techniques depend on fluorogenic probes containing target-specific sequences. That complicates the adaption to different targets leading to time-consuming assay optimization. Here, we present the first universal real-time detection technique for multiplex LAMP. The novel approach allows simple assay design and is easy to implement for various targets. The innovation features a mediator displacement probe and a universal reporter. During amplification of target DNA the mediator is displaced from the mediator displacement probe. Then it hybridizes to the reporter generating a fluorescence signal. The novel Mediator Displacement (MD) detection was validated against state-of-the-art molecular beacon (MB) detection by means of a HIV-1 RT-LAMP: MD surpassed MB detection by accelerated probe design (MD: 10 min, MB: 3-4 h), shorter times to positive (MD 4.1±0.1 min shorter than MB, n = 36), improved signal to noise fluorescence ratio (MD: 5.9±0.4, MB: 2.7±0.4; n = 15) and showed equally good or better analytical performance parameters. The usability of one universal mediator-reporter set in different multiplex assays was successfully demonstrated for a biplex RT-LAMP of HIV-1 & HTLV-1 and a biplex LAMP of Haemophilus ducreyi & Treponema pallidum, both showing good correlation between target concentration and time to positive. Due to its simple implementation it is suggested to extend the use of the universal mediator-reporter sets to the detection of various other diagnostic panels.
J. Madjarov, A. Götze, R. Zengerle, S. Kerzenmacher
Simultaneous use of a crossflow filtration membrane as microbial fuel cell anode – permeate flow leads to 4-fold increased current densities
2018 Bioresource Technol, Band: 257, Seiten: 274 - 280
KurzfassungA new concept for the combination of membrane bioreactors and microbial fuel cells is introduced, that aims at the production of electricity for reducing the overall energy consumption of wastewater treatment. In contrast to previous approaches, the anode is integrated as microfiltration membrane in sidestream crossflow configuration. Using a stainless steel filtration membrane with G. sulfurreducens and an acetatebased synthetic medium, up to 4-fold higher current densities are achieved. In a standard setup without filtration, a membrane of filter grade 1 μm shows current densities of 5.8 A m-2 ± 0.5 A m-2 compared to >11 A m-2 when it is used simultaneously as membrane filter. With smaller pore sizes of filter grade 0.5 μm 4.4 A m-2 ± 0.5 A m-2 in a standard setup and >15 A m-2 in a filtration setup are achieved. The permeate flow was identified as the main parameter leading to increased current densities.
E. Kipf, J. Erben, R. Zengerle, J. Gescher, S. Kerzenmacher
Systematic investigation of anode materials for microbial fuel cells with the model organism G. sulfurreducens
2018 Bioresource Technology Reports, Band: 2, Seiten: 29 - 37
KurzfassungDifferent carbon and metal-based anode materials for microbial fuel cells were systematically investigated with a pure culture of the model organism G. sulfurreducens. The highest limiting current density of 756 ± 15 μA cm-2 at -0.253 ± 0.037 V vs. SCE was achieved with graphite foil using a step-wise galvanostatic technique. But also the application of completely different anode materials such as activated carbon cloth, stainless steel and graphite felt led to similar high limiting current densities, suggesting that G. sulfurreducens is able to use a large range of substantially different anode materials as external electron acceptor. Additionally, we could show that a step-wise galvanostatic technique to record polarization curves yields similar current densities as potentiostatic control at -0.400 V vs. SCE with the investigated carbon-based materials. In case of stainless steel these techniques yield slightly different results, presumably due to an effect related to the material’s surface properties.
S. Hin, N. Paust, M. Keller, M. Rombach, O. Strohmeier, R. Zengerle, K. Mitsakakis
Temperature change rate actuated bubble mixing for homogeneous rehydration of dry pre-stored reagents in centrifugal microfluidics
2018 Lab Chip, Band: 18, Seiten: 362 - 370
KurzfassungIn centrifugal microfluidics, dead volumes in valves downstream of mixing chambers can hardly be avoided. These dead volumes are excluded from mixing processes and hence cause a concentration gradient. Here we present a new bubble mixing concept which avoids such dead volumes. The mixing concept employs heating to create a temperature change rate (TCR) induced overpressure in the air volume downstream of mixing chambers. The main feature is an air vent with a high fluidic resistance, representing a low pass filter with respect to pressure changes. Fast temperature increase causes rapid pressure increase in downstream structures pushing the liquid from downstream channels into the mixing chamber. As air further penetrates into the mixing chamber, bubbles form, ascend due to buoyancy and mix the liquid. Slow temperature/ pressure changes equilibrate through the high fluidic resistance air vent enabling sequential heating/cooling cycles to repeat the mixing process. After mixing, a complete transfer of the reaction volume into the downstream fluidic structure is possible by a rapid cooling step triggering TCR actuated valving. The new mixing concept is applied to rehydrate reagents for loop-mediated isothermal amplification (LAMP). After mixing, the reaction mix is aliquoted into several reaction chambers for geometric multiplexing. As a measure for mixing efficiency, the mean coefficient of variation (C —— V, n = 4 LabDisks) of the time to positivity (tp) of the LAMP reactions (n = 11 replicates per LabDisk) is taken. The C —— V of the tp is reduced from 18.5% (when using standard shake mode mixing) to 3.3% (when applying TCR actuated bubble mixing). The bubble mixer has been implemented in a monolithic fashion without the need for any additional actuation besides rotation and temperature control, which are needed anyhow for the assay workflow.
F. Hegge, R. Moroni, P. Trinke, B. Bensmann, R. Hanke-Rauschenbach, S. Thiele, S. Vierrath
Three-dimensional microstructure analysis of a polymer electrolyte membrane water electrolyzer anode
2018 J Power Sources, Band: 393, Seiten: 62 - 66
KurzfassungThe anode catalyst layer of a PEM water electrolyzer is reconstructed using a combination of FIB-SEM tomography and ionomer modeling. The pore space is infiltrated with silicone, enabling good discrimination between pores and IrRuOx catalyst material, while the ionomer cannot be imaged. The reconstructed volume of 29 μm × 24 μm x 7 μm contains catalyst particles with a median size of 0.5 μm and has a porosity of 55%. By modeling different ionomer contents inside the pore space, the impact on microstructural and transport parameters is investigated. At an ionomer content of 40–50% of the pore volume, all transport parameters are in a reasonable range, confirming experimental results from literature. At an ionomer content of 48% the catalyst layer has a porosity of 29%, a median pore size of 0.94 μm, a permeability of the pore space of and a mean ionomer film thickness of . The tortuosities of the ionomer and the pore space are calculated to 3.5 and 6.7 at the corresponding phase fractions of 26% and 29% respectively. The electrochemically active surface area estimated from the tomography () is considerably lower than literature values, indicating a roughness below FIB-SEM resolution.
N. P. Kocatürk-Schumacher, J. Madjarov, P. Viwatthanasittiphong, S. Kerzenmacher
Toward an Energy Efficient Wastewater Treatment: Combining a Microbial Fuel Cell/Electrolysis Cell Anode With an Anaerobic Membrane Bioreactor
2018 Frontiers in Energy Research, Band: 6, Seite: 95
KurzfassungRecently, it has been shown that combining a bioelectrochemical system (BES) with an anaerobic membrane bioreactor (AnMBR) to produce electricity can reduce the overall energy consumption of wastewater treatment. In this study, we tested the recently proposed concept that integrates a microbial anode into an AnMBR, under application relevant conditions, for the treatment of synthetic brewery wastewater. We developed two system configurations: a filtering anode with stainless steel filter plate; and a hybrid anode, in which a polymeric membrane is combined with stainless steel mesh. As fouling is problematic in AnMBRs, we investigated the effect of two fouling mitigation methods, namely electrochemical cleaning and application of a turbulence promotor, on the permeate fluxes and current densities.We also investigated the effect of cathode (counter electrode) position on the permeate fluxes and current densities in filtering and hybrid anode. Our results revealed that permeate fluxes were influenced by the membrane pore size; and dropped below 5 L m−2 hr−1 on day 3 with filter grade 0.5μm; whereas similar values of permeate flux were observed after 5 days of operation with the membrane with filter grade 0.1μm. COD removal across the membrane reached up to 644mg L−1 indicating improvement in energy efficiency and effluent quality of the AnMBR. The location of cathode did not influence permeate fluxes and current densities, but permeate pH was largely affected. Electrochemical cleaning improved permeate fluxes more than 2-fold (18.9 L m−2 hr−1 after 7 days of operation) compared to the operation of the 0.1μm membrane without a cleaning procedure. Application of a turbulence promotor increased permeate fluxes and current densities in filtering anode. The hybrid anode resulted in similar current densities, but higher permeate fluxes as compared to the filtering anode, which dropped below 20 L m−2 hr−1 only after 8 days of operation. The Kocatürk-Schumacher et al. Microbial Anode Combined With AnMBR hybrid anode configuration is an attractive option that combines high permeate fluxes on conventional non-conductive filters with current generation on an inexpensive conductive material. In summary, our results demonstrate that combining BES with AnMBR is a promising approach toward an energy efficient wastewater treatment.

2017

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M. Bühler, C. Klose, F. Hegge, T. Lickert, S. Thiele
A Novel Fabrication Technique for Electrodes of PEM Water Electrolyzers
2017 ECS Transactions, Band: 80, Seiten: 1069 - 1075
KurzfassungIn this work the improvement of material interfaces at electrodes for proton exchange membrane (PEM) water electrolyzers is addressed by a novel fabrication technique. In this approach the electrode and the membrane are directly deposited on the porous transport layers (PTLs), which serve as substrate for the electrodes. The aim is to stabilize and increase the oxygen and hydrogen evolution rate at high current densities leading to a reduction of the noble metal loading of the electrodes – and additionally to develop a cost effective novel fabrication technique applicable for the large scale industrial fabrication of electrodes for PEM water electrolyzers. The innovative manufacturing technique is described in this transaction, and current challenges regarding the coating of porous substrates in terms of parameter control, reliability and homogeneity are pointed out.
M. Breitwieser, T. Bayer, A. Büchler, R. Zengerle, S. M. Lyth, S. Thiele
A fully spray-coated fuel cell membrane electrode assembly using Aquivion ionomer with a graphene oxide/cerium oxide interlayer
2017 J Power Sources, Band: 351, Seiten: 145 - 150
KurzfassungA novel multilayer membrane electrode assembly (MEA) for polymer electrolyte membrane fuel cells (PEMFCs) is fabricated in this work, within a single spray-coating device. For the first time, direct membrane deposition is used to fabricate a PEMFC by spraying the short-side-chain ionomer Aquivion directly onto the gas diffusion electrodes. The fully sprayed MEA, with an Aquivion membrane 10 mm in thickness, achieved a high power density of 1.6 W/cm2 for H2/air operation at 300 kPaabs. This is one of the highest reported values for thin composite membranes operated in H2/air atmosphere. By the means of confocal laser scanning microscopy, individual carbon fibers from the gas diffusion layer are identified to penetrate through the micro porous layer (MPL), likely causing a low electrical cell resistance in the range of 150 U cm2 through the thin sprayed membranes. By spraying a 200 nm graphene oxide/cerium oxide (GO/CeO2) interlayer between two layers of Aquivion ionomer, the impact of the electrical short is eliminated and the hydrogen crossover current density is reduced to about 1 mA/cm2. The peak power density of the interlayer-containing MEA drops only by 10% compared to a pure Aquivion membrane of similar thickness.
N. Borst, F. Schuler, S. Wadle, M. Schulz, M. Specht, J. Li, L. Becherer, M. Trotter, A. B. Rodríguez-Martínez, N. Paust, R. Zengerle, F. von Stetten
A technology platform for digital nucleic acid diagnostics at the point of care
2017 Laboratoriumsmedizin, Band: 41, Nummer: 5
KurzfassungThe combination of digital amplification and centrifugal microfluidics can enable quantitative and fast diagnostics at the point of care (PoC). The new unit operation of centrifugal step emulsification allows high throughput droplet generation. Different methods for digital nucleic acid analysis, including PCR, recombinase polymerase amplification (RPA) and loop mediated isothermal amplification (LAMP), have already been demonstrated. Our novel approach of integrated sample-to-answer analysis is introduced, and examples for the detection of HIV and single cell analysis of antibiotic resistant bacteria are presented. Next to these LabDisk based systems, a microfluidic cartridge termed DropChip allows for digital amplification using only commercially available laboratory devices.
L. Benning, L. Gutzweiler, K. Tröndle, J. Riba, R. Zengerle, P. Koltay, S. Zimmermann, G. B. Stark, G. Finkenzeller
Assessment of hydrogels for bioprinting of endothelial cells
2017 J Biomed Mater Res A, Seiten: 935 - 947
KurzfassungIn tissue engineering applications, vascularization can be accomplished by co-implantation of tissue forming cells and endothelial cells (ECs), whereby the latter are able to form functional blood vessels. The use of three-dimensional (3D) bioprinting technologies has the potential to improve the classical tissue engineering approach because these will allow the generation of scaffolds with high spatial control of endothelial cell allocation. This study focuses on a side by side comparisons of popular commercially available bioprinting hydrogels (matrigel, fibrin, collagen, gelatin, agarose, Pluronic F-127, alginate and alginate/gelatin) in the context of their physicochemical parameters, their swelling/degradation characteristics, their biological effects on vasculogenesis-related EC parameters and their printability. The aim of this study was to identify the most suitable hydrogel or hydrogel combination for inkjet printing of ECs to build pre-vascularized tissue constructs. Most tested hydrogels displayed physicochemical characteristics suitable for inkjet printing. However, Pluronic F-127 and the alginate/gelatin blend were rapidly degraded when incubated in cell culture medium. Agarose, Pluronic F-127, alginate and alginate/gelatin hydrogels turned out to be unsuitable for bioprinting of ECs because of their non-adherent properties and/or their incapability to support EC proliferation. Gelatin was able to support EC proliferation and viability but was unable to support endothelial cell sprouting. Our experiments revealed fibrin and collagen to be most suitable for bioprinting of ECs, because these hydrogels showed acceptable swelling/degradation characteristics, supported vasculogenesis-related EC parameters and showed good printability. Moreover, ECs in constructs of preformed spheroids survived the printing process and formed capillary-like cords.
T. Gleichmann, A. Rostas, J. Wörner, E. Schleicher, L. Gutzweiler, B. Hamouda, R. Zengerle, P. Koltay, L. Riegger
Atmospheric Photopolymerization of Acrylamide Enabled by Aqueous Glycerol Mixtures: Characterization and Application for Surface-Based Microfluidics
2017 Macromol Mater Eng, Seite: 1600518
KurzfassungPolyacrylamide usually is the material of choice for electrophoretic separation in slab gels, capillaries, and microfluidic devices. So far its polymerization requires anaerobic environments because oxygen impurities inhibit or even terminate the polymerization reaction of acrylamide. Here, it is demonstrated that gel precursor solutions with glycerol contents above 20 vol% enable direct atmospheric photopolymerization of acrylamide with no need for sealing or degassing the solution in advance. The positive effect of glycerol on the polymerization reaction is proven by simulation-validated electron paramagnetic resonance measurements. Nuclear magnetic resonance reveals that glycerol does not interfere with the reaction indicating that the observed enhancement in polymerization is owed to the low oxygen solubility of aqueous glycerol mixtures. Glycerol concentrations of >60 vol% in the gel precursor solution enable complete polymerization of volumes down to 5 nL within less than 5 s. This enables using liquid handling robots to fabricate channel-free open microfluidic structures of solid polyacrylamide hydrogel in a low-cost automated manner in a standard lab environment.
Y. Zhao, G. Czilwik, V. Klein, K. Mitsakakis, R. Zengerle, N. Paust
C-reactive protein and Interleukin 6 microfluidic immunoassays with on-chip pre-stored reagents and centrifugo-pneumatic liquid control
2017 Lab Chip, Band: 17, Nummer: 9, Seiten: 1666 - 1677
KurzfassungWe present a fully automated centrifugal microfluidic method for particle based protein immunoassays. Stick-pack technology is employed for pre-storage and release of liquid reagents. Quantitative layout of centrifugo-pneumatic particle handling, including timed valving, switching and pumping is assisted by network simulations. The automation is exclusively controlled by the spinning frequency and does not require any additional means. New centrifugal microfluidic process chains are developed in order to sequentially supply wash buffer based on frequency dependent stick-pack opening and pneumatic pumping to perform two washing steps from one stored wash buffer; pre-store and re-suspend functionalized microparticles on disk; and switch between the path of the waste fluid and the path of the substrate reaction product with 100% efficiency. The automated immunoassay concept comprises on demand ligand binding, two washing steps, substrate reaction, timed separation of the reaction products, and termination of the substrate reaction. We demonstrated separation of particles from three different liquids with particle loss below 4 % and residual liquid remaining within particles below 3 %. The automated immunoassay concept was demonstrated by means of detecting Creactive protein (CRP) in the range of 1 - 81 ng ml-1 and Interleukin 6 (IL-6) in the range of 64 - 13500 pg ml-1. The limit of detection and quantification were 1.0 ng ml-1 and 2.1 ng ml-1 for CRP; 64 pg ml-1 and 205 pg ml-1 for IL-6, respectively.
M. Breitwieser, C. Klose, A. Hartmann, A. Büchler, M. Klingele, S. Vierrath, R. Zengerle, S. Thiele
Cerium Oxide Decorated Polymer Nanoﬁbers as Effective Membrane Reinforcement for Durable, High-Performance Fuel Cells
2017 Adv Energy Mater, Seite: 1602100
KurzfassungHigh-power, durable composite fuel cell membranes are fabricated here by direct membrane deposition (DMD). Poly(vinylidene ﬂuoride-co-hexaﬂuo- ropropylene) (PVDF-HFP) nanoﬁbers, decorated with CeO 2 nanoparticles are directly electrospun onto gas diffusion electrodes. The nanoﬁber mesh is impregnated by inkjet-printed Naﬁon ionomer dispersion. This results in 12 µm thin multicomponent composite membranes. The nanoﬁbers provide membrane reinforcement, whereas the attached CeO 2 nanoparticles promote improved chemical membrane durability due to their radical scavenging properties. In a 100 h accelerated stress test under hot and dry conditions, the reinforced DMD fuel cell shows a more than three times lower voltage decay rate (0.39 mV h −1 ) compared to a comparably thin Gore membrane (1.36 mV h −1 ). The maximum power density of the DMD fuel cell drops by 9%, compared to 54% measured for the reference. Impedance spectroscopy reveals that ionic and mass transport resistance of the DMD fuel cell are unaffected by the accelerated stress test. This is in contrast to the reference, where a 90% increase of the mass transport resistance is measured. Energy dispersive X-ray spectroscopy reveals that no signiﬁcant migration of cerium into the catalyst layers occurs during degradation. This proves that the PVDF- HFP backbone provides strong anchoring of CeO 2 in the membrane.
P. Lettenmeier, S. Kolb, L. Zielke, S. Thiele, A. Fallisch, N. Sata, A. S. Gago, K. A. Friedrich
Comprehensive investigation of novel pore-graded gas diffusion layers for high-performance and cost-effective proton exchange membrane electrolyzers
2017 Energy Environ. Sci., Band: 10, Seiten: 2521 - 2533
KurzfassungHydrogen produced by water electrolysis is a promising storage medium for renewable energy. Reducing the capital cost of proton exchange membrane (PEM) electrolyzers without losing efficiency is one of its most pressing challenges. Gas diffusion layers (GDL), such as felts, foams, meshes and sintered plates, are key stack components, but these are either inefficient or expensive. This study presents a new type of GDL produced via vacuum plasma spraying (VPS), which offers a large potential for cost reduction. With this technology, it is possible to introduce a gradient in the pore-size distribution along the thickness of the GDL by varying the plasma parameters and titanium powder particle sizes. This feature was confirmed by cross-section scanning electron microscopy (SEM). X-ray computed tomography (CT) and mercury intrusion porosimetry allowed determining the porosity, pore radii distribution, and pore entry distribution. Pore radii of ca. 10 μm could be achieved in the layers of the GDL close to the bipolar plate, while those in contact with the electrodes were in the range of 5 μm. The thermally sprayed Ti-GDLs allowed achieving PEM electrolyzer performances comparable to those of the state-of-the-art sintered plates and far superior than those of meshes. Moreover, a numerical model showed that the reduced capillary pressure and tortuosity eliminates mass transport limitations at 2 A cm−2. The results presented herein demonstrate a promising solution to reduce the cost of one of the most expensive components of the stack.
L. Benning, L. Gutzweiler, K. Tröndle, J. Riba, R. Zengerle, P. Koltay, S. Zimmermann, G.B. Stark, G. Finkenzeller
Cytocompatibility testing of hydrogels toward bioprinting of mesenchymal stem cells
2017 J Biomed Mater Res A, Band: 105, Seiten: 3231 - 3241
KurzfassungMesenchymal stem cells (MSCs) represent a very attractive cell source for tissue engineering applications aiming at the generation of artificial bone substitutes. The use of three-dimensional bioprinting technologies has the potential to improve the classical tissue engineering approach because bioprinting will allow the generation of hydrogel scaffolds with high spatial control of MSC allocation within the bioprinted construct. In this study, we have performed direct comparisons between commercially available hydrogels in the context of their cytocompatibility toward MSCs and their physicochemical parameters with the aim to identify the most suitable hydrogel for drop-on-demand (DoD) printing of MSCs. In this context, we examined matrigel, fibrin, collagen, gelatin, and gelatin/alginate at various hydrogel concentrations. Matrigel, fibrin, collagen, and gelatin were able to support cell viability, but the latter showed a limited potential to promote MSC proliferation. We concentrated our study on fibrin and collagen hydrogels and investigated the effect of hydroxyapatite (HA) inclusion. The inclusion of HA enhanced proliferation and osteogenic differentiation of MSCs and prevented degradation of fibrin in vitro. According to viscosity and storage moduli measurements, HA-blends displayed physicochemical characteristics suitable for DoD printing. In bioprinting experiments, we confirmed that fibrin and collagen and their respective HA-blends represent excellent hydrogels for DoD-based printing as evidenced by high survival rates of printed MSCs.
C. Klose, M. Breitwieser, S. Vierrath, M. Klingele, H. Cho, A. Büchler, J. Kerres, S. Thiele
Electrospun sulfonated poly(ether ketone) nanofibers as proton conductive reinforcement for durable Nafion composite membranes
2017 J Power Sources, Band: 361, Seiten: 237 - 242
KurzfassungWe show that the combination of direct membrane deposition with proton conductive nanofiber reinforcement yields highly durable and high power density fuel cells. Sulfonated poly(ether ketone) (SPEK) was directly electrospun onto gas diffusion electrodes and then filled with Nafion by inkjet-printing resulting in a 12 μm thin membrane. The ionic membrane resistance (30 mΩ*cm2) was well below that of a directly deposited membrane reinforced with chemically inert (PVDF-HFP) nanofibers (47 mΩ*cm2) of comparable thickness. The power density of the fuel cell with SPEK reinforced membrane (2.04 W/cm2) is 30% higher than that of the PVDF-HFP reinforced reference sample (1.57 W/cm2). During humidity cycling and open circuit voltage (OCV) hold, the SPEK reinforced Nafion membrane showed no measurable degradation in terms of H2 crossover current density, thus fulfilling the target of 2 mA/cm2 of the DOE after degradation. The chemical accelerated stress test (100 h OCV hold at 90 °C, 30% RH, H2/air, 50/50 kPa) revealed a degradation rate of about 0.8 mV/h for the fuel cell with SPEK reinforced membrane, compared to 1.0 mV/h for the PVDF-HFP reinforced membrane.
K. Lehmann, O. Yurchenko, A. Heilemann, S. Vierrath, L. Zielke, S. Thiele, A. Fischer, G. Urban
High surface hierarchical carbon nanowalls synthesized by plasma deposition using an aromatic precursor
2017 Carbon, Band: 118, Seiten: 578 - 587
KurzfassungHierarchical carbon nanowalls (CNW) are synthesized by plasma-enhanced chemical vapor deposition using p-xylene as a complex precursor. In contrast to ordinary CNW, synthesized with short-chained carbons, hierarchical CNW show a unique multi-scale pore structure, made up of micro- and mesopores connected by tubular macropores, offering higher surface area and surface accessibility. Their morphology, graphitic structure, surface area and accessibility are verified by transmission and scanning electron microscopy, gas sorption and impedance spectroscopy. Focused ion beam scanning electron microscopy tomography demonstrates the presence of macropores ensuring pore connectivity down to the substrate. Nitrogen/krypton physisorption confirms the micro- and mesoporous structure contributing extensively to the surface area. The impedance spectra are evaluated according to standard RC and transmission line models. The sample deposited for 60 min, with a structure height of 4.75 μm, features a volumetric capacitance of 2.6 F cm−3 and a response time of 25 ms. Hierarchical CNW exhibit a two to six times higher volumetric capacitance than CNW of similar proportions, reported in literature. Hierarchical CNW offer a promising way to realize high power and energy density requirements in electrochemical energy systems, like supercapacitors, due to their good conductivity, high surface area and open pore structure.
A. Fallisch, L. Schellhase, J. Fresko, M. Zedda, J. Ohlmann, M. Steiner, A. Bösch, L. Zielke, S. Thiele, F. Dimroth, T. Smolinka
Hydrogen concentrator demonstrator module with 19.8% solar-to-hydrogen conversion efficiency according to the higher heating value
2017 Int J Hydrogen Energ, Seiten: 26804 - 26815
KurzfassungRenewable hydrogen is a key element to a sustainable energy system of the future. Therefore solar hydrogen generation has been investigated by various research groups in recent years. The patented concept of the Hydrogen Concentrator (HyCon), which combines III-V multi-junction solar cells with polymer electrolyte membrane electrolysis, has been constantly developed over the last years. In this work, a unique weatherproof HyCon module with an area of 8 × 90.7 cm2 was build and characterized in an outdoor measurement for over two month. During this measurement period, the module showed a stable operation regardless of the water volume flow. The module works under natural convection without any circulation pumps at a suitable maximum temperature of 60–70 °C. The HyCon module consists of eight individual units (HyCon cells), each combining a photovoltaic and an electrolysis cell. Some of the HyCon cells reach a solar-to-hydrogen conversion efficiency of 20% according to the higher heating value at high current densities of 0.8 A/cm2. On the module level a maximum efficiency of 19.8% is reached. To the best of our knowledge this is the highest conversion efficiency so far achieved at such high current densities using a dual junction solar cell.
A. Fallisch, L. Schellhase, J. Fresko, M. Zechmeister, M. Zedda, J. Ohlmann, L. Zielke, N. Paust, T. Smolinka
Investigation on PEM water electrolysis cell design and components for a HyCon solar hydrogen generator
2017 Int J Hydrogen Energ, Band: 42, Seiten: 13544 - 13553
KurzfassungHydrogen as a secondary energy carrier promises a large potential as a long term storage for fluctuating renewable energies. In this sense a highly efficient solar hydrogen generation is of great interest especially in southern countries having high solar irradiation. The patented Hydrogen Concentrator (HyCon) concept yields high efficiencies combining multi-junction solar cells with proton exchange (PEM) membrane water electrolysis. In this work, a special PEM electrolysis cell for the HyCon concept was developed and investigated. It is shown that the purpose-made PEM cell shows a high performance using a titanium hybrid fiber sinter function both as a porous transport layer and flow field. The electrolysis cell shows a high performance with 1.83 V at 1 A/cm2 and 24 °C working under natural convection with a commercially available catalyst coated membrane. A theoretical examination predicts a total efficiency for the HyCon module from sunlight to hydrogen of approximately 19.5% according to the higher heating value.
L. Gutzweiler, S. Kartmann, K. Troendle, L. Benning, G. Finkenzeller, R. Zengerle, P. Koltay, B. Stark, S. Zimmermann
Large scale production and controlled deposition of single HUVEC spheroids for bioprinting applications
2017 Biofabrication, Band: 9 (2), Seite: 02502
KurzfassungWe present 1.) a fast and automated method for large scale production of HUVEC spheroids based on the hanging drop method and 2.) a novel method for well-controlled lateral deposition of single spheroids by drop-on-demand printing. Large scale spheroid production is achieved via printing 1536 droplets of HUVEC cell suspension having a volume of 1 µl each within 3 minutes at a pitch of 2.3 mm within an array of 48 x 32 droplets onto a flat substrate. Printing efficiencies between 97.9% and 100% and plating efficiencies between 87.3% and 100% were achieved. Harvested spheroids (consisting of approx. 250 HUVECs each) appear uniform in size and shape. After incubation and harvesting, the spheroids are deposited individually in user-defined patterns onto hydrogels using an automated drop-on-demand dispenser setup. Controlled by an image detection algorithm focusing the dispenser nozzle, droplets containing exactly one spheroid are printed onto a substrate, while all other droplets are discarded. Using this approach an array of 6 x 3 HUVEC spheroids with intermediate distances of 500 µm embedded in fibrin was generated. Successful progress of spheroid sprouting and merging of neighboring sprouts was observed during the first 72 hours of incubation indicating a good viability of the deposited spheroids.
M. Kokko, F. Bayerköhler, J. Erben, R. Zengerle, P. Kurz, S. Kerzenmacher
Molybdenum sulphides on carbon supports as electrocatalysts for hydrogen evolution in acidic industrial wastewater
2017 Appl Energ, Band: 190, Seiten: 1221 - 1233
KurzfassungMicrobial electrolysis cells (MECs) are an attractive future alternative technology to generate renewable hydrogen and simultaneously treat wastewaters. The thermodynamics of hydrogen evolution in MECs can be greatly improved by operating the cathode at acidic pH in combination with a neutral pH microbial anode. This can easily be achieved with acidic industrial wastewaters that have to be neutralised before discharge. For the hydrogen evolution reaction (HER) in acidic wastewater, efficient and inexpensive catalysts are required that are compatible with the often complex chemical composition of wastewaters. In this study, molybdenum sulphides (MoSx) on different carbon supports were successfully used for hydrogen evolution in different acidic media. At first, the cathodes were screened by linear sweep voltammetry in sulphuric acid (pH 0) or phosphate buffer (pH 2.2). After this, the overpotentials for H2 production of the best cathodes and their long term performances (>=1 week) were determined in acidic industrial wastewater (pH 2.4) obtained from a plant mainly producing cellulose acetate. For the most promising MoSx cathodes, the overpotentials for HER (at 3 mA cm-2) were only ~40 mV higher than for a platinum electrode. Most importantly, the catalytic efficiency of the MoSx electrodes improved in the wastewater over time (7–17 days), while Pt electrodes were found to be slowly deactivated. Thus, MoSx emerges as an affordable, efficient and especially durable electrocatalyst for HER in real acidic wastewaters and this could be an important contribution to take energy production from wastewaters in the form of hydrogen towards practical applications.
M. Klingele, R. Moroni, S. Vierrath, S. Thiele
Multiscale Tomography-Based Analysis of Fuel Cells: Towards a Fully Resolved Fuel Cell Reconstruction
2017 J Electrochem Energy, Band: 15, Seite: 014701
KurzfassungThe microstructure of a fuel cell electrode largely determines the performance of the whole fuel cell system. In this regard, tomographic imaging is a valuable tool for the understanding and control of the electrode morphology. The distribution of pore- and feature-sizes within fuel cell electrodes covers several orders of magnitude, ranging from millimeters in the gas diffusion layer down to few nanometers in the catalyst layer. This obligates the application of various tomographic methods for imaging every aspect of a fuel cell. This perspective evaluates the capabilities, limits and challenges of each of these methods. Further it highlights and suggests efforts towards the integration of multiple tomographic methods into single multiscale datasets, a venture which aims at large scale, and morphologically fully resolved fuel cell reconstructions.
M. Frei, J. Erben, J. Martin, R. Zengerle, S. Kerzenmacher
Nanofiber-deposited porous platinum enables glucose fuel cell anodes with high current density in body fluids
2017 J Power Sources, Band: 362, Seiten: 168 - 173
KurzfassungThe poisoning of platinum anodes by body-fluid constituents such as amino acids is currently the main hurdle preventing the application of abiotic glucose fuel cells as battery-independent power supply for medical implants. We present a novel anode material that enables continuous operation of glucose oxidation anodes in horse serum for at least 30 days at a current density of (7.2 ± 1.9) μA cm−2. The fabrication process is based on the electro-deposition of highly porous platinum onto a 3-dimensional carbon nanofiber support, leading to approximately 2-fold increased electrode roughness factors (up to 16500 ± 2300). The material's superior performance is not only related to its high specific surface area, but also to an improved catalytic activity and/or poisoning resistance. Presumably, this results from the micro- and nanostructure of the platinum deposits. This represents a major step forward in the development of implantable glucose fuel cells based on long-term stable platinum electrodes.
S. Zehnle, M. Rombach, R. Zengerle, F. von Stetten, N. Paust
Network simulation-based optimization of centrifugo-pneumatic blood plasma separation
2017 Biomicrofluidics, Band: 11, Seite: 024114
KurzfassungAutomated and robust separation of 14 ll of plasma from 40 ll of whole blood at a purity of 99.81%60.11% within 43 s is demonstrated for the hematocrit range of 20%–60% in a centrifugal microfluidic polymer disk. At high rotational frequency, red blood cells (RBCs) within whole blood are concentrated in a radial outer RBC collection chamber. Simultaneously, plasma is concentrated in a radial inner pneumatic chamber, where a defined air volume is enclosed and compressed. Subsequent reduction of the rotational frequency to not lower than 25 Hz enables rapid transfer of supernatant plasma into a plasma collection chamber, with highly suppressed resuspension of red blood cells. Disk design and the rotational protocol are optimized to make the process fast, robust, and insusceptible for undesired cell resuspension. Numerical network simulation with lumped model elements is used to predict and optimize the fluidic characteristics. Lysis of the remaining red blood cells in the purified plasma, followed by measurement of the hemoglobin concentration, was used to determine plasma purity. Due to the pneumatic actuation, no surface treatment of the fluidic cartridge or any additional external means are required, offering the possibility for low-cost mass fabrication technologies, such as injection molding or thermoforming.
L. Gutzweiler, T. Gleichmann, L. Tanguy, P. Koltay, R. Zengerle, L. Riegger, , ,
Open microfluidic gel electrophoresis: Rapid and low cost separation and analysis of DNA at the nanoliter scale
2017 Electrophoresis, Band: 38, Seiten: 1764 - 1770
KurzfassungGel electrophoresis is one of the most applied and standardized tools for separation and analysis of macromolecules and their fragments in academic research and in industry. In this work we present a novel approach for conducting on-demand electrophoretic separations of DNA molecules in open microfluidic (OM) systems on planar polymer substrates. The approach combines advantages of slab gel, capillary- & chip-based methods offering low consumable costs (< 0.1 $) circumventing cost intensive microfluidic chip fabrication, short process times (5 minutes per analysis) and high sensitivity (4 ng/µl dsDNA) combined with reasonable resolution (17 bases). The open microfluidic separation system comprises two opposing reservoirs of 2-4 µl in volume, a semi-contact written gel line acting as separation channel interconnecting the reservoirs and sample injected into the line via non-contact droplet dispensing and thus enabling the precise control of the injection plug and sample concentration. Evaporation is prevented by covering aqueous structures with PCR-grade mineral oil while maintaining surface temperature at 15°C. The liquid gel line exhibits a semi-circular cross section of adaptable width (~200-600 µm) and height (~30-80 µm) as well as a typical length of 15-55 mm. Layout of such liquid structures is adaptable on-demand not requiring time consuming and repetitive fabrication steps. The approach was successfully demonstrated by the separation of a standard label-free DNA ladder (100-1000 bp) at 100 V/cm via in-line staining and laser induced fluorescent end-point detection using an automated prototype.
J. Madjarov, S.C. Popat, J. Erben, A. Götze, R. Zengerle, S. Kerzenmacher
Revisiting methods to characterize bioelectrochemical systems: The influence of uncompensated resistance (iRu-drop), double layer capacitance, and junction potential
2017 J Power Sources, Band: 356, Seiten: 408 - 418
KurzfassungBioelectrochemical systems (BES) are characterized with methods derived from the electrochemistry field, for e.g. linear sweep voltammetry (LSV), cyclic voltammetry (CV), and chronoamperometry. The limitations of electrochemical measurements are well known and described, but there are new challenges when these are applied to biological systems. For instance, the electrolyte conditions are predefined by the application involving the use of low conductivities, leading to an increase of two error sources: the iRu-drop and junction potential. Furthermore, the use of electrodes with high surface areas and thus high double layer capacitance lead to capacitive currents that superimpose the biocatalytic current of interest. Even though these problems have often been mentioned in the bioelectrochemistry field, they are seldom considered and reported in publications. The scope of this work is to present and discuss methods to quantify the Ru and double layer capacitance, and to demonstrate their significant influence on the recording of polarization curves. In a typical BES setup, it is exemplarily shown that due to iRu-drop measured potentials can deviate by more than 200 mV from the actual potential. Similarly, more than 40% of a recorded electrode current can originate from the electrode material's double layer capacitance.
M. Keller, G. Czilwik, J. Schott, I. Schwarz, K. Dormanns, F. von Stetten, R. Zengerle, N. Paust
Robust temperature change rate actuated valving and switching for highly integrated centrifugal microfluidics
2017 Lab Chip, Band: 17, Seiten: 864 - 875
KurzfassungWe present new unit operations for valving and switching in centrifugal microfluidics that are actuated by a temperature change rate (TCR) and controlled by the rotational frequency. Implementation is realized simply by introducing a comparatively large fluidic resistance to an air vent of a fluidic structure downstream of a siphon channel. During temperature decrease at a given TCR, air pressure inside the downstream structure decreases and the fluidic resistance of the air vent slows down air pressure compensation allowing for a thermally induced underpressure to build up temporarily. Thereby the rate of temperature change determines the time course of the underpressure for a given geometry. The thermally induced underpressure pulls liquid against a centrifugal counterpressure above a siphon crest, which triggers the valve or switch. The centrifugal counterpressure (adjusted by rotation) serves as independent control parameter to allow or prevent valving or switching at any TCR. The unit operations are thus compatible to any temperature or centrifugation protocol prior to valving or switching. In contrast to existing methods, this compatibility is achieved at no additional costs: neither additional fabrication steps, nor additional disk space or external means are required besides global temperature control, which is per se needed for the assay. For layout, an analytical model is provided and verified. The TCR actuated unit operations are demonstrated, first, by a stand-alone switch that routes liquid to either one of the two collection chambers (n = 6) and, second, by studying robustness of TCR actuated valving within a microfluidic cartridge for highly integrated nucleic acid testing. Valving could safely be prevented during PCR by compensating the thermally induced underpressure of 3.52 kPa by centrifugal counterpressure at a rotational frequency of 30 Hz with a minimum safety range to valving of 2.03 kPa. Subsequently, a thermally induced underpressure of 2.55 kPa was utilized for robust siphon valving at 3 Hz with a minimum safety range of 2.32 kPa.
M. Breitwieser, C. Klose, M. Klingele, A. Hartmann, J. Erben, H. Cho, J. Kerres, R. Zengerle, S. Thiele
Simple fabrication of 12 μm thin nanocomposite fuel cell membranes by direct electrospinning and printing
2017 J Power Sources, Band: 337, Seiten: 137 - 144
KurzfassungDirect membrane deposition (DMD) was recently introduced as a novel polymer electrolyte membrane fabrication method. Here, this approach is extended to fabricate 12 μm thin nanocomposite fuel cell membranes. Poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) nanofibers are directly electrospun onto gas diffusion electrodes. By inkjet-printing Nafion ionomer dispersion into the pore space of PVDF-HFP nanofiber mats, composite membranes of 12 mm thickness were fabricated. At 120 C and 35% relative humidity, stoichiometric 1.5/2.5 H2/air flow and atmospheric pressure, the power density of the DMD fuel cell (0.19Wcm-2), was about 1.7 times higher than that of the reference fuel cell (0.11Wcm-2) with Nafion HP membrane and identical catalyst. A lower ionic resistance and, especially at 120 C, a reduced charge transfer resistance is found compared to the Nafion HP membrane. A 100 h accelerated stress test revealed a voltage decay of below 0.8 mV h-1, which is in the range of literature values for significantly thicker reinforced membranes. Finally, this novel fabrication approach enables new degrees of freedom in the design of complex composite membranes. The presented combination of scalable deposition techniques has the potential to simplify and thus reduce cost of composite membrane fabrication at a larger scale.
F. Sun, R. Moroni, K. Dong, H. Markötter, D. Zhou, A. Hilger, L. Zielke, R. Zengerle, S. Thiele, J. Banhart, I. Manke
Study of the Mechanisms of Internal Short Circuit in a Li/Li Cell by Synchrotron X‑ray Phase Contrast Tomography
2017 ACS Energy Lett., Band: 2, Seiten: 94 - 104
KurzfassungKnowledge about degradation and failure of Li-ion batteries (LIBs) is of paramount importance, especially because failure can be accompanied by severe hazards. To contribute to the understanding of such phenomena, synchrotron in-line phase contrast X-ray tomography was employed to investigate internal cell deformation and degradation caused by an internal short circuit (ISC). The tomographic images taken from an uncycled Li/Li cell and a short-circuited Li/Li cell reveal how lithium microstructures (LmSs) develop during electrochemical stripping and plating during discharge and charge and how the three-layer separator used is damaged by growing LmSs and delaminates and melts as a consequence of an ISC. Previously unknown insights into the internal cell degradation and deformation mechanisms caused by an ISC are obtained and provide hints of how the properties of the separator could be modified to improve the reliability and safety of current- and next-generation LIBs.
M. Klingele, C. Pham, K. Rao Vuyyurud, B. Britton, S. Holdcroft, A. Fischer, S. Thiele
Sulfur doped reduced graphene oxide as metal-free catalyst for the oxygen reduction reaction in anion and proton exchange fuel cells
2017 Electrochem Commun, Band: 77, Seiten: 71 - 75
KurzfassungSulfur doped reduced graphene oxide (S-rGO) is investigated for catalytic activity towards the oxygen reduction reaction (ORR) in acidic and alkaline electrolytes. X-ray photoelectron spectroscopy shows that sulfur in S-rGO is predominantly integrated as thiophene motifs within graphene sheets. The overall sulfur content is determined to be approximately 2.2 at.% (elemental analysis). The catalytic activity of S-rGO towards the ORR is investigated by both rotating disc electrode (RDE) and polymer electrolyte fuel cell (PEFC) measurements. RDE measurements reveal onset potentials of 0.3 V and 0.74 V (vs. RHE) in acidic and alkaline electrolyte, respectively. In a solid electrolyte fuel cell with S-rGO as cathode material, this is reflected in an open circuit voltage of 0.37 V and 0.78 V and a maximum power density of 1.19 mW/cm2 and 2.38 mW/cm2 in acidic and alkaline polymer electrolyte, respectively. This is the first report investigating the catalytic activity of a sulfur doped carbon material in both acidic and alkaline liquid electrolyte, as well as in both proton and anion exchange polymer electrolyte fuel cells.
M. Breitwieser, M. Klingele, S. Vierrath, R. Zengerle, S. Thiele
Tailoring the membrane-electrode interface in PEM fuel cells: A review and perspective on novel engineering approaches
2017 Adv Energy Mater, Seite: 1701257
C. Van Pham, M. Klingele, B. Britton, K. R. Vuyyuru, T. Unmuessig, S. Holdcroft, A. Fischer,, S. Thiele
Tridoped Reduced Graphene Oxide as a Metal-Free Catalyst for Oxygen Reduction Reaction Demonstrated in Acidic and Alkaline Polymer Electrolyte Fuel Cells
2017 Advanced Sustainable Systems, Band: 1, Seite: 1600038
KurzfassungRecently, it has been demonstrated that doping of graphene by elements such as N, S, or F creates active sites for the oxygen reduction reaction (ORR). This results from bond polarization caused by the difference in electron- egativity between heteroatom dopants and carbon, and/or the presence of defects within the graphene lattice. In this work, ﬂuorine, nitrogen, and sulfur tridoped reduced graphene oxide (F,N,S-rGO) is designed to combine these catalytically active sites. F,N,S-rGO can be inexpensively synthesized by a facile and scalable route involving pyrolysis at 600 °C of sulfur-doped rGO in the presence of Naﬁon and dimethyl formamide (DMF). The pyrolysis of Naﬁon and DMF provides F • and N • radicals which serve as doping agents. Rotating disk electrode investigations reveal the ORR catalytic activities of F,N,S-rGO in both acidic and alkaline media, which are consistent with the real performances of the respective polymer electrolyte fuel cells (PEFCs). Maximum power densities of 14 and 46 mW cm −2 are obtained for the acidic and alkaline PEFCs, respectively, using F,N,S-rGO as ORR catalysts. To the best of knowledge, this is the ﬁrst report on the synthesis of F,N,S tridoped rGO and on its ORR activity in both acidic and alkaline PEFCs.

2016

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M. Hagner, J. M. Fritz, P. Alknes, C. Scheuerlein, L. Zielke, S. Vierrath, S. Thiele, B. Bordini, A. Ballarino
3D Analysis of the Porosity in MgB2 Wires Using FIB Nanotomography
2016 Ieee T Appl Supercon, Band: 26, Seite: 6200305
KurzfassungPorosity is one of several current limiting mechanisms in MgB2 wires. We have compared the microstructural homogeneity and the porosity distribution in different ex situ and in situ MgB2 Powder-in-Tube (PIT) wires. The sub-micrometer structure was determined using Focused Ion Beam (FIB) nanotomography. The ex situ wires exhibit an isotropic microstructure, which has been quantified in terms of an identical tortuosity in transverse and longitudinal filament direction. The very homogenous microstructure in the new ex situ wire generation is probably one reason for its strongly improved critical current density. The in situ wire has an anisotropic microstructure with a lower tortuosity in the axial direction. The microstructural inhomogeneity of the in situ filaments makes microstructural characterization and the comparison between materials and superconducting properties particularly challenging.
M. Klingele, B. Britton, M. Breitwieser, S. Vierrath, R. Zengerle, S. Holdcroft, S. Thiele
A Completely Spray-Coated Membrane Electrode Assembly
2016 Electrochem Commun, Band: 70, Seiten: 65 - 68
KurzfassungWe present a proton exchange membrane fuel cell (PEMFC) manufacturing route, in which a thin layer of polymer electrolyte solution is spray-coated on top of gas diffusion electrodes (GDEs) to work as a proton exchange membrane. Without the need for a pre-made membrane foil, this allows inexpensive, fast, large-scale fabrication of membrane-electrode assemblies (MEAs), with a spray-coater comprising the sole manufacturing device. In this work, a catalyst layer and a membrane layer are consecutively sprayed onto a fibrous gas diffusion layer with applied microporous layer as substrate. A fuel cell is then assembled by stacking anode and cathode half-cells with the membrane layers facing each other. The resultant fuel cell with a low catalyst loading of 0.1 mg Pt/cm2 on each anode and cathode side is tested with pure H2 and O2 supply at 80 °C cell temperature and 92% relative humidity at atmospheric pressure. The obtained peak power density is 1.29 W/cm2 at a current density of 3.25 A/cm2. By comparison, a lower peak power density of 0.93 W/cm2 at 2.2 A/cm2 is found for a Nafion NR211 catalyst coated membrane (CCM) reference, although equally thick membrane layers (approx. 25 μm), and identical catalyst layers and gas diffusion media were used. The superior performance of the fuel cell with spray-coated membrane can be explained by a decreased low frequency (mass transport) resistance, especially at high current densities, as determined by electrochemical impedance spectroscopy.
W.E. Kaman, G. Elshout, P.J.E. Bindels, K. Mitsakakis, J.P. Hays
Current problems associated with the microbiological point-of-care testing of respiratory tract infections in primary care
2016 Future Microbiol, Band: 11, Seiten: 607 - 610
KurzfassungCurrently, the world is facing a potential ‘antibiotic apocalypse’, whereby clinically relevant bacteria are becoming increasingly resistant to all currently available antibiotics [1]. Several factors are contributing to this global increase in antibiotic resistance, including the unnecessary prescription of antibiotics for nonbacterial (viral and fungal) infections [2]. General practitioners (GPs) sit on the front line of antibiotic prescribing practice, having regular and broad-based contact with members of society that present to their offices with a range of disease states. One of the major reasons for visiting a GP is when a patient is apparently suffering from a respiratory tract infection [3]. The accurate diagnosis of the cause (i.e., the causative pathogen) of this infection can be difficult for the GP to make when only based on clinical symptoms. In the absence of sufficient diagnostic or clinical evidence, the GP may decide to prescribe antibiotics, or alternatively may withhold antibiotic therapy (suspecting a viral infection) when antibiotic therapy is actually required. On the one hand, the ‘overprescribing’ of antibiotics for nonbacterial infections may not only lead to the acquisition of antibiotic resistance in the resident flora of the patient, but also result in unnecessary healthcare costs for the patient and society [4]. It will also expose the patients to unwanted side effects from the antibiotic [5]. On the other hand, not prescribing antibiotics in case of a bacterial pneumonia, may result in extra morbidity for the patient and subsequent healthcare costs [6]. Access to point-of-care (POC) tests may reduce the prescription of antibiotics in primary care [7], although current POC testing performed by GPs for diagnosing respiratory tract infections tends to rely on the use of nonspecific biomarkers, such as CRP [8]. These biomarkers only provide information on the likelihood of a complicated (lower) respiratory tract infection being present. They do not identify pathogens or any antibiotic resistance that may be associated with a pathogen. For this reason, more advanced POC testing devices are currently being developed for specific use in the primary care environment. Such devices could potentially accurately diagnose the causative pathogen associated with a respiratory tract infection and any accompanying antibiotic resistance genes (if present), thereby potentially helping the GP to personalize their antibiotic prescribing practices to the needs of each patient. Unfortunately, however, many hurdles currently exist to the successful implementation of infectious disease POC diagnostics into primary care, the most important of which are described below.
F. Schuler, M. Trotter, M. Geltman, F. Schwemmer, S. Wadle, E. Domínguez-Garrido, M. López, C. Cervera-Acedo, P. Santibáñez, F. von Stetten, R. Zengerle, N. Paust
Digital Droplet PCR on Disk
2016 Lab Chip, Band: 16, Seiten: 208 - 216
KurzfassungExisting systems for digital droplet PCR (ddPCR) either suffer from low integration or are difficult to introduce to mass fabrication. Here we present an integrated system that is compatible to mass fabrication and combines emulsification, PCR, and fluorescence readout in a single chamber within a disposable cartridge (disk). Droplets are generated by injecting the sample into fluorinated oil via centrifugal step emulsification. The resulting emulsion is aligned in the PCR and readout zone by capillary action. During thermocycling, gas bubbles generated by degassing are removed by capillary driven transport through tapered regions in the PCR chamber. Thereby, the positioning of the emulsion within the readout zone of the PCR chamber is ensured at any time and no bubbles are present during readout. Manual handling of the disk solely requires pipetting of oil and PCR mix into the inlet structures, placing the disk into the thermocycler and subsequently into a microarray scanner. The functionality of the ddPCR process chain is demonstrated by quantitative detection of the cystic fibrosis causing mutation p.Phe508del, which is of interest for non-invasive prenatal testing (NIPT). The mutation was detected in a concentration range spanning four orders of magnitude. We envision that this work will lay the base for the development of highly integrated sample-to-digital-answer PCR systems that can be employed in routine clinical diagnosis.
F. Schuler, C. Siber, S. Hin, S. Wadle, N. Paust, R. Zengerle, F. von Stetten
Digital droplet LAMP as microfluidic App on standard laboratory devices
2016 Anal Methods-uk, Band: 8, Seiten: 2750 - 2755
KurzfassungDigital nucleic acid amplification methods are a growing research field that allows for absolute quantification of DNA making the need of standard curves redundant. However, most existing digital amplification systems require specialized laboratory devices and costly investments. The required disposable cartridges are device specific and not interchangeable. Here, we present digital droplet loopmediated isothermal amplification (ddLAMP) as a microfluidic App on standard laboratory devices. ddLAMP is implemented on a disposable polymer chip (DropChip) of the format of a standard microscope slide. After DNA denaturation off-chip the reaction mix is emulsified in the DropChip in a mini-centrifuge in 6 minutes. The DropChip is transferred to an in situ thermal cycler for 1 hour of incubation. Afterwards, a fluorescence scan in a microarray scanner is performed. The DropChip allows for absolute quantification with a dynamic range of 15-1500 DNA copies μl-1. Assay conditions were optimized for ddLAMP and comparison of ddPCR and ddLAMP for genomic E. coli DNA reveals very good concordance.
N. Wehkamp, M. Breitwieser, A. Büchler, M. Klingele, R. Zengerle, S. Thiele
Directly deposited Nafion/TiO2 composite membranes for high power medium temperature fuel cells
2016 Rsc Adv, Band: 6, Seiten: 24261 - 24266
KurzfassungThis work presents a simple production method for TiO2 reinforced Nafion® membranes which are stable up to a 120 °C operation temperature. The novel TiO2 reinforced membranes yield a maximum power density of 2.02 W cm−2 at 120 °C; H2/O2; 0.5/0.5 L min−1; 90% RH, 300/300 kPaabs. This is 2.8 times higher than the highest power density for TiO2 reinforced membranes so far published in literature. The described membranes even exceed the maximum power density of a commercial Nafion® HP membrane in an identical measurement setup at 100 °C and 120 °C. Compared to the commercial Nafion® HP membrane the maximum power density was increased by 27% and 9% at 100 °C and 120 °C, respectively. The membrane is manufactured by drop-casting a dispersion of Nafion® and TiO2 nanoparticles onto both the anode and cathode gas diffusion electrodes. Furthermore pure Nafion® membranes manufactured by the same method had higher membrane resistances at temperatures >100 °C than TiO2-reinforced Nafion® membranes.
X. Wu, N. Schneider, A. Platen, I. Mitra, R. Zengerle, R. Schüle, M. Meier
In situ characterization of the mTORC1 during adipogenesis of human adult stem cells on chip
2016 PNAS, Band: 113, Seiten: 4143 - 4150
KurzfassungMammalian target of rapamycin (mTOR) is a central kinase in- tegrating nutrient, energy, and metabolite signals. The kinase forms two distinct complexes: mTORC1 and mTORC2. mTORC1 plays an essential but undefined regulatory function for regeneration of adipose tissue. Analysis of mTOR in general is hampered by the complexity of regulatory mechanisms, including protein interac- tions and/or phosphorylation, in an ever-changing cellular microen- vironment. Here, we developed a microfluidic large-scale integration chip platform for culturing and differentiating human adipose- derived stem cells (hASCs) in 128 separated microchambers under standardized nutrient conditions over 3 wk. The progression of the stem cell differentiation was measured by determining the lipid accumulation rates in hASC cultures. For in situ protein analytics, we developed a multiplex in situ proximity ligation assay (mPLA) that can detect mTOR in its two complexes selectively in single cells and implemented it on the same chip. With this combined technology, it was possible to reveal that the mTORC1 is regulated in its abundance, phosphorylation state, and localization in coordination with lyso- somes during adipogenesis. High-content image analysis and param- eterization of the in situ PLA signals in over 1 million cells cultured on four individual chips showed that mTORC1 and lysosomes are temporally and spatially coordinated but not in its composition during adipogenesis.
M. Zeiger, S. Fleischmann, B. Krüner, A. Tolosa, S. Bechtel, M. Baltes, A. Schreiber, R. Moroni, S. Vierrath, S. Thiele, V. Presser
Influence of carbon substrate on the electrochemical performance of carbon/manganese oxide hybrids in aqueous and organic electrolytes
2016 Rsc Adv, Band: 6, Seiten: 107163 - 107
KurzfassungManganese oxide presents very promising electrochemical properties as an electrode material in supercapacitors, but there remain important open questions to guide further development of the complex manganese oxide/carbon/electrolyte system. Our work addresses specifically the influence of carbon ordering and the difference between outer and inner porosity of carbon particles for the application in aqueous 1 M Na2SO4 and 1 M LiClO4 in acetonitrile. Birnessite-type manganese oxide was hydrothermally hybridized on two kinds of carbon onions with only outer surface area and different electrical conductivity, and conventional activated carbon with a high inner porosity. Carbon onions with a high degree of carbon ordering, high conductivity, and high outer surface area were identified as the most promising material, yielding 179 F g−1. Pore blocking in activated carbon yields unfavorable electrochemical performances. The highest specific energy of 16.4 W h kg−1 was measured for a symmetric full-cell arrangement of manganese oxide coated high temperature carbon onions in the organic electrolyte. High stability during 10 000 cycles was achieved for asymmetric full-cells, which proved as a facile way to enhance the electrochemical performance stability.
F. Schwemmer, C. E. Blanchet, A. Spilotros, D. Kosse, S. Zehnle, H. D. T. Mertens, M. A. Graewert, M. Rössle, N. Paust, D. I. Svergun, F. von Stetten, R. Zengerle, D. Mark
LabDisk for SAXS: a centrifugal microfluidic sample preparation platform for small-angle X-ray scattering
2016 Lab Chip, Band: 16, Seiten: 1161 - 1170
KurzfassungWe present a centrifugal microfluidic LabDisk for protein structure analysis via small-angle X-ray scattering (SAXS) on synchrotron beamlines. One LabDisk prepares 120 different measurement conditions, grouped into six dilution matrices. Each dilution matrix: (1) features automatic generation of 20 different measurement conditions from three input liquids and (2) requires only 2.5 μl of protein solution, which corresponds to a tenfold reduction in sample volume in comparison to the state of the art. Total hands on time for preparation of 120 different measurement conditions is less than 5 min. Read-out is performed on disk within the synchrotron beamline P12 at EMBL Hamburg (PETRA III, DESY). We demonstrate: (1) aliquoting of 40 nl aliquots for five different liquids typically used in SAXS and (2) confirm fluidic performance of aliquoting, merging, mixing and read-out from SAXS experiments (2.7–4.4% CV of protein concentration). We apply the LabDisk for SAXS for basic analysis methods, such as measurement of the radius of gyration, and advanced analysis methods, such as the ab initio calculation of 3D models. The suitability of the LabDisk for SAXS for protein structure analysis under different environmental conditions is demonstrated for glucose isomerase under varying protein and NaCl concentrations. We show that the apparent radius of gyration of the negatively charged glucose isomerase decreases with increasing protein concentration at low salt concentration. At high salt concentration the radius of gyration (Rg) does not change with protein concentrations. Such experiments can be performed by a non-expert, since the LabDisk for SAXS does not require attachment of tubings or pumps and can be filled with regular pipettes. The new platform has the potential to introduce routine high-throughput SAXS screening of protein structures with minimal input volumes to the regular operation of synchrotron beamlines.
F. Stumpf, F. Schwemmer, T. Hutzenlaub, D. Baumann, O. Strohmeier, G. Dingemanns, G. Simons, C. Sager, L. Plobner, F. von Stetten, R. Zengerle, D. Mark
LabDisk with complete reagent prestorage for sample-to-answer nucleic acid based detection of respiratory pathogens verified with influenza A H3N2 virus
2016 Lab Chip, Band: 16, Seiten: 199 - 207
KurzfassungPortable point-of-care devices for pathogen detection require easy, minimal and user-friendly handling steps and need to have the same diagnostic performance compared to centralized laboratories. In this work we present a fully automated sample-to-answer detection of influenza A H3N2 virus in a centrifugal LabDisk with complete prestorage of reagents. Thus, the initial supply of the sample remains the only manual handling step. The self-contained LabDisk automates by centrifugal microfluidics all necessary process chains for PCR-based pathogen detection: pathogen lysis, magnetic bead based nucleic acid extraction, aliquoting of the eluate into 8 reaction cavities, and real-time reverse transcription polymerase chain reaction (RT-PCR). Prestored reagents comprise air dried specific primers and fluorescence probes, lyophilized RT-PCR mastermix and stick-packaged liquid reagents for nucleic acid extraction. Employing two different release frequencies for the stick-packaged liquid reagents enables on-demand release of highly wetting extraction buffers, such as sequential release of lysis and binding buffer. Microfluidic process-flow was successful in 54 out of 55 tested LabDisks. We demonstrate successful detection of the respiratory pathogen influenza A H3N2 virus in a total of 18 LabDisks with sample concentrations down to 2.39 × 104 viral RNA copies per ml, which is in the range of clinical relevance. Furthermore, we detected RNA bacteriophage MS2 acting as internal control in 3 LabDisks with a sample concentration down to 75 plaque forming units (pfu) per ml. All experiments were applied in a 2 kg portable, laptop controlled point-of-care device. The turnaround time of the complete analysis from sample-to-answer was less than 3.5 hours.
J. Riba, T. Gleichmann, S. Zimmermann, R. Zengerle, P. Koltay
Label-free isolation and deposition of single bacterial cells from heterogeneous samples for clonal culturing
2016 Scientific Reports, Band: 6, Seite: 32837
KurzfassungThe isolation and analysis of single prokaryotic cells down to 1 μm and less in size poses a special challenge and requires micro-engineered devices to handle volumes in the picoliter to nanoliter range. Here, an advanced Single-Cell Printer (SCP) was applied for automated and label-free isolation and deposition of bacterial cells encapsulated in 35 pl droplets by inkjet-like printing. To achieve this, dispenser chips to generate micro droplets have been fabricated with nozzles 20 μm in size. Further, the magnification of the optical system used for cell detection was increased. Redesign of the optical path allows for collision-free addressing of any flat substrate since no compartment protrudes below the nozzle of the dispenser chip anymore. The improved system allows for deterministic isolation of individual bacterial cells. A single-cell printing efficiency of 93% was obtained as shown by printing fluorescent labeled E. coli. A 96-well plate filled with growth medium is inoculated with single bacteria cells on average within about 8 min. Finally, individual bacterial cells from a heterogeneous sample of E. coli and E. faecalis were isolated for clonal culturing directly on agar plates in user-defined array geometry.
K. G. Kraiczek, J. Mannion, S. Post, A. Tsupryk, V. Raghunathan, R. Brennen, R. Zengerle
Micromachined Fused Silica Liquid Core Waveguide Capillary Flow Cell
2016 Anal Chem, Band: 88, Seiten: 1100 - 1105
KurzfassungA planar, chip-based flow cell for UV−vis absorbance detection in HPLC is presented. The device features a microfabricated free-standing liquid core waveguide (LCW) capillary detection tube of long path length that is based on total internal reflection. We report on the linearity and calibration slope characteristics of lithographically produced LCWs with different interior/exterior geometries. 3D ray tracing was indispensable in modeling behavior in the more demanding geometries: multipath behavior may be intrinsic to these waveguides with consequent nonlinearity. Fortunately, nonlinearity in lithographically easy-to-produce waveguide geometries (such as with a flat, concave exterior and a round interior) is not as detrimental as might be initially expected. Experimental performance is predictably affected by the attainable surface quality of the LCW and efficient and reproducible coupling of the input light into the LCW.
J. Riba, N. Renz, C. Niemöller, S. Bleul, D. Pfeifer, J. M. Stosch, K. H. Metzeler, B. Hackanson, M. Lübbert, J. Duyster, P. Koltay, R. Zengerle, R. Claus, S. Zimmermann, H. Becker
Molecular Genetic Characterization of Individual Cancer Cells Isolated via Single-Cell Printing
2016 Plos One, Band: 6, Seite: 32837
KurzfassungIntratumoral genetic heterogeneity may impact disease outcome. Gold standard for dissecting clonal heterogeneity are single-cell analyses. Here, we present an efficient workflow based on an advanced Single-Cell Printer (SCP) device for the study of gene variants in single cancer cells. To allow for precise cell deposition into microwells the SCP was equipped with an automatic dispenser offset compensation, and the 384-microwell plates were electrostatically neutralized. The ejection efficiency was 99.7% for fluorescent beads (n = 2304) and 98.7% for human cells (U-2 OS or Kasumi-1 cancer cell line, acute myeloid leukemia [AML] patient; n = 150). Per fluorescence microscopy, 98.8% of beads were correctly delivered into the wells. A subset of single cells (n = 81) was subjected to whole genome amplification (WGA), which was successful in all cells. On empty droplets, a PCR on LINE1 retrotransposons yielded no product after WGA, verifying the absence of free-floating DNA in SCP-generated droplets. Representative gene variants identified in bulk specimens were sequenced in single-cell WGA DNA. In U-2 OS, 22 of 25 cells yielded results for both an SLC34A2 and TET2 mutation site, including cells harboring the SLC34A2 but not the TET2 mutation. In one cell, the TET2 mutation analysis was inconclusive due to allelic dropout, as assessed via polymorphisms located close to the mutation. Of Kasumi-1, 23 of 33 cells with data on both the KIT and TP53 mutation site harbored both mutations. In the AML patient, 21 of 23 cells were informative for a TP53 polymorphism; the identified alleles matched the loss of chromosome arm 17p. The advanced SCP allows efficient, precise and gentle isolation of individual cells for subsequent WGA and routine PCR/sequencing-based analyses of gene variants. This makes single-cell information readily accessible to a wide range of applications and can provide insights into clonal heterogeneity that were indeterminable solely by analyses of bulk specimens.
F. Schuler, M. Trotter, R. Zengerle, F. von Stetten
Monochrome Multiplexing in Polymerase Chain Reaction by Photobleaching of Fluorogenic Hydrolysis Probes
2016 Anal Chem, Band: 88, Nummer: 5, Seiten: 2590 - 2595
KurzfassungMultiplexing in polymerase chain reaction (PCR) is a technique widely used to save cost and sample material and to increase sensitivity compared to distributing a sample to several singleplex reactions. One of the most common methods to detect the different amplification products is the use of fluorogenic probes that emit at different wavelengths (colors). To reduce the number of detection channels, several methods for monochrome multiplexing have been suggested. However, they pose restrictions to the amplifiable target length, the sequence, or the melting temperature. To circumvent these limitations, we suggest a novel approach that uses different fluorophores with the same emission maximum. Discrimination is achieved by their different fluorescence stability during photobleaching. Atto488 (emitting at the same wavelength as 6-carboxyfluorescein, FAM) and Atto467N (emitting at the same wavelength as cyanine 5, Cy5) were found to bleach significantly less than FAM and Cy5; i.e., the final fluorescence of Atto dyes was more than tripled compared to FAM and Cy5. We successfully applied this method by performing a 4-plex PCR targeting antibiotic resistance genes in S. aureus using only 2 color channels. Confidence of discrimination between the targets was >99.9% at high copy initial copy numbers of 100 000 copies. Cases where both targets were present could be discriminated with equal confidence for Cy5 channel and reduced levels of confidence (>68%) for FAM channel. Moreover, a 2- plex digital PCR reaction in 1 color channel was shown. In the future, the degree of multiplexing may be increased by adding fluorogenic probe pairs with other emission wavelengths. The method may also be applied to other probe and assay formats, such as Förster resonance energy transfer (FRET) probes and immunoassays.
F. Sun, L. Zielke, H. Markötter, A. Hilger, D. Zhou, R. Moroni, R. Zengerle, S. Thiele, J. Banhart, I. Manke
Morphological Evolution of Electrochemically Plated/Stripped Lithium Microstructures Investigated by Synchrotron X‑ray Phase Contrast Tomography
2016 Acs Nano, Band: 10, Seiten: 7990 - 7997
KurzfassungDue to its low redox potential and high theoretical specific capacity, Li metal has drawn worldwide research attention because of its potential use in nextgeneration battery technologies such as Li−S and Li−O2. Unfortunately, uncontrollable growth of Li microstructures (LmSs, e.g., dendrites, fibers) during electrochemical Li stripping/plating has prevented their practical commercialization. Despite various strategies proposed to mitigate LmS nucleation and/or block its growth, a fundamental understanding of the underlying evolution mechanisms remains elusive. Herein, synchrotron in-line phase contrast X-ray tomography was employed to investigate the morphological evolution of electrochemically deposited/dissolved LmSs nondestructively. We present a 3D characterization of electrochemically stripped Li electrodes with regard to electrochemically plated LmSs. We clarify fundamentally the origin of the porous lithium interface growing into Li electrodes. Moreover, cleavage of the separator caused by growing LmS was experimentally observed and visualized in 3D. Our systematic investigation provides fundamental insights into LmS evolution and enables us to understand the evolution mechanisms in Li electrodes more profoundly.
R. Moroni, M. Börner, L. Zielke, M. Schroeder, S. Nowak, M. Winter, I. Manke, R. Zengerle, S. Thiele
Multi-Scale Correlative Tomography of a Li-Ion Battery Composite Cathode
2016 Sci Rep-uk, Band: 6, Seite: 30109
KurzfassungFocused ion beam/scanning electron microscopy tomography (FIB/SEMt) and synchrotron X-ray tomography (Xt) are used to investigate the same lithium manganese oxide composite cathode at the same specific spot. This correlative approach allows the investigation of three central issues in the tomographic analysis of composite battery electrodes: (i) Validation of state-of-the-art binary active material (AM) segmentation: Although threshold segmentation by standard algorithms leads to very good segmentation results, limited Xt resolution results in an AM underestimation of 6 vol% and severe overestimation of AM connectivity. (ii) Carbon binder domain (CBD) segmentation in Xt data: While threshold segmentation cannot be applied for this purpose, a suitable classification method is introduced. Based on correlative tomography, it allows for reliable ternary segmentation of Xt data into the pore space, CBD, and AM. (iii) Pore space analysis in the micrometer regime: This segmentation technique is applied to an Xt reconstruction with several hundred microns edge length, thus validating the segmentation of pores within the micrometer regime for the first time. The analyzed cathode volume exhibits a bimodal pore size distribution in the ranges between 0–1 μm and 1–12 μm. These ranges can be attributed to different pore formation mechanisms.
S. Wadle, M. Lehnert, S. Rubenwolf, R. Zengerle, F. von Stetten
Real-time PCR probe optimization using design of experiments approach
2016 Biomolecular Detection and Quantification, Band: 7, Seiten: 1 - 8
KurzfassungPrimer and probe sequence designs are among the most critical input factors in real-time polymerase chain reaction (PCR) assay optimization. In this study, we present the use of statistical design of experiments (DOE) approach as a general guideline for probe optimization and more specifically focus on design optimization of label-free hydrolysis probes that are designated as mediator probes (MPs), which are used in reverse transcription MP PCR (RT-MP PCR). The effect of three input factors on assay performance was investigated: distance between primer and mediator probe cleavage site; dimer stability of MP and target sequence (influenza B virus); and dimer stability of the mediator and universal reporter (UR). The results indicated that the latter dimer stability had the greatest influence on assay performance, with RT-MP PCR efficiency increased by up to 10% with changes to this input factor. With an optimal design configuration, a detection limit of 3–14 target copies/10 μl reaction could be achieved. This improved detection limit was confirmed for another UR design and for a second target sequence, human metapneumovirus, with 7–11 copies/10 μl reaction detected in an optimum case. The DOE approach for improving oligonucleotide designs for real-time PCR not only produces excellent results but may also reduce the number of experiments that need to be performed, thus reducing costs and experimental times.
S. Burger, M. Schulz, F. von Stetten, R. Zengerle, N. Paust
Rigorous buoyancy driven bubble mixing for centrifugal microfluidics
2016 Lab Chip, Seiten: 261 - 268
KurzfassungWe present batch-mode mixing for centrifugal microfluidics operated at fixed rotational frequency. Gas is generated by the disk integrated decomposition of hydrogen peroxide (H2O2) to liquid water (H2O) and gaseous oxygen (O2) and inserted into a mixing chamber. There, bubbles are formed that ascent through the liquid in the artificial gravity field and lead to drag flow. Additionaly, strong buoyancy causes deformation and rupture of the gas bubbles and induces strong mixing flows in the liquids. Buoyancy driven bubble mixing is quantitatively compared to shake mode mixing, mixing by reciprocation and vortex mixing. To determine mixing efficiencies in a meaningful way, the different mixers are employed for mixing of a lysis reagent and human whole blood. Subsequently, DNA is extracted from the lysate and the amount of DNA recovered is taken as a measure for mixing efficiency. Relative to standard vortex mixing, DNA extraction based on buoyancy driven bubble mixing resulted in yields of 92 ± 8% (100 s mixing time) and 100 ± 8% (600 s) at 130g centrifugal acceleration. Shake mode mixing yields 96 ± 11% and is thus equal to buoyancy driven bubble mixing. An advantage of buoyancy driven bubble mixing is that it can be operated at fixed rotational frequency, however. The additional costs of implementing buoyancy driven bubble mixing are low since both the activation liquid and the catalyst are very low cost and no external means are required in the processing device. Furthermore, buoyancy driven bubble mixing can easily be integrated in a monolithic manner and is compatible to scalable manufacturing technologies such as injection moulding or thermoforming. We consider buoyancy driven bubble mixing an excellent alternative to shake mode mixing, in particular if the processing device is not capable of providing fast changes of rotational frequency or if the low average rotational frequency is challenging for the other integrated fluidic operations.
L. Gutzweiler, F. Stumpf, L. Tanguy, G. Roth, P. Koltay, R. Zengerle, L. Riegger
Semi-contact-writing of polymer molds for prototyping PDMS chips with low surface roughness, sharp edges and locally varying channel heights
2016 J Micromech Microeng, Band: 26, Nummer: 4, Seiten: 45018 - 45027
KurzfassungMicrofluidic systems fabricated in polydimethylsiloxane (PDMS) enable a broad variety of applications and are widespread in the field of Lab-on-a-Chip. Here we demonstrate semi-contact-writing, a novel method for fabrication of polymer based molds for casting microfluidic PDMS chips in a highly flexible, time and cost-efficient manner. The method is related to direct-writing of an aqueous polymer solution on a planar glass substrate and substitutes conventional, time- and cost-consuming UV-lithography. This technique facilitates on-demand prototyping in a low-cost manner and is therefore ideally suited for rapid chip layout iterations. No cleanroom facilities and less expertise are required. Fabrication time from scratch to ready-to-use PDMS-chip is less than 5 h. This polymer writing method enables structure widths down to 140 μm and controllable structure heights ranging from 5.5 μm for writing single layers up to 98 μm by stacking. As a unique property, freely selectable height variations across a substrate can be achieved by application of local stacking. Furthermore, the molds exhibit low surface roughness (R a = 24 nm, R RMS = 28 nm) and high fidelity edge sharpness. We validated the method by fabrication of molds to cast PDMS chips for droplet based flow-through PCR with single-cell sensitivity.
S. Wadle, M. Lehnert, F. Schuler, R. Köppel, A. Serr, R. Zengerle, F. von Stetten
Simplified development of multiplex real-time PCR through master mix augmented by universal fluorogenic reporters
2016 BioTechniques, Band: 61, Seiten: 123 - 128
KurzfassungMediator probe (MP) PCR is a real-time PCR approach that uses standardized universal fluorogenic reporter oligonucleotides (UR) in conjunction with label-free sequence-specific probes. To enable multiplex real-time MP PCR, we designed a set of five optimized URs with different fluorescent labels. Performance of the optimized URs was verified in multiplex real-time MP PCR for the detection of a pentaplex food panel and a quadruplex methicillin-resistant Staphylococcus aureus (MRSA) panel. Results were comparable to corresponding multiplex hydrolysis probe (HP) PCR, also designated as TaqMan PCR. Analyses of MRSA DNA standards and DNA extracted from patient swab samples showed improved lower limits of detection (LoDs) by a factor of 2–5 when using quadruplex real-time MP PCR instead of HP PCR. The novel set of standardized URs we present here simplifies development of multiplex real-time PCR assays by requiring only the design of label-free probes. In the future, real-time PCR master mixes could be augmented with up to five standardized fluorogenic URs, each emitting light at a different wavelength.
S. Kartmann, F. Koch, P. Koltay, R. Zengerle, A. Ernst
Single-use capacitive pressure sensor employing radial expansion of a silicone tube
2016 Sensor Actuat A-phys, Band: 247
KurzfassungThis paper reports on a single-use pressure sensor for medical applications. The sensor principle makes use of the radial expansion of a silicone tube which occurs when there is a pressure difference between the inside and the outside of the tube. The change in outer diameter is detected by a capacitive measurement method, whereas the amplification electronics can be separated from the tube being in contact with the fluid. This enables a cross-contamination-free measurement system for patient near application as e.g. within infusion systems. The sensor includes a novel highly sensitive and fast analog amplification circuit in combination with gold electrodes fabricated in PCB technology. This circuit enables to amplify even highly dynamic pressure changes, in the range of a few milliseconds causing capacitive changes on the electrodes in the fF range to a readable voltage level. A functional model is developed based on flex board technology which allows for studying the influence of the electrode geometry as well as the material properties of the silicone tube with respect to the sensitivity of the sensor. The best performing electrode geometry determined by experiments features a sensitivity of 0.195 fF/kPa at a mean coefficient of variation (CV) of 6.4%, considering three individual sensor assemblies. A sensor prototype is designed and fabricated based on the results of the investigated functional model. The performance of the prototype is investigated experimentally in a pressure range from 0 to 40 kPa. As a result a sensitivity of 0.135 V/kPa for DI water as measurement liquid could be achieved and a good linearity of the signal (R² = 0.996) was observed up to 35 kPa.
L. Zielke, F. Sun, H. Markötter, A. Hilger, R. Moroni, R. Zengerle, S. Thiele, J. Banhart, I. Manke
Synchrotron X-ray tomographic study of a silicon electrode before and after discharge and the effect of cavities on particle fracturing
2016 Chemelectrochem, Band: 3, Seiten: 1170 - 1177
KurzfassungSilicon (Si) has been proposed as one of the most promising anode materials for next-generation lithium ion batter- ies, but unsatisfactory discharge capacity and inevitable perfor- mance deterioration prevent their commercialization. We apply in situ synchrotron X-ray tomography to a Si-composite elec- trode in its pristine and firstly discharged state and quantitatively investigate degradation of the electron- and/or ion- conducting network as well as degradation of Si particles. Thus this study is complementary to previous X-ray tomographic studies focusing on the Si particles only. We found that on the electrode level the Si particles located in the central part of the electrode primarily experience crack formation; on the particle level, lithiation be- haviour is heterogeneous and cavities are formed during elec- trode preparation and battery operation. The correlation between the electrochemical activities of Si particles and their individual contact with the conducting network is investigated and quanti- fied: Si particles will experience lithiation only under the condi- tion that at least 40% of their surface is electrically and ionically connected.
I. Schwarz, S. Zehnle, T. Hutzenlaub, R. Zengerle, N. Paust
System-level network simulation for robust centrifugal-microfluidic lab-on-a-chip systems
2016 Lab Chip, Band: 16, Seiten: 1873 - 1885
KurzfassungCentrifugal microfluidics shows a clear trend towards a higher degree of integration and parallelization1. This trend leads to an increase in number and density of integrated microfluidic unit operations. The fact that all unit operations are processed by the same common spin protocol turns higher integration into higher complexity. To allow for efficient development anyhow, we introduce advanced lumped models for network simulations in centrifugal microfluidics. These models consider the interplay of centrifugal and Euler pressures, viscous dissipation, capillary pressures and pneumatic pressures. The simulations are fast and simple to set up and allow for the precise prediction of flow rates as well as switching and valving events. During development, channel and chamber geometry variations due to manufacturing tolerances can be taken into account as well as pipetting errors, variations of contact angles, compliant chamber walls and temperature variations in the processing device. As an example for considering these parameters during development, we demonstrate simulation based robustness analysis for pneumatic siphon valving in centrifugal microfluidics. Subsequently the influence of liquid properties on pumping and valving is studied for four liquids relevant for biochemical analysis, namely: water (large surface tension), blood plasma (large contact angle hysteresis), ethanol/water (highly wetting) and glycerine/water (highly viscous). In a second example, we derive a spin protocol to attain a constant flow rate under varying pressure conditions. Both examples show excellent agreement to experimental validations.
J. Madjarov, A. Prokhorova, T. Messinger, J. Gescher, S. Kerzenmacher
The performance of microbial anodes in municipal wastewater: Pre-grown multispecies biofilm vs. natural inocula
2016 Bioresour Technol., Band: 221, Seiten: 165 - 171
KurzfassungIn this study, different inoculation strategies for continuously operated microbial anodes are analyzed and compared. After 20 days of operation with municipal wastewater anodes pre-incubated with a biofilm of the exoelectrogenic species Geobacter and Shewanella showed current densities of (65 ± 8) μA/cm2. This is comparable to the current densities of non-inoculated anodes and anodes inoculated with sewage sludge. Analysis of the barcoded pre-grown multispecies biofilms reveal that 99% of the original biofilm was detached after 20 days of operation with municipal wastewater. This is in contrast to previous experiments where a pre-grown biofilm of exoelectrogens was operated in batch mode. To implement pre-grown biofilms in continuous systems it will thus be necessary to reveal a window of process parameters in which typical exoelectrogenic microorganisms including model organisms can be kept and/or enriched on anodes.
S. Vierrath, M. Breitwieser, M. Klingele, B. Britton, S. Holdcroft, R. Zengerle, S. Thiele
The reasons for the high power density of fuel cells fabricated with directly deposited membranes
2016 J. of Power Sources, Band: 326, Seiten: 170 - 175
KurzfassungIn a previous study, we reported that polymer electrolyte fuel cells prepared by direct membrane deposition (DMD) produced power densities in excess of 4 W/cm2. In this study, the underlying origins that give rise to these high power densities are investigated and reported. The membranes of high power, DMD-fabricated fuel cells are relatively thin (12 mm) compared to typical benchmark, commercially available membranes. Electrochemical impedance spectroscopy, at high current densities (2.2 A/cm2) reveals that mass transport resistance was half that of reference, catalyst-coated-membranes (CCM). This is attributed to an improved oxygen supply in the cathode catalyst layer by way of a reduced propensity of flooding, and which is facilitated by an enhancement in the back diffusion of water from cathode to anode through the thin directly deposited membrane. DMD-fabricated membrane-electrode-assemblies possess 50% reduction in ionic resistance (15 mUcm2) compared to conventional CCMs, with contributions of 9 mUcm2 for the membrane resistance and 6 mUcm2 for the contact resistance of the membrane and catalyst layer ionomer. The improved mass transport is responsible for 90% of the increase in power density of the DMD fuel cell, while the reduced ionic resistance accounts for a 10% of the improvement.
L. Zielke, S. Vierrath, R. Moroni, A. Mondon, R. Zengerle, S. Thiele
Three-dimensional Morphology of the Interface between Micro Porous Layer and Catalyst Layer in a Polymer Electrolyte Membrane Fuel Cell
2016 Rsc Advances, Band: 6, Seiten: 80700 - 80705
KurzfassungInterfaces between the different layers in proton exchange membrane fuel cells are expected to influence transport properties and therefore cell performance. So far the interface between micro porous layer (MPL) and catalyst layer (CL) was difficult to investigate due to its nanometer scale morphology. We apply focused ion beam scanning electron microscopy tomography with pore contrasting via atomic layer deposition to reconstruct a representative volume of 5.1 μm x 1.5 μm x 4.5 μm containing CL, MPL and their interface. We find that platinum in the CL results in brighter SEM image intensities, compared to the MPL. This allows i) estimating the extension of the interfacial region (530 nm), ii) evaluating Pt-content homogeneity in the CL and iii) calculating the individual roughnesses for the CL (102 nm) and for the MPL (129 nm). We further calculate porosity, pore sizes, and oxygen diffusivities. Thus, we find that the values of the parameters of the interfacial region are between those of the CL and the MPL, meaning that on the investigated scale, the interface is a homogeneous transitional region. A representativeness analysis shows that our reconstructed volume is sufficiently large concerning all calculated parameters.
M. Breitwieser, R. Moroni, J. Schock, M. Schulz, B. Schillinger, F. Pfeiffer, R. Zengerle, S. Thiele
Water management in novel direct membrane deposition fuel cells under low humidification
2016 Int J Hydrog Energ, Band: 41, Seiten: 11412 - 11417
KurzfassungPolymer electrolyte membrane fuel cells (PEMFCs) fabricated by direct membrane deposition (DMD) were shown to work even at dry conditions without significant deterioration of the membrane resistance. Here, in situ neutron radiography is used to investigate the water management in those fuel cells to uncover the phenomena that lead to the robust operation under low humidification. A constant level of humidification within the membrane electrode assembly (MEA) of a DMD fuel cell is observed even under dry anode operation and 15% relative humidity on the cathode side. This proves a pronounced back diffusion of generated water from the cathode side to the anode side through the thin deposited membrane layer. Over the entire range of polarization curves a very high similarity of the water evolution in anode and cathode flow fields is found in spite of different humidification levels. It is shown that the power density of directly deposited membranes in contrast to a 50 mm thick N-112 membrane is only marginally affected by dry operation conditions. Water profiles in through-plane direction of the MEA reveal that the water content in the DMD fuel cell remains steady even at high current densities. This is in contrast to the N-112 reference fuel cell which shows a strong increase in membrane resistance and a reduced MEA water content with raising current densities. Thus this new MEA fabrication technique has a promising perspective, since dry operation conditions are highly requested in order to reduce fuel cell system costs.

2015

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S. Kartmann, P. Koltay, R. Zengerle, A. Ernst
A Disposable Dispensing Valve for Non-Contact Microliter Applications in a 96-Well Plate Format
2015 Micromachines, Band: 6, Seiten: 423 - 436
KurzfassungWe present a miniaturized, disposable, normally-closed electromagnetic dispensing valve for the microliter range to process 96-well plates. The novel injection-molded valve is designed to fit into a 9 mm grid to realize an eight channel dispensing head, enabling the serial processing of well plates row-by-row. The presented dispensing valve design originates from a miniaturization study of a previously developed functional model. The outer diameter of the valve, including all actuating components, was reduced by 8 mm to an overall diameter of 8.5 mm without compromising the performance. Additionally, the actuation current of the valve could be reduced to 5 A. The valve is characterized for a volume range between 840 nL and 5.3 μL. The performance of the injection molded valve is competitive to commercially available dispensing valves, featuring the advantages of low fabrication costs, disposability, low mounting size, easy handling, and super silent actuation.
D. Czurratis, Y. Beyl, S. Zinober, F. Lärmer, R. Zengerle
A novel concept for long-term pre-storage and release of liquids for pressure-driven lab-on-a-chip devices
2015 J Micromech Microeng, Band: 25, Seite: 045002
KurzfassungOn-chip storage of liquids is one of the major challenges of polymer-based lab-on-a-chip (LoC) devices. To ensure long-term storage of even highly volatile reagents in polymer disposal LoC cartridges, robust reagent storage concepts are necessary. Tubular bags, so-called stick packs, are widely used in the packaging industry. They offer sufficient vapor barrier properties for liquid storage. Here we present a polymer multilayer LoC-stack with integrated stick packs for the long-term storage of liquid reagents required for diagnostic applications. The storage concept fulfils two main requirements: firstly, the long-term storage of reagents in stick packs without significant losses or interaction with the surroundings and secondly, the on-demand release of liquids, which is realized by the delamination of a stick pack’s peel seam through pneumatic pressure. Furthermore, effects on the opening behavior of stick packs through accelerated aging were investigated after different storage conditions to proof repeatability. This concept enables on-chip storage of liquid reagents at room temperature and allows the implementation in different pressure driven LoC devices or similar applications. Since liquid storage in stick packs is well-established, emerging fields such as lab-on-achip combined with novel reagent release mechanisms should be of great interest for the commercialization of life science products.
S.K. Vashist, T. van Oordt, E. M. Schneider, R. Zengerle, F. von Stetten, J.H.T. Luong
A smartphone-based colorimetric reader for bioanalytical applications using the screen-based bottom illumination provided by gadgets
2015 Biosens Bioelectron, Band: 67, Seiten: 248 - 255
KurzfassungA smartphone-based colorimetric reader (SBCR) was developed using a Samsung Galaxy SIII mini, a gadget (iPAD mini, iPAD4 or iPhone 5s), integrated with a custom-made dark hood and base holder assembly. The smartphone equipped with a back camera (5 megapixels resolution) was used for colorimetric imaging via the hood and base-holder assembly. A 96- or 24-well microtiter plate (MTP) was positioned on the gadget's screensaver that provides white light-based bottom illumination only in the specific regions corresponding to the bottom of MTP's wells. The pixel intensity of the captured images was determined by an image processing algorithm. The developed SBCR was evaluated and compared with a commercial MTP reader (MTPR) for three model assays: our recently developed human C-reactive protein sandwich enzyme-linked immunosorbent assay (ELISA), horseradish peroxidase direct ELISA, and bicinchoninic acid protein estimation assay. SBCR had the same precision, dynamic range, detection limit and sensitivity as MTPR for all three assays. With advanced microfabrication and data processing, SBCR will become more compact, lighter, inexpensive and enriched with more features. Therefore, SBCR with a remarkable computing power could be an ideal point-of-care (POC) colorimetric detection device for the next-generation of cost-effective POC diagnostics, immunoassays and diversified bioanalytical applications.
M. Blazek, T. Silva Santisteban, R. Zengerle, M. Meier
Analysis of fast protein phosphorylation kinetics in single cells on a microfluidic chip
2015 Lab Chip, Band: 15, Seiten: 726 - 734
KurzfassungIn the present study, we developed a microfluidic large-scale integration (mLSI) platform for the temporal and chemical control of cell cultures to study fast kinetics of protein phosphorylation. For in situ protein analysis the mLSI chip integrates the Proximity Ligation Assay (PLA). To investigate cell-signaling events with a time resolution of a few seconds we first engineered and optimized the fluidic layout of the chip with 128 individual addressable cell culture chambers. The functionality of the cell culture operations and PLA is demonstrated by the determination of the minimum cell sample size for obtaining robust quantitative PLA signals at the single-cell level. We show that at least 350 cells per assay condition are required to statistically evaluate single cell PLA data. In the following we used the PLA chip with over 500 hundred cells per condition to record sequential phosphorylation reactions of the canonical protein kinase within the Akt pathway, which is activated in various human cancer types. This was achieved by stimulating mouse fibroblast cell cultures with either the platelet-derived growth factor (PDGF) or insulin-like growth factor (IGF-1). Fluidic cell stimulation pulses of 5 seconds were followed by precisely time shifted cell fixation pulses to obtain a temporal resolution of 10 seconds. PLA was then performed on all fixed arrays of cell cultures to extract the characteristic phosphorylation times at the single cell level for either the PDGF, or IGF-1 receptor and the Akt and GSK3 beta kinases. Characteristic phosphorylation times for the receptors were between 13 and 35 seconds, whereas for downstream kinases between 25 and 200 seconds. Thus we could reveal a molecular order of the phosphorylation reactions during the signal transduction through the Akt pathway. In dependence of the stimulus we found a temporal difference for the characteristic phosphorylation time of 20 and 150 seconds for the Ser-473 and Thr-308 residues on the Akt kinase, respectively. Temporal alteration of sequential phosphorylation reactions on Akt has been proposed as molecular mechanism to differentiate between stimuli and biophysically determined in the present study.
M. Keller, J. Naue, R. Zengerle, F. von Stetten, U. Schmidt
Automated Forensic Animal Family Identification by Nested PCR and Melt Curve Analysis on an Off-the-Shelf Thermocycler Augmented with a Centrifugal Microfluidic Disk Segment
2015 Plos One, Band: 10, Nummer: 7, Seite: e0131845
KurzfassungNested PCR remains a labor-intensive and error-prone biomolecular analysis. Laboratory workflow automation by precise control of minute liquid volumes in centrifugal microfluidic Lab-on-a-Chip systems holds great potential for such applications. However, the majority of these systems require costly custom-made processing devices. Our idea is to augment a standard laboratory device, here a centrifugal real-time PCR thermocycler, with inbuilt liquid handling capabilities for automation. We have developed a microfluidic disk segment enabling an automated nested real-time PCR assay for identification of common European animal groups adapted to forensic standards. For the first time we utilize a novel combination of fluidic elements, including pre-storage of reagents, to automate the assay at constant rotational frequency of an off-the-shelf thermocycler. It provides a universal duplex pre-amplification of short fragments of the mitochondrial 12S rRNA and cytochrome b genes, animal-group-specific main-amplifications, and melting curve analysis for differentiation. The system was characterized with respect to assay sensitivity, specificity, risk of cross-contamination, and detection of minor components in mixtures. 92.2% of the performed tests were recognized as fluidically failure-free sample handling and used for evaluation. Altogether, augmentation of the standard real-time thermocycler with a self-contained centrifugal microfluidic disk segment resulted in an accelerated and automated analysis reducing hands-on time, and circumventing the risk of contamination associated with regular nested PCR protocols.
O. Strohmeier, S. Keil, B. Kanat, P. Patel, M. Niedrig, M. Weidmann, F. Hufert, J. Drexler, R. Zengerle, F. von Stetten
Automated nucleic acid extraction from whole blood, B . subtilis, E. coli, and Rift Valley fever virus on a centrifugal microfluidic LabDisk
2015 Rsc Adv, Band: 5, Seite: 32144
KurzfassungWe present total nucleic acid extraction from whole blood, Gram‐positive Bacillus subtilis, Gram‐negative Escherichia coli, and Rift Valley fever RNA virus on a low‐cost, centrifugal microfluidic LabDisk cartridge processed in a light‐weight (< 2 kg) and portable processing device. Compared to earlier work in disk based centrifugal microfluidics, this includes the following advances: combined lysis and nucleic acid purification on one cartridge and handling of sample volumes as large as 200 μL. The presented system has been validated for logarithmic dilutions of aforementioned bacteria and viruses from various sample matrices including blood plasma and culture media and extraction of human DNA from whole blood. Recovered DNA and RNA concentrations in the eluate were characterized by quantitative PCR to: 58.2 % ‐ 98.5 %, 45.3 % ‐ 102.1 % and 29.5 % ‐ 34.2 % versus manual reference for Bacillus subtilis, Escherichia coli and Rift Valley fever virus, respectively. For extraction of human DNA from whole blood, similar results for on‐disk ((10.1 ± 7.6) x 104 DNA copies) and manual reference extraction ((10.2 ± 6.3) x 104 DNA copies)) could be achieved. Eluates from on‐disk extraction show slightly increased ethanol concentrations of 4.1 ± 0.3 % to 5.5 ± 0.2 % compared to manual reference (2.0 ± 0.5 % to 3.6 ± 0.6 %). The complete process chain for sample preparation is automatically performed within ~30 minutes, including ~15 minutes lysis time. It is amenable to concatenation with downstream modules for multiplex nucleic acid amplification as recently demonstrated for panel testing of various pathogens at the point of care.
F. Schuler, N. Paust, R. Zengerle, F. von Stetten
Centrifugal Step Emulsification can Produce Water in Oil Emulsions with Extremely High Internal Volume Fractions
2015 Micromachines, Band: 6, Nummer: 8, Seiten: 1180 - 1188
KurzfassungThe high throughput preparation of emulsions with high internal volume fractions is important for many different applications, e.g., drug delivery. However, most emulsification techniques reach only low internal volume fractions and need stable flow rates that are often difficult to control. Here, we present a centrifugal high throughput step emulsification disk for the fast and easy production of emulsions with high internal volume fractions above 95%. The disk produces droplets at generation rates of up to 3700 droplets/s and, for the first time, enables the generation of emulsions with internal volume fractions of >97%. The coefficient of variation between droplet sizes is very good (4%). We apply our system to show the in situ generation of gel emulsion. In the future, the recently introduced unit operation of centrifugal step emulsification may be used for the high throughput production of droplets as reaction compartments for clinical diagnostics or as starting material for micromaterial synthesis.
F. Schuler, F. Schwemmer, M. Trotter, S. Wadle, R. Zengerle, F. von Stetten, N. Paust
Centrifugal step emulsification applied for absolute quantification of nucleic acids by digital droplet RPA
2015 Lab Chip, Band: 15, Seiten: 2759 - 2766
KurzfassungAqueous microdroplets provide miniaturized reaction compartments for numerous chemical, biochemical or pharmaceutical applications. We introduce centrifugal step emulsification for the fast and easy production of monodispers droplets. Homogenous droplets with preselectable diameters in a range from 120 μm to 170 μm were generated with coefficients of variation of 2-4% and zero run-in time or dead volume. The droplet diameter depends on the nozzle geometry (depth, width, and step size) and interfacial tensions, only. Droplet size is demonstrated to be independent of the dispersed phase flow rate between 0.01-1 μl/s, proving the robustness of the centrifugal approach. Centrifugal step emulsification can easily be combined with existing centrifugal microfluidic unit operations, is compatible to scalable manufacturing technologies such as thermoforming or injection moulding and enables fast emulsification (> 500 droplets per second and nozzle) with minimal handling effort (2-3 pipetting steps). The centrifugal microfluidic droplet generation was used to perform the first digital droplet recombinase polymerase amplification (ddRPA). It was used for absolute quantification of Listerias monocytogenes DNA concentration standards with a total analysis time below 30 min. Compared to digital droplet polymerase chain reaction (ddPCR), with processing times of about 2 hours, the overall processing time of digital analysis was reduced by more than a factor of 4.
F. Schwemmer, T. Hutzenlaub, D. Buselmeier, N. Paust, F. von Stetten, D. Mark, R. Zengerle, D. Kosse
Centrifugo-pneumatic multi-liquid aliquoting – parallel aliquoting and combination of multiple liquids in centrifugal microfluidics
2015 Lab Chip, Band: 15, Seiten: 3250 - 3258
KurzfassungThe generation of mixtures with precisely metered volumes is essential for reproducible automation of laboratory workflows. Splitting a given liquid into well-defined metered sub-volumes, the so-called aliquoting, has been frequently demonstrated on centrifugal microfluidics. However, so far no solution exists for assays that require simultaneous aliquoting of multiple, different liquids and the subsequent pairwise combination of aliquots with full fluidic separation before combination. Here, we introduce the centrifugo-pneumatic multi-liquid aliquoting designed for parallel aliquoting and pairwise combination of multiple liquids. All pumping and aliquoting steps are based on a combination of centrifugal forces and pneumatic forces. The pneumatic forces are thereby provided intrinsically by centrifugal transport of the assay liquids into dead end chambers to compress the enclosed air. As an example, we demonstrate simultaneous aliquoting of 1.) a common assay reagent into twenty 5 µl aliquots and 2.) five different sample liquids, each into four aliquots of 5 µl. Subsequently, the reagent and sample aliquots are simultaneously transported and combined into twenty collection chambers. All coefficients of variation for metered volumes were between 0.4% - 1.0% for intra-run variations and 0.5% - 1.2% for inter-run variations. The aliquoting structure is compatible to common assay reagents with a wide range of liquid and material properties, demonstrated here for contact angles between 20° and 60°, densities between 789 and 1855 kg / m3 and viscosities between 0.89 and 4.1 mPa s. The centrifugo-pneumatic multi-liquid aliquoting is implemented as a passive fluidic structure into a single fluidic layer. Fabrication is compatible to scalable fabrication technologies such as injection molding or thermoforming and does not require any additional fabrication steps such as hydrophilic or hydrophobic coatings or integration of active valves.
Y. Zhao, F. Schwemmer, S. Zehnle, F. von Stetten, R. Zengerle, N. Paust
Centrifugo-pneumatic sedimentation, re-suspension and transport of microparticles
2015 Lab Chip, Seiten: 4133 - 4137
KurzfassungMicroparticles are widely used as solid phase for affinity based separation. Here, we introduce a new method for automated handling of microparticles in centrifugal microfluidics that is not restricted by the particle size and requires neither auxiliary means such as magnets nor coating of microfluidic structures. All steps are initiated and controlled by the speed of rotation, only. It is based on storage and “on demand” release of pneumatic energy within tuneable time frames: A slow release of the pneumatic energy triggers a first fluidic path through which the supernatant above the sedimented particles is removed. An abrupt release triggers a second path which allows for liquid routing and transport of the re-suspended particles. Re-suspension of particles is thereby achieved by quickly changing the speed of rotation. We demonstrate the exchange of the particle carrier medium with supernatant removal efficiency of more than 99.5% and particle loss below 4%. Re-suspension and subsequent transport of suspended particles shows particle loss below 7%. The method targets for the automation of particle based assays e.g. DNA extractions and immunoassays. It is compatible to monolithic integration and suitable for mass production technologies e.g. thermoforming or injection moulding.
M. Keller, S. Wadle, N. Paust, L. Dreesen, C. Nuese, O. Strohmeier, R. Zengerle, F. von Stetten
Centrifugo-thermopneumatic fluid control for valving and aliquoting applied to multiplex real-time PCR on off-the-shelf centrifugal thermocycler
2015 Rsc Adv, Band: 5, Seiten: 89603 - 89611
KurzfassungWe introduce microfluidic automation of geometrically multiplexed real-time PCR to off-the-shelf Rotor-Gene Q thermocyclers (RGQ, QIAGEN GmbH, Hilden, Germany). For centrifugal fluid control the RGQ provides low and constant rotation of 400 rpm, only. Compatibility to this very limited flexibility of centrifugal actuation is achieved by using thermal gas compression and expansion for valving and aliquoting. In contrast to existing thermo-pneumatic actuation, centrifugo-thermopneumatic (CTP) fluid control employs the induced change of partial vapor pressure by global temperature control as actuation parameter for two new unit operations: CTP siphon valving and CTP two-stage aliquoting. CTP siphon valving was demonstrated to reliably transfer sample liquid in all cases (n = 35) and CTP two-step aliquoting transfers metered aliquots of 18.2 ± 1.2 μl (CV 6.7%, n = 8) into reaction cavities within 5 s (n = 24). Thermal characteristics of CTP two-stage aliquoting were found to be in good agreement with an introduced analytical model (R2 = 0.9876, n = 3). A microfluidic disk segment comprising both new unit operations was used for automation of real-time PCR amplification of Escherichia coli DNA. Required primers and probes were pre-stored in the reaction cavities and a comparison with reference reactions in conventional PCR tubes yielded the same PCR efficiency, repeatability, and reproducibility.
L. Zielke, C. Barchasz, S. Waluś, F. Alloin, J.-C. Leprêtre, A. Spettl, V. Schmidt, A. Hilger, I. Manke, J. Banhart, R. Zengerle, S. Thiele
Degradation of Li/S Battery Electrodes On 3D Current Collectors Studied Using X-ray Phase Contrast Tomography
2015 Sci Rep-uk, Band: 5, Seite: 10921
KurzfassungLithium/sulphur batteries are promising candidates for future energy storage systems, mainly due to their high potential capacity. However low sulphur utilization and capacity fading hinder practical realizations. In order to improve understanding of the system, we investigate Li/S electrode morphology changes for different ageing steps, using X-ray phase contrast tomography. Thereby we find a strong decrease of sulphur loading after the first cycle, and a constant loading of about 15% of the initial loading afterwards. While cycling, the mean sulphur particle diameters decrease in a qualitatively similar fashion as the discharge capacity fades. The particles spread, migrate into the current collector and accumulate in the upper part again. Simultaneously sulphur particles lose contact area with the conducting network but regain it after ten cycles because their decreasing size results in higher surface areas. Since the capacity still decreases, this regain could be associated with effects such as surface area passivation and increasing charge transfer resistance.
M. Klingele, M. Breitwieser, R. Zengerle, S. Thiele
Direct Deposition of Proton Exchange Membranes Enabling High Performance Hydrogen Fuel Cells
2015 J. Mat. Chem. A, Band: 3, Seiten: 11239 - 11245
KurzfassungWe apply drop-on-demand inkjet printing to fabricate proton exchange membranes for polymer electrolyte fuel cells. This completely substitutes the commonly used membrane foil. A Nafion® dispersion is deposited directly onto the catalyst layers of anode and cathode gas diffusion electrodes, and the two electrodes are pressed together with membrane layers facing each other. Fuel cells constructed utilizing this method reveal a thin overall membrane thickness of 8-25 µm and a good adhesion of membrane and catalyst layers. This results in a membrane ionic resistance of only 12.7 mΩ*cm² without compromising hydrogen crossover, which was determined to be less than 2 mA/cm². We achieve a cell power density exceeding 4 W/cm² with pure oxygen as cathode fuel, which, to our knowledge, is the highest reported power density with a Nafion® membrane hydrogen fuel cell. The membrane shows a stable performance over the entire range of reactant gas humidification from 0 to 100 % relative humidity. Power densities exceeding 1.0 W/cm² are achieved under dry operation with air as cathode fuel. A 576 hour combined mechanical and chemical accelerated stress test reveals no significant degradation of hydrogen crossover, indicating a promising lifetime of the membrane.
L. Drechsel, M. Schulz, F. von Stetten, C. Moldovanc, R. Zengerle, N. Paust
Electrochemical pesticide detection with AutoDip – a portable platform for automation of crude sample analyses
2015 Lab Chip, Band: 15, Seiten: 704 - 710
KurzfassungLab-on-a-chip devices hold promise for automation of complex workflows from sample to answer with minimal consumption of reagents in portable devices. However, complex, inhomogeneous samples as they occur in environmental or food analysis may block microchannels and thus often cause malfunction of the system. Here we present the novel AutoDip platform which is based on the movement of a solid phase through the reagents and sample instead of transporting a sequence of reagents through a fixed solid phase. A ball-pen mechanism operated by an external actuator automates unit operations such as incubation and washing by consecutively dipping the solid phase into the corresponding liquids. The platform is applied to electrochemical detection of organophosphorus pesticides in real food samples using an acetylcholinesterase (AChE) biosensor. Minimal sample preparation and an integrated reagent pre-storage module hold promise for easy handling of the assay. Detection of the pesticide chlorpyrifos-oxon (CPO) spiked into apple samples at concentrations of 10−7 M has been demonstrated. This concentration is below the maximum residue level for chlorpyrifos in apples defined by the European Commission.
I. Leibacher, J. Schoendube, J. Dual, R. Zengerle, P. Koltay
Enhanced single-cell printing by acoustophoretic cell focusing
2015 Biomicrofluidics, Band: 9, Seite: 024109
KurzfassungRecent years have witnessed a strong trend towards analysis of single-cells. To access and handle single-cells, many new tools are needed and have partly been developed. Here, we present an improved version of a single-cell printer which is able to deliver individual single cells and beads encapsulated in free-flying picoliter droplets at a single-bead efficiency of 96% and with a throughput of more than 10 beads per minute. By integration of acoustophoretic focusing, the cells could be focused in x and y direction. This way, the cells were lined-up in front of a 40 µm nozzle, where they were analyzed individually by an optical system prior to printing. In agreement with acoustic simulations, the focusing of 10 µm beads and Raji cells has been achieved with an efficiency of 99% (beads) and 86% (Raji cells) to a 40 µm wide center region in the 1mm wide microfluidic channel. This enabled improved optical analysis and reduced bead losses. The loss of beads that ended up in the waste (because printing them as single beads arrangements could not be ensured) was reduced from 52 ± 6% to 28 ± 1%. The piezoelectric transducer employed for cell focusing could be positioned on an outer part of the device, which proves the acoustophoretic focusing to be versatile and adaptable.
S. Vierrath, F. Güder, A. Menzel, M. Hagner, R. Zengerle, M. Zacharias, S. Thiele
Enhancing the Quality of the Tomography of Nanoporous Materials for Better Understanding of Polymer Electrolyte Fuel Cell Materials
2015 J Power Sources, Seiten: 413 - 417
KurzfassungTo investigate the nanostructure of polymer electrolyte fuel cell catalyst layers, focused ion beam - scanning electron microscopy (FIB-SEM) tomography is a common technique. However, as FIB-SEM tomography lacks of image contrast between the catalyst layer and its pores, state-of-the-art reconstruction methods by threshold cannot accurately distinguish between these two phases. We show that this inability leads to an underestimation of the porosity by a factor of nearly two, a reconstruction with channel-like artifacts and that these artifacts make it impossible to calculate reliable diffusivities. To overcome this problem, we fill the pores of the catalyst layer with ZnO via atomic layer deposition prior to tomography. By using atomic layer deposition, even smallest pores can be filled with ZnO, which exhibits a good contrast to the catalyst layer in SEM images. As a result, we present the porosity of the catalyst layer (65%) and its three-dimensional representation without typical reconstruction artifacts. Calculated O2 diffusivities (23.05 - 25.40 x 10-7 m2s-1) inside the catalyst layer are in good agreement with experimental values from the literature. Furthermore, filling with ZnO permits the identification of large Pt clusters inside the catalyst layer, which were estimated to reduce the catalyst surface area by 9%.
A.G. Venkatesh, S. K. Vashist, E. M. Schneider, R. Zengerle, F. von Stetten, J. H.T. Luong
Graphene-based C-reactive protein immunoassay with smartphone readout
2015 Protocol Exchange
KurzfassungA highly-sensitive immunoassay (IA) procedure with minimal process steps has been developed for the detection of human C-reactive protein (CRP) in less than 30 min. Graphene nanoplatelets (GNP) was admixed with 3-aminopropyltriethoxysilane (APTES) and EDC-activated anti-human CRP antibody (Ab) to form a stable complex that was then covalently attached to a KOH-pretreated polystyrene microtiter plate (MTP). The developed one-step kinetics-based IA involves the formation of a sandwich immune complex followed by two washings and an enzyme-based colorimetric reaction that was read by a smartphone-based colorimetric reader (SBCR). The detection range of CRP was 0.03-81 ng mL-1 with a limit of detection (LOD) and a limit of quantification (LOQ) of 0.07 ng mL-1 and 0.9 ng mL-1, respectively. Moreover, the developed IA enabled the detection of CRP spiked in diluted human whole blood and plasma as well as CRP present in clinical plasma samples with high analytical precision, thereby demonstrating its immense utility for biomedical diagnostics.
M. Breitwieser, M. Klingele, B. Britton, S. Holdcroft, R. Zengerle, S. Thiele
Improved Pt-utilization efficiency of low Pt-loading PEM fuel cell electrodes using direct membrane deposition
2015 Electrochem Commun, Band: 60, Seiten: 168 - 171
KurzfassungDirect membrane deposition was used to produce record platinum catalyst utilization efficiency polymer electrolyte membrane fuel cells. The novel membrane fabrication technique was applied to gas diffusion electrodes with low Pt-loadings of 0.102 and 0.029 mg/cm2. Under oxygen atmosphere and 300 kPaabs total pressure, 88 kW/gPt cathodic catalyst utilization efficiency with a symmetrical Pt-loading of 0.029 mg/cm2 on the anode and cathode side was achieved. This is 2.3 times higher than the Pt-utilization efficiency of a reference fuel cell prepared using a commercial Nafion N-211 membrane and identical catalyst layers, emphasizing that the improvement is purely attributable to the novel membrane fabrication technique. This value represents the highest Pt-utilization efficiency reported in literature. The results strongly motivate the application of employing direct membrane deposition techniques to prepare low resistance polymer electrolyte thin films in order to compensate for kinetic losses introduced when using low catalyst loadings.
D. Czurratis, Y. Beyl, A. Grimm, T. Brettschneider, S. Zinober, F. Lärmer, R. Zengerle
Liquids on-chip: direct storage and release employing micro-perforated vapor barrier films
2015 Lab Chip, Band: 15, Seiten: 2887 - 2895
KurzfassungLiquids on-chip describes a reagent storage concept for disposable pressure driven Lab-on-Chip (LoC) devices, which enables liquid storage in reservoirs without additional packaging. On-chip storage of liquids can be considered as one of the major challenges for the commercial break through of polymer-based LoC devices. Especially the ability for long-term storage and reagent release on demand are the most important aspects for a fully developed technology. On-chip storage not only replaces manual pipetting, it creates numerous advantages: fully automated processing, ease of use, reduction of contamination and transportation risks. Previous concepts for on-chip storage are based on liquid packaging solutions (e.g. stick packs, blisters, glass ampoules), which implicate manufacturing complexity and additional pick and place processes. That is why we prefer on-chip storage of liquids directly in reservoirs. The liquids are collected in reservoirs, which are made of high barrier polymers or coated by selected barrier layers. Therefore, commonly used polymers for LoC applications as cyclic olefin polymer (COP) and polycarbonate (PC) were investigated in the context of novel polymer composites. To ensure long-term stability the reservoirs are sealed with a commercially available barrier film by hot embossing. The barrier film is structured by pulsed laser ablation, which installs rated break points without affecting the barrier properties. A flexible membrane is actuated through pneumatic pressure for reagent release on demand. The membrane deflection breaks the barrier film and leads to efficient cleaning of the reservoirs in order to provide the liquids for further processing.
G.Czilwik, S.K.Vashist, V.Klein, G.Roth, A.Buderer, F. von Stetten, R. Zengerle, D.Mark
Magnetic chemiluminescent immunoassay for human C-reactive protein on the centrifugal microfluidics platform
2015 Rsc Adv, Band: 5, Seiten: 61906 - 61912
KurzfassungHuman C-reactive protein (CRP) has been reported as an inflammatory biomarker with the highest reference for use in clinical practice. However, the existing analytical techniques are lacking automation and simplicity, as desired for a prospective immunoassay format for point-of-care (PoC) analysis. We have developed an automated magnetic chemiluminescent immunoassay (MCIA) on a mobile analyser for rapid PoC determination of CRP. The MCIA is fully automated after the initial loading of sample and immunoreagents at the inlet ports. The automated protocol involves the transportation of magnetic capture microparticles between adjacent reaction compartments using a set of stationary magnets, a microfluidic polymer disposable and a specific centrifugal protocol. The developed MCIA has a sample-to-answer time of 25 min and hands-on time of approximately 5 min. It detects the entire pathophysiological range of CRP, as desired for clinically-relevant high sensitivity CRP immunoassay format, i.e. 3–81 ng mL−1 in diluted human serum with a limit of detection (LOD) and limit of quantification (LOQ) of 1.5 ng mL−1 and 1.8 ng mL−1, respectively.
F. Schwemmer, S. Zehnle, D. Mark, F. von Stetten, R. Zengerle, N. Paust
Microfluidic timer for timed valving and pumping in centrifugal microfluidics
2015 Lab Chip, Band: 15, Seiten: 1545 - 1553
KurzfassungAccurate timing of microfluidic operations is essential for the automation of complex laboratory workflows, in particular for the supply of sample and reagents. Here we present a new unit operation for timed valving and pumping in centrifugal microfluidics. It is based on temporary storage of pneumatic energy and time delayed sudden release of said energy. The timer is loaded at a relatively higher spinning frequency. The countdown is started by reducing to a relatively lower release frequency, at which the timer releases after a pre-defined delay time. We demonstrate timing for 1.) the sequential release of 4 liquids at times of 2.7 s ± 0.2 s, 14.0 s ± 0.5 s, 43.4 s ± 1.0 s and 133.8 s ± 2.3 s, 2.) timed valving of typical assay reagents (contact angles 36° - 78°, viscosities 0.9 mPa s - 5.6 mPa s) and 3.) “on demand” valving of liquids from 4 inlet chambers in any user defined sequence controlled by the spinning protocol. The microfluidic timer is compatible to all wetting properties and viscosities of common assay reagents and does neither require assistive equipment, nor coatings. It can be monolithically integrated into a microfluidic test carrier and is compatible to scalable fabrication technologies such as thermoforming or injection molding.
G. Czilwik, I. Schwarz, M. Keller, S. Wadle, S. Zehnle, F. von Stetten, D. Mark, R. Zengerle, N. Paust
Microfluidic vapor-diffusion barrier for pressure reduction in fully closed PCR modules
2015 Lab Chip, Band: 15, Seiten: 1084 - 1091
KurzfassungMicrofluidic systems for polymerase chain reaction (PCR) should be fully closed to avoid vapor loss and to exclude the risk of contaminating the test environment. In closed systems however, the high temperatures of up to 95°C associated with PCR cause high overpressures up to 100 kPa, dominated by the increase of vapor partial pressure upon evaporation. Such high overpressures pose challenges to the mechanical stability of microfluidic chips as well as to the liquid handling in integrated sample-to-answer systems. In this work, we drastically reduce the pressure increase in fully closed PCR systems by integrating a microchannel that serves as a vapor-diffusion barrier (VDB), separating the liquid-filled PCR chamber from an auxiliary air chamber. In such configurations, propagation of vapor from the PCR chamber into the auxiliary air chamber and as a consequence the increase of pressure is limited by the slow diffusion process of vapor through the VDB. At temperature increase from 23°C to 95°C, we demonstrate the reduction of overpressure from more than 80 kPa without the VDB to only 35 kPa with the VDB. We further demonstrate proper function of VDB and its easy integration with downstream processes for PCR based nucleic acid amplification within centrifugal microfluidics. Without integration of the VDB, malfunction due to pressure-induced delamination of the microfluidic chip occurred.
G. Czilwik, D. Baumann, D. Mark, R. Zengerle, F. von Stetten
Mikrofluidische Automatisierung in der Molekulardiagnostik
2015 BIOspektrum, Band: 21, Seiten: 622 - 624
KurzfassungEasy-to-use point-of-care (POC) tests provide rapid diagnostic results near the patient, enabling fast decision-making in patient management. However, the implementation of automated molecular diagnostic POC tests still faces technical challenges. We demonstrate a highly sensitive POC platform for automated molecular diagnostics of neonatal sepsis that uses a mobile analyzer and unit-use test carriers.
S. Vierrath, L. Zielke, R. Moroni, A. Mondon, D. R. Wheeler, R. Zengerle, S. Thiele
Morphology of nanoporous carbon-binder domains in Li-ion batteries—A FIB-SEM study
2015 Electrochem Commun, Band: 60, Seiten: 176 - 179
KurzfassungFIB-SEM tomography is used to reconstruct the carbon-binder domain (CBD) of a LiCoO2 battery cathode (3.9 × 5 × 2.3 μm3) with contrast enhancement by ZnO infiltration via atomic layer deposition. We calculate the porosity inside the CBD (57.6%), the cluster-size distribution with a peak at 54 nm, and the pore-size distribution with a peak at 64 nm. The tortuosities of the pore space (1.6–2.0) and the CBD (2.3–3.5) show a mild anisotropy, which is attributed to the fabrication process. A comparison to a modeled homogenous CBD reveals that clustering in the CBD decreases its electronic conductivity while increasing the ionic diffusivity. To account for the higher calculated diffusivity compared to experimental values from literature, a simple binder swelling model is implemented, suggesting a swelling of 75 vol%. The prevention of both clustering and swelling could increase the volume available for active material and therefore the energy density.
S. Zehnle, F. Schwemmer, R. Bergmann, F. von Stetten, R. Zengerle, N. Paust
Pneumatic siphon valving and switching in centrifugal microfluidics controlled by rotational frequency or rotational acceleration
2015 Microfluid Nanofluid, Band: 19, Seiten: 1259 - 1269
KurzfassungAir-pressure-mediated, pneumatic siphon valves employ temporary storage and subsequent release of pneumatic energy, exclusively controlled by rotation of the disk. Implementation is easy, and robust valves can be integrated in a monolithic way at minimum additional costs. However, so far, pneumatic siphon valving requires deceleration from high to low rotational frequencies. Valve opening is performed always when the rotation of the disk drops below a critical rotational frequency. To overcome this limitation, we introduce new concepts for pneumatic siphon valving which enable operation of the disk at any rotational frequency without unwanted bursts of the siphon valves. Thus, the design space for pneumatic siphon valves in centrifugal microfluidics is significantly extended. Three types of pneumatic siphon valves are presented with release control at (1) rotational frequencies between 25 and 48 Hz, (2) positive rotational accelerations between 1 and 22 Hz s−1, and (3) negative rotational accelerations between 5 and 20 Hz s−1. Finally, we combine two valve types to realize robust switching into two fluidic paths with flow rate ratios of 94/6 and 0/100.
C. Köhler, L. Bleck, M. Frei, R. Zengerle, S. Kerzenmacher
Poisoning of Highly Porous Platinum Electrodes by Amino Acids and Tissue Fluid Constituents
2015 ChemElectroChem, Band: 2, Seiten: 1785 - 1793
KurzfassungThe first comprehensive study of the poisoning behavior of physiological amino acids and important tissue fluid constituents on porous platinum electrodes was performed. On the basis of chronoamperometry under physiological conditions, the results are highly relevant for the development of enzyme-free implantable glucose fuel cells and possibly also glucose sensors. The strongest poisoning was exhibited by positively charged alkaline amino acids and by some of the neutral amino acids, as well as by uric acid and creatinine. In contrast to previous work, sulfur-containing amino acids showed no poisoning effect. This was explained by the use of highly porous platinum electrodes in the current study and experimental methods that were more relevant for practical applications. Furthermore, comprehensive analysis regarding the degree of recovery in the absence of poisoning species and the extent of electrode regeneration by cyclic voltammetry was performed for each of the amino acids and physiological substances.
M. Klingele, R. Zengerle, S. Thiele
Quantification of artifacts in scanning electron microscopy tomography: Improving the reliability of calculated transport parameters in energy applications such as fuel cell and battery electrodes
2015 J Power Sources, Band: 275, Seiten: 852 - 859
KurzfassungFocused ion beam and scanning electron microscopy tomography (FIB-SEMt) is commonly used to extract reactant transport relevant parameters from nano-porous materials in energy applications, such as fuel cells or batteries. Here we present an approach to virtually model the errors in FIB-SEMt which are caused by the FIB cutting distance. The errors are evaluated in terms of connectivity, solid volume fraction (SVF), conductivity, diffusivity, as well as mean grain and pore sizes. For state-of-the-art FIB-SEMt experiments, where a hydrogen fuel cell catalyst layer with 60 nm mean grain size and 40% SVF is sectioned with a cutting distance of 15 nm, the error in our simulation ranges up to 51% (conductivity), whereas other parameters remain largely unaffected (Laplace diffusivity, 4%). We further present a method, employing virtual coarsening and back interpolation, to reduce FIB cutting distance errors in all investigated parameters. Both error evaluation and correction are applicable to sphere based porous materials with relevance for the energy conversion and storage sector such as polymer electrolyte membrane fuel cell catalyst layer (PEMFC CL), battery carbon binder domain (CBD) or supercapacitor electrodes.
G. Czilwik, T. Messinger, O. Strohmeier, S. Wadle, F. von Stetten, N. Paust, G. Roth, R. Zengerle, P. Saarinen, J. Niittymäki, K. McAllister, O. Sheils, J. O'Leary, D. Mark
Rapid and fully automated bacterial pathogen detection on a centrifugal-microfluidic LabDisk using highly sensitive nested PCR with integrated sample preparation
2015 Lab Chip, Band: 15, Seiten: 3749 - 3759
KurzfassungDiagnosis of infectious diseases suffers from long turnaround times for gold standard culture-based identification of bacterial pathogens, therefore impeding timely specific antimicrobial treatment based on laboratory evidence. Rapid molecular diagnostics-based technologies enable detection of microorganisms within hours however cumbersome workflows and complex equipment still prevent their widespread use in the routine clinical microbiology setting. We developed a centrifugal-microfluidic “LabDisk” system for rapid and highly-sensitive pathogen detection on a point-of-care analyser. The unit-use LabDisk with pre-stored reagents features fully automated and integrated DNA extraction, consensus multiplex PCR pre-amplification and geometrically-multiplexed species-specific real-time PCR. Processing merely requires loading of the sample and DNA extraction reagents with minimal hands-on time of approximately 5 min. We demonstrate detection of as few as 3 colony-forming-units (cfu) of Staphylococcus warneri, 200 cfu of Streptococcus agalactiae, 5 cfu of Escherichia coli and 2 cfu of Haemophilus influenzae in a 200 μL serum sample. The turnaround time of the complete analysis from “sample-to-result” was 3 h and 45 min. The LabDisk consequently provides an easy-to-use molecular diagnostic platform for rapid and highly-sensitive detection of bacterial pathogens without requiring major hands-on time and complex laboratory instrumentation.
F. Stumpf, J. Schoendube, A. Gross, C. Rath, S. Niekrawietz, P. Koltay, G. Roth
Single-cell PCR of genomic DNA enabled by automated single-cell printing for cell isolation
2015 Biosens Bioelectron, Band: 69, Seiten: 301 - 306
KurzfassungSingle-cell analysis has developed into a key topic in cell biology with future applications in personalized medicine, tumor identification as well as tumor discovery (Editorial, 2013). Here we employ inkjet-like printing to isolate individual living single human B cells (Raji cellline) and load them directly into standard PCR tubes. Single cells are optically detected in the nozzle of the microfluidic piezoelectric dispenser chip to ensure printing of droplets with single cells only. The printing process has been characterized by using microbeads (10 µm diameter) resulting in a single bead delivery in 27 ou tof 28 cases and relative positional precision of ± 350 µm at a printing distance of 6 mm between nozzle and tube lid. Process-integrated optical imaging enabled to identify the printing failure as void droplet and to exclude it from downstream processing. PCR of truly single-cell DNA was performed without pre-amplification directly from single Raji cells with 33% success rate (N=197) and Cq values of 36.3 ± 2.5. Additionally single cell whole genome amplification (WGA) was employed to pre-amplify the single-cell DNA by a factor of >1000. This facilitated subsequent PCR for the same gene yielding a success rate of 64% (N=33) which will allow more sophisticated downstream analysis like sequencing, electrophoresis or multiplexing.
J. Schoendube, D. Wright, R. Zengerle, P. Koltay
Single-cell printing based on impedance detection
2015 Biomicrofluidics, Band: 9, Seite: 014117
KurzfassungLabel-free isolation of single cells is essential for the growing field of single-cell analysis. Here, we present a device which prints single living cells encapsulated in free-flying picoliter droplets. It combines inkjet printing and impedance flow cytometry. Droplet volume can be controlled in the range of 500 pl–800 pl by piezo actuator displacement. Two sets of parallel facing electrodes in a 50 µm x 55 µm channel are applied to measure the presence and velocity of a single cell in real-time. Polystyrene beads with <5% variation in diameter generated signal variations of 12%–17% coefficients of variation. Single bead efficiency (i.e., printing events with single beads vs. total number of printing events) was 73%611% at a throughput of approximately 9 events/min. Viability of printed HeLa cells and human primary fibroblasts was demonstrated by culturing cells for at least eight days.
C. E. Blanchet, A. Spilotros, F. Schwemmer, M. A. Graewert, A. Kikhney, C. M. Jeffries, D. Franke, D. Mark, R. Zengerle, F. Cipriani, S. Fiedler, M. Roessle, D. I. Sverguna
Versatile sample environments and automation for biological solution X-ray scattering experiments at the P12 beamline (PETRA III, DESY)
2015 J Appl Crystallogr, Band: 48, Seiten: 431 - 443
KurzfassungA high-brilliance synchrotron P12 beamline of the EMBL located at the PETRA III storage ring (DESY, Hamburg) is dedicated to biological smallangle X-ray scattering (SAXS) and has been designed and optimized for scattering experiments on macromolecular solutions. Scatterless slits reduce the parasitic scattering, a custom-designed miniature active beamstop ensures accurate data normalization and the photon-counting PILATUS 2M detector enables the background-free detection of weak scattering signals. The high flux and small beam size allow for rapid experiments with exposure time down to 30– 50 ms covering the resolution range from about 300 to 0.5 nm. P12 possesses a versatile and flexible sample environment system that caters for the diverse experimental needs required to study macromolecular solutions. These include an in-vacuum capillary mode for standard batch sample analyses with robotic sample delivery and for continuous-flow in-line sample purification and characterization, as well as an in-air capillary time-resolved stopped-flow setup. A novel microfluidic centrifugal mixing device (SAXS disc) is developed for a high-throughput screening mode using sub-microlitre sample volumes. Automation is a key feature of P12; it is controlled by a beamline meta server, which coordinates and schedules experiments from either standard or nonstandard operational setups. The integrated SASFLOWpipeline automatically checks for consistency, and processes and analyses the data, providing near real-time assessments of overall parameters and the generation of low-resolution models within minutes of data collection. These advances, combined with a remote access option, allow for rapid high-throughput analysis, as well as time-resolved and screening experiments for novice and expert biological SAXS users.
J. Schoendube, A. Yusof, K. Kalkandjiev, R. Zengerle, P. Koltay
Wafer level fabrication of single cell dispenser chips with integrated electrodes for particle detection
2015 J Micromech Microeng, Band: 25, Seite: 025008
KurzfassungThis work presents the microfabrication and experimental evaluation of a dispenser chip, designed for isolation and printing of single cells by combining impedance sensing and drop-on-demand dispensing. The dispenser chip features 50 × 55 μm (width × height) microchannels, a droplet generator and microelectrodes for impedance measurements. The chip is fabricated by sandwiching a dry film photopolymer (TMMF) between a silicon and a Pyrex wafer. TMMF has been used to define microfluidic channels, to serve as low temperature (75 °C) bonding adhesive and as etch mask during 300 μm deep HF etching of the Pyrex wafer. Due to the novel fabrication technology involving the dry film resist, it became possible to fabricate facing electrodes at the top and bottom of the channel and to apply electrical impedance sensing for particle detection with improved performance. The presented microchip is capable of dispensing liquid and detecting microparticles via impedance measurement. Single polystyrene particles of 10 μm size could be detected with a mean signal amplitude of 0.39 ± 0.13 V (n = 439) at particle velocities of up to 9.6 mm s−1 inside the chip.

2014

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L. Zielke, T. Hutzenlaub, D. R. Wheeler, I. Manke, T. Arlt, N. Paust, R. Zengerle, S. Thiele
A Combination of X-Ray Tomography and Carbon Binder Modeling: Reconstructing the Three Phases of LiCoO2 Li-Ion Battery Cathodes
2014 Adv Energy Mater, Band: 4, Seite: 1301617
KurzfassungX-ray tomography allows the active-material domain (LiCoO2) of Li-ion battery cathodes to be imaged, but it is unable to resolve the carbon-binder domain (CBD). Here, a new method for creating a complete 3D representation (virtual design) of all three phases of a cathode is provided; this includes the active-material domain, the CBD, and the electrolyte-filled pore space. It combines X-ray tomographic data of active material with a statistically modeled CBD. Two different statistical CBD morphology models are compared as examples: i) a random cluster model representing a standard mixture of carbon black and polyvenylidene fluoride (PVDF) and ii) a fiber model. The transport parameters are compared in a charged and a discharged cathode. The results demonstrate that the CBD content and morphology changes the ionic and electronic transport parameters dramatically and thus cannot be neglected. Calculations yield that the fiber model shows up to three times higher electrical conductivity at the same CBD content (discharged case) and better ionic diffusion conditions for all CBD contents. In the charged case, the morphology impact on electrical conduction is small. This effective method to generate transport parameters for different CBDs can be transferred to other CBD morphologies and electrodes.
S.K. Vashist, G. Czilwik, T. van Oordt, F. von Stetten, R. Zengerle,, E.M. Schneider, J.H.T. Luong
A rapid one-step kinetics-based immunoassay procedure for the highly-sensitive detection of C-reactive protein
2014 Protocol Exchange
M. Hoehl, E. Schulte Bocholt, A. Kloke, N. Paust, F. von Stetten, R. Zengerle, J. Steigert, A. Slocum
A versatile-deployable bacterial detection system for food and environmental safety based on LabTube-automated DNA purification, LabReader-integrated amplification, readout and analysis
2014 Analyst, Band: 139, Seiten: 2788 - 2798
KurzfassungContamination of foods is a public health hazard that episodically causes thousands of deaths and sickens millions worldwide. To ensure food safety and quality, rapid, low-cost and easy-to-use detection methods 10 are desirable. Here, the LabSystem is introduced for integrated, automated DNA purification, amplification and detection. It consists of a disposable, centrifugally-driven DNA purification platform (LabTube) and the subsequent amplification and detection in a low-cost UV/vis-reader (LabReader). For demonstration of the LabSystem in the context of food safety, purification of Escherichia coli (nonpathogenic E. coli and pathogenic verotoxin-producing E. coli (VTEC)) in water and milk, and the 15 product-spoiler Alicyclobacillus acidoterrestris (A. acidoterrestris) in apple juice was integrated and optimized in the LabTube. Inside the LabReader, the purified DNA was amplified, readout and analyzed using both qualitative isothermal loop-mediated DNA amplification (LAMP) and quantitative real-time PCR. For the LAMP-LabSystem, the combined detection limits for purification and amplification of externally lysed VTEC and A. acidoterrestris is 102-103 cell-equivalents. In the PCR-LabSystem for E. coli cells, the quantification limit is 102 20 cell-equivalents including LabTube-integrated lysis. The demonstrated LabSystem only requires a laboratory centrifuge (to operate the disposable, fully closed LabTube) and the low-cost LabReader for DNA amplification, readout and analysis. Compared with commercial DNA amplification devices, the LabReader improves sensitivity and specificity by the simultaneous readout of four wavelengths and the continuous readout during temperature cycling. The 25 use of a detachable eluate tube as an interface affords semi-automation of the LabSystem, which does not require specialized training. It reduces hands-on time from about 50 to 3 min with only two handling steps: sample input and transfer of the detachable detection tube.
S. K. Vashist, O. Mudanyali, E. M. Schneider, R. Zengerle, A. Ozcan
Cellphone-based devices for bioanalytical sciences
2014 Anal Bioanal Chem, Band: 406, Nummer: 14, Seiten: 3263 - 3277
KurzfassungDuring the last decade, there has been a rapidly growing trend toward the use of cellphone-based devices (CBDs) in bioanalytical sciences. For example, they have been used for digital microscopy, cytometry, read-out of immunoassays and lateral flow tests, electrochemical and surface plasmon resonance based bio-sensing, colorimetric detection and healthcare monitoring, among others. Cellphone can be considered as one of the most prospective devices for the development of next-generation point-of-care (POC) diagnostics platforms, enabling mobile healthcare delivery and personalized medicine. With more than 6.5 billion cellphone subscribers worldwide and approximately 1.6 billion new devices being sold each year, cellphone technology is also creating new business and research opportunities. Many cellphone-based devices, such as those targeted for diabetic management, weight management, monitoring of blood pressure and pulse rate, have already become commerciallyavailable in recent years. In addition to such monitoring platforms, several other CBDs are also being introduced, targeting e.g., microscopic imaging and sensing applications for medical diagnostics using novel computational algorithms and components already embedded on cellphones. This report aims to review these recent developments in CBDs for bioanalytical sciences along with some of the challenges involved and the future opportunities.
M. Hoehl, M. Weissert, A. Dannenberg, T. Nesch, N. Paust, F. von Stetten, R. Zengerle, A. Slocum, J. Steigert
Centrifugal LabTube platform for fully automated DNA purification and LAMP amplification based on an integrated, low-cost heating-system
2014 Biomed Microdevices, Band: 16, Nummer: 3, Seiten: 375 - 385
KurzfassungThis paper introduces a disposable battery-driven heating system for loop-mediated isothermal DNA amplification (LAMP) inside a centrifugally-driven DNA purification platform (LabTube). We demonstrate LabTube-based fully automated DNA purification of as low as 100 cell-equivalents of verotoxin-producing Escherichia coli (VTEC) in water, milk and apple juice in a laboratory centrifuge, followed by integrated and automated LAMP amplification with a reduction of hands-on time from 45 to 1 min. The heating system consists of two parallel SMD thick film resistors and a NTC as heating and temperature sensing elements. They are driven by a 3 V battery and controlled by a microcontroller. The LAMP reagents are stored in the elution chamber and the amplification starts immediately after the eluate is purged into the chamber. The LabTube, including a microcontroller-based heating system, demonstrates contamination-free and automated sample-to-answer nucleic acid testing within a laboratory centrifuge. The heating system can be easily parallelized within one LabTube and it is deployable for a variety of heating and electrical applications.
K. Dolch, J. Danzer, T. Kabbeck, B. Bierer, J. Erben, A. H. Förster, J. Maisch, P. Nick, S. Kerzenmacher, J. Gescher
Characterization of microbial current production as a function of microbe-electrode-interaction
2014 Bioresource Technol, Band: 157, Seiten: 284 - 292
KurzfassungMicrobe–electrode-interactions are keys for microbial fuel cell technology. Nevertheless, standard measurement routines to analyze the interplay of microbial physiology and material characteristics have not been introduced yet. In this study, graphite anodes with varying surface properties were evaluated using pure cultures of Shewanella oneidensis and Geobacter sulfurreducens, as well as defined and undefined mixed cultures. The evaluation routine consisted of a galvanostatic period, a current sweep and an evaluation of population density. The results show that surface area correlates only to a certain extent with population density and anode performance. Furthermore, the study highlights a strain-specific microbe–electrode-interaction, which is affected by the introduction of another microorganism. Moreover, evidence is provided for the possibility of translating results from pure culture to undefined mixed species experiments. This is the first study on microbe–electrode-interaction that systematically integrates and compares electrochemical and biological data.
S. Sané, C. Heilemann, P. Salvei, S. Rubenwolf, C. Jolivalt, C. Madzak, R. Zengerle, P. J. Nielsen, S. Kerzenmacher
Enzymatic fuel cells solely supplied with unpurified cellobiose dehydrogenaseand laccase in microorganism´s culture supernatans
2014 ChemElectroChem, Band: 1, Seiten: 1886 - 1894
KurzfassungEnzymatic electrodes have great potential for catalysing the direct conversion of chemical compounds into electricity with the use of redox enzymes. However, expensive and time-consuming enzyme purification and the frequent need to add mediators are considered as drawbacks of enzymatic electrodes. We report a biofuel cell at pH 5, supplied with the unpurified enzymes laccase and cellobiose dehydrogenase (CDH) in crude culture supernatant, without the further addition of mediators. A maximum power output of 6.2±1.2 μW cm−2 was achieved by using supernatants containing laccase from Trametes versicolor (2.84 UmL−1) and CDH (0.90 UmL−1) from a recombinant yeast Yarrowia lipolytica YPC4. In comparison, the supply of purified enzymes (laccase: 2.40 UmL−1, CDH: 0.15 UmL−1) in a buffer solution yielded only about a twofold higher power density. Our results demonstrate the feasibility of using unpurified laccase and CDH in an enzymatic biofuel cell, which can simplify its construction and operation.
S. K. Vashist, E.M. Schneider, R. Zengerle, F. von Stetten, J.H.T. Luong
Graphene-based rapid and highly-sensitive immunoassay for C-re active protein using a smartphone-based colorimetric reader
2014 Biosens Bioelectron, Band: 66, Seiten: 169 - 176
KurzfassungA novel immunoassay (IA) has been developed for human C-reactive protein (CRP), an important biomarker and tissue preserving factor for infection and inflammation. Graphene nanoplatelets (GNP) and 3-aminopropyltriethoxysilane (APTES) were admixed and covalently attached to a polystyrene based-microtiter plate (MTP), pretreated with KOH. The resulting surface served as a stable layer for the covalent attachment of the anti-human CRP antibody. The IA procedure was based on the one-step kinetics-based sandwich IA employing a minimum number of process steps, whereas the enzymatic reaction solution was monitored by a smartphone-based colorimetric reader. With a limit of detection and a limit of quantification of 0.07 ng mL−1 and 0.9 ng mL−1, it precisely detected CRP spiked in diluted human whole blood and plasma as well as the CRP levels in clinical plasma samples. The results obtained for “real-world” patient samples agreed well with those of the conventional immunosorbent assay and the clinically-accredited analyzer-based IA. The antibody-bound GNP-functionalized MTPs retained its original activity after 6 weeks of storage in 0.1 M PBS, pH 7.4 at 4 °C.
K.G. Kraiczek, R. Bonjour, Y. Salvadé, R. Zengerle
Highly Flexible UV-Vis Radiation Sources and Novel Detection Schemes for Spectrophotometric HPLC Detection
2014 Anal Chem, Band: 86, Nummer: 2, Seiten: 1146 - 1152
KurzfassungThe concept and performance of the first multiwavelength deep UV light-emitting-diode-based high-performance liquid chromatography (HPLC) absorbance detector are presented. In single-wavelength mode and with optical reference, the limit of detection (LOD) is comparable to conventional state-of-theart HPLC absorbance detectors. In multiwavelength modeat present up to eight wavelengths without optical referencethe LOD is about 10 times higher than in single-wavelength mode. Multiplexing and demultiplexing methods are used to separate chromatographic signals in multiwavelength mode and keeps the detector configuration simple and yet flexible. Depending on the operation mode, stray light is either totally negligible or controlled electronically and digitally.
E. Kipf, R. Zengerle, J. Gescher, S. Kerzenmacher
How Does the Choice of Anode Material Influence Electrical Performance? A Comparison of Two Microbial Fuel Cell Model Organisms
2014 ChemElectroChem, Band: 1, Seiten: 1849 - 1853
KurzfassungThe influence of the anode material on the electrical performance of the two microbial fuel cell model organisms Geobacter sulfurreducens and Shewanella oneidensis is investigated. High-surface-area activated carbon and low-surface-area graphite felt are compared in terms of polarization curves under quasi-steady-state conditions. Unexpectedly, G. sulfurreducens exhibits similar current densities up to 700 mAcm_2 independent of the anode material. This is ~50% higher than steady-state values reported previously. The negligible influence of electrode material on the electrical performance of G. sulfurreducens is attributed to the fact that it performs only direct electron transfer, but forms thick biofilms. In contrast, S. oneidensis, relying mainly on mediated electron transfer, apparently makes better use of high-surface-area activated carbon and achieves higher current densities compared to graphite felt. This underlines the importance of tailoring anode materials according to the used organisms.
O. Fokina, J. Eipper, L. Winandy, S. Kerzenmacher, R. Fischer
Improving the performance of a biofuel cell cathode with laccase from Pycnoporus sanguineus
2014 Bioresource Technol, Band: 175C, Seiten: 445 - 453
T. van Oordt, Y. Barb, R. Zengerle, F. von Stetten
Lamination of Polyethylene Composite Films by Ultrasonic Welding: Investigation of Peel Behavior and Identification of Optimum Welding Parameters
2014 J Appl Polym Sci, Band: 131, Seiten: 40291 - 40298
KurzfassungThe lamination of different polyethylene (PE) composite films by ultrasonic welding to fabricate peelable seals that open at defined burst pressures is investigated. The sealing time, pressure, and amplitude were varied within the range of 100–400 ms, 50– 250 kPa, and 12–24 mm, respectively. T-peel tests and electron micrographs revealed four different peel regimes, depending on the parameter combination: (I) Interlaminar peeling at low-peel strength with uniform peeling along a weakly bonded PE lamination layer; (II) transition tearing at intermediate peel strength showing areas of interlaminar peeling and translaminar tearing; (III) translaminar tearing at high-peel strength showing tears through the entire film; and, (IV) undefined tearing at varying tear strength occurring when vibration effects during welding lead to insufficient contact of the films or high pressures lead to a displacement of PE. This study will allow the systematic adjustment of ultrasonic welding parameters for PE films.
D. Liang, J. Zhang, M.T. Govindaiah, L. Tanguy, A. Ernst, R. Zengerle, P. Koltay
Liquid volume measurement method for the picoliter to nanoliter volume range based on quartz crystal microbalance technology
2014 Meas Sci Technol, Band: 25, Seite: 095302
KurzfassungIn this article, a quantitative liquid volume measurement method for the sub-nanoliter range using a quartz crystal microbalance (QCM) is described and experimentally analyzed. The primary measurement device to determine the volume of small liquid droplets is a QCM sensor coated with a surface-attached hydrogel to improve the mechanical coupling of the liquid to the sensor surface. An experimental evaluation of measured volumes in the range of 3 nl to 15 nl in normal room conditions has been performed with three identical sensors prepared with a PDMAA-1%MaBP hydrogel coating with a thickness of 1.5 µm ± 0.12 µm. A linearity of R2 more than 0.87, an average coefficient of variation (CV) within one experimental run of 5.7%, a mean absolute relative bias of 5.5%, and a sensor-to-sensor variation of 6.3% have been experimentally determined. The feasibility of this method has also been experimentally proven for the picoliter volume range down to 200 pl, with an average CV of 5.3% and a mean absolute relative bias of 6.5%. Furthermore, a stability evaluation consisting of 10 experimental series with approximately 150 measurements over the course of one week has been performed. This evaluation showed that the experimental setup, although exhibiting highly consistent performance within one measurement run, is not yet reproducible enough for long-term and repeated use because of undefined swelling and crack formation in the hydrogel layer. The low reproducibility implies a relatively high expanded uncertainty, with k = 2 according to the JCGM 'Evaluation of Measurement Data—Guide to the Expression of Uncertainty in Measurement' (GUM) for the total measurement method of approximately 3.82 nl when measuring a 10 nl liquid droplet. Nevertheless, the QCM method as described here contributes to significant progress beyond the state-of-the-art that might allow new opportunities for precise measurement of sub-nanoliter liquid volumes.
K. Mutschler, S. Dwivedi, S. Kartmann, S. Bammesberger, P. Koltay, R. Zengerle, L. Tanguy
Multi physics network simulation of a solenoid dispensing valve
2014 Mechatronics, Band: 24, Seiten: 209 - 221
Kurzfassungsignificant effects in a complete technical system. In a solenoid dispensing valve the involved physical effects are electro-magnetic (coil and magnet interaction), fluid flow and fluid structure interaction. It is challenging and time consuming to establish a full model description of these different effects even by using the most up-to-date Computational Fluid Dynamics (CFDs) software tools. This article therefore presents an alternative approach using network simulation methods for modelling of a dispensing valve using the simulation software SABER (Synopsys). To create the model, the different parts of the valve and the relevant physical effects occurring therein are described by partial differential equations and implemented as lumped elements. The lumped elements are then linked together to form a complete model of the dispensing valve including electrical, mechanical and fluid dynamic properties. A comparison with experimental data obtained from a real valve is presented at the end of the paper to discuss and validate the model. In particular the correct prediction of the dispensed liquid volume in dependence of the main parameters like pressure and opening time are considered. Using ab initio simulation deviations of the predicted dispensed liquid volume from the experimental results in the range 0.65–7.4% was found for different actuating pressures at valve opening times larger than 20 ms.
M. Salzer, S. Thiele, R. Zengerle, V. Schmidt
On the importance of FIB-SEM specific segmentation algorithms for porous media
2014 Mater Charact, Band: 95, Seiten: 36 - 43
KurzfassungA new algorithmic approach to segmentation of highly porous three dimensional image data gained by focused ion beam tomography is described which extends the key-principle of local threshold backpropagation described in [1]. The technique of focused ion beam tomography has shown to be capable of imaging the microstructure of functional materials. In order to perform a quantitative analysis on the corresponding microstructure a segmentation task needs to be performed. However, algorithmic segmentation of images obtained with focused ion beam tomography is a challenging problem for highly porous materials if filling the pore phase, e.g. with epoxy resin, is difficult. The grey intensities of individual voxels are not sufficient to determine the phase represented by them and usual thresholding methods are not applicable. We thus propose a new approach to segmentation, that pays respect to the specifics of the imaging process of focused ion beam tomography. As an application of our approach, the segmentation of three dimensional images for a cathode material used in polymer electrolyte membrane fuel cells is discussed. We show that our approach preserves significantly more of the original nanostructure than an thresholding approach.
S.K. Vashist, G. Czilwik, T. van Oordt, F. von Stetten, R. Zengerle, E.M. Schneider, J.H.T. Luong
One-step kinetics-based immunoassay for the highly-sensitive detection of C-reactive protein in less than 30 minutes
2014 Anal Biochem, Band: 456, Seiten: 32 - 37
KurzfassungThe article reveals a rapid sandwich enzyme-linked immunosorbent assay (ELISA) for the highly-sensitive detection of human C-reactive protein (CRP) in less than 30 min. It employs a one-step kinetics-based highly simplified and cost-effective sandwich ELISA procedure with minimum process steps. The procedure involves the formation of a sandwich immune complex on capture anti-human CRP antibody-bound Dynabeads® in 15 min followed by two magnet-assisted washings and one enzymatic reaction. The developed sandwich ELISA detects CRP in the dynamic range of 0.3-81 ng mL-1 with a limit of detection and analytical sensitivity of 0.4 ng mL-1 and 0.7 ng mL-1, respectively. It detects CRP spiked in diluted human whole blood and serum with high analytical precision as confirmed by conventional sandwich ELISA. Moreover, the results of the developed ELISA for the determination of CRP in the ethylenediaminetetraacetic acid (EDTA) plasma samples of patients are in good agreement with those obtained by the conventional ELISA. The developed immunoassay has immense potential for the development of rapid and cost-effective in vitro diagnostic kits.
M. Pospischil, T. Fellmeth, A. Brand, S. Nold, M. Kuchler, M. Klawitter, H. Gentischer, M. König, M. Hörteis, L. Wende, O. Doll, R. Zengerle, F. Clement, D. Biro
Optimizing fine line dispensed contact grids
2014 Energy Procedia, Band: 55, Seiten: 693 - 701
KurzfassungPrevious studies on dispensing as an alternative front side metallization process in crystalline silicon photovoltaics demonstrated, how an adaption of paste rheology allows for a precise adjustment of contact finger geometry in a wide range. In order to demonstrate the benefit of this advantage, the analytical simulation tool Gridmaster was extended to observe the effect of various geometrical parameters on solar cell results and manufacturing costs. In addition, respective geometrical parameters of thick film printed contact fingers were determined using a special in house developed tool based on MATLAB. As a result, contact geometries as achievable by means of ultrafine line dispensing are ideally suited for contacting silicon solar cells. Compared with standard fine line single screen printed finger geometries, an efficiency increase of up to Δ = 0.4%abs. as well as a reduction of manufacturing costs of 1 €ct./Wp on module level can be achieved using dispensing technology. In order to obtain suitable data, simulation results were compared with solar cell results on industrial pre-processed Cz-Si p-type wafer material applying the novel ten nozzle parallel fine line dispensing unit. Therefore, a new dispensing paste was developed combining optimum optical finger aspect ratios of ARo = 0.7 with excellent contacting behavior. A successful first test of applicability already led to a maximum cell efficiency of  = 18.7%, demonstrated on an industrial emitter with a sheet resistance of around Rsh = 90Ω/sq.
C. Köhler, M. Frei, R. Zengerle, S. Kerzenmacher
Performance Loss of a Pt-Based Implantable Glucose Fuel Cell in Simulated Tissue and Cerebrospinal Fluids
2014 ChemElectroChem, Band: 1, Seiten: 1895 - 1900
KurzfassungWe present an electrode-resolved analysis of the performance of platinum-based abiotically catalyzed glucose fuel cells in realistically simulated tissue fluid (STF) and cerebrospinal fluid (SCF). The presence of amino acids and small organic molecules at physiological concentration leads to a drastic breakdown in fuel cell voltage, resulting in a maximum lifetime of 19 h in STF or 37 h in SCF. The performance loss mainly originates from catalyst poisoning at the anode, which causes 92% or 80% of the overall fuel cell voltage loss in STF or SCF, respectively. The results underline the necessity to further investigate and improve catalyst poisoning at the anode under realistic body conditions in order to improve the lifetime of platinum- based implantable glucose fuel cells.
C. Escadafal, O. Faye, A. A. Sall, O. Faye, M. Weidmann, O. Strohmeier, F. von Stetten, J. Drexler, M. Eberhard, M. Niedrig, P. Patel
Rapid molecular assys for the detection of yellow fever virus in low-resource settings
2014 Plos Neglect Trop D, Band: 8, Nummer: 3, Seite: e2730
KurzfassungDespite the use of a safe and effective vaccine, yellow fever virus is still causing hundreds of thousands of infections and tens of thousands of deaths every year. The disease is widespread in South America and Africa where several outbreaks have occurred in the past years. As the disease is difficult to distinguish from other illnesses during its early stage, it is necessary to develop reliable, rapid and simple diagnostic methods to confirm YF cases to be able to respond effectively to outbreaks through vaccination and vector control. In this study, we describe the development a diagnostic method for YFV, using an isothermal technology called recombinase polymerase amplification which allows detection of the virus within 20 minutes, using a portable and easy-to-use device. The YFV RPA assay proved to be a specific and sensitive detection method during testing in the laboratory and under field conditions in Senegal.
O. Strohmeier, N. Marquart, D. Mark, G. Roth, R. Zengerle, F. von Stetten
Real-time PCR based detection of a panel of foodborne pathogens on a centrifugal microfluidic “LabDisk” with on-disk quality controls and standards for quantification
2014 Anal Methods-uk, Band: 6, Seiten: 2038 - 2046
M. Rombach, D. Kosse, B. Faltin, S. Wadle, G. Roth, R. Zengerle, F. von Stetten
Real-time stability testing of air-dried primers and fluorogenic hydrolysis probes stabilized by trehalose and xanthan
2014 Biotechniques, Band: 57, Nummer: 3, Seiten: 151 - 155
KurzfassungA method for conserving primers and differently labeled fluorogenic hydrolysis (i.e., TaqMan) probes at ambient conditions is presented. Primers and hydrolysis probes with four different fluorophore-quencher combinations (6- FAM–BHQ1, HEX–BHQ1, ROX–BHQ650, and Cy5–BHQ2) were mixed with trehalose and xanthan at final concentrations of 56 mM and 2.78 mM, respectively. Mixtures were air-dried at 23°C for 30 min on strips composed of cyclo olefin polymer (COP), a material widely used in the manufacturing of in vitro diagnostic (IVD) test carriers. After one year of storage, the functionality of the primers and fluorophore-quencher combinations was validated by real-time polymerase chain reaction (real-time PCR), confirming their stability when stored in the presence of stabilizers, with the best results achieved using trehalose. This approach could be of great benefit for manufacturing IVD systems, for example, for genotyping applications based on multiplexing using different fluorescent dyes.
S. K. Vashist, E.M. Schneider, J.H.T. Luong
Surface plasmon resonance-based immunoassay for human fetuin A
2014 Analyst, Band: 139, Seiten: 2237 - 2242
KurzfassungThis article describes a highly-sensitive surface plasmon resonance (SPR)-based immunoassay (IA) for human fetuin A (HFA), a specific biomarker for atherosclerosis and hepatocellular carcinoma. The assay is based on a novel immobilization procedure that simply involves the dilution of an anti-HFA capture antibody (Ab) in 1% (v/v) 3-aminopropyltriethoxysilane (APTES), followed by its dispensing on a KOH-treated gold (Au)-coated SPR chip and incubation for 30 min. The developed SPR IA detected 0.3-20 ng mL(-1) of HFA with a limit of detection and sensitivity of 0.7 ng mL(-1) and 1 ng mL(-1), respectively. The highly-simplified Ab immobilization procedure is also 5-fold more rapid than conventional procedures. It leads to the leach-proof binding of the capture Ab, which means that the developed SPR IA is highly cost-effective, as the Ab-bound SPR chip could be reused for many repeated HFA IAs after regeneration with 10 mM glycine-HCl, pH 2.0. The Ab-bound SPR chip, stored at 4 °C, lost only 18% of its original activity after 4 months. For the detection of HFA spiked in diluted human whole blood and plasma, the results obtained by the developed SPR IA agreed well with the commercial HFA sandwich ELISA.
A. Kloke, A. R. Fiebach, S. Zhang, L. Drechsel, S. Niekrawietz, M. Hoehl, R. Kneusel, K. Panthel, J. Steigert, F. von Stetten, R. Zengerle, N. Paust
The LabTube – A novel microfluidic platform for assay automation in laboratory centrifuges
2014 Lab Chip, Band: 14, Seiten: 1527 - 1537
KurzfassungAssay automation is the key for successful transformation of modern biotechnology into routine workflows. Yet, it requires considerable investment in processing devices and auxiliary infrastructure, which is not cost-efficient for laboratories with low or medium sample throughput or point-of-care testing. To close this gap, we present the LabTube platform, which is based on assay specific disposable cartridges for processing in laboratory centrifuges. LabTube cartridges comprise interfaces for sample loading and downstream applications and fluidic unit operations for release of prestored reagents, mixing, and solid phase extraction. Process control is achieved by a centrifugally-actuated ballpen mechanism. To demonstrate the workflow and functionality of the LabTube platform, we show two LabTube automated sample preparation assays from laboratory routine: DNA extractions from whole blood and purification of His-tagged proteins. Equal DNA and protein yield were observed compared to manual reference runs, while LabTube automation could significantly reduce the hands-ontime to one minute per extraction.
L. Zielke, T. Hutzenlaub, D. R. Wheeler, C.-W. Chao, I. Manke, A. Hilger, N. Paust, R. Zengerle, S. Thiele
Three-Phase Multiscale Modeling of a LiCoO 2 Cathode: Combining the Advantages of FIB–SEM Imaging and X-Ray Tomography
2014 Adv Energy Mater, Band: 5, Seite: 1401612
KurzfassungLiCoO 2 electrodes contain three phases, or domains, each having specific-intended functions: ion-conducting pore space, lithium-ion-reacting active material, and electron conducting carbon-binder domain (CBD). Transport processes take place in all domains on different characteristic length scales: from the micrometer scale in the active material grains through to the nanopores in the carbon-binder phase. Consequently, more than one imaging approach must be utilized to obtain a hierarchical geometric representation of the electrode. An approach incorporating information from the micro- and nanoscale to calculate 3D transport-relevant properties in a largereconstructed active domain is presented. Advantages of focused ion beam/ scanning electron microscopy imaging and X-ray tomography combined by a spatial stochastic model, validated with an artifi cially produced reference structure are used. This novel approach leads to signifi cantly different transport relevant properties compared with previous tomographic approaches: nanoporosity of the CBD leads to up to 42% additional contact area between active material and pore space and increases ionic conduction by a factor of up to 3.6. The results show that nanoporosity within the CBD cannot be neglected.
T. Hutzenlaub, S. Thiele, N. Paust, R. Spotnitz, R. Zengerle, C. Walchshofer
Three-dimensional electrochemical Li-ion battery modelling featuring a focused ion-beam/scanning electron microscopy based three-phase reconstruction of a LiCoO2 cathode
2014 Electrochim Acta, Band: 115, Seiten: 131 - 139
KurzfassungWe combine a three-phase, three-dimensional reconstruction of a LiCoO2battery cathode based onfocused ion-beam/scanning electron microscopy (FIB/SEM) imaging with an electrochemical model. Themodel considers the electric potential and lithium/salt concentration distribution in both the liquid elec-trolyte and the solid active-material phases. In contrast to previously presented models, we spatiallyresolve the carbon-binder phase to provide a more realistic description of the electric potential. Weobserve that carbon-binder coverage of the solid electrolyte interface (SEI) impedes local surface reac-tions and thus affects lithium redistribution. For the considered cathode, the total surface to volumeratio of the SEI is reduced from 11.2 × 105to 6.5 × 105m2m−3when the carbon-binder phase is modelledexplicitly. This leads to increased inhomogeneity of the lithium concentration in active-material grainsduring charging.Additionally, we study lithium/salt concentration in the electrolyte, revealing gradients between 0.9and 1.5 kmol m−3depending on the distance to the separator. This is significant because the lithium/saltconcentration directly affects the ion transport properties of the electrolyte.
T. S. Santisteban, R. Zengerle, M. Meier
Through-holes, cavities and perforations in polydimethylsiloxane (PDMS) chips
2014 Rsc Adv, Band: 4, Seiten: 48012 - 48016
KurzfassungWe present a method to fabricate through-holes between 10 to 180 µm between polydimethylsiloxane (PDMS) layers of microfluidic large-scale integration platforms. Therefore we employed standard PDMS spin-coating processes onto silicon molds with microstructures formed from SU-8 and AZ photoresists. Our approach is based on the modification of the surface polarity of the PDMS prototyping molds by a 250 nm thick layer of octafluorocyclobutane (C4F8), which resulted in a contact angle of 125 ± 3 degrees for water. This super hydrophobic surface repelled PDMS from microstructures protruding out of the spin coated PDMS layer. Subsequently, we applied and characterized the C4F8 coating for the robust fabrication of interlayer connectors between PDMS membranes of 40 µm thickness. To enable embedding of through-holes, perforations and/or cavities in very thin layers of PDMS (<20 µm) we mixed PDMS with inert silicone oil to reduce its viscosity. In difference to previous attempts to lower the viscosity of PDMS using organic solvents, the silicone oil cross-linked to PDMS and was thus, unable to freely diffuse into the polymerized PDMS. This reduces the risk for bleeding of hazardous components in biological applications. Finally, we manufactured a three layer mLSI chip with integrated cavities for catching fluorescently labeled beads and cells. The presented process parameters can easily be adapted to specific needs in fabrication of multi-layer PDMS arrangements by following the systematic parameter screening.
L. Zielke, A. Fallisch, N. Paust, R. Zengerle, S. Thiele
Tomography based screening of flow field / current collector combinations for PEM water electrolysis
2014 Rsc Adv, Band: 4, Seiten: 58888 - 58894
KurzfassungCurrent collectors in PEM water electrolysis perform several functions that influence overall performance. These include conducting heat and electrons, as well as transporting water and gas. X-ray tomography, standardized reconstruction, and calculation methods are used to compare the morphological and transport parameters of eight different current collectors functioning as flow fields for PEM water electrolysis. We find simple exponential relations between through-plane thermal conductivity l and porosity p (l20 C(p) ¼ 1749p 1.306 4.420), as well as between through-plane electrical conductivity s and water permeability K (s(K) ¼ 10 6 K 0.6376). In addition, we use both local and global concepts to investigate the pore space of current collectors. We hereby investigate homogeneity and characteristic sizes, like mean pore diameter or mean distance between solid parts at the catalytic interface. Moreover, we find that the local concept of mean chord lengths can be used to explain electrical and thermal conductivity anisotropies. These chords can be used to predict the direction of the largest conductivity for fibrous current collectors.
S. Sané, K. Richter, S. Rubenwolf, N. J. Matschke, C. Jolivalt, C. Madzak, R. Zengerle, J. Gescher, S. Kerzenmacher
Using planktonic microorganisms to supply the unpurified multi-copper oxidases laccase and copper efflux oxidases at a biofuel cell cathode
2014 Bioresource Technol, Band: 158, Seiten: 231 - 238
KurzfassungThe feasibility to apply crude culture supernatants that contain the multicopper oxidases laccase or copper efflux oxidase (CueO) as oxygen reducing catalysts in a biofuel cell cathode is shown. As enzyme-secreting recombinant planktonic microorganisms, the yeast Yarrowia lipolytica and the bacterium Escherichia coli were investigated. The cultivation and operation conditions (choice of medium, pH) had distinct effects on the electro-catalytic performance. The highest current density of 119 ± 23 μAcm-2 at 0.400 V vs. NHE was obtained with the crude culture supernatant of E. coli cells overexpressing CueO and tested at pH 5.0. In comparison, at pH 7.4 the electrode potential at 100 μAcm-2 is 0.25 V lower. Laccase-containing supernatants of Y. lipolytica yielded a maximum current density of 6.7 ± 0.4 μAcm-2 at 0.644 V vs. NHE. These results open future possibilities to circumvent elaborate enzyme purification procedures and realize cost effective and easy-to-operate enzymatic biofuel cells.

2013

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S. Bammesberger, S. Kartmann, L. Tanguy, D. Liang, K. Mutschler, A. Ernst, R. Zengerle, P. Koltay
A Low-Cost, Normally Closed, Solenoid Valve for Non-Contact Dispensing in the Sub-μL Range
2013 Micromachines, Band: 4, Seiten: 9 - 21
KurzfassungWe present a disposable, normally closed, non-contact dispensing valve for the sub-μL range. The miniaturized solenoid valve (diameter: 8 mm, height: 27.25 mm) is compatible to standard Luer-Lock interfaces. A highly dynamic actuation principle enables opening times down to 1 ms. The dispensing performance was evaluated for water (η = 1.03 mPas) and a 66% (w/w) glycerol/water solution (η = 16.98 mPas), at pressures varying from 200 to 800 mbar. The experimentally determined minimal dispensing volume was 163 nL (CV 1.6%) for water and 123 nL (CV 4.5%) for 66% (w/w) glycerol/water. The low-cost polymer valve enables high precision dispensing of liquid volumes down to the lower end of the sub-μL range comparable to high-end non-disposable micro-dispensing valves.
S. Bammesberger, I. Malki, A. Ernst, R. Zengerle, P. Koltay
A calibration-free, noncontact, disposable liquid dispensing cartridge featuring an online process control
2013 Journal of Laboratory Automation, Band: 27, Seiten: 394 - 402
KurzfassungWe present a noncontact liquid dispenser that uses a disposable cartridge for the calibration-free dosage of diverse biochemical reagents from the nanoliter to the microliter range. The dispensing system combines the advantages of a positive displacement syringe pump (responsible for defining the aliquot’s volume with high accuracy) with a highly dynamic noncontact dispenser (providing kinetic energy to detach the liquid from the tip). The disposable, noncontact dispensing cartridge system renders elaborate washing procedures of tips obsolete. A noncontact sensor monitors the dispensing process to enable an online process control. To further increase confidence and reliability for particularly critical biomedical applications, an optional closed-loop control prevents malfunctions. The dispensing performance was characterized experimentally in the range of 0.25 to 10.0 µL using liquids of different rheological properties (viscosity 1.03–16.98 mPas, surface tension 30.49–70.83 mN/m) without adjusting or calibrating the actuation parameters. The precision ranged between a coefficient of variation of 0.5% and 5.3%, and the accuracy was below ±10%. The presented technology has the potential to contribute significantly to the improvement of biochemical liquid handling for laboratory automation in terms of usability, miniaturization, cost reduction, and safety.
Y. Abbas, J. Miwa, R. Zengerle, F. von Stetten
Active Continuous-Flow Micromixer Using an External Braille Pin Actuator Array
2013 Micromachines, Band: 4, Seiten: 80 - 89
KurzfassungWe present a continuous-flow active micromixer based on channel-wall deflection in a polydimethylsiloxane (PDMS) chip for volume flows in the range up to 2 μL s−1 which is intended as a novel unit operation for the microfluidic Braille pin actuated platform. The chip design comprises a main microchannel connected to a series of side channels with dead ends aligned on the Braille pins. Computer-controlled deflection of the side-channel walls induces chaotic advection in the main-channel, which substantially accelerates mixing in low-Reynolds number flow. Sufficient mixing (mixing index MI below 0.1) of volume flows up to 0.5 μL s−1 could be achieved within residence times ~500 ms in the micromixer. As an application, continuous dilution of a yeast cell sample by a ratio down to 1:10 was successfully demonstrated. The mixer is intended to serve as a component of bio-analytical devices or as a unit operation in the microfluidic Braille pin actuated platform.
S. Spieth, A. Schumacher, F. Trenkle, O. Brett, K. Seidl, S. Herwik, S. Kisban, P. Ruther, O. Paul, A. A. Aarts, H. P. Neves, P. D. Rich, D. E. Theobald, T. Holtzman, J. W. Dalley, B.-E. Verhoef, P. Janssen, R. Zengerle
Approaches for drug delivery with intracortical probes
2013 Biomed Eng Online, Band: 59, Nummer: 4, Seiten: 291 - 303
KurzfassungIntracortical microprobes allow the precise monitoring of electrical and chemical signaling and are widely used in neuroscience. Microelectromechanical system (MEMS) technologies have greatly enhanced the integration of multifunctional probes by facilitating the combination of multiple recording electrodes and drug delivery channels in a single probe. Depending on the neuroscientific application, various assembly strategies are required in addition to the microprobe fabrication itself. This paper summarizes recent advances in the fabrication and assembly of micromachined silicon probes for drug delivery achieved within the EU-funded research project NeuroProbes. The described fabrication process combines a two-wafer silicon bonding process with deep reactive ion etching, wafer grinding, and thin film patterning and offers a maximum in design flexibility. By applying this process, three general comb-like microprobe designs featuring up to four 8-mm-long shafts, cross sections from 150×200 to 250×250 µm², and different electrode and fluidic channel configurations are realized. Furthermore, we discuss the development and application of different probe assemblies for acute, semichronic, and chronic applications, including comb and array assemblies, floating microprobe arrays, as well as the complete drug delivery system NeuroMedicator for small animal research.
N. Wangler, M. Welsche, M. Blazek, M. Blessing, M. Vervliet-Scheebaum, R. Reski, C. Müller, H. Reinecke, J. Steigert, G. Roth, R. Zengerle, N. Paust
Bubble Jet agent release cartridge for chemical single cell stimulation
2013 Biomed Microdevices, Band: 15, Seiten: 1 - 8
KurzfassungWe present a new method for the distinct specific chemical stimulation of single cells and small cell clusters within their natural environment. By single-drop release of chemical agents with droplets in size of typical cell diameters (d <30 μm) on-demand micro gradients can be generated for the specific manipulation of single cells. A single channel and a double channel agent release cartridge with integrated fluidic structures and integrated agent reservoirs are shown, tested, and compared in this publication. The single channel setup features a fluidic structure fabricated by anisotropic etching of silicon. To allow for simultaneous release of different agents even though maintaining the same device size, the second type comprises a double channel fluidic structure, fabricated by photolithographic patterning of TMMF. Dispensed droplet volumes are V015 pl and V0 10 pl for the silicon and the TMMF based setups, respectively. Utilizing the agent release cartridges, the application in biological assays was demonstrated by hormone-stimulated premature bud formation in Physcomitrella patens and the individual staining of one single L 929 cell within a confluent grown cell culture.
O. Strohmeier, A. Emperle, G. Roth, D. Mark, R. Zengerle, F. von Stetten
Centrifugal gas-phase transition magnetophoresis (GTM) – a generic method for automation of magnetic bead based assays on the centrifugal microfluidic platform and application to DNA purification
2013 Lab Chip (Lab On A Chip) 2013, Band: 13, Seiten: 146 - 155
KurzfassungTransportation of magnetic beads between different reagents plays a crucial role in many biological assays e.g. for purification of biomolecules or cells where the beads act as a mobile solid support. Therefore, usually a complex set-up either for fluidic processing or for manipulation of magnetic beads is required. To circumvent these drawbacks, we present a facile and automated method for the transportation of magnetic beads between multiple microfluidic chambers on a centrifugal microfluidic cartridge ‘‘LabDisk’’. The method excels by requiring only one stack of stationary permanent magnets, a specific microfluidic layout without actively controlled valves and a predefined frequency protocol for rotation of the LabDisk. Magnetic beads were transported through three fluidically separated chambers with a yield of 82.6% ¡ 3.6%. Bead based DNA purification from a dilution series of a Listeria innocua lysate and from a lambda phage DNA standard was demonstrated where the three chambers were used for binding, washing and elution of DNA. Recovery of L. innocua DNA was up to 68% ¡ 24% and for lambda phage DNA 43% ¡ 10% compared to manual reference purification in test tubes. Complete purification was conducted automatically within 12.5 min. Since all reagents can be preloaded onto the LabDisk prior to purification, no further hands-on steps are required during processing. Due to its modular and generic character, the presented method could also be adapted to other magnetic bead based assays e.g. to immunoassays or protein affinity purification, solely requiring the adjustment of number and volumes of the fluidic chambers.
D. Mark, F. von Stetten, R. Zengerle
Chips with everything: microfluidics and diagnostics
2013 Medical Device Developments
N. Lass, L. Riegger, R. Zengerle, P. Koltay
Enhanced Liquid Metal Micro Droplet Generation by Pneumatic Actuation Based on the StarJet Method
2013 Micromachines, Band: 4, Seiten: 49 - 66
KurzfassungWe present a novel pneumatic actuation system for generation of liquid metal droplets according to the so-called StarJet method. In contrast to our previous work, the performance of the device has been significantly improved: the maximum droplet generation frequency in continuous mode has been increased to fmax = 11 kHz (formerly fmax = 4 kHz). In addition, the droplet diameter has been reduced to 60 μm. Therefore, a new fabrication process for the silicon nozzle chips has been developed enabling the production of smaller nozzle chips with higher surface quality. The size of the metal reservoir has been increased to hold up to 22 mL liquid metal and the performance and durability of the actuator has been improved by using stainless steel and a second pneumatic connection to control the sheath flow. Experimental results are presented regarding the characterization of the droplet generation, as well as printed metal structures.
T. Hutzenlaub, A. Asthana, J. Becker, R. Wheeler, R. Zengerle, S. Thiele
FIB/SEM-based calculation of tortuosity in a porous LiCoO2 cathode for a Li-ion battery
2013 Electrochem Commun, Band: 27, Seiten: 77 - 80
KurzfassungWe present a new method to quantify tortuosity in the porous, LiCoO2 cathode of a Li-ion battery. The starting point is a previously published 3D reconstruction from FIB/SEM images with three phases, the active material domain, carbon-binder domain and pore space. Based on this geometrical configuration, we compute effective diffusivities, from which we in turn derive tortuosity values for the pore space ranging between 5 and 11.6 for the three spatial directions. In a next step, we compare our approach to an imaging method that employs back-filling material. These methods do not differentiate between the carbon-binder domain and the pore space. Thus we remove the carbon-binder domain from our 3D reconstruction and add its volume to the pore space. As a result of this procedure, the tortuosity is greatly reduced to values between 1.5 and 1.9. Experiments suggest that both results for tortuosity are inaccurate and that the real values lie somewhere between these parameter sets. Hence, based on experimental data, we propose a nanoporous carbon-binder domain and derive intermediate tortuosity values between 4.2 and 6.1. These values are consistent with experimental values for similar Li-ion cathodes reported previously.
A. Kloke, C. Köhler, A. Dryzga, R. Gerwig, K. Schumann, M. Ade, R. Zengerle, S. Kerzenmacher
Fabrication of Highly Porous Platinum by Cyclic Electrodeposition of PtCu Alloys: How do Process Parameters Affect Morphology?
2013 J Electrochem Soc, Band: 160, Nummer: 2, Seiten: D111 - D118
KurzfassungIn this work we analyze the influence of process parameters on the morphology of highly porous platinum electrodes, fabricated by co-deposition of platinum-copper alloy and subsequent selective dissolution of the less noble copper during multiple cyclic voltammetry scans. Thereto the Cu2+ concentration in the deposition electrolyte, the negative scan limit, and the scan rate were varied. Corresponding electrodes were characterized by their surface texture (scanning electron microscopy, X-ray diffractometry), specific surface area, and elemental compositions (X-ray photoelectron spectroscopy and energy dispersive X-ray spectroscopy). Under conditions enforcing precursor depletion a sphere-dominated structure is observed, whereas oppositional configurations lead to smoother, mud-crack pattern like structures. Electrodes of high specific surface area are obtained particularly when high copper ion concentrations (100 mmol l−1 CuSO4, roughness factor 3740 ± 270), high negative scan limits (−0.800 V vs. SCE, roughness factor 3790 ± 370) and low scan speeds (1 mV s−1, roughness factor 3930 ± 370) compared to standard parameters (20 mmol l−1 CuSO4, −0.600 V vs. SCE negative scan limit, 1 mV s−1, roughness factor 3040 ± 300) were applied during fabrication. Since the fabrication of these highly rough electrodes requires the deposition of high amounts of platinum (10–20 mg per cm2 footprint area) it is mainly relevant to applications such as neurostimulation electrodes or implantable glucose fuel cells in which platinum costs are less relevant than electrode properties and functionality.
C. Köhler, A. Kloke, A. Drzyzga, R. Zengerle, S. Kerzenmacher
Fabrication of highly porous platinum electrodes for micro-scale applications by pulsed electrodeposition and dealloying
2013 Journal of Power Sources, Band: 242, Seiten: 255 - 263
KurzfassungWe present the implementation and optimization of a novel electrodeposition method for the fabrication of highly porous platinum electrodes. It is based on the co-deposition of platinum and copper and the selective dealloying of copper in a pulsed manner. The new process yields mechanically stable platinum electrodes with roughness factors of up to RF = 6500 ± 700, compared to the state-of-the-art cyclic electrodeposition method this corresponds to an improvement in RF by 111 %. Furthermore the time demand for fabrication is reduced by 59 %, whereas the platinum utilization is increased by 53 %. The method is particularly advantageous for applications such as micro fuel cells since it enables the precise deposition of catalytically active electrodes on micro-structured conductive areas. In this context the novel platinum electrodes show higher current densities for the oxidation of formic acid and glucose than state-of-the-art electrodes. In terms of methanol oxidation their catalytic activity is comparable to commercial direct methanol fuel cell (DMFC) electrodes, fabricated from Pt-Ru nanoparticles dispersed on carbon black.
T. Hutzenlaub, J. Becker, R. Zengerle, S. Thiele
How Coarsening the 3D Reconstruction of a Porous Material Influences Diffusivity and Conductivity Values
2013 ECS Electrochemistry Letters, Band: 2, Seiten: F14 - F17
KurzfassungCoarsening the resolution of a 3D reconstruction is a common approach to make simulations feasible with regard to computational resources. We coarsen the reconstruction of a PEMFC cathode catalyst layer and investigate how this influences parameters such as diffusivity and conductivity. This is also an indication of how trustworthy these parameters are in the first place, because imaging itself is a coarsened representation of the real morphology. While diffusivity remains approximately constant due to the opposing behavior of bulk and Knudsen diffusivity, conductivity is strongly affected. The method introduced here is transferable to evaluate 3D reconstructions of other porous materials.
T. Brettschneider, C. Dorrer, D. Czurratis, R. Zengerle, M. Daub
Laser micromachining as a metallization tool for microfluidic polymer stacks
2013 J Micromech Microeng, Band: 23, Seiten: 035020 - 035030
KurzfassungA novel assembly approach for the integration of metal structures into polymeric microfluidic systems is described. The presented production process is completely based on a single solid-state laser source, which is used to incorporate metal foils into a polymeric multi-layer stack by laser bonding and ablation processes. Chemical reagents or glues are not required. The polymer stack contains a flexible membrane which can be used for realizing microfluidic valves and pumps. The metal-to-polymer bond was investigated for different metal foils and plasma treatments, yielding a maximum peel strength of Rps = 1.33N mm−1. A minimum structure size of 10 μm was determined by 3D microscopy of the laser cut line. As an example application, two different metal foils were used in combination to micromachine a standardized type-T thermocouple on a polymer substrate. An additional laser process was developed which allows metal-to-metal welding in close vicinity to the polymer substrate. With this process step, the reliability of the electrical contact could be increased to survive at least 400 PCR temperature cycles at very low contact resistances.
C. Cupelli, T. Borchardt, T. Steiner, N. Paust, R. Zengerle, M. Santer
Leukocyte enrichment based on a modified pinched flow fractionation approach
2013 Microfluid Nanofluid, Band: 14, Nummer: 3-4, Seiten: 551 - 563
KurzfassungIn this paper, a simple and robust design for a passive hydrodynamic cell sorter based on pinched flow-field fractionation is presented and analyzed. Two principal layouts of the sorter are discussed and investigated experimentally as well as numerically based on the dissipative particle dynamics (DPD) method. Experimentally, design 1 approximately sorts 87 % of the erythrocytes to their designated outlet, while 100 % of the leukocytes branch correctly. This also holds for design 2 differing merely in the direction of the outlet for erythrocytes, but here only 69 % of the red blood cells are redirected to the designated outlet. This behavior can be elucidated by employing DPD simulations, where erythrocytes advected with the flow are modeled explicitly. Our results suggest that if a cell sorter is designed to operate at high throughput, its layout may not entirely rely on commonly assumed idealizing conditions, because cells cannot be considered as point-like, isolated objects following definite stream lines. Hydrodynamic forces originating from the cells as extended objects must be taken into account.
T. van Oordt, Y. Barb, J. Smetana, R. Zengerle, F. von Stetten
Miniature stick-packaging – an industrial technology for pre-storage and release of reagents in lab-on-a-chip systems
2013 Lab Chip, Band: 13, Nummer: 15, Seiten: 2888 - 2892
KurzfassungStick-packaging of goods in tubular-shaped composite-foil pouches has become a popular technology for food and drug packaging. We miniaturized stick-packaging for use in lab-on-a-chip (LOAC) systems to prestore and on-demand release the liquid and dry reagents in a volume range of 80–500 ml. An integrated frangible seal enables the pressure-controlled release of reagents and simplifies the layout of LOAC systems, thereby making the package a functional microfluidic release unit. The frangible seal is adjusted to defined burst pressures ranging from 20 to 140 kPa. The applied ultrasonic welding process allows the packaging of temperature sensitive reagents. Stick-packs have been successfully tested applying recovery tests (where 99% (STDV = 1%) of 250 ml pre-stored liquid is released), long-term storage tests (where there is loss of only ,0.5% for simulated 2 years) and air transport simulation tests. The developed technology enables the storage of a combination of liquid and dry reagents. It is a scalable technology suitable for rapid prototyping and low-cost mass production.
D. Trebbels, A. Kern, F. Fellhauer, C. Huebner, R. Zengerle
Miniaturized FPGA-Based High-Resolution Time-Domain Reflectometer
2013 Ieee, Band: 62, Nummer: 7, Seiten: 2101 - 2113
KurzfassungTime-domain reflectometry (TDR) is a well-known measurement principle for evaluating frequency-dependent electric and dielectric properties of various materials and substances. Although TDR is a proven method, the high price for TDR measurement equipment and complex laboratory setups is often a limiting factor for cost-sensitive applications or large-scale field experiments, where a large number of TDR meters is required. This paper reports on the development of a new miniaturized low-cost TDR meter capable of sampling a repetitive rectangular waveform, which is used as an excitation signal. The developed sampling circuit is based on a digital delta modulator (DM) and allows for capturing the waveform of a repetitive measurement signal. A 1-MHz signal can be captured with a virtual sampling resolution of 1 ps within a measurement interval of 1 s. The generated pulses have a rise time of 2 ns and can be captured with an amplitude resolution of approximately 10 bit and an accuracy of approximately 8 bit. The developed digital DM architecture is implemented inside a small field programmable gate array and integrated into a miniaturized low-power TDR meter prototype for battery-powered outdoor applications. The captured measurement data are stored on integrated micro-SD card memory and can be read out either via a Universal Serial Bus, an RS-485 bus system, or a wireless interface. The TDR meter is controlled by an integrated microcontroller and a real-time clock and therefore can operate completely independent from any additional control setup. The TDR meter targets applications within the field of geoscience and agricultural monitoring, where large-scale measurement systems are required.
N. Losleben, J. Spinke, S. Adler, N. Oranth, R. Zengerle
Model fluids representing aqueous in-vitro diagnostic reagents for the development of dispensing systems
2013 Drug Discov Today, Seiten: 1035 - 1042
KurzfassungAnalyzers for in-vitro diagnostic (IVD) testing facilitate the determination of medical information from biological samples. To reach a high quality, the detection reagents have to be dispensed with a high degree of precision and accuracy. A technology change from conventional pipetting systems to contactfree dispensers provides the opportunity to reduce carry-over and handle reagents in the microliter range. A great challenge for the development and validation of new systems is the huge variety of the IVD reagents. This work presents the fluidic properties of 646 different aqueous IVD reagents and how they can be represented by a set of easy-to-prepare model fluids, covering the rheological range of the reagents. In addition, based on the model fluids, a standardized approach is presented for the evaluation of dispensers for IVD applications.
T. Hutzenlaub, J. Becker, R. Zengerle, S. Thiele
Modelling the water distribution within a hydrophilic and hydrophobic 3D reconstructed cathode catalyst layer of a proton exchange membrane fuel cell
2013 J Power Sources, Band: 227, Seiten: 260 - 266
KurzfassungWe reconstruct a section of the cathode catalyst layer (CCL) of a Gore PEMFC membrane electrode assembly three-dimensionally with nanometre scale resolution. Subsequently, we present a new modelling method to fill the pore space of this matrix stepwise with water, enabling the description of varying saturation conditions of the CCL. The method is based on a 3D pore size distribution and enables to differentiate between a hydrophilic and a hydrophobic CCL. It utilizes a sequence to fill the pores according to their size, going from small to large (hydrophilic) or vice versa (hydrophobic), until a predefined value of water saturation is reached. We compare both cases by calculating an effective diffusivity for oxygen in nitrogen in all spatial directions. Both the hydrophilic and the hydrophobic case display a similar ability to transport oxygen up to approximately 50% water saturation of the pore space. At higher water saturation, we calculate larger diffusivity values for the hydrophobic case. Finally, we calculate the specific reaction surface area that is accessible from the gas diffusion layer via unfilled pores for all water saturation conditions. At 50% saturation, the hydrophobic case displays a twenty times larger reaction surface area than the hydrophilic case.
O. Strohmeier, S. Laßmann, B. Riedel, D. Mark, G. Roth, M. Werner, R. Zengerle, F. von Stetten
Multiplex genotyping of KRAS point mutations in tumor cell DNA by allele-specific real-time PCR on a centrifugal microfluidic disk segment
2013 Microchim Acta, Band: 181, Seiten: 1681 - 1688
KurzfassungPoint Mutations on the Kirsten rat sarcoma viral oncogene homolog (KRAS) have been identified as an important predictive biomarker for response to cancer therapy targeting the epidermal growth factor receptor. KRAS mutations are prevalent in up to 40 % of all colorectal carcinomas, and routinely conducted KRAS genotyping is becoming mandatory to predict therapy success and to reduce therapy costs. We report a low-cost, disposable and ready-to-use centrifugal microfluidic cartridge (termed GeneSlice) containing preloaded primers and probes. The GeneSlice cartridge enables the parallel detection of the seven most relevant KRAS point mutations by allele-specific real-time PCR. It represents a cost effective alternative to dideoxy-sequencing with a faster time-to-result (~ 2 h versus up to 20 h in case of dd-sequencing). Microfluidic processing of the GeneSlice along with allele-specific amplification and real-time detection are conducted in a slightly modified, commercially available PCR thermocycler. Intra-chip standard deviation of Cq values on the GeneSlices is negligible (GeneSlice 1: Cq,std.dev. = 0.13; GeneSlice 2: Cq,std.dev = 0.26). In 23 of 24 experiments, the data for genotyping 6 cancer cell lines (n = 4 per cell line) agreed with dd-sequencing. Additionally, DNA derived from microdissected formalin-fixed and paraffin embedded colorectal carcinomas of two cases was genotyped correctly and reproducibly (n = 3 per patient; one GeneSlice excluded from evaluation). The GeneSlice therefore clearly demonstrated the potential to become a valuable tool for routine diagnostics of KRAS mutations by reducing costs and hands-on time.
S. Thiele, T. Fürstenhaupt, D. Banham, T. Hutzenlaub, V. Birss, C. Ziegler, R. Zengerle
Multiscale tomography of nanoporous carbon-supported noble metal catalyst layers
2013 J Power Sources, Band: 228, Seiten: 185 - 192
KurzfassungNoble metal catalysts are a scarce, non-renewable resource, and yet are required in a wide range of industrial applications, including in polymer electrolyte membrane fuel cells (PEMFCs). The effectiveness of PEMFCs depends not only on the size, active surface area, and distribution of the Pt catalyst nanoparticles, which affects reaction kinetics, but also on the porous structure of the carbon support, which affects mass transport. Unfortunately, the very different size scales – several nm for the Pt catalyst vs. several μm for the porosity features – cannot be characterized by a single method. Here, we present a novel approach for integrating information from both of these size scales to build a single geometrical model. Focused Ion Beam – Scanning Electron Microscope tomography (SEMt) was carried out on a commercial PEMFC cathode catalyst layer to characterize porosity, connectivity as well as pore-size and grain-size distribution. Transmission Electron Microscopy tomography (TEMt) was used to analyze volume and surface area distributions of nanometer sized platinum catalyst particles. Further, we propose an up-scaling approach to translate the information obtained from TEMt to SEMt. Knowledge of catalyst particle locations within the solid support matrix will be critical in enabling the analysis of limiting transport processes in PEMFC CCLs.
D. Liang, C. Steinert, S. Bammesberger, L. Tanguy, A. Ernst, R. Zengerle, P. Koltay
Novel gravimetric measurement technique for quantitative volume calibration in the sub-microliter range
2013 Meas Sci Technol, Band: 24, Seiten: 025301 - 025311
KurzfassungWe present a novel measurement method based on the gravimetric principles adapted from the ASTM E542 and ISO 4787 standards for quantitative volume determination in the sub-microliter range. Such a method is particularly important for the calibration of non-contact micro dispensers as well as other microfluidic devices. The novel method is based on the linear regression analysis of continuously monitored gravimetric results and therefore is referred to as ‘gravimetric regression method (GRM)’. In this context, the regression analysis is necessary to compensate the mass loss due to evaporation that is significant for very small dispensing volumes. A full assessment of the measurement uncertainty of GRM is presented and results in a standard measurement uncertainty around 6 nl for dosage volumes in the range from 40 nl to 1 μl. The GRM has been experimentally benchmarked with a dual-dye ratiometric photometric method (Artel Inc., Westbrook, ME, USA), which can provide traceability of measurement to the International System of Units (SI) through reference standards maintained by NIST. Good precision (max. CV = 2.8%) and consistency (bias around 7 nl in the volume range from 40 to 400 nl) have been observed comparing the two methods. Based on the ASTM and ISO standards on the one hand and the benchmark with the photometric method on the other hand, two different approaches for establishing traceability for the GRM are discussed.
S. Sané, C. Jolivalt, G. Mittler, P. Nielsen, S. Rubenwolf, R. Zengerle, S. Kerzenmacher
Overcoming Bottlenecks of Enzymatic Biofuel Cell Cathodes: Crude Fungal Culture Supernatant Can Help to Extend Lifetime and Reduce Cost
2013 ChemSusChem, Band: 6, Nummer: 7, Seiten: 1209 - 1215
KurzfassungEnzymatic biofuel cells (BFCs) show great potential for the direct conversion of biochemically stored energy from renewable biomass resources into electricity. However, enzyme purification is time-consuming and expensive. Furthermore, the long-term use of enzymatic BFCs is hindered by enzyme degradation, which limits their lifetime to only a few weeks. We show, for the first time, that crude culture supernatant from enzyme-secreting microorganisms (Trametes versicolor) can be used without further treatment to supply the enzyme laccase to the cathode of a mediatorless BFC. Polarization curves show that there is no significant difference in the cathode performance when using crude supernatant that contains laccase compared to purified laccase in culture medium or buffer solution. Furthermore, we demonstrate that the oxygen reduction activity of this enzymatic cathode can be sustained over a period of at least 120 days by periodic resupply of crude culture supernatant. This is more than five times longer than control cathodes without the resupply of culture supernatant. During the operation period of 120 days, no progressive loss of potential is observed, which suggests that significantly longer lifetimes than shown in this work may be possible. Our results demonstrate the possibility to establish simple, cost efficient, and mediatorless enzymatic BFC cathodes that do not require expensive enzyme purification procedures. Furthermore, they show the feasibility of an enzymatic BFC with an extended lifetime, in which self-replicating microorganisms provide the electrode with catalytically active enzymes in a continuous or periodic manner.
M. Blazek, C. Betz, M. N. Hall, M. Reth, R. Zengerle, M. Meier
Proximity Ligation Assay for High Content Profiling of Cell Signaling Pathways on a Microfluidic Chip
2013 Mol Cell Proteomics, Band: 12, Nummer: 12, Seiten: 3898 - 3907
KurzfassungHere, we present the full integration of a proximity ligation assay (PLA) on a microfluidic chip for systematic cell signaling studies. PLA is an in situ technology for detection of protein interaction, post-translational modification, concentration, and cellular location with single molecule resolution. Analytical performance advances on chip are achieved, including full automation of the biochemical PLA steps, target multiplexing, and reduction of antibody consumption by two orders of magnitudes compared to standard procedures. In combination with a microfluidic cell-culturing platform, control over 128 cell culture microenvironments is gained. We demonstrate the use of the combined cell-culture and protein analytic assay on chip by characterizing the Akt signaling pathway upon PDGF stimulation. Signal transduction is detected by monitoring the phosphorylation state of Akt, GSK-3β, p70S6K, S6, Erk1/2, mTOR, and the cellular location of FoxO3a in parallel with the PLA. Single-cell PLA results revealed for Akt and direct targets of Akt a maximum activation time of 4–8 min upon PDGF stimulation. Activation times for phosphorylation events downwards in the Akt signaling pathway including phosphorylation of S6, p70S6K, and mTOR are delayed by 8–10 min or exhibit a response time of at least 1 h. Quantitative confirmation of the Akt phosphorylation signal was determined with the help of a mouse embryonic fibroblast cell line (MEF) deficient for rictor. Taken together, the miniaturized PLA chip establishes a biotechnological tool for general cell signaling studies and their dynamics relevant for a broad range of biological inquiry.
S. Bammesberger, A. Ernst, N. Losleben, L. Tanguy, R. Zengerle, P. Koltay
Quantitative characterization of non-contact microdispensing technologies for the sub-microliter range
2013 Drug Discov Today, Band: 18, Nummer: 9-10, Seiten: 435 - 446
KurzfassungThis work describes how to effectively compare non-contact dispensing technologies for automated liquid handling under high-throughput screening (HTS) conditions in the range of 0.05–10 ml. Exemplarily, we characterize five established technologies and categorize them into valve-based and positive displacement-based technologies. Furthermore we introduce dispensing accuracy and precision in an ‘intrarun’, ‘inter-run’ and ‘tip-to-tip’ context as universally applicable performance parameters. A NIST traceable spectrophotometric measurement method is utilized for experimental characterization. It yields an Intra-Run CV (Inter-Run CV) between 0.4% to 7.7% (0.5 to 10.9%) and a Tip-to-Tip CV between 1.4% and 9.9% for target volumes <1 ml. An absolute accuracy of better than 5.0% is generally difficult to achieve in the sub-microliter range.
T. van Oordt, G. B. Stevens, S. K. Vashist, R. Zengerle, F. von Stetten
Rapid and highly sensitive luciferase reporter assay for the automated detection of botulinum toxin in the centrifugal microfluidic LabDisk platform
2013 Rsc Adv, Band: 3, Seiten: 22046 - 22052
KurzfassungWe developed a system for the detection of botulinum neurotoxin (BoNT) type A based on a highly sensitive luciferase reporter assay automated by the centrifugal microfluidic LabDisk platform. The assay is based on the detection of BoNT's proteolytic activity and generation of a bioluminescent signal due to the release of firefly luciferase, pre-bound to microbeads via a cleavable peptide linker, in response to BoNT. It detected purified BoNT, BoNT in complex with neurotoxin associated proteins, and the recombinant enzymatic BoNT light chain in buffer and whole milk in the concentration range of 8 pM to 6 nM with an analytical sensitivity and limit of detection of 10–39 pM and 6–14 pM, respectively. The intra-disk, intra-day and inter-day variability were in the range of 1–13%, 1–7% and 10–13%, respectively. The developed assay correlated well with the conventional microwell plate assay. It is superior to the conventional BoNT assays in terms of portability, cost-effectiveness, lesser sample requirement, lesser number of steps and detection of a broad spectrum of BoNT serotypes and subtypes. It takes only 30 minutes, which is ideal for point-of-need BoNT detection in the case of security threats and food monitoring.
K. G. Kraiczek, G. P. Rozing, R. Zengerle
Relation between chromatographic resolution and signal-to-noise ratio in spectrophotometric HPLC detection
2013 Anal Chem, Band: 85, Seiten: 4829 - 4835
KurzfassungAbsorption spectrophotometry has been and still is the industry standard for detection in HPLC. Limit of detection (LOD) and linear dynamic range (LDR) are the primary performance requirements and have driven continuous improvement of spectrophotometric HPLC detectors. Recent advances in HPLC column technology have led to low flow-rate HPLC such as capillary HPLC and nanoflow HPLC and put higher demands on optical HPLC signal detection. However, fundamental principles in spectrophotometric HPLC detection have not been reviewed for many years. In particular the relationship between the detector’s signalto- noise ratio (SNR) and band broadening needs to be re-evaluated. In this work, a new quantitative model is presented which allows the calculation of the trade-off made between chromatographic resolution and SNR in spectrophotometric HPLC detection. Modern optics flow cells based on total internal reflection are included and compared to conventional flow cells.
K. Kliche, G. Kattinger, S. Billat, L. Shen, S. Messner, R. Zengerle
Sensor for thermal gas analysis based on micromachined silicon-microwires
2013 Ieee Sens J, Band: 13, Nummer: 7, Seiten: 2626 - 2635
KurzfassungWe present a microelectromechanical systems-based sensor for the thermal detection of changes of gas mixtures such as the CO2 concentration in air that is of interest in air conditioning climate control within buildings. Key properties of the system are low power consumption (<10 mW) and high longterm stability through the absence of moving or consumptive components. The used sensor chip has three silicon-microwires (thermistors) surrounded by the gas mixture to be analyzed. A centered wire (heater) is supplied with sinusoidal heating power. This induces a thermal response via the surrounding gas to measurement wires (detectors) located in different distances from the heater. The phase shift between heating power and induced thermal responses at the detectors is analyzed and depends on the thermal properties of the gas. After calibration, the sensor is able to quantify the concentration of an individual component within a mixture of different but known gas components. This is demonstrated by measuring the CO2 concentration in N2/CO2 mixtures with a resolution of 0.2% at constant pressure and temperature.
A. Gross, J. Schöndube, S. Niekrawitz, W. Streule, L. Riegger, R. Zengerle, P. Koltay
Single-Cell Printer: Automated,On Demand, and Label Free
2013 JALA - J Lab Autom, Band: 18, Nummer: 6, Seiten: 504 - 518
KurzfassungWithin the past years, single-cell analysis has developed into a key topic in cell biology to study cellular functions that are not accessible by investigation of larger cell populations. Engineering approaches aiming to access single cells to extract information about their physiology, phenotype, and genotype at the single-cell level are going manifold ways, meanwhile allowing separation, sorting, culturing, and analysis of individual cells. Based on our earlier research toward inkjet-like printing of single cells, this article presents further characterization results obtained with a fully automated prototype instrument for printing of single living cells in a noncontact inkjet-like manner. The presented technology is based on a transparent microfluidic drop-on-demand dispenser chip coupled with a camera-assisted automatic detection system. Cells inside the chip are detected and classified with this detection system before they are expelled from the nozzle confined in microdroplets, thus enabling a “one cell per droplet” printing mode. To demonstrate the prototype instrument’s suitability for biological and biomedical applications, basic experiments such as printing of single-bead and cell arrays as well as deposition and culture of single cells in microwell plates are presented. Printing efficiencies greater than 80% and viability rates about 90% were achieved.
E. Kipf, J. Koch, B. Geiger, J. Erben, K. Richter, J. Gescher, R. Zengerle, S. Kerzenmacher
Systematic screening of carbon-based anode materials for microbial fuel cells with Shewanella oneidensis MR-1
2013 Bioresource Technol, Band: 146, Seiten: 386 - 329
KurzfassungWe present a systematic screening of carbon-based anode materials for microbial fuel cells with Shewanella oneidensis MR-1. Under anoxic conditions nanoporous activated carbon cloth is a superior anode material in terms of current density normalized to the projected anode area and anode volume (24.0 ± 0.3 μA cm−2 and 482 ± 7 μA cm−3 at −0.2 vs. SCE, respectively). The good performance can be attributed to the high specific surface area of the material, which is available for mediated electron transfer through self-secreted flavins. Under aerated conditions no influence of the specific surface area is observed, which we attribute to a shift from primary indirect electron transfer by mediators to direct electron transfer via adherent cells. Furthermore, we show that an aerated initial growth phase enhances the current density under subsequent anoxic conditions fivefold when compared to a similar experiment that was conducted under permanently anoxic conditions.
T. Brettschneider, C. Dorrer, M. Bründel, R. Zengerle, M. Daub
Wafer-level packaging and laser bonding as an approach for silicon-into-lab-on-chip integration
2013 J. Micromech. Microeng., Band: 23, Seiten: 055005 - 055014
KurzfassungA novel approach for the integration of silicon biosensors into microfluidics is presented. Our approach is based on wafer-level packaging of the silicon die and a laser-bonding process of the resulting mold package into a polymer-multilayer stack. The introduction of a flexible and 40 μm thin hot melt foil as an intermediate layer enables laser bonding between materials with different melting temperatures, where standard laser welding processes cannot be employed. All process steps are suitable for mass production, e.g. the approach does not involve any dispensing steps for glue or underfiller. The integration approach was demonstrated and evaluated regarding process technology by wafer-level redistribution of daisy chain silicon dies representing a generic biosensor. Electrical connection was successfully established and laser-bonding tensile strength of 5.7 N mm−2 and burst pressure of 587 kPa at a temperature of 100 °C were achieved for the new material combination. The feasibility of the complete packaging approach was shown by the fabrication of a microfluidic flow cell with embedded mold package.

2012

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Vosseler M, Clemenz M, Zengerle R
A flat and cost effective actuator based on superabsorbent polymer driving a skin attachable drug delivery system
2012 Smart Materials and Structures, Band: 21, Seiten: 105002 - 105013
KurzfassungWe present a flat and cost effective volume displacement actuator based on superabsorbent polymer. It offers slow kinetics and is able to work against reasonable back-pressures,e.g. 0.50 ml in 235 min at 140 kPa. It is predestined for low-cost skin attachable drug delivery devices. The actuator consists of a plastic ring filled with superabsorbent polymer granulate. It is sealed with a thermoplastic elastomeric membrane on one side and a stiff filter membrane on the other side. After adding a defined amount (e.g. 2 or 10 ml) of swelling agent the actuator shows a fast initial volume displacement within a few minutes followed by a slow continuous increase of this volume within hours. Minimized initial volume displacement and maximized displaced volume after 4 h cannot be combined in one actuator. A minimized initial displacement can be as low as 0.10 ml +/- 0.03 ml. A maximized displaced volume after 4 h can be 1.71 ml +/- 0.18 ml, not considering the initial effect. The back-pressure dependency of one selected actuator design was studied. At a back-pressure of 100 kPa the displaced volume is reduced by 33%. We investigated various actuator designs with varying surface area, hardness of the elastomeric membrane and superabsorbent polymer. Finally, we demonstrate a skin attachable drug delivery system based on the employment of the superabsorbent polymer actuator.
M Kunze, J Merz, W-J Hummel, H Glosch, S Messner, R Zengerle
A micro dew point sensor with a thermal detection principle
2012 Meas Sci Technol, Band: 23, Seiten: 014004 - (10pp)
KurzfassungWe present a dew point temperature sensor with the thermal detection of condensed water on a thin membrane, fabricated by silicon micromachining. The membrane (600 × 600×∼1 μm3) is part of a silicon chip and contains a heating element as well as a thermopile for temperature measurement. By dynamically heating the membrane and simultaneously analyzing the transient increase of its temperature it is detected whether condensed water is on the membrane or not. To cool the membrane down, a peltier cooler is used and electronically controlled in a way that the temperature of the membrane is constantly held at a value where condensation of water begins. This temperature is measured and output as dew point temperature. The sensor system works in a wide range of dew point temperatures between 1 K and down to 44 K below air temperature. In experimental investigations it could be proven that the deviation of the measured dew point temperatures compared to reference values is below ±0.2 K in an air temperature range of 22 to 70 ◦C. At low dew point temperatures of −20 ◦C (air temperature = 22 ◦C) the deviation increases to nearly −1 K.
S. Spieth, A. Schumacher, T. Holtzman, P. D. Rich, D. E. Theobald, J. W. Dalley, R. Nouna, S. Messner, R. Zengerle
An intra-cerebral drug delivery system for freely moving animals
2012 Biomed Microdevices, Band: 14, Seiten: 799 - 809
KurzfassungMicroinfusions of drugs directly into the central nervous system of awake animals represent a widely used means of unravelling brain functions related to behaviour. However, current approaches generally use tethered liquid infusion systems and a syringe pump to deliver drugs into the brain, which often interfere with behaviour. We address this shortfall with a miniaturised electronically-controlled drug delivery system (20×17.5×5 mm3) designed to be skull-mounted in rats. The device features a micropump connected to two 8-mm-long silicon microprobes with a cross section of 250×250 μm2 and integrated fluid microchannels. Using an external electronic control unit, the device allows infusion of 16 metered doses (0.25 μL each, 8 per silicon shaft). Each dosage requires 3.375 Ws of electrical power making the device additionally compatible with state-of-the-art wireless headstages. A dosage precision of 0.25±0.01 μL was determined in vitro before in vivo tests were carried out in awake rats. No passive leakage from the loaded devices into the brain could be detected using methylene blue dye. Finally, the device was used to investigate the effects of the NMDA-receptor antagonist 3-((R)-2-Carboxypiperazin-4-yl)-propyl-1- phosphonic acid, (R)-CPP, administered directly into the prefrontal cortex of rats during performance on a task to assess visual attention and impulsivity. In agreement with previous findings using conventional tethered infusion systems, acute (R)-CPP administration produced a marked increase in impulsivity.
S. Zehnle, F. Schwemmer, G. Roth, F. von Stetten, R. Zengerle, N. Paust
Centrifugo-dynamic inward pumping of liquids on a centrifugal microfluidic platform
2012 Lab Chip (Lab on a Chip) 2012, Band: 12, Seiten: 5142 - 5145
KurzfassungWe present a method to pump liquids in a centrifugal microfluidic spinning disk from a radial outward position to a radial inward position. Centrifugal forces are applied to compress air in a cavity, this way storing pneumatic energy. The cavity is connected to an outlet channel having a lower hydraulic resistance compared to the inlet channel. The stored pneumatic energy is quickly released by fast reduction of rotational frequency. This way liquid is transported mainly through the channel with lower resistance, directing the liquid radially inwards. Pump efficiencies of .75% per pump cycle have been demonstrated for water, ethanol, a highly viscous lysis buffer and whole blood. By employing three pump cycles, water has been pumped radially inwards with an efficiency of .90%. The inward pumping requires centrifugation only, which is intrinsically available on every centrifugal microfluidic platform.

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A. Tropmann, L. Tanguy, P. Koltay, R. Zengerle, L. Riegger
Completely superhydrophobic PDMS surfaces for microfluidics
2012 Langmuir, Band: 28, Nummer: 22, Seiten: 8292 - 8295
G. Lammers, G. Roth, M. Heck, R. Zengerle, G. S. Tjabringa, E. M. Versteeg, T. Hafmans, R. Wismans, D. P. Reinhardt, E. T. P. Verwiel, P. L. J. M. Zeeuwen, J. Schalkwijk, R. Brock, W. F. Daamen, T. H. van Kuppevelt
Construction of a Microstructured Collagen Membrane Mimicking the Papillary Dermis Architecture and Guiding Keratinocyte Morphology and Gene Expression
2012 Macromol Biosci, Band: 12, Seiten: 675 - 691
KurzfassungA papillary-structured collagen fibril membrane is created, mimicking the 3D-architecture of the human papillary dermis. Primary human keratinocytes cultured to confluency on papillarstructured films are compared to keratinocytes cultured on flat membranes. Microscopical evaluation reveals the presence of morphologically distinct cells at the base of the papillar structures that are not observed on flat membranes. Gene expression microarrays and RT-qPCR indicate that these cells are in a more proliferative/ migrational state, whereas cells on flat membranes have a more differentiated expression profile. Immunohistochemical stainings confirm these results. In conclusion, specific collagen architecture can direct keratinocyte behavior, and this may be used to further improve skin regeneration.
Mitsakakis K, Sekula-Neuner S, Lenhert S, Fuchs H, Gizeli E
Convergence of Dip-pen nanolithography and acoustic biosensors towards a rapid-analysis multi-sample microsystem
2012 Analyst, Band: 137, Seiten: 3076 - 3082
A. Kloke, C. Köhler, R. Gerwig, R. Zengerle, S. Kerzenmacher
Cyclic Electrodeposition of PtCu Alloy: Facile Fabrication of Highly Porous Platinum Electrodes
2012 Adv Mater, Band: 24, Seiten: 2916 - 2921
B. Faltin, S. Wadle, G. Roth, R. Zengerle, F. von Stetten
Mediator Probe PCR: A Novel Approach for Detection of Real-Time PCR Based on Label-Free Primary Probes and Standardized Secondary Universal Fluorogenic Reporters
2012 Clin Chem, Band: 58, Nummer: 11, Seiten: 1546 - 1556
Daniel Mark, Felix von Stetten, Roland Zengerle
Microfluidic Apps for off-the-shelf instruments
2012 Lab Chip, Band: 12, Seiten: 2464 - 2468
B. Landenberger, H. Hoefemann, S. Wadle, A. Rohrbacha
Microfluidic sorting of arbitrary cells with dynamic optical tweezers
2012 Lab Chip, Band: 12, Seiten: 3177 - 3183
KurzfassungOptical gradient forces generated by fast steerable optical tweezers are highly effective for sorting small populations of cells in a lab-on-a-chip environment. The presented system can sort a broad range of different biological specimens by an automated optimisation of the tweezer path and velocity profile. The optimal grab positions for subsequent trap and cell displacements are estimated from the intensity of the bright field image, which is derived theoretically and proven experimentally. We exhibit rapid displacements of 2 µm small mitochondria, yeast cells, rod-shaped bacteria and 30 mm large protoplasts. Reliable sorting of yeast cells in a microfluidic chamber by both morphological criteria and by fluorescence emission is demonstrated.
S.K. Vashist, A. G. Venkatesh, K. Mitsakakis, G. Czilwik, G. Roth, F. von Stetten, R. Zengerle
Nanotechnology-Based Biosensors and Diagnostics: Technology Push versus Industrial/Healthcare Requirements
2012 BioNanoSci., Band: 2, Seiten: 115 - 126
KurzfassungThere have been considerable advances in the field of nanotechnology-based biosensors and diagnostics (NBBD) during the last two decades. These include the production of nanomaterials (NMs), employing them for new biosensing and diagnostic applications, their extensive characterization for in vitro and in vivo applications, and toxicity analysis. All these developments have led to tremendous technology push and successful demonstrations of several promising NBBD. However, there has been a significant lag in their commercialization, especially due to the lack of international regulatory guidelines for evaluating the safety of NMs and the growing public concerns about their toxicity. Despite these numerous advances and the recent regulatory approval of several NMs, it still remains to be seen if NBBD are superior to conventional ones (not based on NMs), reliable, reproducible, cost effective, and robust enough to meet the requirements of industries and healthcare. This manuscript provides a critical review of NBBD, the technology push, and the industrial/healthcare requirements.
A. Ernst, K. Mutschler, L. Tanguy, N. Paust, R. Zengerle, P. Koltay
Numerical Investigations on Electric Field Characteristics with Respect to Capacitive Detection of Free-Flying Droplets
2012 sensors, Band: 12, Seiten: 10550 - 10565
KurzfassungIn this paper a multi-disciplinary simulation of a capacitive droplet sensor based on an open plate capacitor as transducing element is presented. The numerical simulations are based on the finite volume method (FVM), including calculations of an electric field which changes according to the presence of a liquid droplet. The volume of fluid (VOF) method is applied for the simulation of the ejection process of a liquid droplet out of a dispenser nozzle. The simulations were realised using the computational fluid dynamic (CFD) software CFD ACE+. The investigated capacitive sensing principle enables to determine the volume of a micro droplet passing the sensor capacitor due to the induced change in capacity. It could be found that single droplets in the considered volume range of 5 nL < Vdrop < 100 nL lead to a linear change of the capacity up to ΔQ < 30 fC. The sensitivity of the focused capacitor geometry was evaluated to be Si = 0.3 fC/nL. The simulation results are validated by experiments which exhibit good agreement.
Dennis Trebbels, Felix Fellhauer, Michael Jugl, Gerd Haimerl, Mart Min, Roland Zengerle
Online Tissue Discrimination for Transcutaneous Needle Guidance Applications Using Broadband Impedance Spectroscopy
2012 Ieee T Bio-med Eng, Band: 59, Nummer: 2, Seiten: 494 - 503
KurzfassungThis paper reports on a novel system architecture for measuring impedance spectra of a biological tissue close to the tip of a hollow needle. The measurement is performed online using fast broadband chirp signals. The time domain measurement raw data are transformed into the transfer function of the tissue in frequency domain. Correlation technique is used to analyze the characteristic shape of the derived tissue transfer function with respect to known “library functions” for different types of tissue derived in earlier experiments. Based on the resulting correlation coefficients the exact type of tissue is determined. A bipolar coaxial needle is constructed, simulated by finite element method and tested during various in vitro and in vivo experiments. The results show a good spatial resolution of approximately 1.0mm for a needle with a diameter of 2.0 mm. The correlation coefficients for the three tested tissue types muscle, fat, and blood allow for a clear tissue classification. Best results have been obtained using the characteristic phase diagrams for each tissue. Correlated to the corresponding library transfer function the coefficients are in the range of+0.96 to +0.99 for the matching tissue. In return, the resulting coefficients for correlation with nonmatching tissues are in the range of −0.93 to +0.81.
J. Hoffmann, L. Riegger, F. Bundgaard, D. Mark, R. Zengerle, J. Ducrée
Optical non-contact localization of liquid-gas interfaces on disk during rotation for measuring flow rates and viscosities
2012 Lab Chip (Lab on a Chip) 2012, Band: 12, Seiten: 5231 - 5236
KurzfassungWe present a novel technique for the spatio-temporally resolved localization of liquid-gas interfaces on centrifugal microfluidic platforms based on total internal reflection (TIR) at the channel wall. The simple setup consists of a line laser and a linear image sensor array mounted in a stationary instrument. Apart from identifying the presence of usually unwanted gas bubbles, the here described online meniscus detection allows to measure liquid volumes with a high precision of 1.9%. Additionally, flow rates and viscosities (range: 1–12 mPa s, precision of 4.3%) can be sensed even during rotation at frequencies up to 30 Hz.

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S.Herrlich, S.Spieth, S.Messner, R.Zengerle
Osmotic micropumps for drug delivery
2012 Adv Drug Deliver Rev, Band: 64, Seiten: 1617 - 1627
KurzfassungThis paper reviews miniaturized drug delivery systems applying osmotic principles for pumping. Osmotic micropumps require no electrical energy and consequently enable drug delivery systems of smallest size for a broad field of new applications. In contrast to common tablets, these pumps provide constant (zeroorder) drug release rates. This facilitates systems for long term use not limited by gastrointestinal transit time and first-pass metabolism. The review focuses on parenteral routes of administration targeting drug delivery either in a site-specific or systemic way. Osmotic pumps consist of three building blocks: osmotic agent, solvent, and drug. This is used to categorize pumps into (i) single compartment systems using water from body fluids as solvent and the drug itself as the osmotic agent, (ii) two compartment systems employing a separate osmotic agent, and (iii) multi-compartment architectures employing solvent, drug and osmotic agent separately. In parallel to the micropumps, relevant applications and therapies are discussed.
A. Tropmann, N. Lass, N. Paust, T. Metz, C. Ziegler, R. Zengerle, P. Koltay
Pneumatic Dispensing of Nano- to Picoliter Droplets of Liquid Metal with the StarJet Method for Rapid Prototyping of Metal Microstructures
2012 Microfluid Nanofluid, Band: 12, Seiten: 75 - 84
KurzfassungThis work presents a new, simple and robust, pneumatically actuated method for the generation of liquid metal micro droplets in the nano- to picoliter range. The so called StarJet dispenser utilizes a star-shaped nozzle geometry that stabilizes liquid plugs in its center by means of capillary forces. Single droplets of liquid metal can be pneumatically generated by interaction of the sheathing gas flow in the outer grooves of the nozzle and the liquid metal. For experimental validation, a print head was build consisting of silicon chips with a star-shaped nozzle geometry and a heated actuator (up to 280 °C). The silicon chips are fabricated by Deep Reactive Ion Etching (DRIE). Chip designs with different star-shaped geometries were able to generate droplets with diameters in the range of the corresponding nozzle diameters. The StarJet can be operated in two modes: Either continuous droplet dispensing mode or drop on demand (DoD) mode. The continuous droplet generation mode for a nozzle with 188 µm diameter shows tear-off frequencies between 25 Hz and 120 Hz, while droplet diameters remain constant at 210 µm for each pressure level. Metal columns were printed with a thickness of 0.5 to 1.0 mm and 30 mm height (aspect ratio >30) to demonstrate the directional stability of droplet ejection and its potential as a suitable tool for direct prototyping of metal microstructures.
Arne Kloke, Christian Köhler, Roland Zengerle, Sven Kerzenmacher
Porous Platinum Electrodes Fabricated by Cyclic Electrodeposition of PtCu Alloy: Application to Implantable Glucose Fuel Cells
2012 J Phys Chem C, Band: 116, Seiten: 19689 - 19698
KurzfassungWe demonstrate the application of cyclic electrodeposition of PtCu alloy to fabricate porous platinum electrodes for implantable glucose fuel cells. Depending on the number of deposition cycles, electrodes with controllable specific surface area can be fabricated, their roughness factors ranging from 20 (slightly roughened) to 3100 (highly porous). Adjusting the specific surface area of the electrode from low to high determines whether it functions as cathode or anode, respectively. Compared to state of the art, this process is beneficial due to shorter fabrication times, lower temperatures, and the requirement of only one process for the fabrication of both electrodes. Correspondingly fabricated glucose fuel cells showed a power density of 5.1 μW cm−2 under close to physiological conditions, which is an improvement by 16% compared to earlier designs. During continuous operation over 90 days the fuel cell showed a mean continuous decay of about 0.8% per day, which is related to catalyst poisoning at the anode. Future work will thus have to focus on the improvement of long-term stability instead of power density. ■ INTRODUCTION
S. Rubenwolf, S. Sané, L. Hussein, J. Kestel, F. von Stetten, G. Urban, M. Krueger, R. Zengerle, S. Kerzenmacher
Prolongation of electrode lifetime in biofuel cells by periodic enzyme renewal
2012 Appl Microbiol Biotechnol, Band: 96, Seiten: 841 - 849
KurzfassungAbstract Enzymatically catalyzed biofuel cells show unique specificity and promise high power densities, but suffer from a limited lifetime due to enzyme deactivation. In the present work, we demonstrate a novel concept to extend the lifetime of a laccase-catalyzed oxygen reduction cathode in which we decouple the electrode lifetime from the limited enzyme lifetime by a regular resupply of fresh enzymes. Thereto, the adsorption behavior of laccase from Trametes versicolor to buckypaper electrode material, as well as its time-dependent deactivation characteristics, has been investigated. Laccase shows a Langmuir-type adsorption to the carbon nanotube-based buckypaper electrodes, with a mean residence time of 2 days per molecule. In a citrate buffer of pH 5, laccase does not show any deactivation at room temperature for 2 days and exhibits a half-life of 9 days. In a long-term experiment, the laccase electrodes were operated at a constant galvanostatic load. The laccase-containing catholyte was periodically exchanged against a freshly prepared one every second day to provide sufficient active enzymes in the catholyte for the replacement of desorbed inactive enzymes. Compared to a corresponding control experiment without catholyte exchange, this procedure resulted in a 2.5 times longer cathode lifetime of 19±9 days in which the electrode showed a potential above 0.744 V vs. normal hydrogen electrode at 110 μAcm−2. This clearly indicates the successful exchange of molecules by desorption and re-adsorption and is a first step toward the realization of a selfregenerating enzymatic biofuel cell in which enzyme-producing microorganisms are integrated into the electrode to continuously resupply fresh enzymes.
Jochen Rupp, Manuela Schmidt, Susanne Münch, Markus Cavalar, Ulf Steller, Jürgen Steigert, Michael Stumber, Christian Dorrer, Peter Rothacher, Roland Zengerle, Martina Daub
Rapid microarray processing using a disposable hybridization chamber with an integrated micropump
2012 Lab Chip, Band: 12, Seiten: 1384 - 1388
KurzfassungWe present a disposable microarray hybridization chamber with an integrated micropump to speed up diffusion based reaction kinetics by generating convective flow. The time-to-result for the hybridization reaction was reduced from 60 min (standard protocol) down to 15 min for a commercially available microarray. The integrated displacement micropump is pneumatically actuated. It includes two active microvalves and is designed for low-cost, high volume manufacturing. The setup is made out of two microstructured polymer parts realized in polycarbonate (PC) separated by a 25 mm thermoplastic elastomer (TPE) membrane. Pump rate can be controlled between 0.3 µl/s and 5.7 µl/s at actuation frequencies between 0.2 Hz and 8.0 Hz, respectively.
Jochen Hoffmann, Martin Trotter, Felix von Stetten, Roland Zengerle, Günter Roth
Solid-phase PCR in a picowell array for immobilizing and arraying 100,000 PCR products to a microscope slide
2012 Lab Chip, Band: 12, Nummer: 17, Seiten: 3049 - 3054
KurzfassungWe present a method for performing highly parallel PCR reactions in a picowell array (PWA) simultaneously immobilizing generated PCR products covalent and spatially-resolved onto a microscope slide via solid-phase PCR (SP-PCR). This so called PWA-SP-PCR is performed in picowell arrays featuring 100,000 wells∙cm^-2 of 19 pL reaction volumes with a surface-to-volume-ratio of 0.2 µm-1. Positive signals are obtained in 97.2 % of the 110,000 wells on an area of 110 mm^2. Immobilized DNA is either detected sequence-unspecific via streptavidin-Cy5 or sequence-specific by Cy3 labeled hybridization probes. Amplification and immobilization is demonstrated for template DNA ranging from 100 bp up to 1513 bp length. Compared to widely established emulsion based PCR (emPCR) approaches, leading to PCR products immobilized onto bead surfaces in highly parallel manner, the novel technique results in direct spatial registration of immobilized PCR products in a microarray format. This enables the subsequent use for massively parallel analysis similar to standard microarrays.
H. Hoefemann, S. Wadle, N. Bakhtina, V. Kondrashov, N. Wangler, R. Zengerle
Sorting and lysis of single cells by BubbleJet technology
2012 Sensors and Actuators B, Band: 168, Seiten: 442 - 445
S Spieth, A Schumacher, C Kallenbach, S Messner, R Zengerle
The NeuroMedicator—a micropump integrated with silicon microprobes for drug delivery in neural research
2012 J Micromech Microeng, Band: 22, Seite: 065020
T. Hutzenlaub, S. Thiele, R. Zengerle, C. Ziegler
Three-Dimensional Reconstruction of a LiCoO2 Li-Ion Battery Cathode
2012 Electrochem Solid St, Band: 15, Nummer: 3, Seiten: A33 - A36
KurzfassungIn the reported work, we reconstruct a LiCoO2 cathode three-dimensionally, for the first time differentiating between all three constituents: (i) active material, (ii) binder and (iii) pore space for this specific material. We apply a hybrid method of manual and grey-scale threshold segmentation to reconstruct a cuboid with a volume of approximately 4500 µm3. The reconstructed geometry is characterised to support the data basis of homogenized cathode models. We solve numerically for electrical conductivity and derive electrical tortuosity analytically from the result. Pore space connectivity and pore size distribution are also calculated. The segmented images are provided as supplementary electronic material.
A. Gulliksen, H. Keegan, C. Martin, J. O’Leary, L. A. Solli, I. M. Falang, P. Grønn, A. Karlg°ard, M. M. Mielnik, Ib-R.Johansen, Terje R. Tofteberg, T. Baier, R. Gransee, K. Drese, T. Hansen-Hagge, L. Riegger, P. Koltay, R. Zengerle, F. Karlsen, D. Ausen, , , Liv Furuberg2, 4
Towards a “Sample-In, Answer-Out” Point-of-Care Platform for Nucleic Acid Extraction and Amplification: Using an HPV E6/E7mRNAModel System
2012 Journal of Oncology, Band: 2012, Seite: ID 905024
KurzfassungThe paper presents the development of a “proof-of-principle” hands-free and self-contained diagnostic platform for detection of human papillomavirus (HPV) E6/E7 mRNA in clinical specimens. The automated platform performs chip-based sample preconcentration, nucleic acid extraction, amplification, and real-time fluorescent detection with minimal user interfacing. It consists of two modular prototypes, one for sample preparation and one for amplification and detection; however, a common interface is available to facilitate later integration into one single module. Nucleic acid extracts (n = 28) from cervical cytology specimens extracted on the sample preparation chip were tested using the PreTect HPV-Proofer and achieved an overall detection rate for HPV across all dilutions of 50%–85.7%. A subset of 6 clinical samples extracted on the sample preparation chip module was chosen for complete validation on the NASBA chip module. For 4 of the samples, a 100% amplification for HPV 16 or 33 was obtained at the 1 : 10 dilution for microfluidic channels that filled correctly. The modules of a “sample-in, answer-out” diagnostic platform have been demonstrated from clinical sample input through sample preparation, amplification and final detection.
Jochen Hoffmann, Sebastian Hin, Felix von Stetten, Roland Zengerle, Günter Roth
Universal protocol for grafting PCR primers onto various lab-on-a-chip substrates for solid-phase PCR
2012 RSC Advances, Band: 2, Nummer: 9, Seiten: 3885 - 3889
KurzfassungA universal protocol for grafting PCR primers onto glass, PDMS, COP, COC, and PP is developed and evaluated by solid-phase PCR (SP-PCR). Primers are immobilized in a PCR compatible way featuring spots with high homogeneity and integrity. Furthermore, we show a protocol for binding a PCR product to immobilized PCR primers via solid-phase PCR (SP-PCR). Previously reported ‘‘enhanced SP-PCR’’ (Z. Kahn et al. Anal. Biochem., 2008, 375, 391–393) is improved in terms of factorial signal increase from 9.9 to 86.8 and specificity from 11.7 to 45.9. The presented immobilization- and SP-PCR protocols may enable integration of DNA microarrays directly into microfluidic lab-on-a-chip cartridges of various materials for analysis via SP-PCR. Beside planar microarrays, another interesting application could be to coat the inner surfaces of a chip with PCR primers to recover generated PCR products in digital PCR systems.

2011

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A. Kloke, B. Biller, U. Kräling, S. Kerzenmacher, R. Zengerle, F. von Stetten
A Single Layer Glucose Fuel Cell Intended as Power Supplying Coating for Medical Implants
2011 Fuel Cells, Band: 11, Nummer: 2, Seiten: 316 - 326
KurzfassungWe present a novel type of abiotically catalysed implantable glucose fuel cell with anode and cathode placed side by side,using a Raney-platinum glucose oxidation anode with high tolerance towards oxygen. In contrast to conventional assembly designs used for implantable glucose fuel cells, no permeable cathode mounted in front of the anode to effect oxygen depletion is required. At 2.2 ± 0.1 lW cm–2 the single layer fuel cell exhibits only half the maximum power density of the conventional fuel cell, which solely stems from the doubled total fuel cell area demand. Nevertheless, the novel single layer design is advantageous in terms of simplified fabrication and reduced overall thickness, facilitating implementation of the fuel cell as a power supplying coating directly on the surface of medical implants. Furthermore,the single layer design offers an attractive possibility to diminish the reduction of power density by limited oxygen mass transfer to the cathode by increasing the cathode to anode area proportion. With doubled cathode area proportion a by 36% higher power density can be reached. To calculate the optimum cathode to anode area proportions,we introduced an analytical model based on the experimentally determined polarisation resistances of the individual electrodes. Keywords: Biomedical Devices, Energy Harvesting, Implantable Glucose Fuel Cell, Oxygen Tolerant Platinum Electrodes, Power Supply
S Spieth, O Brett, K Seidl, A A A Aarts, M A Erismis, S Herwik, F Trenkle, S Tätzner, J Auber, M Daub, H P Neves, R Puers, O Paul, P Ruther, R Zengerle
A floating 3D silicon microprobe array for neural drug delivery compatible with electrical recording
2011 J Micromech Microeng, Band: 21, Seiten: 125001 - (16pp)
KurzfassungThis paper reports on the design, fabrication, assembly, and characterization of a three-dimensional (3D) silicon-based floating microprobe array for localized drug delivery to be applied in neuroscience research. The microprobe array is composed of a silicon platform into which up to four silicon probe combs with needle-like probe shafts can be inserted. Two dedicated positions in the array allow the integration of combs for drug delivery. The implemented comb variants feature 8-mm-long probe shafts with two individually addressable microchannels incorporated in one single shaft or distributed to two shafts. Liquid supply to the array is realized by a highly flexible 250-µm-thick multi-lumen microfluidic cable made from polydimethylsiloxane (PDMS). The specific design concept of the slim-base platform enables floating implantation of the array in the small space between brain and skull. In turn, the flexible cable mechanically decouples the array from any microfluidic interface rigidly fixed to the skull. After assembly of the array, full functionality is demonstrated and characterized at infusion rates from 1 to 5 µL/min. Further, the effect of a parylene-C coating on the water vapour and osmotic liquid water transport through the PDMS cable walls is experimentally evaluated by determining the respective transmission rates including the water vapour permeability of the used PDMS type.
L. Hussein, S. Rubenwolf, F. von Stetten, G. Urban, R. Zengerle, M. Krueger, S. Kerzenmacher
A highly efficient buckypaper-based electrode material for mediatorless laccase-catalyzed dioxygen reduction
2011 Biosens Bioelectron, Band: 26, Seiten: 4133 - 4138
KurzfassungThe redox enzyme laccase from Trametes versicolor efficiently catalyzes the oxygen reduction reaction (ORR) in mediatorless biofuel cell cathodes when adsorbed onto multi-walled carbon nanotubes (MWCNTs). In this work we demonstrate that the fabrication of MWCNTs in form of buckypaper (BP) results in an excellent electrode material for laccase-catalyzed cathodes. BPs are mechanically stable, self-entangling mats with high dispersion of MWCNTs resulting in easy to handle homogeneous layers with highly mesoporous structures and excellent electrical conductivities. All biocathodes have been electrochemically investigated in oxygen-saturated buffer at pH 5 by galvanostatic polarization and potentiodynamic linear sweep voltammetry. Both methods confirm an efficient direct interaction of laccase with BP with a high open circuit potential of 0.882V vs. normal hydrogen electrode (NHE). The high oxygen reduction performance leads to high current densities of 422±71 µAcm−2 at a typical cathode potential of 0.744V vs. NHE. When the current density is normalized to the mass of the electrode material (mass activity), the BPbased film electrodes exhibit a 68-fold higher current density at 0.744Vvs.NHEthan electrodes fabricated from the same MWCNTs in a non-dispersed agglomerated form as packed electrodes. This clearly shows that MWCNTs can act more efficiently as cathode when prepared in form of BP. This can be attributed to reduced diffusional mass transfer limitations and enhanced electrical conductivity. BP is thus a very promising material for the construction of mediatorless laccase cathodes for ORR in biofuel cells. In addition we demonstrated that these electrodes exhibit a high tolerance towards glucose, the most common bioanode fuel.
S. Kerzenmacher, U. Kräling, T. Metz, R. Zengerle, F. von Stetten
A potentially implantable glucose fuel cell with Raney-platinum film electrodes for improved hydrolytic and oxidative stability
2011 J Power Sources, Band: 196, Seiten: 1264 - 1272
KurzfassungWe present an improved abiotically catalyzed glucose fuel cell, intended as energy harvesting tissue implantable power supply for medical implants. The fuel cell is constructed from a Raney-platinum film cathode deposited on a silicon substrate with micro-machined feedholes for glucose permeability, arranged in front of a Raney-platinum film anode. A novelty is the application of platinum for both electrodes and the complete abdication of hydrogel binders. This overcomes the limited stability against hydrolytic and oxidative attack encountered with previous glucose fuel cells fabricated from activated carbon particles dispersed in a hydrogel matrix. During performance characterization in phosphate buffered saline under physiological concentrations of glucose and oxygen the diffusion resistance to be expected from tissue capsule formation was taken into account. Despite the resulting limited oxygen supply, the Raney-platinum fuel cells exhibit a power density of up to (4.4±0.2)µWcm−2 at 7.0% oxygen saturation. This exceeds the performance of our previous carbon-based prototypes, and can be attributed to the higher catalytic activity of platinum cathodes and in particular the increased oxygen tolerance of the Raney-platinum film anodes.
Michael Vosseler, Michael Jugl, Roland Zengerle
A smart interface for reliable intradermal injection and infusion of high and low viscosity solutions
2011 Pharm Res-dordr, Band: 28, Seiten: 647 - 661
KurzfassungPurpose: We present a smart intradermal interface suitable for skin attached drug delivery devices. Our solution enables injections or infusions that are less invasive compared to subcutaneous injections and is leakage-free at the location of penetration. Methods: The intradermal interface is based on a 31 gauge cannula embedded in a slider, movable relative to a carrier plate that can easily be fixed onto the skin. By simply pushing the slider the cannula is inserted into the dermis. Results: We performed injections and infusions with stained water and polyethylene glycol (PEG) solution in ex vivo pig skin. The sizes of coloured spots in the skin range from 3.5 mm² to 15.4 mm² for stained water depending on the infused volume. Infusing stained PEG solution resulted in stained tissue areas about one order of magnitude larger. One of three investigated leakage modes is unacceptable but can be reliably avoided by proper site selection. At low flow rates and at the beginning of an infusion an initial back pressure overshoot was identified. This effect was identified as the limiting parameter for the design of small programmable or intelligent devices based on micro actuators. Conclusions: With the proposed easy-to-use interface, intradermal injections and infusions can be performed reliably. Therefore, it is supposed to be an ideal and clinically relevant solution for self-administration of parenteral drugs in home care applications.
Daniel Mark, Patrick Weber, Sascha Lutz, Maximilian Focke, Roland Zengerle, Felix von Stetten
Aliquoting on the centrifugal microfluidic platform based on centrifugo-pneumatic valves
2011 Microfluid Nanofluid, Band: 10, Seiten: 1279 - 1288
KurzfassungWe present a new method for aliquoting liquids on the centrifugal microfluidic platform. Aliquoting is an essential unit operation to perform multiple parallel assays (‘‘geometric multiplexing’’) from one individual sample, such as genotyping by real-time polymerase chain reactions (PCR), or homogeneous immunoassay panels. Our method is a two-stage process with an initial metering phase and a subsequent transport phase initiated by switching a centrifugo- pneumatic valve. The method enables aliquoting liquids into completely separated reaction cavities. It includes precise metering that is independent on the volume of prestored reagents in the receiving cavities. It further excludes any cross-contamination between the receiving cavities. We characterized the performance for prototypes fabricated by three different technologies: micro-milling, thermoforming of foils, and injection molding. An initial volume of*90 ll was split into 8 aliquots of 10 ll volume each plus a waste reservoir on a thermoformed foil disk resulting in a coefficient of variation (CV) of the metered volumes of 3.6%. A similar volume of*105 ll was split into 16 aliquots of 6 ll volume each on micro-milled and injection-molded disks and the corresponding CVs were 2.8 and 2.2%, respectively. Thus, the compatibility of the novel aliquoting structure to the aforementioned prototyping and production technologies is demonstrated. Additionally, the important question of achievable volume precision of the aliquoting structure with respect to the production tolerances inherent to each of these production technologies is addressed experimentally and theoretically. The new method is amenable to low cost mass production, since it does not require any post-replication surface modifications like hydrophobic patches.
O Frey, P D van derWal, S Spieth, O Brett, K Seidl, O Paul, P Ruther, R Zengerle, N F de Rooij
Biosensor microprobes with integrated microfluidic channels for bi-directional neurochemical interaction
2011 J Neural Eng, Band: 8, Seite: 066001
KurzfassungThis paper reports on silicon-based microprobes, 8 mm long and 250 μm × 250 μm cross-section, comprising four recessed biosensor microelectrodes (50 μm × 150 μm) per probe shank coated with an enzymatic layer for the selective detection of choline at multiple sites in brain tissue. Integrated in the same probe shank are up to two microfluidic channels for controlled local liquid delivery at a defined distance from the biosensor microelectrodes. State-of-the-art silicon micromachining processing was applied for reproducible fabrication of these experiment-tailored multi-functional probe arrays. Reliable electric and fluidic interconnections to the microprobes are guaranteed by a custom-made holder. The reversible packaging method implemented in this holder significantly reduces cost and assembly time and simplifies storage of the biosensor probes between consecutive experiments. The functionalization of the electrodes is carried out using electrochemically aided adsorption. This spatially controlled deposition technique enables a parallel deposition of membranes and is especially useful when working with microelectrode arrays. The achieved biosensors show adequate characteristics to detect choline in physiologically relevant concentrations at sufficient temporal and spatial resolution for brain research. Sensitivity to choline better than 10 pA μM−1, detection limit below 1 μM and response time of 2 s were obtained. The proposed combination of biosensors and microfluidic injectors on the same microprobe allows simultaneous chemical stimulation and recording as demonstrated in an agarose gel-based brain phantom.
Marc Karle, Johannes Wöhrle, Junichi Miwa, Nils Paust, Günter Roth, Roland Zengerle, Felix von Stetten
Controlled counter-flow motion of magnetic bead chains rolling along microchannels
2011 Microfluid Nanofluid, Band: 10, Nummer: 4, Seiten: 935 - 939
KurzfassungWe demonstrate controlled transport of superparamagnetic beads in the opposite direction of a laminar flow. A permanent magnet assembles 200 nm magnetic particles into about 200 lm long bead chains that are aligned in parallel to the magnetic field lines. Due to a magnetic field gradient, the bead chains are attracted towards the wall of a microfluidic channel. A rotation of the permanent magnet results in a rotation of the bead chains in the opposite direction to the magnet. Due to friction on the surface, the bead chains roll along the channel wall, even in counter-flow direction, up to at a maximum counter-flow velocity of 8 mm s(-1). Based on this approach, magnetic beads can be accurately manoeuvred within microfluidic channels. This counter-flow motion can be efficiently be used in Lab-on-a-Chip systems, e.g. for implementing washing steps in DNA purification.
Mitsakakis K, Gizeli E
Detection of multiple cardiac markers with an integrated acoustic platform for cardiovascular risk assessment
2011 Anal Chim Acta, Band: 699, Seiten: 1 - 5
Christoph Ziegler, Simon Thiele, Roland Zengerle
Direct three-dimensional reconstruction of a nanoporous catalyst layer for a polymer electrolyte fuel cell
2011 J Power Sources, Band: 196, Nummer: 4, Seiten: 2094 - 2097
KurzfassungThe direct three-dimensional reconstruction of a polymer electrolyte fuel cell cathode catalyst layer from focused ion beam/scanning electron microscope (FIB/SEM) images is presented. The carbon and pore distribution is shown and quantitatively analysed. A new catalyst layer sample (Fumapem-F950/HiSpec13100) is sliced with FIB and a series of SEM images is taken. The images are registered, segmented and a three-dimensional stack is reconstructed. The three-dimensional carbon and pore distribution is shown. Based on the reconstruction the pore size distribution is evaluated. The total porosity and the unconnected pores space is analysed. The fully segmented 2D images are provided as supplemental material to this paper for future analysis and modeling work. Keywords Polymer electrolyte fuel cell; Porous catalyst layer; Three-dimensional reconstruction
N Wangler, L Gutzweiler, K Kalkandjiev, C Müller, F Mayenfels, H Reinecke, R Zengerle, N Paust
High-resolution permanent photoresist laminate TMMF for sealed microfluidic structures in biological applications
2011 J Micromech Microeng, Band: 21, Seite: 095009
KurzfassungWe demonstrate the use of photosensitive epoxy laminate TMMF S2045 for the fabrication and sealing of tapered microfluidic channels. The 45 μm thick resist enables the fabrication of shallow sealed cavities featuring extreme aspect ratios of less than 1:40 (h = 45 μm, w = 2000 μm). It also provides high resolution and enables minimum feature sizes of 10 μm. For the fabrication of free-standing structures, an aspect ratio of up to 7:1 was achieved. The dry-film photoresist can be applied easily by lamination onto structured substrates. The total thickness variation of the resist across a 100 mm wafer was determined to be less than ±0.6 μm. Process parameters for the fabrication and sealing of various micro-channels are discussed and optimized in this paper. The main focus was to minimize thermal impact during lamination, soft-bake, exposure and post–exposure bake, which could lead to lid sagging or channel clogging due to liquefaction of uncured resist. We tested TMMF according to ISO 10995-5 and found it to be non-cytotoxic, enabling its use for biological applications. Swelling of less than 5% for incubation of the dry-film resist in several biologically relevant solvents, buffers and cleaning solutions was observed.
Azmi Yusof, Helen Keegan, Cathy D. Spillane, Orla M. Sheils, Cara M. Martin, John J. O’Leary, Roland Zengerle, Peter Koltay
Inkjet-like printing of single-cells
2011 Lab Chip, Band: 11, Seiten: 2447 - 2454
KurzfassungCell sorting and separation techniques are essential tools for cell biology research and for many diagnostic and therapeutic applications. For many of these applications, it is imperative that heterogeneous populations of cells are segregated according to their cell type and that individual cells can be isolated and analysed. We present a novel technique to isolate single cells encapsulated in a picolitre sized droplet that are then deposited by inkjet-like printing at defined locations for downstream genomic analysis. The single-cell-manipulator (SCM) developed for this purpose consists of a dispenser chip to print cells contained in a free flying droplet, a computer vision system to detect single-cells inside the dispenser chip prior to printing, and appropriate automation equipment to print single-cells onto defined locations on a substrate. This technique is spatially dynamic, enabling cell printing on a wide range of commonly used substrates such as microscope slides, membranes and microtiter plates. Demonstration experiments performed using the SCM resulted in a printing efficiency of 87% for polystyrene microbeads of 10 mm size. When the SCM was applied to a cervical cancer cell line (HeLa), a printing efficiency of 87% was observed and a post-SCM cell viability rate of 75% was achieved.
M. Pospischil, K. Zengerle, J. Specht, G. Birkle, P. Koltay, R. Zengerle, A. Henning, M. Neidert, C. Mohr, F. Clement, D. Biro
Investigations on Thick-Film-Paste Rheology for Dispensing Applications
2011 Energy Procedia, Band: 8, Seiten: 449 - 454
KurzfassungIn order to establish dispensing as a promising metallization process in silicon photovoltaics, equipment and metal pastes require further optimization. By conducting several rheological experiments based on rotational tests, shear thinning as well as thixotropic behavior of thick-film pastes were investigated. Both are crucial parameters for continuous dispensing of 60 μm fingers with high aspect ratios. Flow rate fluctuations during dispensing though imply stress peaks that may disturb a continuous paste flow. Thus, a comparison of the flow rate of two pastes was conducted. A comparison of dispensed cells with screen-printed reference cells, on multi-crystalline wafer-material, showed an efficiency increase of 0.3%abs. on average. This is mainly caused by reduced finger widths and higher aspect ratios of dispensed fingers.
K Kalkandjiev, L Riegger, D Kosse, M Welsche, L Gutzweiler, R Zengerle, P Koltay
Microfluidics in silicon/polymer technology as a cost-efficient alternative to silicon/glas
2011 J Micromech Microeng, Band: 21, Seite: 025008 (8p
KurzfassungWe investigate TMMF photopolymer as a cost efficient alternative to glass for the liquid tight sealing of high density silicon microchannels. TMMF enables low temperature sealing and access to structures underneath via lamination and standard UV lithography instead of costly glass machining and anodic bonding. TMMF is highly transparent and has a low autofluorescence for wavelengths larger than 400 nm. As the photopolymer is too thin for implementing bulky World-to-Chip-interfaces, we propose adhesive bonding of COC modules. All materials were tested according ISO 10993-5 and showed no cytotoxic effects on the proliferation of L929 cells. To quantify the cost efficiency of the proposed techniques, we used an established Si/Pyrex nanoliter dispenser as a reference and replaced structured Pyrex wafers by TMMF laminates and COC modules. Thus, consumable costs and time effort were reduced by 90 % respectively 35 % for the sealing and 80 % respectively 75 % for implementing the World-to-Chip interface. Liquid tightness was proved by applying a pressure of 0,2 MPa for 5 h without delamination or cross talk between neighbouring microchannels separated from each other by 100 µm. In contrast to anodic bonding, the proposed techniques are tolerant to surface inhomogenities. They enable manufacturing of silicon/polymer microfluidics at significantly lower costs and without compromising the performance compared to corresponding silicon/glass devices.
M. Focke, D. Kosse, D. Al-Bamerni, S. Lutz, C. Mueller, H. Reinecke, R. Zengerle, F. von Stetten
Microthermoforming of microfluidic substrates by soft lithography (µTSL): optimization using design of experiments
2011 J Micromech Microeng, Band: 21, Nummer: 11, Seiten: 115001 - 115012
KurzfassungWe present a detailed analysis of microthermoforming by soft lithography (µTSL) for replication of foil-based microfluidic substrates. The process was systematically optimized by design of experiments (DOE) enabling fabrication of defect-free lab-on-a-chip devices. After the assessment of typical error patterns we optimized the process toward the minimum deviation between mold and thermoformed foil substrates. The following process parameters have most significant impact on the dimensional responses (p < 0.05): critical temperature before start of evacuation, molding temperature, pressure of pre-stretching and duration of pre-stretching as well as duration of molding pressure. The most relevant parameter is molding temperature with >40% relative impact. The DOE results in an empirical process model with a maximum deviation between the prediction and experimental proof of 2% for the optimum parameter set. Finally, process optimization is validated by the fabrication and testing of a microfluidic structure for blood plasma separation from human whole blood. The optimized process enabled metering of a nominal volume of 4.0 mu l of blood plasma with an accuracy deviation of 3% and a metering precision of +/- 7.0%. The µTSL process takes about 30 min and easily enables the replication of 300 mu m wide microchannels having vertical sidewalls without any draft angles in a well-controllable way. It proves to be suitable for multiple applications in the field of microfluidic devices.
Mitsakakis K, Gizeli E
Multi-sample acoustic biosensing microsystem for protein interaction analysis
2011 Biosens Bioelectron, Band: 26, Seiten: 4579 - 4584
Simon Thiele, Roland Zengerle, Christoph Ziegler
Nano-Morphology of a Polymer Electrolyte Fuel Cell Catalyst Layer—Imaging, Reconstruction and Analysis
2011 Nano Res, Band: 4, Nummer: 9, Seiten: 849 - 860
KurzfassungThe oxygen reduction reaction (ORR) in the cathode catalyst layer (CCL) of polymer electrolyte fuel cells (PEFC) is one of the major causes of performance loss during operation. In addition, the CCL is the most expensive component due to the use of a Pt catalyst. Apart from the ORR itself, the species transport to and from the reactive sites determines the performance of the PEFC. The effective transport properties of the species in the CCL depend on its nanostructure. Therefore a three-dimensional reconstruction of the CCL is required. A series of two-dimensional images was obtained from focused ion beam - scanning electron microscope (FIB-SEM) imaging and a segmentation method for the two-dimensional images has been developed. The pore size distribution (PSD) was calculated for the three-dimensional geometry. The influence of the alignment and the anisotropic pixel size on the PSD has been investigated. Pores were found in the range between 5 nm and 205 nm. Evaluation of the Knudsen number showed that gas transport in the CCL is governed by the transition flow regime. The liquid water transport can be described within continuum hydrodynamics by including suitable slip flow boundary conditions.
Ernst, Andreas, Ju, Lin, Vondenbusch, Bernhard, Zengerle, Roland, Koltay, Peter
Noncontact Determination of Velocity and Volume of Nanoliter Droplets on the Fly
2011 Ieee Sens J, Band: 11, Nummer: 8, Seiten: 1736 - 1742
KurzfassungWe present a sensor for measuring volume and velocity of dispensed nanoliter droplets in a noncontact manner on the fly. The sensor-setup has a total thickness of 3.2 mm and can easily be mounted underneath any given nanoliter dispenser for continuous online monitoring of its dispensing performance. The principle is based on the interaction of dispensed single droplets of sample liquid passing the electric field of an open plate capacitor. The effect depends on droplet parameters like volume, velocity, and dielectric constant and is discussed in the paper. The presented data analysis enables a velocity independent volume determination of water droplets in the range from 26 to 82 nl with an accuracy of 3 nl. The sensor signal is sensitive to the alignment of the flight path of the nanoliter droplets within the 1.2-mm wide open capacitor and can lead to systematic volume errors of up to Delta V approx. 12 nl. The impact of different dielectric constants can only be differentiated for very high variations; thus, the sensor needs to be calibrated to the different types of liquids.
F. Trenkle, S. Haeberle, R. Zengerle
Normally-closed peristaltic micropump with re-usable actuator and disposable fluidic chip
2011 Sensor Actuat B-chem, Band: 154, Nummer: 2, Seiten: 137 - 141
KurzfassungWe present a new peristaltic micropump offering three key features: (i) a disposable pump body and a reuseable actuator unit, (ii) an intrinsic normally-closed mechanism blocking unintended liquid flows up to a pressure of 100 kPa and (iii) a backpressure independent pump performance up to 40 kPa. The modular concept basing on a re-usable actuator unit and a low-cost disposable microfluidic chip enables an easy and cost-efficient exchange of all contaminated parts after use, which addresses especially the needs in the health care sector. The intrinsic normally-closed feature blocks liquid flow in both directions up to a pressure difference of 100 kPa when the electric power is off. The micropump is actuated in a peristaltic manner by three piezostack actuators. Up to a frequency of 15 Hz the pump rate increases linearly with operation frequency leading to a pump rate of 120 µL/min. This was proved for an operation voltage of 140V by pumping water. In addition the pump rate is independent on backpressure up to 40 kPa and shows a linear decrease for higher pressure differences. The maximum achievable backpressure at zero flow rate was extrapolated to be 180 kPa. As for all peristaltic micropumps, the pump is bidirectional, e.g. the pump direction can be changed forward to reverse mode.
Stefanie Rubenwolf, Sven Kerzenmacher, Roland Zengerle, Felix von Stetten
Strategies to extend the lifetime of bioelectrochemical enzyme electrodes for biosensing and biofuel cell applications
2011 Appl Microbiol Biot, Band: 89, Nummer: 5, Seiten: 1315 - 1322
KurzfassungEnzymes are powerful catalysts for biosensor and biofuel cell electrodes due to their unique substrate specificity. This specificity is defined by the amino acid chain's complex three-dimensional structure based on noncovalent forces, being also responsible for the very limited enzyme lifetime of days to weeks. Many electrochemical applications, however, would benefit from lifetimes over months to years. This mini-review provides a critical overview of strategies and ideas dealing with the problem of short enzyme lifetime, which limits the overall lifetime of bioelectrochemical electrodes. The most common approaches aim to stabilize the enzyme itself. Various immobilization techniques have been used to reduce flexibility of the amino acid chain by introducing covalent or non-covalent binding forces to external molecules. The enzyme can also be stabilized using genetic engineering methods to increase the binding forces within the protein or by optimizing the environment in order to reduce destabilizing interactions. In contrast, renewing the inactivated catalyst decouples overall system lifetime from the limited enzyme lifetime and thereby promises theoretically unlimited electrode lifetimes. Active catalyst can be supplied by exchanging the electrolyte repeatedly. Alternatively, integrated microorganisms can display the enzymes on their surface or secrete them to the electrolyte, allowing unattended power supply for long-term applications. Keywords Enzyme inactivation . Biofuel cell . Biosensor . Amino acid replacement . Immobilization . Self-regeneration
G. Grossmann, Woei-Jiun Guo, D. W. Ehrhardt, W. B. Frommer, R. V. Sit, S. R. Quake, M. Meier
The RootChip: An Integrated Microfluidic Chip for Plant Science
2011 The Plant Cell, Band: 23, Seiten: 4234 - 4240
KurzfassungStudying development and physiology of growing roots is challenging due to limitations regarding cellular and subcellular analysis under controlled environmental conditions. We describe a microfluidic chip platform, called RootChip, that integrates live-cell imaging of growth and metabolism of Arabidopsis thaliana roots with rapid modulation of environmental conditions. The RootChip has separate chambers for individual regulation of the microenvironment of multiple roots from multiple seedlings in parallel. We demonstrate the utility of The RootChip by monitoring time-resolved growth and cytosolic sugar levels at subcellular resolution in plants by a genetically encoded fluorescence sensor for glucose and galactose. The RootChip can be modified for use with roots from other plant species by adapting the chamber geometry and facilitates the systematic analysis of root growth and metabolism from multiple seedlings, paving the way for large-scale phenotyping of root metabolism and signaling.
T. Hutzenlaub, N. Paust, R. Zengerle, C. Ziegler
The effect of wetting properties on bubble dynamics and fuel distribution in the flow field of direct methanol fuel cells
2011 J Power Sources, Band: 196, Seiten: 8048 - 8056
KurzfassungWe investigate CO2 bubble dynamics on the anode side of a direct methanol fuel cell (DMFC). In contrast to previous studies, we analyse the effect of both channel wall and diffusion layer wettability by observing two-phase flow from the side at different mean velocities of the fuel supply. Hydrophobic and hydrophilic flow channel surfaces are compared experimentally. The hydrophilic flow channel leads to a minimum pressure drop along the channel. Bubbles show virtually no pinning and consequently travel at approximately the mean fuel velocity inside the channel. In contrast to this, we observe bubble pinning in the hydrophobic flow channels. The critical fuel velocities necessary for detachment of the bubbles mainly depends on bubble length. We identify and describe a new bubble bypass configuration where fuel bypass channels are solely generated in a favourable position underneath a blocking bubble along the diffusion layer. This enforces fuel to bypass the CO2 bubble at a large relative velocity close to the diffusion layer, thus enhancing mass transfer. Our experimental findings are in excellent agreement with a CFD/analytical model. This model allows for quantitative prediction of average bypass flow velocity.

2010

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A. Kloke, S. Rubenwolf, C. Bücking, J. Gescher, S. Kerzenmacher, R. Zengerle, F. von Stetten
A versatile miniature bioreactor and its application to bioelectrochemistry studies
2010 Biosens Bioelectron, Band: 25, Seiten: 2559 - 2565
KurzfassungOften, reproducible investigations on bio-microsystems essentially require a flexible but well-defined experimental setup, which in its features corresponds to a bioreactor. We therefore developed a miniature bioreactor with a volume in the range of a few millilitre that is assembled by alternate stacking of individual polycarbonate elements and silicone gaskets. All the necessary supply pipes are incorporated as bore holes or cavities within the individual elements. Their combination allows for a bioreactor assembly that is easily adaptable in size and functionality to experimental demands. It allows for controlling oxygen transfer as well as the monitoring of dissolved oxygen concentration and pH-value. The system provides access for media exchange or sterile sampling. A mass transfer coefficient for oxygen (kLa) of 4.3×10−3 s−1 at aflowrate of only 15 ml min−1 and a mixing time of 1.5 s at aflowrate of 11 ml min−1 were observed for the modular bioreactor. Single reactor chambers can be interconnected via ion-conductive membranes to form a two-chamber test setup for investigations on electrochemical systems such as fuel cells or sensors. The versatile applicability of this modular and flexible bioreactor was demonstrated by recording a growth curve of Escherichia coli (including monitoring of pH and oxygen) saturation, and also as by two bioelectrochemical experiments. In the first electrochemical experiment the use of the bioreactor enabled a direct comparison of electrode materials for a laccase-catalyzed oxygen reduction electrode. In a second experiment, the bioreactor was utilized to characterize the influence of outer membrane cytochromes on the performance of Shewanella oneidensis in a microbial fuel cell.
Lutz Riegger, Oliver Strohmeier, Bernd Faltin, Roland Zengerle, Peter Koltay
Adhesive bonding of microfluidic chips: influence of process parameters
2010 J Micromech Microeng, Band: 20, Seiten: 087003 - (5pp)
KurzfassungIn this note, the influence of process parameters for adhesive bonding as a versatile approach for the sealing of polymer microfluidic chips is investigated. Specifically, a process chain comprising pre-processing, adhesive transfer as well as post-processing is presented and parameter recommendations are provided. As a device for adhesive transfer, a modified laminator is utilized which transfers thin layers of adhesive onto the chip surface, only via a silicone roll. Using this device and a high temperature (Tg > 100 ◦C) epoxy adhesive, adhesive layers in the range of 2–4 μm can be reproducibly transferred (CV < 4%). For best bonding results, it is recommended to provide 2.5 μm thin layers of adhesive in combination with a subsequent evacuation step at 10 mbar for 3 h. Further, it is proposed to integrate capture channels near large, featureless areas to compensate for variations in processing and thus prevent clogging of channels.
K. Bürk, M. Wick, G. Roth, P. Decker, R. Voltz
Antineuronal antibodies in sporadic late-onset cerebellar ataxia
2010 J Neurol, Band: 257, Seiten: 59 - 62
KurzfassungSporadic late-onset cerebellar ataxia of unknown cause is considered a neurodegenerative disorder whose underlying mechanisms are still unknown. To identify antineuronal autoantibodies, immunohistochemical and immunoblotting techniques were performed in 67 patients with sporadic cerebellar degeneration of unknown cause. Elevated P/Q-type voltage-gated calcium channel (VGCC)-specific antibodies were found in eight patients (11.9%). There was no hint of a paraneoplastic disorder in any of the patients. The present findings suggest an autoimmune contribution to the pathophysiology of a subgroup of sporadic late-onset cerebellar ataxia.
Tobias Metz, Nils Paust, Roland Zengerle, Peter Koltay
Capillary driven movement of gas bubbles in tapered structures
2010 Microfluid Nanofluid, Band: 9, Seiten: 341 - 355
KurzfassungThis article presents a study on the capillary driven movement of gas bubbles confined in tapered channel configurations. These configurations can be used to transport growing gas bubbles in micro fluidic systems in a passive way, i.e. without external actuation. A typical application is the passive degassing of CO2 in micro direct methanol fuel cells (lDMFC). Here, a one-dimensional model for the bubble movement in wide tapered channels is derived and calibrated by experimental observations. The movement of gas bubbles is modelled on straight trajectories based on a balance of forces. The bubble geometry is considered as three dimensional. In the development of the model, the effects of surface tension, inertia, viscosity, dynamic contact angle and thin film deposition are considered. It is found that in addition to viscous dissipation, the dynamics related to the contact line—dynamic contact angle and thin film deposition—are essential to describe the gas bubble’s movement. Nevertheless, it was also found that both of these effects, as modelled within this work, have similar impact and are hard to distinguish. The model was calibrated against experiments in a parameter range relevant for the application of travelling gas bubbles in passive degassing structures for lDMFCs.
Stefanie Rubenwolf, Oliver Strohmeier, Arne Kloke, Sven Kerzenmacher, Roland Zengerle, Felix von Stetten
Carbon electrodes for direct electron transfer type laccase cathodes investigated by current density–cathode potential behaviour
2010 Biosens Bioelectron, Band: 26, Seiten: 841 - 845
KurzfassungDirect electron transfer from carbon electrodes to adsorbed laccase (EC 1.10.3.2) from Trametes versicolor is widely used to enable mediatorless enzymatic biofuel cell cathodes. However, data published so far are poorly comparable in terms of oxygen reduction performance. We thus present a comparative characterization of carbon-based electrode materials as cathode in half-cell configuration, employing adsorbed laccase as oxygen reduction catalyst. Open circuit potentials and performances were significantly increased by laccase adsorption, indicating the occurrence of direct electron transfer. At a potential of 0.5V vs. SCE volume-normalized current densities of approximately 10, 37, 40, 70, and 77 µAcm−3 were measured for cathodes nanotubes, carbon nanofibers and multi-walled carbon nanotubes, respectively. In addition, we could show that both, carbon nanotubes and porous carbon tubes exhibit dramatically lower current densities compared to graphite felt and carbon nanofibers when normalized to BET surface instead of electrode volume. Further work will be required to clarify whether this stems from material-dependent interaction of enzyme and electrode surface or constricted enzyme adsorption due to agglomeration of the nanotubes. In case of the latter, an improved dispersion of the nanotubes upon electrode fabrication may greatly enhance their performance.
Maximilian Focke, Fabian Stumpf, Günter Roth, Roland Zengerle, Felix von Stetten
Centrifugal microfluidic system für primary amplification and secondary real-time PCR
2010 Lab Chip, Band: 10, Seiten: 3210 - 3212
KurzfassungPre-amplification is a basis for numerous polymerase chain reaction (PCR) protocols but bears severe contamination risks due to handling of high-copy DNA samples. Therefore we developed a selfcontained centrifugal microfluidic system comprising pre-stored reagents; it enables pre-amplification of specific DNA sequences prior to automated aliquoting and real-time PCR in a modified commercial thermocycler.
Marc Karle, Junichi Miwa, Gregor Czilwik, Volker Auwärter, Günter Roth, Roland Zengerle, Felix von Stetten
Continuous microfluidic DNA extraction using phase-transfer magnetophoresis
2010 Lab Chip, Band: 10, Seiten: 3284 - 3290
KurzfassungThis paper reports a novel microfluidic-chip based platform using "phase-transfer magnetophoresis" enabling continuous biomolecule processing. As an example we demonstrate for the first time continuous DNA extraction from cell lysate on a microfluidic chip. After mixing bacterial Escherichia coli culture with superparamagnetic bead suspension, lysis and binding buffers, DNA is released from cells and captured by the beads. These DNA carrying beads are continuously transported across the interfaces between co-flowing laminar streams of sample mixture, washing and elution buffer. Bead actuation is achieved by applying a time-varying magnetic field generated by a rotating permanent magnet. Flagella-like chains of magnetic beads are formed and transported along the microfluidic channels by an interplay of fluid drag and periodic magnetic entrapment. The turnover time for DNA extraction was approximately 2 minutes with a sample flow rate of 0.75 µl/s and an eluate flow rate of 0.35 µl/s. DNA recovery was 147% (on average) compared to bead based batch-wise extraction in reference tubes within a dilution series experiment over 7 orders of magnitude. The novel platform is suggested for automation of various magnetic bead based applications that require continuous sample processing, e.g. continuous DNA extraction for flow-through PCR, capture and analysis of cells and continuous immunoassays. Potential applications are seen in the field of biological safety monitoring, bioprocess control, environmental monitoring, or epidemiological studies such as monitoring the load of antibiotic resistant bacteria in waste water from hospitals.
L. Riegger, M.M. Mielnik, A. Gulliksen, D. Mark, J. Steigert, S. Lutz, M. Clad, R. Zengerle, P. Koltay, J. Hoffmann
Dye-based coatings for hydrophobic valves and their application to polymer labs-on-a-chip
2010 J Micromech Microeng, Band: 20, Seite: 045021
KurzfassungWe provide a method for the selective surface patterning of microfluidic chips with hydrophobic fluoropolymers which is demonstrated by the fabrication of hydrophobic valves via dispensing. It enables efficient optical quality control for the surface patterning thus permitting the low-cost production of highly reproducible hydrophobic valves. Specifically, different dyes for fluoropolymers enabling visual quality control (QC) are investigated, and two fluoropolymer-solvent-dye solutions based on fluorescent quantum dots (QD) and carbon black (CB) are presented in detail. The latter creates superhydrophobic surfaces on arbitrary substrates, e.g. chips made from cyclic olefin copolymer (COC, water contact angle = 157.9◦), provides good visibility for the visual QC in polymer labs-on-a-chip and increases the burst pressures of the hydrophobic valves. Finally, an application is presented which aims at the on-chip amplification of mRNA based on defined flow control by hydrophobic valves is presented. Here, the optimization based on QC in combination with the Teflon-CB coating improves the burst pressure reproducibility from 14.5% down to 6.1% compared to Teflon-coated valves.
K Seidl, S Spieth, S Herwik, J Steigert, R Zengerle, O Paul, P Ruther
In-plane silicon probes for simultaneous neural recording and drug delivery
2010 J Micromech Microeng, Band: 20, Seiten: 105006 - (11pp)
KurzfassungThis paper reports on the design, fabrication and characterization of silicon-based microprobes for simultaneous neural recording and drug delivery. The fabrication technology is based on two-stage deep reactive ion etching combined with silicon wafer bonding and grinding to realize channel structures integrated in needle-like probe shafts. Liquids can be supplied to microfluidic devices via in-plane and out-of-plane ports. The liquid is dispensed at circular out-of-plane ports with a diameter of 25 μm and rectangular in-plane ports with dimensions of 50 × 50 μm2. Two-shaft probes with a pitch between shafts of 1.0 and 1.5 mm were realized. The probe shafts have a length of 8 mm and rectangular cross-sections of w x h (w = 250 μm and h = 200 or 250 μm). Each shaft contains one or two fluidic channels with a cross-section of 50 x 50 μm2. In addition, each probe shaft comprises four recording sites with diameters of 20 μm close to the outlet ports. Mechanical and fluidic characterization demonstrated the functionality of the probes. Typical infusion rates of 1.5 μL min−1 are achieved at a differential pressure of 1 kPa. The Pt-gray electrodes have an average electrode impedance of 260 ± 59 k Ohm at 1 kHz.
C. Bücking, F. Popp, S. Kerzenmacher, J. Gescher
Involvement and specificity of Shewanella oneidensis outer membrane cytochromes in the reduction of soluble and solid-phase terminal electronacceptors
2010 Fems Microbiol Lett, Band: 306, Seiten: 144 - 151
KurzfassungThe formation of outer membrane (OM) cytochromes seems to be a key step in the evolution of dissimilatory iron-reducing bacteria. They are believed to be the endpoints of an extended respiratory chain to the surface of the cell that establishes the connection to insoluble electron acceptors such as iron or manganese oxides. The gammaproteobacterium Shewanella oneidensis MR-1 contains the genetic information for five putative OM cytochromes. In this study, the role and specificity of these proteins were investigated. All experiments were conducted using a markerless deletion mutant in all five OM cytochromes that was complemented via the expression of single, plasmid-encoded genes. MtrC and MtrF were shown to be potent reductases of chelated ferric iron, birnessite, and a carbon anode in a microbial fuel cell. OmcA-producing cells were unable to catalyze iron and electrode reduction, although the protein was correctly produced and oriented. However, OmcA production resulted in a higher birnessite reduction rate compared with the mutant. The presence of the decaheme cytochrome SO_2931 as well as the diheme cytochrome SO_1659 did not rescue the phenotype of the deletion mutant.
Sascha Lutz, Patrick Weber, Max Focke, Bernd Faltin, Jochen Hoffmann, Claas Müller, Daniel Mark, Günter Roth, Peter Munday, Niall Armes, Olaf Piepenburg, Roland Zengerle, Felix von Stetten
Microfluidic lab-on-a-foil for nucleic acid analysis based on isothermal recombinase polymerase amplification (RPA)
2010 Lab Chip, Band: 10, Seiten: 887 - 893
KurzfassungFor the first time we demonstrate a self-sufficient lab-on-a-foil system for the fully automated analysis of nucleic acids which is based on the recently available isothermal recombinase polymerase amplification (RPA). The system consists of a novel, foil-based centrifugal microfluidic cartridge including prestored liquid and dry reagents, and a commercially available centrifugal analyzer for incubation at 37 C and real-time fluorescence detection. The system was characterized with an assay for the detection of the antibiotic resistance gene mecA of Staphylococcus aureus. The limit of detection was <10 copies and time-to-result was <20 min. Microfluidic unit operations comprise storage and release of liquid reagents, reconstitution of lyophilized reagents, aliquoting the sample into #30 independent reaction cavities, and mixing of reagents with the DNA samples. The foil-based cartridge was produced by blow-molding and sealed with a self-adhesive tape. The demonstrated system excels existing PCR based lab-on-a-chip platforms in terms of energy efficiency and time-to-result. Applications are suggested in the field of mobile point-of-care analysis, B-detection, or in combination with continuous monitoring systems.
M. Focke, F. Stumpf, B. Faltin, P. Reith, D. Bamarni, S. Wadle, C. Müller, H. Reinecke, J. Schrenzel, P. Francois, D. Mark, G. Roth, R. Zengerle, F. von Stetten
Microstructuring of polymer films for sensitive genotyping by real-time PCR on a centrifugal microfluidic platform
2010 Lab Chip, Band: 10, Seiten: 2519 - 2526
KurzfassungWe present a novel process flow enabling prototyping of microfluidic cartridges made out of polymer films. Its high performance is proven by implementation of a microfluidic genotyping assay testing 22 DNA samples including clinical isolates from patients infected by methicilin-resistant Staphylococcus aureus (MRSA). The microfluidic cartridges (disks) are fabricated by a novel process called microthermoforming by soft lithography (mTSL). Positive moulds are applied allowing for higher moulding precision and very easy demoulding when compared to conventional microthermoforming. High replication accuracies with geometric disk-to-disk variations of less than 1% are typical. We describe and characterise fabrication and application of microfluidic cartridges with wall thicknesses <188 mm thus enabling efficient thermocycling during real-time polymerase chain reaction (PCR). The microfluidic cartridges are designed for operation in a slightly modified commercial thermocycling instrument. This approach demonstrates new opportunities for both microfluidic developments and well-established laboratory instruments. The microfluidic protocol is controlled by centrifugal forces and divides the liquid sample parallely into independent aliquots of 9.8 ml (CV 3.4%, N ¼ 32 wells). The genotyping assays are performed with pre-stored primers and probes for real-time PCR showing a limit of detection well below 10 copies of DNA per reaction well (N ¼ 24 wells in 3 independent disks). The system was evaluated by 44 genotyping assays comprising 22 DNA samples plus duplicates in a total of 11 disks. The samples contained clinical samples of seven different genotypes of MRSA as well as positive and negative controls. The results are in excellent agreement with the reference in microtubes.
J. Tröndle, A. Ernst, W. Streule, R. Zengerle, P. Koltay
Non-contact optical sensor to detect free flying droplets in the nanolitre range
2010 Sensor Actuat A-phys, Band: 158, Seiten: 254 - 262
KurzfassungThis paper reports on a non-contact optical sensor for the detection of single droplets in flight. The sensor allows for online process control of non-contact dispensing systems delivering droplets in the nanolitre range. A dispensed liquid droplet, which passes through the optical transducer, leads to a change of the light intensity caused by absorption, reflection and diffraction. The change in light intensity measured by a photo transistor provides information about, e.g. droplet size, velocity and shape. This information is encoded in the time dependent signal shape that yields a characteristic “fingerprint”- signal for each droplet. The fabrication of the sensor is achieved by standard printing circuit board (PCB) technology. Therefore, an easy adaption of the sensor to different kinds of contactless dispensing system and furthermore a very cost efficient production is granted.
A. Hoff, A.-C. Bagu, T. André, G. Roth, K.-H. Wiesmüller, B. Gückel, R. Brock
Peptide microarrays for the profiling of cytotoxic T-lymphocyte activity using minimum numbers of cells
2010 Cancer Immunol Immunother, Band: 59, Seiten: 1379 - 1387
KurzfassungThe identification of epitopes that elicit cytotoxic T-lymphocyte activity is a prerequisite for the development of cancer-specific immunotherapies. However, especially the parallel characterization of several epitopes is limited by the availability of T cells. Microarrays have enabled an unprecedented miniaturization and parallelization in biological assays. Here, we developed peptide microarrays for the detection of CTL activity. MHC class I-binding peptide epitopes were pipetted onto polymer-coated glass slides. Target cells, loaded with the cell-impermeant dye calcein, were incubated on these arrays, followed by incubation with antigen-expanded CTLs. Cytotoxic activity was detected by release of calcein and detachment of target cells. With only 200,000 cells per microarray, CTLs could be detected at a frequency of 0.5% corresponding to 1,000 antigen-specific T cells. Target cells and CTLs only settled on peptide spots enabling a clear separation of individual epitopes. Even though no physical boundaries were present between the individual spots, peptide loading only occurred locally and cytolytic activity was confined to the spots carrying the specific epitope. The peptide microarrays provide a robust platform that implements the whole process from antigen presentation to the detection of CTL activity in a miniaturized format. The method surpasses all established methods in the minimum numbers of cells required. With antigen uptake occurring on the microarray, further applications are foreseen in the testing of antigen precursors that require uptake and processing prior to presentation.
Jochen Hoffmann, Daniel Mark, Sascha Lutz, Roland Zengerle, Felix von Stetten
Pre-storage of liquid reagents in glass ampoules for DNA extraction on a fully integrated lab-on-a-chip cartridge
2010 Lab Chip, Band: 10, Seiten: 1480 - 1484
KurzfassungSelf-containing, ready-to-use cartridges are essential for mobile Lab-on-a-Chip (LoaC) systems intended for Point-of-Care (POC) use. Up to now, a common weak point in many LoaC developments is the need to dispense liquid reagents into the test cartridge before or during processing of the assay. To address this issue we have developed an efficient method for fusing liquid reagents into glass ampoules, which are then sealed into a centrifugally operated cartridge. For on-demand reagent release, the ampoules are disrupted through the flexible lid of the cartridge. Upon centrifugation, 98.7 mL out of 100 mL (CV ¼ 2.5%) of the pre-stored contents are released into the microfluidic system. No liquid loss is observed for ethanol and H2O stored for 300 days at room temperature. Frozen storage is possible without damage to the ampoules. Applicability of this concept is demonstrated by performing a LoaC integrated DNA extraction after 140 days of reagent pre-storage. DNA yield from 32 mL of whole blood was up to 199 ng, which is 77% of an off-chip reference extraction. The presented approach allows the improvement of existing LoaC cartridges where pre-storage of liquid reagents was not implemented yet.
S. Kerzenmacher, U. Kräling, M. Schroeder, R. Brämer, R. Zengerle, F. von Stetten
Raney-platinum film electrodes for potentially implantable glucose fuel cells. Part 1: Nickel-free glucose oxidation anodes
2010 J Power Sources, Band: 195, Seiten: 6516 - 6523
KurzfassungWe present a novel fabrication route yielding Raney-platinum film electrodes intended as glucose oxidation anodes for potentially implantable fuel cells. Fabrication roots on thermal alloying of an extractable metal with bulk platinum at 200 ◦C for 48 h. In contrast to earlier works using carcinogenic nickel, we employ zinc as potentially biocompatible alloying partner. Microstructure analysis indicates that after removal of extractable zinc the porous Raney-platinum film (roughness factor ∼2700) consists predominantly of the Pt3Zn phase. Release of zinc during electrode operation can be expected to have no significant effect on physiological normal levels in blood and serum, which promises good biocompatibility. In contrast to previous anodes based on hydrogel-bound catalyst particles the novel anodes exhibit excellent resistance against hydrolytic and oxidative attack. Furthermore, they exhibit significantly lower polarization with up to approximately 100mV more negative electrode potentials in the current density range relevant for fuel cell operation. The anodes’ amenability to surface modification with protective polymers is demonstrated by the exemplary application of an approximately 300nm thin Nafion coating. This had only a marginal effect on the anode long-term stability and amino acid tolerance. While in physiological glucose solution after approximately 100 h of operation gradually increasing performance degradation occurs, rapid electrode polarization within 24 h is observed in artificial tissue fluid. Optimization approaches may include catalyst enhancement by adatom surface modification and the application of specifically designed protective polymers with controlled charge and mesh size.
S. Kerzenmacher, U. Kräling, M. Schroeder, R. Brämer, R. Zengerle, F. von Stetten
Raney-platinum film electrodes for potentially implantable glucose fuel cells. Part 2: Glucose-tolerant oxygen reduction cathodes
2010 J Power Sources, Band: 195, Seiten: 6524 - 6531
KurzfassungWe report the fabrication and characterization of glucose-tolerant Raney-platinum cathodes for oxygen reduction in potentially implantable glucose fuel. Fabricated by extraction of aluminum from 1µm thin platinum–aluminum bi-layers annealed at 300 °C, the novel cathodes show excellent resistance against hydrolytic and oxidative attack. This renders them superior over previous cathodes fabricated from hydrogel-bound catalyst particles. Annealing times of 60, 120, and 240 min result in approximately 400–550nm thin porous films (roughness factors ∼100–150), which contain platinum and aluminum in a ratio of ∼9:1. Aluminum release during electrode operation can be expected to have no significant effect on physiological normal levels, which promises good biocompatibility. Annealing time has a distinct influence on the density of trenches formed in the cathode. Higher trench densities lead to lower electrode potentials in the presence of glucose. This suggests that glucose sensitivity is governed by mixed potential formation resulting from oxygen depletion within the trenches. During performance characterization the diffusion resistance to be expected from tissue capsule formation upon electrode implantation was taken into account by placing a membrane in front of the cathode. Despite the resulting limited oxygen supply, cathodes prepared by annealing for 60 min show more positive electrode potentials than previous cathodes fabricated from hydrogel-bound activated carbon. Compared to operation in phosphate buffered saline containing 3.0mMglucose, a potential loss of approximately 120mV occurs in artificial tissue fluid. This can be reduced to approximately 90mV with a protective Nafion layer that is easily electro-coated onto the Raney-platinum film.
J. Leemhuis, E. Bouché, M. Frotscher, F. Henle, L. Hein, J. Herz, D. K. Meyer, M. Pichler, G. Roth, C. Schwan, H. H. Bock
Reelin Signals through Apolipoprotein E Receptor 2 and Cdc42 to Increase Growth Cone Motility and Filopodia Formation
2010 The Journal of Neuroscience, Band: 30, Nummer: 44, Seiten: 14759 - 14772
KurzfassungLipoprotein receptor signaling regulates the positioning and differentiation of postmitotic neurons during development and modulates neuronal plasticity in the mature brain. Depending on the contextual situation, the lipoprotein receptor ligand Reelin can have opposing effects on cortical neurons. We show that Reelin increases growth cone motility and filopodia formation, and identify the underlying signaling cascade. Reelin activates the Rho GTPase Cdc42, known for its role in neuronal morphogenesis and directed migration, in an apolipoprotein E receptor 2-, Disabled-1-, and phosphatidylinositol 3-kinase-dependent manner. We demonstrate that neuronal vesicle trafficking, a Cdc42-controlled process, is increased after Reelin treatment and further provide evidence that the peptidergic VIP/ PACAP38 system and Reelin can functionally interact to promote axonal branching. In conclusion, Reelin-induced activation of Cdc42 contributes to the regulation of the cytoskeleton of individual responsive neurons and converges with other signaling cascades to orchestrate Rho GTPase activity and promote neuronal development. Our data link the observation that defects in Rho GTPases and Reelin signaling are responsible for developmental defects leading to neurological and psychiatric disorders.
J. D. Jeyaprakash S. Samuel, T. Brenner, O. Prucker, M. Grumann, J. Ducree, R. Zengerle, J. Rühe
Tailormade Microfluidic Devices Through Photochemical Surface Modification
2010 Macromol Chem Phys, Band: 211, Seiten: 195 - 203
KurzfassungA new pathway for the generation of polymer-based microfluidic devices with tailor-made surface chemistry is described. A simple photochemical process is used to covalently bind polymer molecules to the surfaces of microchannels fabricated by hot embossing. The substrates for the embossing process have the format of a compact disk (CD). CDs from polymethylmethacrylate and polyethylene-co-norbornene were chosen due to their good optical properties. Thin films of polymers containing photoactive benzophenone units were deposited onto the surface of the thus generated devices. These films were subsequently irradiated with UV light leading to the surface-attachment of ultrathin polymer networks. In contrast to their unmodified peers, the obtained,modified microfluidic channels coated with hydrophilic, photoattached layers can be filled in a straightforward manner with water by capillary forces. Channels coated by thin films of poly(ethyloxazoline) show complete resistance to non-specific protein binding. Generation of hydrophobic patches inside the modified microfluidic channels using benzophenone-containing fluoropolymers allows the generation of passive microfluidic valves to direct fluid motion in these CD-based devices.
F. Hedrich, K. Kliche, M. Storz, S. Billat, M. Ashauer, R. Zengerle
Thermal flow sensors for MEMS spirometric devices
2010 Sensors and Actuators A, Band: 162, Seiten: 373 - 378
KurzfassungSleep-specific respiration disturbances and their coprevalences with basic cardiovascular diseases constitute a supplementary risk for the cardiovascular system and require both urgent diagnostic assessment as well as consistent therapeutic measures. Thus, the need for controlling the breathing of these patients over a long period has become a new focus of interest. Due to its small thermal mass, the micro-machined thermal flow sensor fits the specific requirements in the patient respiration control of high dynamic flow range combined with a fast response time. We present the development of our flow sensor with a special adaptation for spirometric applications. The sensor exhibits a high accuracy, a short response time (<1 ms) and a low power consumption (10mW). Furthermore, heating structures are added onto the chip to prevent condensation. Hence, it represents an attractive solution for the use of portable equipment for preventive exploration of breathing in home-care applications.

2009

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A. Ernst, W. Streule, N. Schmitt, R. Zengerle, P. Koltay
A capacitive sensor for non-contact nanoliter droplet detection
2009 Sensor Actuat A-phys, Band: 153, Seiten: 57 - 63
KurzfassungThis paper reports on a sensor for the detection of microdroplets in flight. The presented sensor is based on a capacitive principle, which allows for non-contact monitoring of a complete droplet dispensing process. In the presented experiments the change in capacity caused by liquid droplets in the range of a few nanoliters passing through the electric field of the sensor is studied. From the capacitive change the droplet presence can be deduced with a reliability of 100%, which means that every single droplet dispensed within the experiments caused a significant signal change. In addition, the sensor signal is sensitive to the droplet’s volume V, dielectric constant εr (epsilon) and velocity v. It turns out that every specific droplet exhibits a characteristic “fingerprint” signal dependingonthese parameters. Especially the droplet volume correlates very well with the peak value of the extracted signal. Therefore, the calibrated sensor is able to determine the volume of dispensed droplets in the range from20 to 65 nl with a resolution of less than 2 nl. Furthermore, the printed circuit board (PCB) technology applied for fabrication of the sensor enables a very cost efficient and flexible realisation of the whole sensor unit. The non-contact capacitive principle prevents contamination and loss of media. Therefore, the proposed approach is well suited for high precision droplet presence detection and low cost online monitoring of liquid volumes in microdispensing processes for various applications.
S. Kerzenmacher, K. Mutschler, U. Kräling, H. Baumer, J. Ducrée, R. Zengerle, F. von Stetten
A complete testing environment for the automated parallel performance characterization of biofuel cells: design, validation, and application
2009 J Appl Electrochem, Band: 39, Nummer: 9, Seiten: 1477 - 1485
KurzfassungWe present a complete testing environment for the parallel performance characterization of biofuel cells. Besides rapid-assembly electrode fixtures and an aseptic electrochemical reactor, it comprises a 24-channel electrical testing system that bridges the gap between simple load resistors and costly multi-channel potentiostats. The computer- controlled testing system features active current control to enable the forced operation of half-cell electrodes, whereas galvanic isolation between individual channels ensures interference-free operation of multiple fuel cells immersed in a common testing solution. Implemented into the control software is an automated procedure for the step-wise recording of polarization curves. This way, performance overestimation due to a too fast increase in load current can be circumvented. As an applicational example, three abiotically catalyzed glucose fuel cells are characterized simultaneously in a common testing solution. Complete disclosure of the electrical system (incl. printed circuit board layout, control software, and circuit diagrams) in the online supplementary material accompanying this paper allows researchers to replicate our setup in their lab and can serve as inspiration for the design of similar systems adapted to specific requirements.
Steigert, Jürgen, Strasser, Monika, Wangler, Nicolai, Brett, Olivia, Streule, Wolfgang, Koltay, Peter, Daub, Martina, Zengerle, Roland
A modular diffusion barrier based on phase separation for localized delivery of discrete drug volumes in aqueous environments
2009 Lab Chip, Band: 9, Seiten: 1801 - 1805
KurzfassungWe present a new tool for the precisely controlled transfer of individual picoliter (pL) droplets in the range of 150–950 pL at user defined local positions within aqueous liquid environments while avoiding any leakage by diffusion. This is achieved by a low-cost, disposable and biocompatible cap that can be placed on top of any pL-dispenser and generates a phase-gap between dispensing agent and target liquid when the dispenser is dipped into the latter. We developed two different working modes: (i) the standard mode enables an instant injection (<< 1 ms) of the droplet into the liquid environment and (ii) the focus mode further increases the spatial resolution from 100 µm to 50 µm at the cost of slowing down the injection time. For the phase-gap we have proven an excellent long-term stability of more than 30 hours against capillary priming.
N. Paust, Ch. Litterst, T. Metz, M. Eck, Ch. Ziegler, R. Zengerle, P. Koltay
Capillary-driven pumping for passive degassing and fuel supply in direct methanol fuel cells
2009 Microfluid Nanofluid, Band: 7, Seiten: 531 - 543
KurzfassungIn this paper we present a new concept of creating and using capillary pressure gradients for passive degassing and passive methanol supply in direct methanol fuel cells (DMFCs). An anode flow field consisting of parallel tapered channels structures is applied to achieve the passive supply mechanism. The flow is propelled by the surface forces of deformed CO2 bubbles, generated as a reaction product during DMFC operation. This work focuses on studying the influence of channel geometry and surface properties on the capillary-induced liquid flow rates at various bubbly gas flow rates. Besides the aspect ratios and opening angles of the tapered channels, the static contact angle as well as the effect of contact angle hysteresis has been identified to significantly influence the liquid flow rates induced by capillary forces at the bubble menisci. Applying the novel concept, we show that the liquid flow rates are up to thirteen times higher than the methanol oxidation reaction on the anode requires. Experimental results are presented that demonstrate the continuous passive operation of a DMFC for more than 15 h.
Daniel Mark, Tobias Metz, Stefan Haeberle, Sascha Lutz, Jens Ducrée, Roland Zengerle, Felix von Stetten
Centrifugo-Pneumatic Valve for Metering of Highly Wetting Liquids on Centrifugal Microfluidic Platforms
2009 Lab Chip, Band: 9, Seiten: 3599 - 3603
KurzfassungWe designed and experimentally validated a new type of passive valve for centrifugal microfluidic platforms. A liquid column entering an unvented receiving chamber is stopped by the counter-pressure of compressed air. This valve opens under defined conditions at high centrifugal frequencies at which the interface between liquid and air becomes unstable and enables a phase exchange, forwarding the liquid. Burst frequencies of the valve were determined for liquids typically used in biochemical assays: pure water, water with detergent concentrations between 0.01 % and 10 %, and pure ethanol. Burst frequencies between 8.5 ± 0.6 Hz and 27.9 ± 2.0 Hz were measured for different surface tensions. The burst frequencies can be tuned by simple geometrical changes in the valving structure. The valve does not require ultra-precise structures or local surface modifications and is therefore ideal for low-cost microfluidic polymer disks. Potential applications are in the field of mulitparameter- and panel analysis, such as PCR-genotyping.
Mark, Daniel, Haeberle, Stefan, Zengerle, Roland, Ducree, Jens, Vladisavljevic, Goran T.
Manufacture of chitosan microbeads using centrifugally driven flow of gel-forming solutions through a polymeric micronozzle
2009 J Colloid Interf Sci, Band: 336, Seiten: 634 - 641
KurzfassungA centrifugally driven pulse-free flow was used for the generation of uniform chitosan beads tunable in diameter between 148 and 257 µm. The 2 % chitosan solution was extruded through a polymeric nozzle and the drops were gelated in 10 % tripolyphosphate (TPP) solution at pH 4.0. The coefficient of variation (CV) of the bead diameters issued from different nozzles could be reduced to 15 %.The production process requires a single motor as the sole actively actuated component. The production rate was 45 beads per second with one nozzle spinning at 44 Hz, scaling with the sixth power of the rotational frequency. An analytical model for the bead diameter and production rate is presented and validated by the experimental data. The shrinkage of chitosan drops during gelation was estimated from the observations and the theoretical model. Keywords: microbeads, chitosan, centrifugal, encapsulation, microfluidics
Katrin Bürk, Marie-Louise Farecki, Georg Lamprecht, Guenter Roth, Patrice Decker, Michael Weller, Hans-Georg Rammensee, Wolfang Oertel
Neurological Symptoms in Patients with Biopsy Proven Celiac Disease
2009 Movement Disord, Band: 24, Nummer: 26, Seiten: 2358 - 2362
KurzfassungIn celiac disease (CD), the gut is the typical manifestation site but atypical neurological presentations are thought to occur in 6 to 10% with cerebellar ataxia being the most frequent symptom. Most studies in this field are focused on patients under primary neurological care. To exclude such an observation bias, patients with biopsy proven celiac disease were screened for neurological disease. A total of 72 patients with biopsy proven celiac disease (CD) (mean age 51 6 15 years, mean disease duration 8 6 11 years) were recruited through advertisements. All participants adhered to a gluten-free diet. Patients were interviewed following a standard questionnaire and examined clinically for neurological symptoms. Medical history revealed neurological disorders such as migraine (28%), carpal tunnel syndrome (20%), vestibular dysfunction (8%), seizures (6%), and myelitis (3%). Interestingly, 35% of patients with CD reported of a history of psychiatric disease including depression, personality changes, or even psychosis. Physical examination yielded stance and gait problems in about one third of patients that could be attributed to afferent ataxia in 26%, vestibular dysfunction in 6%, and cerebellar ataxia in 6%. Other motor features such as basal ganglia symptoms, pyramidal tract signs, tics, and myoclonus were infrequent. 35% of patients with CD showed deep sensory loss and reduced ankle reflexes in 14%. Gait disturbances in CD do not only result from cerebellar ataxia but also from proprioceptive or vestibular impairment. Neurological problems may even develop despite strict adherence to a gluten-free diet.
Paust, N, Krumbholz, S, Munt, S, Müller, C, Koltay, P, Zengerle, R, Ziegler, C
Self-Regulating Passive Fuel Supply for Small Direct Methanol Fuel Cells Operating in All Orientations
2009 J Power Sources, Band: 192, Seiten: 442 - 450
KurzfassungA microfluidic fuel supply concept for passive and portable Direct Methanol Fuel Cells (DMFCs) that operate in all spatial orientations is presented. The concept has been proven by fabricating and testing a passive DMFC prototype. Methanol transport at the anode is propelled by the surface energy of deformed carbon dioxide bubbles, generated as a reaction product during DMFC operation. The experimental study reveals that in any orientation, the proposed pumping mechanism transports at least 3.5 times more methanol to the reactive area of the DMFC than the stoichiometry of the methanol oxidation would require to sustain DMFC operation. Additionally, the flow rates closely follow the applied electric load; hence the pumping mechanism is self-regulating. Oxygen is supplied to the cathode by diffusion and the reaction product water is transported out of the fuel cell along a continuous capillary pressure gradient. Results are presented that demonstrate the continuous passive operation for more than 40 hours at ambient temperature with a power output of p = 4 mW cm-2 in the preferred vertical orientation and of p = 3.2 mW cm-2 in the least favourable horizontal orientation with the anode facing downwards. Keywords: passive DMFC; self-regulating fuel supply; capillary-force-driven bubble pump
Thomas Steiner, Claudio Cupelli, Roland Zengerle, Mark Santer
Simulation of advanced microfluidic systems with dissipative particle dynamics
2009 Microfluid Nanofluid, Band: 7, Nummer: 3, Seiten: 307 - 323
Jochen Rupp, Manuela Schmidt, Bettina Günther, Michael Stumber, Sven Zinober, Roland Müller-Fiedler, Bashir Alabsi, Peter Rothacher, Claas Müller, Holger Reinecke, Roland Zengerle, Martina Daub
The Way to High Volume Fabrication of Lab-on-a-Chip Devices – A Technological Approach for Polymer Based Microfluidic Systems with Integrated Active Valves and Pumps
2009 J Electron Packaging, Band: 6, Seiten: 1 - 7
Steinert C.P., Kalkandjiev, K., Zengerle, R., Koltay, P.
TopSpot® Vario: a novel microarrayer system for highly flexible and highly parallel picoliter dispensing
2009 Biomed Microdevices, Band: 11, Nummer: 4, Seiten: 755 - 761
KurzfassungThe standard TopSpot® technology has been successfully used in the recent years for the highly parallel nanoliter dispensing of bio-chemical substances for microarray printing. It is based on a pneumatically actuated printhead which enables non-contact microarray fabrication at a pitch of typically 500 μm. This paper reports on a new and improved way of operating the printheads termed TopSpot® Vario technology, using an incompressible material between the piezo actuator and the dispensing medium. The advantage of the incompressible medium is the direct relation between the displacement amplitude and the ejected liquid volume. Earlier reports stated that the filling of the printheads is a key issue. In this paper we report on the implementation and characterization of a new printhead design including microchannels for bubble free priming of blind channels. Microarray fabrication was successfully conducted with four different types of protein.
C. Ziegler, D. Gerteisen
Validity of two-phase polymer electrolyte membrane fuel cell models with respect to the gas diffusion layer
2009 J Power Sources, Band: 188, Nummer: 1, Seiten: 184 - 191
KurzfassungA dynamic two-phase model of a proton exchange membrane fuel cell with respect to the gas diffusion layer (GDL) is presented and compared with chronoamperometric experiments. Very good agreement between experiment and simulation is achieved for potential step voltammetry (PSV) and sine wave testing (SWT). Homogenized two-phase models can be categorized in unsaturated flow theory (UFT) and multiphase mixture (M2) models. Both model approaches use the continuum hypothesis as fundamental assumption. Cyclic voltammetry experiments show that there is a deterministic and a stochastic liquid transport mode depending on the fraction of hydrophilic pores of the GDL. ESEM imaging is used to investigate the morphology of the liquid water accumulation in the pores oftwo different media (unteflonated Toray-TGP-H-090 and hydrophobic Freudenberg H2315 I3). The morphology of the liquid water accumulation are related with the cell behavior. The results show that UFT and M2two-phase models are a valid approach for diffusion media with large fraction of hydrophilic pores such as unteflonated Toray-TGP-H paper. However, the use of the homgenized UFT and M2 models appears to be invalid for GDLs with large fraction of hydrophobic pores that corresponds to a high average contact angle of the GDL. Keywords Proton exchange membrane fuel cell; Two-phase model; Validity; GDL

2008

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Jürgen Steigert, Olivia Brett, Claas Müller, Monika Strasser, Nicolai Wangler, Holger Reinecke, Martina Daub, Roland Zengerle
A versatile and flexible low-temperature full-wafer bonding process of monolithic 3D microfluidic structures in SU-8
2008 J Micromech Microeng, Band: 18, Nummer: 9, Seiten: 1 - 8
KurzfassungWe present a versatile fabrication process for the precise fabrication of embedded three-dimensional microfluidic structures in SU-8 photoresist. The full-wafer bond process based on a polyester (PET) handling layer enhances the previous low-temperature bonding technology. We achieved an extremely high bond strength of 45 MPa while requiring only small anchoring structures. Small channel structures with an aspect ratio >2 as well as wide membranes with an aspect ratio <0.02 were successfully bonded to realize precisely defined channel structures. Furthermore, the developed process features high yields (>80%) and enables the integration of microelectronics. The flexibility of the fabrication process is presented in two contrary applications. A completely freestanding and transparent SU-8 foil with a thickness of 225 μm featuring embedded 3D microchannels was fabricated. Also, high quality ink-jet dispensers were successfully fabricated whereas the dispenser quality mainly depends on the channel quality.
S. Haeberle, L. Naegele, R. Burger, F. von Stetten, R. Zengerle, J. Ducrée
Alginate bead fabrication and encapsulation of living cells under centrifugally induced artificial gravity conditions
2008 J Microencapsul, Band: 25, Nummer: 4, Seiten: 267 - 274
KurzfassungWe present a novel method for the direct, centrifugally induced fabrication of small, Ca2+-hardened alginate beads at polymer-tube micronozzles. The bead diameter can arbitrarily be adjusted between 180 µm and 800 µm by the nozzle geometry and spinning frequencies between 5 Hz and 28 Hz. The size distribution of the main peak features a CV of 7 – 16%, only. Up to 600 beads per second and channel are issued from the micronozzle through an air gap towards the curing agent contained in a standard lab tube (“Eppi”). Several tubes can be mounted on a “flying bucket” rotor where they align horizontally under rotation and return to a vertical position as soon as the rotor is at rest. The centrifugally induced, ultra-high artificial gravity conditions (up to 180 g) even allow the micro-encapsulation of alginate solutions displaying viscosities up to 50 Pa s, i.e. about 50,000 times the viscosity of water! With this low cost technology for micro encapsulation, HN25 and PC12 cells have successfully been encapsulated while maintaining vitality.
Kerzenmacher S, Ducree J, Zengerle R, von Stetten F
An Abiotically Catalyzed Glucose Fuel Cell for Powering Medical Implants: Reconstructed Manufacturing Protocol and Analysis of Performance
2008 J Power Sources, Band: 182, Nummer: 1, Seiten: 66 - 75
KurzfassungAlthough the first abiotically catalyzed glucose fuel cells have already been developed as sustainable power supply for medical implants in the 1970s, no detailed information concerning the fabrication of these devices has been published so far. Here we present a comprehensive manufacturing protocol for such a fuel cell, together with a detailed analysis of long-term stability performance in neutral buffer containing physiological amounts of glucose and oxygen. In air saturated solution a power density of (3.3 +/- 0.2) µW cm-2 is displayed after 10 days of operation, that gradually decreases to a value of (1.0 +/- 0.05) µW cm-2 in the course of 224 days. A novelty of this work is the characterization of fuel cell performance with individually resolved electrode potentials. Using this technique, we can show that the major part of performance degradation originates from a positive shift of the anode potential, indicating that a more poisoning resistant glucose oxidation catalyst would improve the degradation behavior of the fuel cell. As further factors influencing performance an incomplete reactant separation and a mass transfer governed cathode reaction under the relatively low oxygen partial pressures of body tissue have been identified. Consequently we propose an oxygen depleting electrode interlayer and the application of more effective oxygen reduction catalysts as promising strategies to further improve the fuel cell performance under physiological concentrations of glucose and oxygen.
M. Daub, R. Zengerle
Bioprinting on Chip
2008 Encyclopedia of Microfluidics and Nanofluidics, Seiten: 124 - 138
Glatzel T, Cupelli C, Lindemann T, Litterst C, Moosmann C, Niekrawietz R, Streule W, Zengerle R, Koltay P
Computational fluid dynamics (CFD) software tools for microfluidic applications - A case study
2008 Comput Fluids, Band: 37, Nummer: 3, Seiten: 218 - 235
Claudio Cupelli, Björn Henrich, Thomas Glatzel, Roland Zengerle, Michael Moseler, Mark Santer
Dynamic capillary wetting studied with dissipative particle dynamics
2008 New Journal of Physics, Band: 10, Seite: 043009
KurzfassungWe present a study on dynamic capillary wetting in the framework of dissipative particle dynamics (DPD) based on a novel wall model for wetting on solid boundaries. We consider capillary impregnation of a slit pore in two situations: (i) forced (piston-driven) steady state flow and (ii) capillarity driven imbibition out of a finite reservoir. The dynamic contact angle behavior under condition (i) is consistent with the hydrodynamic theories of Cox under partial wetting conditions and Eggers for complete wetting. The flow field near the contact line shows a region of apparent slip flow which provides a natural way of avoiding a stress singularity at the triple line. The dynamics of the capillary imbibition, i.e. condition (ii), is consistently described by the Lucas–Washburn equation augmented by expressions that account for inertia and the influence of the dynamic contact angle.
Diana Hodgins, Arnaud Bertsch, Nils Post, Manfred Frischholz, Bart Volckaerts, John Spensley, J.M. Wasikiewicz, Henry Higgins, Felix von Stetten, Laurence Kenney
Healthy Aims: Developing New Medical Implants and Diagnostic Equipment
2008 Pervasive Computing, Band: 7, Nummer: 1, Seiten: 14 - 21
J. Hermann, C. Ziegler
Modeling the Dynamic Water Transport in the Porous Layers of PEM Fuel Cells Based on Numerical Upscaling
2008 J Electrochem Soc, Band: 155, Nummer: 10, Seiten: B1066 - B1076
Billat,S., Kliche,K., Gronmaier,R, Nommensen,P., Auber,J., Hedrich,F., Zengerle,R.
Monolithic integration of micro-channel on disposable flow sensors for medical applications
2008 Sensors and Actuators A, Band: 145-146, Seiten: 66 - 74
T. Metz, J. Viertel, C. Müller, S. Kerzenmacher, N. Paust, R. Zengerle, P. Koltay
Passive water management for µfuel-cells using capillary microstructures
2008 J Micromech Microeng, Band: 18, Nummer: 10
KurzfassungIn this work we present a novel system for the passive water management in polymer electrolyte fuel cells (PEMFC) based on capillary effects in microstructures. The system removes abundant water that occurs at low temperatures at a fuel cell cathode and secures the humidity of the electrolyte membrane on higher temperatures. Liquid water is removed by hydrophilic gas supply channels with a tapered cross section as presented previously, and further transported by a system of capillary channels and a layer of nonwoven material. To prevent the membrane from running dry, a storage area in the nonwoven layer is introduced, controlled by a novel passive capillary overflow valve. The valve controls whether water is stored or finally disposed by gravity and evaporation. Experiments in a model system show that the nonwoven material is capable of removing all liquid water that can be produced by the fuel cell. A miniaturized fuel cell utilizing the novel water removal system was fabricated and experiments show that the system can stabilize the performance during changes of electrical load. Clearing the drowned miniaturized fuel cell flow field was proven and required 2 min. To make the capillary effects available for the originally hydrophobic graphite composite materials that were used to fabricate the flow fields, hydrophilic grafting based on photochemistry was applied to the material and contact angles of about 40° could be achieved and preserved for at least three months.
Tobias Metz, Wolfgang Streule, Roland Zengerle, Peter Koltay
StarTube: A tube with reduced contact line for minimized gas bubble resistance
2008 Langmuir, Band: 24, Nummer: 17, Seiten: 9204 - 9206
KurzfassungIn this work we introduce a novel tubing design for multiphase flow that minimizes gas bubble resistance. The design termed “StarTube” has a lamella-like wall structure and was developed to prevent clogging by gas bubbles. This is performed by forcing gas bubbles into the center of the tube by capillary forces, allowing liquid to bypass in the outer grooves. It was found that the mobility of gas bubbles in such a tube is increased more than 1 order of magnitude. The reason is that the contact line perpendicular to the direction of flow is minimized, reducing resistant effects related to the contact linesin particular, contact angle hysteresis.
C. Litterst, T. Metz, R. Zengerle, P. Koltay
Static and dynamic behaviour of gas bubbles in T-shaped non-clogging micro-channels
2008 Microfluid Nanofluid, Band: 5, Nummer: 6, Seiten: 775 - 784
KurzfassungPreventing micro-channels from clogging is a major issue in most micro and nanofluidic systems. The T-shaped channel first reported by Kohnle et al. prevents micro-channels from clogging by the aid of the equilibrium bubble position in such a geometry. This work is concerned with the static and dynamic behaviour of bubbles in such T-shaped microchannels. The aspect ratio of a rectangle enclosing the Tshaped channel and the contact angle of the walls are the main parameters influencing the static and dynamic bubble behaviour. It is investigated in this article how these parameters relate to the equilibrium bubble shape and how optimum bubble velocities can be achieved inside the channel. An analytical model depending on the contact angle and the channel geometry is presented that allows to determine the bubble configuration inside the channel by minimizing the bubble’s surface energy. A second model is derived to predict the velocity of gas bubbles driven by buoyancy in vertical T-shaped channels. The model is applied to design T-shaped channels with a maximum mobility of gas bubbles. Experiments with MEMS fabricated devices and CFD simulations are used to verify the models. Furthermore design rules for an optimum nonclogging channel geometry which provides the highest gas bubble mobility are given. Keywords Gas bubble, Micro-channel, Clogging, Interfacial energy

2007

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Björn Henrich, Claudio Cupelli, Michael Moseler, Mark Santer
An adhesive DPD wall model for dynamic wetting
2007 Europhys Lett, Band: 80, Seite: 60004
KurzfassungA novel method for the treatment of solid-liquid interfaces in the framework of dissipative particle dynamics (DPD) is presented. The solid is represented by an amorphous, thermally rough ensemble of particles. Since the density of this phase is chosen commensurate to the liquid, artefacts of alternative wall models such as particle layering or spurious variations in temperature are avoided. An adjustable static contact angle permits the convenient study of complex wetting phenomena. We explore the physical behaviour of this boundary model with respect to bulk Poiseuille and Couette flow as well as forced wetting and the behaviour of dynamic contact angles.
Haeberle S, Zengerle R, Ducrée J
Centrifugal Generation and Manipulation of Droplet Emulsions
2007 Microfluidics Nanofluidics, Band: 3, Nummer: 1, Seiten: 65 - 75
Haeberle,S., Schmitt,N., Zengerle,R., Ducrée,J.
Centrifugo-Magnetic Pump for Gas-to-Liquid Sampling
2007 Sensors and Actuators A-Physical, Band: 135, Nummer: 1, Seiten: 28 - 33
Hu Min, Lindemann T, Goettsche T, Kohnle J, Zengerle R, Koltay P
Discrete Chemical Release from a Microfluidic Chip
2007 J Microelectromech S, Band: 16, Nummer: 4, Seiten: 786 - 794
KurzfassungWe demonstrate a discrete chemical release method, capable of delivering picoliter volumes of chemical solutions with 100 μm of spatial resolution and 20 μs of response time. The releasing mechanism is based on the transfer of pulsed liquid plugs through a hydrophobic air chamber. A microfluidic chip consisting of such a releasing array (2 × 10) is designed and fabricated. Numerical simulation and experimental testing are performed to verify the working principle. Advantages of this release-on-demand technology include leakage-free, fast response and versatile control of release profile. This new method could be a key enabling technology for precisely controlled release of biochemicals for modern pharmacological and biological research. Index Terms: Air gap, discrete chemical stimulation, microfluidic chip, picoliter chemical release, pulsed liquid ejection.
Steigert,J., Brenner,T., Grumann,M., Riegger,L., Lutz,S., Zengerle,R., Ducree,J.
Integrated siphon-based metering and sedimentation of whole blood on a hydrophilic lab-on-a-disk
2007 Biomed.Microdevices, Nummer: 9, Seiten: 675 - 679
Zibek S, Stett A, Koltay P, Hu M, Zengerle R, Nisch W, Stelzle M
Localized functional chemical stimulation of TE 671 cells cultured on nanoporous membrane by calcein and acetylcholine
2007 Biophys J, Band: 92, Nummer: 1, Seiten: L04 - 6L
KurzfassungAcetylcholine sensitive TE 671 cells were cultured on nanoporous membranes and chemically stimulated by localized application of i), calcein-AM and ii), acetylcholine, respectively, onto the bottom face of the membrane employing an ink jet print head. Stimulus correlated response of cells was recorded by fluorescence microscopy with temporal and spatial resolution. Calcein fluorescence develops as a result of intracellular enzymatic conversion of calcein-AM, whereas Ca2+ imaging using fluo-4 dye was employed to visualize cellular response to acetylcholine stimulation. Using 25 pl droplets and substance concentration ranging from 10 µM to 1 mM on Nucleopore membranes with pore diameters between 50 nm and 1 µm, a resolution on the order of 50 µm was achieved.
Haeberle,S., Zengerle,R.
Microfluidic platforms for lab-on-a-chip applications
2007 Lab Chip, Band: 7, Seiten: 1094 - 1110
KurzfassungWe review microfluidic platforms that enable the miniaturization, integration and automation of biochemical assays. Nowadays nearly an unmanageable variety of alternative approaches exists that can do this in principle. Here we focus on those kinds of platforms only that allow performance of a set of microfluidic functions—defined as microfluidic unit operations—which can be easily combined within a well defined and consistent fabrication technology to implement application specific biochemical assays in an easy, flexible and ideally monolithically way. The microfluidic platforms discussed in the following are capillary test strips, also known as lateral flow assays, the ‘‘microfluidic large scale integration’’ approach, centrifugal microfluidics, the electrokinetic platform, pressure driven droplet based microfluidics, electrowetting based microfluidics, SAW driven microfluidics and, last but not least, ‘‘free scalable non-contact dispensing’’. The microfluidic unit operations discussed within those platforms are fluid transport, metering, mixing, switching, incubation, separation, droplet formation, droplet splitting, nL and pL dispensing, and detection.
Lindemann,T., Ashauer,H., Duccio,Y.Y., Sassano,S., Zengerle,R., Koltay,P.
One Inch Thermal Bubble Jet Printhead With Laser Structured Integrated Polyimide Nozzle Plate
2007 Journal of Microelectromechanical Systems, Band: 16, Nummer: 2, Seiten: 420 - 428
Metz,T., Paust,N., Müller,C., Zengerle,R., Koltay,P.
Passive water removal in fuel cells by capillary droplet actuation
2007 Sensors & Actuators: A.Physical, Band: Special Issue MEMS 2007
Steigert J, Haeberle S, Brenner T, Mueller C, Steinert C P, Koltay P, Gottschlich N, Reinecke H, Ruehe J, Zengerle R, Ducrée J
Rapid prototyping of microfluidic chips in COC
2007 J Micromech Microeng, Band: 17, Seiten: 333 - 341
L. Riegger, M. Grumann, J. Steigert, S. Lutz, C.P. Steinert, C. Mueller, J. Viertel, O. Prucker, J. Rühe, R. Zengerle, J. Ducree
Single-step centrifugal hematocrit determination on a 10-$ processing device
2007 Biomed Microdevices, Band: 9, Seiten: 795 - 799
KurzfassungWe present a novel concept to process human blood on a spinning polymer disk for the determination of the hematocrit level by simple visual inspection. The microfluidic disk which is spun by a macroscopic drive unit features an upstream metering structure and a downstream blind channel where the centrifugally enforced sedimentation of the blood is performed. The bubble-free priming of the blind channel is governed by centrifugally assisted capillary filling along the sloped hydrophilic sidewall and the lid as well as the special shape of the dead end of the two-layer channel. The hematocrit is indicated at the sharp phase boundary between the plasma and the segregated cellular pellet on a disk-imprinted calibrated scale. This way, we conduct the hematocrit determination of human blood within 5 min at a high degree of linearity (R2=0.999) and at a high accuracy (CV=4.7%) spanning over the physiological to pathological working range. As all processing steps including the priming, the metering to a defined volume as well as the centrifugation are executed automatically during rotation, the concept is successfully demonstrated in a conventional PC-CDROM drive while delivering the same performance (R2=0.999, CV=4.3%).

2006

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Messner S, Schaible J, Sandmaier H, Zengerle R
3-way silicon microvalve for pneumatic applications with electrostatic actuation principle
2006 Microfluidics and Nanofluidics, Nummer: 2, Seiten: 89 - 96
Haeberle S, Brenner T, Zengerle R, Ducree J
Centrifugal extraction of plasma from whole blood on a rotating disk
2006 Lab on A Chip, Band: 6, Nummer: 6, Seiten: 776 - 781
Steigert J, Grumann M, Dube M, Streule W, Riegger L, Brenner T, Koltay P, Mittmann K, Zengerle R, Ducrée J
Direct Hemoglobin Measurement on a Centrifugal Microfluidic Platform for Point-of-Care Diagnostics
2006 Sensors and Actuators, Seiten: 228 - 233
Steigert J, Grumann M, Brenner T, Riegger L, Harter J, Zengerle R, Ducrée J
Fully Integrated Whole Blood Testing by Real-Time Absorption Measurement on a Centrifugal Platform
2006 Lab Chip, Band: 6, Nummer: 8, Seiten: 1040 - 1044
Litterst C, Eccarius S, Hebling C, Zengerle R, Koltay P
Increasing µDMFC efficiency by passive CO2 bubble removal and discontinuous operation
2006 Journal of Micromechanics and Microengineering, Band: 16, Nummer: 9, Seiten: S248 - S253
Boettcher M, Jaeger M S, Riegger L, Ducrée J, Zengerle R, Duschl C
Lab-on-chip-based cell separation by combining dielectrophoresis and centrifugation
2006 Biophysical Reviews & Letters, Band: 1, Nummer: 4, Seiten: 443 - 451
Ducrée J, Brenner T, Haeberle S, Glatzel T, Zengerle R
Multilamination of flows in planar networks of rotating microchannels
2006 Microfluidics and Nanofluidics, Band: 2006, Nummer: 2, Seiten: 78 - 84
Ducrée J, Zengerle R, Grumann M, Brenner T
One Droplet of Blood – Lab-on-a-Chip System for Rapid Diagnostic
2006 G.I.T Laboratory Journal, Band: 1, Seiten: 34 - 36
Ducrée J, Haeberle S, Brenner T, Glatzel T, Zengerle R
Patterning of flow and mixing in rotating radial microchannels
2006 Microfluidics and Nanofluidics, Band: 2, Nummer: 2, Seiten: 97 - 105
Riegger L, Grumann M, Nann T, Riegler J, Ehlert O, Mittenbühler K, Urban G, Pastewka L, Brenner T, Zengerle R, Ducrée J
Read-out Concepts for Multiplexed Bead-based Fluorescence Immunoassays on Centrifugal Microfluidic Platforms
2006 Sensors and Actuators A-Physical, Band: 126, Seiten: 455 - 462
Grumann M, Steigert J, Riegger L, Moser I, Enderle B, Riebeseel K, Urban G, Zengerle R, Ducree J
Sensitivity enhancement for colorimetric glucose assays on whole blood by on-chip beam-guidance
2006 Biomed Microdevices, Seiten: 209 - 214

2005

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Grumann M, Geipel A, Riegger L, Zengerle R, Ducrée J
Batch-mode mixing on centrifugal microfluidic platforms
2005 Lab on A Chip, Band: 5, Nummer: 5, Seiten: 560 - 565
Haeberle S, Brenner T, Schlosser HP, Zengerle R, Ducrée J
Centrifugal micromixer
2005 Chemical Engineering & Technology, Band: 28, Nummer: 5, Seiten: 613 - 616
Gutmann O, Kuehlewein R, Reinbold S, Niekrawietz R, Steinert CP, de Heij B, Zengerle R, Daub M
Fast and reliable protein microarray production by a new drop-in-drop technique
2005 Lab on A Chip, Band: 5, Nummer: 6, Seiten: 675 - 681
Brenner T, Glatzel T, Zengerle R, Ducrée J
Frequency-dependent transversal flow control in centrifugal microfluidics
2005 Lab on A Chip, Band: 5, Nummer: 2, Seiten: 146 - 150
Steigert J, Grumann M, Brenner T, Mittenbühler K, Nann T, Rühe J, Moser I, Haeberle S, Riegger L, Riegler J, Bessler W, Zengerle R, Ducrée J
Integrated Sample Preparation, Reaction, and Detection on a High-frequency Centrifugal Microfluidic Platform
2005 Journal of the Association for Laboratory Automation (JALA), Band: 10, Nummer: 5, Seiten: 331 - 341
Zengerle R
Micro- and Nano Cluster Freiburg
2005 mst-news, Band: 6, Seite: 38
Jeyaprakash JDS, Steger R, Birkle G, Zengerle R, Koltay P, Ruehe J
Modification of Micronozzle Surfaces Using Fluorinated Polymeric Nanofilms for Enhanced Dispensing of Polar and Nonpolar Fluids
2005 Analytical Chemistry, Band: 77, Nummer: 19, Seiten: 6469 - 6474
Kaack R, Dankbar D, Müller-Chorus B, Jung A, Daub M
Modulare Plattform mit integrierter Nanoliterdosierung
2005 Laborwelt, Band: 6, Nummer: 2, Seiten: 10 - 13
KurzfassungIm Bereich der Genom-Forschung sind in den letzten Jahren erhebliche Fortschritte erzielt worden. Möglich wurden diese durch innovative Entwicklungen in der Automatisierung und Mikrofluidik, die als Schlüsselgebiete für die moderne Biotechnologie betrachtet werden können. Ein Beispiel dafür sind die ersten kommerziellen Ansätze zur hochparallelen Expressionsanalyse in miniaturisierten Formaten. Der nächste Schritt, der zwangsläufig folgen muss, sind Weiterent wicklungen hinsichtlich Quantifizierbarkeit (Sensitivität und Selektivität), Schnelligkeit (Parallelität) und Modularität, so dass mit nur einer Geräteplattform eine Vielzahl möglicher Anwendungen, wie z.B. die routinemäßige Diagnostik von SNPs (single nucleotide polymorphisms) oder die Identifikation und Validierung neuer Rezeptoren in der Wirkstoff-Forschung kostengünstig erschlossen werden können.
Bohl B, Steger R, Zengerle R, Koltay P
Multi-layer SU-8 Lift-Off Technology For Microfluidic Devices
2005 Journal of Micromechanics and Microengineering, Band: 15, Seiten: 1125 - 1130
Goettsche T, Kohnle J, Willmann M, Ernst H, Spieth S, Tischler R, Messner S, Zengerle R, Sandmaier H
Novel approaches to particle tolerant valves for use in drug delivery systems
2005 Sensors and Actuators A-Physical, Band: 118, Nummer: 1, Seiten: 70 - 77
Ducrée J, Zengerle R, Grumann M, Brenner T
Schnelle Diagnose aus einem Tropfen Blut
2005 Mikrosystemtechnik, Band: 3
Daub M
TopSpot Quality Microarrays
2005 Labor Medizin & Diagnostik, Seiten: 25 - 26
KurzfassungTopSpot® technology introduces a new concept into the microarray laboratory: highly parallel non-contact dispensing of bioanalytical reagents for the production of low to medium density microarrays. The technology is based on micromachined multi-channel printheads combined with a piezo-driven droplet ejection process. Different automation environments for these print modules allow TopSpot® technology to cover needs from decentralized laboratories to core facilities
Grumann M, Brenner T, Beer C, Zengerle R, Ducrée J
Visualization of flow patterning in high-speed centrifugal microfluidics
2005 Review of Scientific Instruments, Band: 76, Nummer: 2, Seiten: 025101 - 025101

2004

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Gutmann O, Kuehlewein R, Reinbold S, Niekrawietz R, Steinert CP, De HB, Zengerle R, Daub M
A highly parallel nanoliter dispenser for microarray fabrication
2004 Biomed Microdevices, Band: 6, Nummer: 2, Seiten: 131 - 137
KurzfassungWe report about the correlation between satellite free droplet release and liquid viscosity in a highly parallel, pressure driven nanoliter dispenser. In extensive studies we found that for liquids of different viscosities the duration of the pressure pulse is the predominant effect compared to pressure amplitude. This result is of essential importance when actuation parameters have to be adopted for different media like oligonucleotide, DNA or protein solutions as it is the case for the non contact high throughput fabrication of microarrays (Ducree et al., 2000). Experiments with oligonucleotides as well as with different proteins showed ascertained carry-over and cross-contamination free printing of DNA and protein microarrays. With it a prime critical point of microarray production is solved, leading to high quality whilst high throughput microarray fabrication. For oligonucleotides printing we found CVs to be better than 1% within one single dispensing channel and 1.5 % within all 24 channels of a 24 channel printhead for each used printing buffer. By optimizing the protein printing buffer the CVs for protein printing were reduced to about 1% within all 24 channels. As a serious practical application test oligonucleotides microarrays were produced using our nanoliter dispenser system. With it a full DNA hybridization experiment was performed. Clear positive signals one hand and no signals in the negative controls on the other hand showed that our system is suited for microarray production.
Steinert CP, Goutier I, Gutmann O, Sandmaier H, Daub M, de Heij B, Zengerle R
A highly parallel picoliter dispenser with an integrated, novel capillary channel structure
2004 Sensors and Actuators A-Physical, Band: 116, Nummer: 1, Seiten: 171 - 177
KurzfassungWe present a cross-contamination free highly-parallel picoliter dispenser based on direct liquid displacement. Such dispensers are essential for the (mass) fabrication of microarrays [J. Ducrée, H. Gruhler, N. Hey, M. Mueller, S. Békési, M. Freygang, H. Sandmaier, R. Zengerle, TopSpot—a new method for the fabrication of microarrays, Tech. Digest, The Thirteenth IEEE Annual International Conference on Micro Electro Mechanical Systems, Mizyazaki, Japan, 23–27 January 2000, pp. 317–322] and are able to dispense up to 384 different reagents at a pitch of 500 µm simultaneously [A. Kuoni, M. Boillat, N.F. de Rooij, A highly parallel piezoelectric printing device for microarray technology, Tech. Digest, The 17th International Conference on Micro Electro Mechanical Systems, Maastricht, The Netherlands, 25–29 January 2004, pp. 466–469]. In contrast to an earlier design [Sens. Actuators A 103 (2003) 88] we investigated different nozzle diameters and a novel capillary channel design.We present a systematic study concerning the relation between nozzle diameter and ejected droplet volume. The change from 35 to 60 µm in nozzle diameter resulted in a doubling of dispensed volume for most used elastomers and irrespective of actuation parameters. Minimum and maximum dispensed volumes have been determined to be 125 and 1700 pl. Those results are based on a new design, which also includes passive microstructures for droplet homogeneity as well as modified microchannels for improved priming and prevention of cross-contamination. Based on this, the coefficient of variation (CV) of droplet velocity could be reduced from 50% down to less than 5%. The CV of droplet volume is clearly below the measurement error (8%). Keywords: Picoliter dispenser; Non-contact printing; Microchannel; Microfluidics; Microarrays; Biochips
Grumann M, Dobmeier M, Schippers P, Brenner T, Kuhn C, Fritsche M, Zengerle R, Ducrée J
Aggregation of bead-monolayers in flat microfluidic chambers simulation by the model of porous media
2004 Lab on A Chip, Band: 4, Nummer: 3, Seiten: 209 - 213
KurzfassungIn this paper, we for the first time simulate the process of hydrodynamic bead aggregation in a flat micro-fluidic chamber by a porous-media model in an iterative routine. This allows us to optimize the chamber design of our recently developed experimental method to form periodical monolayers from the flow of bead suspension. Periodical monolayers are advantageous for parallel assay formats since they enhance the mechanical rigidity of the aggregated pattern. This is important to avoid a spatial rearrangement along various steps of a read-out procedure which would impair the correlation between measurements. Furthermore, the monolayer formation guarantees the individual optical accessibility of all probe beads. By modelling the monolayers with porous media, we can drastically reduce the degrees of freedom in a two-phase, multi-particle problem. This way, we are able to compute stationary hydrodynamic flow patterns in the chamber. In order to simulate the complete filling process from these stationary solutions, we developed an iterative master routine which takes the transient aggregation pattern as the initial condition, then evaluates the placement of the newly introduced beads, and finally converts the points of aggregation into porous media.
de Heij B, Daub M, Gutmann O, Niekrawietz R, Sandmaier H, Zengerle R
Highly parallel dispensing of chemical and biological reagents
2004 Analytical and Bioanalytical Chemistry, Band: 378, Nummer: 1, Seiten: 119 - 122
Gutmann O, Niekrawietz R, Kuehlewein R, Steinert CP, de Heij B, Zengerle R, Daub M
Impact of medium properties on droplet release in a highly parallel nanoliter dispenser
2004 Sensors and Actuators A-Physical, Band: 116, Nummer: 2, Seiten: 187 - 194
Gutmann O, Niekrawietz R, Kuehlewein R, Steinert CP, Reinbold S, De HB, Daub M, Zengerle R
Non-contact production of oligonucleotide microarrays using the highly integrated TopSpot nanoliter dispenser
2004 Analyst, Band: 129, Nummer: 9, Seiten: 835 - 840
KurzfassungFor the first time we report on the production of oligonucleotide microarrays using a highly parallel and highly integrated, pressure driven TopSpot nanoliter dispenser. The system enables non-contact printing of different media like oligonucleotides, DNA or protein solutions. We optimized the printing buffer needed for oligonucleotides microarrays production with respect to two major aspects: microfluidical optimum for droplet dispensing and biochemical coupling efficiency on different commercially available microarray slides. Coefficient of variations (CVs) of generated spot diameters were measured to be smaller than 1% within one single dispensing nozzle and smaller than 1.5% within all 24 parallel nozzles of the printhead for all printing buffers used. No carry-over and no cross-talk was found, in extensive experiments with oligonucleotides. Optimized printing buffer compositions and concentrations for oligonucleotide microarrays were found, as well as optimized coupling protocols. Furthermore, buffers and protocols were adapted to a host of different microarray slides used. With this system, prime critical points of microarray production are solved, leading to high quality high throughput microarray fabrication.
Streule W, Lindemann T, Birkle G, Zengerle R, Koltay P
PipeJet: A Simple Disposable Dispenser for the Nano- and Microliter Range
2004 Journal of the Association for Laboratory Automation (JALA), Band: 9, Nummer: 5, Seiten: 300 - 306
KurzfassungThis paper reports on a simple, disposable non-contact dispenser for the nano- and microliter range. In contrast to other known dispensers manufactured by silicon micromachining the new device simply consists of an elastic polymer tube with a circular cross section. Actuation is done by a piezostack driven piston, squeezing the tube at a defined position near the open end by a significant fraction of the cross section. In contrast to drop-on-demand devices based on an acoustic actuation principle,5 the squeezing of the tube leads to a significant mechanical displacement of the liquid. Our experiments tested a large number of media in the viscosity range from 1 to 27 mPas. Some of our experiments tested up to approximately 2,000 mPas. Frequency characteristics showed an independent dosage volume for water up to a frequency of 15 Hz for tubes with an inner diameter of approximately 200 lm. Standard deviation within 1,000 shots resulted in an excellent CV (standard deviation/ dosage volume) of less than 2% of the dosage volume. Using tubes with an inner diameter of approximately 1,000 µm and a print frequency of 340 Hz, a flowrate of less than or equal to 143 µL/s could be reached. Beyond the possibility to dispense pure liquids, emulsion paints with particles that have a diameter of approximately 40 µm have also been printed successfully.
Breisch S, de Heij B, Lohr M, Stelzle M
Selective chemical surface modification of fluidic microsystems and characterization studies
2004 Journal of Micromechanics and Microengineering, Band: 14, Nummer: 4, Seiten: 497 - 505
KurzfassungControl of wetting behaviour of fluidic microsystems was achieved by selective chemical surface modification using either a solution-based procedure or micro-contact printing. The modification procedures were designed in such a way as to obtain optimum wetting in fluid channels, sample reservoirs and nozzles, while at the same time preventing intermixing of fluids from different nozzle exits and thus enabling multiple long-term stable delivery of nano-litre droplets. Analysis included thickness measurements by ellipsometry, contact angle measurements and fluorescence microscopy. Selectively coated TopSpot dosage chips as are used for the fabrication of DNA and protein micro-arrays exhibit superior performance over uncoated dosage chips. Mixed and back-filled silane coatings show enhanced stability versus hydrolysis in basic and acidic solutions, as has been determined from measurements of contact angle as a function of immersion time.
Steger R, Bohl B, Zengerle R, Koltay P
The dispensing well plate: a novel device for nanoliter liquid handling in ultra high-throughput screening
2004 Journal of the Association for Laboratory Automation, Band: 9, Nummer: 5, Seiten: 291 - 299
KurzfassungThis article reports on a novel dispensing system for the massive parallel delivery of liquid volumes in the range of 50 nL. Due to the similarity of the device to conventional micro-well plates used for the storage of liquids, the device has been termed ‘‘dispensing well plate’’ (DWP). In contrast to other known micro dispensers, the DWP can consist of up to 1,536 dispensing units in parallel, all of which hold different reagents. The dispensing units can be arranged very closely at the pitch of conventional micro-well plates (2.25 mm or 4.5 mm). Driven by pneumatic actuation, a fixed volume of different liquids can be dispensed simultaneously and contact-free into micro-well plates or onto flat substrates. Because of this, the liquid handling in many chemical, biochemical, and pharmaceutical applications—especially within highthroughput screening (HTS)—can be sped up by a factor of 10 to 100. In our article, the basic operation principle of the device is presented, and experimental evidence of its extraordinary performance is given: a reproducibility of 2% to 5% and a homogeneity within individual droplet arrays of 1% to 2% has been measured, as well as viscosity independent performance for liquids in the range from 1 to 5 mPas. The applicability of the DWP technology within HTS is demonstrated by performing a miniaturized kinase assay at 1 lL assay volume in a 1536- well plate format.
Koltay P, Steger R, Bohl B, Zengerle R
The dispensing well plate: a novel nanodispenser for the multiparallel delivery of liquids (DWP Part I)
2004 Sensors and Actuators A-Physical, Band: 116, Nummer: 3, Seiten: 483 - 491
KurzfassungThis paper reports on a novel dispensing system for the massive parallel delivery of liquid volumes in the range of 50 nL. Due to the similarity of the device to conventional microwell plates used for storage of liquids, the device has been termed “dispensing well plate” (DWP). In contrast to other known microdispensers the DWP can consist of up to 1536 dispensing units in parallel all holding different reagents. The dispensing units can be arranged very closely at the pitch of conventional microwell plates (2.25 or 4.5 mm). Driven by pneumatic actuation a fixed volume of different liquids can be dispensed simultaneously and contact free into microwell plates or onto flat substrates. By this the liquid-handling in many chemical, biochemical and pharmaceutical applications—especially within high throughput screening (HTS)—can be speed up by a factor 10–100. In this paper the basic operation principle of the device is presented and experimental evidence is given of its extraordinary performance: a reproducibility of 2–5% and a homogeneity within individual droplet arrays of 1–2% has been measured as well as viscosity independent performance for liquids in the range from 1 to 5mPas. The fabrication of DWP prototypes by different micromachining technologies based on silicon dry etching and SU-8 technology is described and various DWP prototypes with different dosage volumes are presented. © 2004 Elsevier B.V. All rights reserved. Keywords: Non-contact dispenser; Jets; High throughput screening; SU-8
Koltay P, Kalix J, Zengerle R
Theoretical evaluation of the dispensing well plate method (DWP part II)
2004 Sensors and Actuators A-Physical, Band: 116, Nummer: 3, Seiten: 472 - 482
KurzfassungThe “dispensing well plate” (DWPTM) method is a technique to deliver fluidic jets or droplets with volumes of several nanoliters contact free to targets likemicro well plates or slides. A cheap and simple pneumatic actuation mechanism allows for the simultaneous delivery of a large number of different liquids. In this paper the dispensing dynamics of a DWP-type nanodispenser is studied theoretically. The device is modelled using computational fluid dynamics (CFD) simulations which are benchmarked to experimental data. Furthermore an analytical discussion is presented providing some insight into the dispensing dynamics. Based on these modelling approaches the dispensing process is studied in detail. Influence of system parameters like driving pressure, nozzle size, channel layout etc. on the jet formation and dispensed volume are quantified and design rules are given to improve the performance. © 2004 Elsevier B.V. All rights reserved. Keywords: Droplet dispensing; Jets; CFD-simulation; Microfluidics

2003

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de Heij B, Steinert C, Sandmaier H, Zengerle R
A tuneable and highly-parallel picolitre-dispenser based on direct liquid displacement
2003 Sensors and Actuators A-Physical, Band: 103, Nummer: 1-2, Seiten: 88 - 92
KurzfassungWe present a new method for the highly-parallel and simultaneous delivery of a multitude of reagents in the picolitre range. This method is based on direct displacement of the liquids using an elastomer-stamp, which simultaneously actuates up to 96 dosing channels, at a pitch of 500 mm. We were able to tune droplet volume from 100 to 700 pl and droplet speed from 0.3 to 4 m/s using printheads with 50 mm diameter nozzles. In contrast to all other inkjet techniques the new direct displacement method enables the precise control of dispensing quantity in the picolitre range regardless of reagent viscosity. © 2003 Elsevier Science B.V. All rights reserved. Keywords: Highly-parallel; Picolitre-dispenser; Bio-molecule; Microfluidics
Waibel G, Kohnle J, Cernosa R, Storz M, Schmitt M, Ernst H, Sandmaier H, Zengerle R, Strobelt T
Highly integrated autonomous microdosage system
2003 Sensors and Actuators A-Physical, Band: 103, Nummer: 1-2, Seiten: 225 - 230

2002

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Ducrée J, Zengerle R
Microfluidics - Markets and Technologies
2002 mstnews, Band: 05, Nummer: 02, Seiten: 8 - 9
KurzfassungThe field of microfluidics has become one of the most dynamically emerging disciplines of microtechnology in the recent decade. Microfluidics offers the mere benefits of miniaturization enabling portable and inexpensive devices, mostly for analytical and diagnostic purposes where the costs per test can be greatly reduced. It has also become evident that microfluidics provides a unique access to the nanoworld of biomolecular chemistry thus setting the pace for many leading edge biotechnological innovations. In the course of the “FlowMap” project , a consortium of European partners such as IMTEK (D), HSG-IMIT (D), Cranfield Biotechnology Center (UK), Yole Dévelopement (F) and Wicht Technology Consulting (D) has analyzed the structure of the field in terms of markets, products and technologies. This information will be the basis for an explorative technology roadmap which we develop for microfluidics in the life sciences. A time frame for the development of technological and economic landmarks will be introduced and sequences as well as dependencies will be illustrated. This will allow to plot the complete road between technologies and markets.

2001

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Peter Koltay, Bas de Heij, Hermann Sandmaier, Roland Zengerle
Automatisiertes Liquid Handling im Nanoliterbereich
2001 “Inno“ Innovative Technik – Anwendungen aus Nordrhein-Westfalen; Nr. 19 (3/01)

2000

nach oben zur Jahresübersicht

Jens Ducrée, Bas de Heij, Hermann Sandmaier, Roland Zengerle
TopSpot – Ein Verfahren zur Massenproduktion von Biochips.
2000 Life Science Technologien; 6/2000

1996

nach oben zur Jahresübersicht

Zengerle R
Mikrosysteme - Chancen für die Dosiertechnik
1996 wägen + dosieren, Band: 1, Seiten: 10 - 15
Zengerle R
Stand der Technik bei mikrofluidischen Aktoren
1996 Feinwerktechnik und Mikrotechnik, Band: 104, Seiten: 241 - 248
Ulrich J, Füller H, Zengerle R
Static and dynamic flow simulation of a KOH-etched micro valve
1996 Sensors and Actuators A, Band: 53, Seiten: 379 - 385
Stehr M, Messner S, Sandmaier H, Zengerle R
The VAMP - A new device for handling liquids and gases
1996 Sensors & Actuators A, Band: 57, Seiten: 153 - 157

1995

nach oben zur Jahresübersicht

Zengerle R, Ulrich J, Kluge S, Richter M, Richter A
A bidirectional silicon micropump
1995 Sensors & Actuators A, Band: 50, Seiten: 81 - 86
Zengerle R, Geiger W, Richter M, Ulrich J, Kluge S, Richter A
Transient measurements on miniaturized diaphragm pumps in microfluidic systems
1995 Sensors & Actuators A, Band: 46-47, Seiten: 557 - 561

1994

nach oben zur Jahresübersicht

Zengerle, R, Richter M
Simulation of microfluid systems
1994 Journal of Micromechanics and Microengineering, Band: 4, Seiten: 192 - 204

1992

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Richter A, Zengerle R, Plettner A, Sandmaier H
Elektrohydrodynamische Mikropumpen
1992 VDI Berichte, Band: 960, Seiten: 235 - 249

1991

nach oben zur Jahresübersicht

Michel-Beyerle M E, Zengerle R
Effect of quinone depletion on lifetime spectra in photosynthetic reaction centers
1991 Chemical Physics Letters, Band: 176, Nummer: 1, Seiten: 85 - 90

Reviews/Übersichtsartikel in wissenschaftlichen Fachzeitschriften

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2023

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J. Disch, L. Bohn, L. Metzler, S. Vierrath
Strategies for the mitigation of salt precipitation in zero-gap CO2 electrolyzers producing CO (Review)
2023 J. Mater. Chem. A, Band: 11, Seiten: 7344 - 7357

2021

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H. C. Ates, A. Brunauer, F. von Stetten, G. A. Urban, F. Güder, A. Merkoçi, S. M. Früh, C. Dincer
Integrated Devices for Non‐Invasive Diagnostics
2021 Advanced Functional Materials, Band: 31, Nummer: 15, Seite: 2010388
Kurzfassung“Sample‐in‐answer‐out” type integrated diagnostic devices have been widely recognized as the ultimate solution to simplify testing across healthcare systems. Such systems are equipped with advanced fluidic, mechanical, chemical, biological, and electronic components to handle patient samples without any manual steps therefore have the potential to accelerate intervention and improve patient outcomes. In this regard, the combination of integrated devices and non‐invasive sampling has gained a substantial interest to further improve the comfort and safety of patients. In this Review, the pioneering developments in integrated diagnostics are covered and their potential in non‐invasive sampling is discussed. The key properties of possible sample types are highlighted by addressing their relevance for the clinical practice. Last, the factors affecting the transition of integrated devices from academia to the market are identified by analyzing the technology readiness levels of selected examples and alternative remedies are explored to increase the rate of survival during this transition.

2020

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M. Trotter, N. Borst, R. Thewes, F. von Stetten
Electrochemical DNA sensing – Principles, commercial systems, and applications
2020 Biosens Bioelectron, Band: 154, Seite: 112069
KurzfassungDriven by the vision of robust and portable, yet sensitive DNA detection systems for point-of-need applications, the development of electrochemical DNA sensing principles has been of high interest. Many different principles have been developed and these are regularly reviewed. However, the maturity of electrochemical principles and their ability to produce competitive real-world applications is rarely assessed. In this review, general electrochemical DNA sensing principles are briefly introduced and categorized into heterogeneous vs. homogeneous approaches, and then the subcategories label-free vs. labeled and reagent-less vs. reagent-dependent principles. We then focus on reviewing the electrochemical sensing principles implemented in DNA detection systems, which are commercially available or close to market entry, considering the complete analysis process, automation and the field of application. This allows us to outline and discuss which principles have proved suitable for which kinds of applications, as well as the stage of integration and automation. Examples from all the identified categories of electrochemical DNA sensing principles have found application in commercial detection systems or advanced prototypes. Various applications have already been demonstrated, ranging from on-site skin care testing, to food safety to the most frequent in vitro diagnostic tests, partially conducted in automated sample-to-answer devices. Our review is intended to enable researchers in areas related to electrochemistry, biochemistry or microfluidics to assess the commercial state of the art of electrochemical nucleic acid testing, and the interdisciplinary challenges for further improvements.

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J. F. Hess, T.A. Kohl, M. Kotrová, K. Roensch, T. Paprotka, V. Mohr, T. Hutzenlaub, M. Brüggemann, R. Zengerle, S. Niemann, N. Paust
Library preparation for next generation sequencing: A review of automation strategies
2020 Biotechnol Adv, Seite: 107537
KurzfassungNext generation sequencing is in the process of evolving from a technology used for research purposes to one which is applied in clinical diagnostics. Recently introduced high throughput and benchtop instruments offer fully automated sequencing runs at a lower cost per base and faster assay times. In turn, the complex and cumbersome library preparation, starting with isolated nucleic acids and resulting in amplified and barcoded DNA with sequencing adapters, has been identified as a significant bottleneck. Library preparation protocols usually consist of a multistep process and require costly reagents and substantial hands-on-time. Considerable emphasis will need to be placed on standardisation to ensure robustness and reproducibility. This review presents an overview of the current state of automation of library preparation for next generation sequencing. Major challenges associated with library preparation are outlined and different automation strategies are classified according to their functional principle. Pipetting workstations allow high-throughput processing yet offer limited flexibility, whereas microfluidic solutions offer great potential due to miniaturisation and decreased investment costs. For the emerging field of single cell transcriptomics for example, microfluidics enable singularisation of tens of thousands of cells in nanolitre droplets and barcoding of the RNA to assign each nucleic acid sequence to its cell of origin. Finally, two applications, the characterisation of bacterial pathogens and the sequencing within human immunogenetics, are outlined and benefits of automation are discussed.

2019

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J. Li, J. Macdonald, F. von Stetten
Correction: Review: a comprehensive summary of a decade development of the recombinase polymerase amplification
2019 Analyst, Band: 144, Nummer: 31

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A. van Belkum, T. T. Bachmann, G. Lüdke, J. G. Lisby, G. Kahlmeter, A. Mohess, K. Becker, J. P. Hays, N. Woodford, K. Mitsakakis, J. Moran- Gilad, J. Vila, H. Peter, J. H. Rex, W. M. Dunne Jr., and the JPIAMR AMR-RDT Working Group
Developmental roadmap for antimicrobial susceptibility testing systems
2019 Nat Rev Microbiol, Band: 17, Seiten: 51 - 62
KurzfassungAntimicrobial susceptibility testing (AST) technologies help to accelerate the initiation of targeted antimicrobial therapy for patients with infections and could potentially extend the lifespan of current narrow-spectrum antimicrobials. Although conceptually new and rapid AST technologies have been described, including new phenotyping methods, digital imaging and genomic approaches, there is no single major, or broadly accepted, technological breakthrough that leads the field of rapid AST platform development. This might be owing to several barriers that prevent the timely development and implementation of novel and rapid AST platforms in health-care settings. In this Consensus Statement, we explore such barriers, which include the utility of new methods, the complex process of validating new technology against reference methods beyond the proof-of-concept phase, the legal and regulatory landscapes, costs, the uptake of new tools, reagent stability, optimization of target product profiles, difficulties conducting clinical trials and issues relating to quality and quality control, and present possible solutions.
J. F. Hess, S. Zehnle, P. Juelg, T. Hutzenlaub, R. Zengerle, N. Paust
Review on pneumatic operations in centrifugal microfluidics
2019 Lab Chip, Band: 22, Seiten: 3745 - 3770
KurzfassungCentrifugal microfluidics allows for miniaturization, automation and parallelization of laboratory workflows. The fact that centrifugal forces are always directed radially outwards has been considered a main drawback for the implementation of complex workflows leading to the requirement of additional actuation forces for pumping, valving and switching. In this work, we review and discuss the combination of centrifugal with pneumatic forces which enables transport of even complex liquids in any direction on centrifugal systems, provides actuation for valving and switching, offers alternatives for mixing and enables accurate and precise metering and aliquoting. In addition, pneumatics can be employed for timing to carry out any of the above listed unit operations in a sequential and cascaded manner. Firstly, different methods to generate pneumatic pressures are discussed. Then, unit operations and applications that employ pneumatics are reviewed. Finally, a tutorial section discusses two examples to provide insight into the design process. The first tutorial explains a comparatively simple implementation of a pneumatic siphon valve and provides a workflow to derive optimum design parameters. The second tutorial discusses cascaded pneumatic operations consisting of temperature change rate actuated valving and subsequent pneumatic pumping. In conclusion, combining pneumatic actuation with centrifugal microfluidics allows for the design of robust fluidic networks with simple fluidic structures that are implemented in a monolithic fashion. No coatings are required and the overall demands on manufacturing are comparatively low. We see the combination of centrifugal forces with pneumatic actuation as a key enabling technology to facilitate compact and robust automation of biochemical analysis.
J. Li, J. Macdonald, F. von Stetten
Review: a comprehensive summary of a decade development of the recombinase polymerase amplification
2019 Analyst, Band: 144, Nummer: 31, Seiten: 31 - 67
KurzfassungNucleic acid amplification has permeated every field in the life sciences since the introduction of the classic polymerase chain reaction (PCR) method in 1983. Yet, despite its fundamental reach, PCR has been constrained within the walls of a laboratory, due to its requirement for a sophisticated thermocycling machine, limiting external application in low-resource settings. New isothermal amplification strategies are seeking to break through traditional laboratory boundaries by providing nucleic acid replication at constant temperatures. Of these methods, recombinase polymerase amplification (RPA) is one of the fastest developing, experiencing rapid uptake and market, even though it was introduced comparatively late. Critically, RPA’s technology potentiates highly accessible and sensitive nucleic acid amplification outside of laboratory, and even self-testing. Here we provide a comprehensive review of the equipmentfree simplicity of RPA over its first decade of development. Our review includes key knowledge of RPA technology, such as its reaction components, mechanism, sensitivities and specificities, and distinctive detection methods. The review also provides know-how for developing RPA assays, and information about commercially available RPA reaction kits and accessories. We summarise critical RPA experimental tips and issues available through data mining the published literature, to assist researchers in mastering the RPA reaction. We also outline influential hotspots of RPA development, and conclude with outlooks for future development and implications for eclipsing PCR and further revolutionising the life sciences.

2018

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K. Mitsakakis, S. Hin, P. Müller, N. Wipf, E. Thomsen, M. Coleman, R. Zengerle, J. Vontas, K. Mavridis
Converging Human and Malaria Vector Diagnostics with Data Management towards an Integrated Holistic One Health Approach
2018 International Journal of Environmental Research and Public Health, Band: 15, Nummer: 2, Seite: E259
KurzfassungMonitoring malaria prevalence in humans, as well as vector populations, for the presence of Plasmodium, is an integral component of effective malaria control, and eventually, elimination. In the field of human diagnostics, a major challenge is the ability to define, precisely, the causative agent of fever, thereby differentiating among several candidate (also non-malaria) febrile diseases. This requires genetic-based pathogen identification and multiplexed analysis, which, in combination, are hardly provided by the current gold standard diagnostic tools. In the field of vectors, an essential component of control programs is the detection of Plasmodium species within its mosquito vectors, particularly in the salivary glands, where the infective sporozoites reside. In addition, the identification of species composition and insecticide resistance alleles within vector populations is a primary task in routine monitoring activities, aiming to support control efforts. In this context, the use of converging diagnostics is highly desirable for providing comprehensive information, including differential fever diagnosis in humans, and mosquito species composition, infection status, and resistance to insecticides of vectors. Nevertheless, the two fields of human diagnostics and vector control are rarely combined, both at the diagnostic and at the data management end, resulting in fragmented data and mis- or non-communication between various stakeholders. To this direction, molecular technologies, their integration in automated platforms, and the co-assessment of data from multiple diagnostic sources through information and communication technologies are possible pathways towards a unified human vector approach.
K. Mitsakakis / V. D’Acremont, S. Hin, F. von Stetten, R. Zengerle
Diagnostic tools for tackling febrile illness and enhancing patient management
2018 Microelectron Eng, Band: 201, Seiten: 26 - 59
KurzfassungMost patients with acute infectious diseases develop fever, which is frequently a reason to visit health facilities in resource-limited settings. The symptomatic overlap between febrile diseases impedes their diagnosis on clinical grounds. Therefore, the World Health Organization promotes an integrated management of febrile illness. Along this line, we present an overview of endemic and epidemic etiologies of fever and state-of-the-art diagnostic tools used in the field. It becomes evident that there is an urgent need for the development of novel technologies to fulfill end-users’ requirements. This need can be met with Point-of-Care and near-patient diagnostic platforms, as well as e-Health clinical algorithms, which co-assess test results with key clinical elements and biosensors, assisting clinicians in patient triage and management, thus enhancing disease surveillance and outbreak alerts. This review gives an overview of diagnostic technologies featuring a platform based approach: (i) assay (nucleic acid amplification technologies are examined); (ii) cartridge (microfluidic technologies are presented); (iii) instrument (various detection technologies are discussed); and at the end proposes a way that such technologies can be interfaced with electronic clinical decision-making algorithms towards a broad and complete diagnostic ecosystem.
M. Kokko, S. Epple, J. Gescher, S. Kerzenmacher
Effects of wastewater constituents and operational conditions on the composition and dynamics of anodic microbial communities in bioelectrochemical systems
2018 Bioresource Technology, Band: 258, Seiten: 376 - 389
KurzfassungOver the last decade, there has been an ever-growing interest in bioelectrochemical systems (BES) as a sustainable technology enabling simultaneous wastewater treatment and biological production of, e.g. electricity, hydrogen, and further commodities. A key component of any BES degrading organic matter is the anode where electric current is biologically generated from the oxidation of organic compounds. The performance of BES depends on the interactions of the anodic microbial communities. To optimize the operational parameters and process design of BES a better comprehension of the microbial community dynamics and interactions at the anode is required. This paper reviews the abundance of different microorganisms in anodic biofilms and discusses their roles and possible side reactions with respect to their implications on the performance of BES utilizing wastewaters. The most important operational parameters affecting anodic microbial communities grown with wastewaters are highlighted and guidelines for controlling the composition of microbial communities are given.

2016

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M. Klingele, C. Van Pham, A. Fischer, S. Thiele
A Review on Metal-Free Doped Carbon Materials Used asOxygen Reduction Catalysts in Solid Electrolyte Proton Exchange Fuel Cells
2016 Fuel Cells, Band: 5, Seiten: 522 - 529
KurzfassungWithin the last decade, metal-free heteroatom doped carbon nanomaterials have gained attention as effective electrocatalysts for the oxygen reduction reaction (ORR) in many electrochemical systems. Since then, reports have stated that the ORR catalytic activity, onset potential, and H2O production selectivity of these materials is similar to that of platinumbased catalysts. These statements rely on cyclic voltammetry (CV) and rotating disc electrode (RDE) measurements in liquid alkaline electrolyte. However, fuel cell researchers aim to replace the costly platinum catalysts in the more prominent acidic solid electrolyte proton exchange fuel cell (PEFC). In this respect, there are only a few reports of unpromising activity, stability, and H2O production selectivity. In addition, only few reports have been presented on the implementation of such materials in cathode catalyst layers of actual PEFC devices. This mini-review aims to summarize and evaluate results of these reports. Material synthesis, cell power, open circuit voltage, stability properties, and proposed active sites are reviewed. To date, the highest reported PEFC power densities with guaranteed metal-free heteroatom doped carbon cathode catalysts have reached up to 321 mW cm–2; which although a promising value is substantially short of values obtained for platinum based catalysts.
M. Karle, S. K. Vashist, R. Zengerle, F. von Stetten
Microfluidic solutions enabling continuous processing and monitoring of biological samples: A Review
2016 Anal Chim Acta, Band: 929, Seiten: 1 - 22
KurzfassungThe last decade has witnessed tremendous advances in employing microfluidic solutions enabling Continuous Processing and Monitoring of Biological Samples (CPMBS), which is an essential requirement for the control of bio-processes. The microfluidic systems are superior to the traditional inline sensors due to their ability to implement complex analytical procedures, such as multi-step sample preparation, and enabling the online measurement of parameters. This manuscript provides a backgound review of microfluidic approaches employing laminar flow, hydrodynamic separation, acoustophoresis, electrophoresis, dielectrophoresis, magnetophoresis and segmented flow for the continuous processing and monitoring of biological samples. The principles, advantages and limitations of each microfluidic approach are described along with its potential applications. The challenges in the field and the future directions are also provided.

2015

nach oben zur Jahresübersicht

O. Strohmeier, M. Keller, F. Schwemmer, S. Zehnle, D. Mark, F. von Stetten, R. Zengerle, N. Paust
Centrifugal microfluidic platforms: advanced unit operations and applications
2015 Chem Soc Rev, Band: 44, Seiten: 6187 - 6229
KurzfassungCentrifugal microfluidics has evolved into a mature technology. Several major diagnostic companies either have products on the market or are currently evaluating centrifugal microfluidics for product development. The fields of application are widespread and include clinical chemistry, immunodiagnostics and protein analysis, cell handling, molecular diagnostics, as well as food, water, and soil analysis. Nevertheless, new fluidic functions and applications that expand the possibilities of centrifugal microfluidics are being introduced at a high pace. In this review, we first present an up-to-date comprehensive overview of centrifugal microfluidic unit operations. Then, we introduce the term “process chain” to review how these unit operations can be combined for the automation of laboratory workflows. Such aggregation of basic functionalities enables efficient fluidic design at a higher level of integration. Furthermore, we analyze how novel, ground-breaking unit operations may foster the integration of more complex applications. Among these are the storage of pneumatic energy to realize complex switching sequences or to pump liquids radially inward, as well as the complete pre-storage and release of reagents. In this context, centrifugal microfluidics provides major advantages over other microfluidic actuation principles: the pulse-free inertial liquid propulsion provided by centrifugal microfluidics allows for closed fluidic systems that are free of any interfaces to external pumps. Processed volumes are easily scalable from nanoliters to milliliters. Volume forces can be adjusted by rotation and thus, even for very small volumes, surface forces may easily be overcome in the centrifugal gravity field which enables the efficient separation of nanoliter volumes from channels, chambers or sensor matrixes as well as the removal of any disturbing bubbles. In summary, centrifugal microfluidics takes advantage of a comprehensive set of fluidic unit operations such as liquid transport, metering, mixing and valving. The available unit operations cover the entire range of automated liquid handling requirements and enable efficient miniaturization, parallelization, and integration of assays.
A. Gross, J. Schoendube, S. Zimmermann, M. Steeb, R. Zengerle, P. Koltay
Technologies for Single-Cell Isolation
2015 Int J Mol Sci, Band: 16, Seiten: 16897 - 16919
KurzfassungThe handling of single cells is of great importance in applications such as cell line development or single-cell analysis, e.g., for cancer research or for emerging diagnostic methods. This review provides an overview of technologies that are currently used or in development to isolate single cells for subsequent single-cell analysis. Data from a dedicated online market survey conducted to identify the most relevant technologies, presented here for the first time, shows that FACS (fluorescence activated cell sorting) respectively Flow cytometry (33% usage), laser microdissection (17%), manual cell picking (17%), random seeding/dilution (15%), and microfluidics/lab-on-a-chip devices (12%) are currently the most frequently used technologies. These most prominent technologies are described in detail and key performance factors are discussed. The survey data indicates a further increasing interest in single-cell isolation tools for the coming years. Additionally, a worldwide patent search was performed to screen for emerging technologies that might become relevant in the future. In total 179 patents were found, out of which 25 were evaluated by screening the title and abstract to be relevant to the field.

2014

nach oben zur Jahresübersicht

S. K. Vashist, E. Lam, S. Hrapovic, K. B. Male, J. H. T. Luong
Immobilization of Antibodies and Enzymes on 3-Aminopropyltriethoxysilane-Functionalized Bioanalytical Platforms for Biosensors and Diagnostics
2014 Chem Rev, Band: 114, Seiten: 11083 - 11130
Kurzfassung1. INTRODUCTION Biosensing and diagnostic platforms with high sensitivity, specificity, and fast response time are based on immobilized biomolecules such as antibodies (Abs), aptamers, enzymes, nucleic acids, receptors, and whole cells for the detection of target analytes. Such sensing biomolecules should be bound to the surface of a signal transducer with a required specific chemical, electrical, or optical property. The biological recognition event generates a quantifiable signal, which is equated to the amount or concentration of the analyte. Thus, the biomolecule immobilization plays a crucial role in achieving high sensitivity and selectivity with prolonged device lifetime. The substrate materials such as electrodes, microtiter plates (MTPs), nanoparticles (NPs), nanotubes, graphene, etc., for biomolecule immobilization must be modified to introduce functional groups that bind to biomolecules with high bonding strength, high activity, good orientation, and excellent long-term stability....

2013

nach oben zur Jahresübersicht

B. Faltin, R. Zengerle, F. von Stetten
Current Methods for Fluorescence-Based Universal Sequence-Dependent Detection of Nucleic Acids in Homogenous Assays and Clinical Applications
2013 Clin Chem, Band: 59, Nummer: 11, Seiten: 1567 - 1582
KurzfassungSpecific and sensitive nucleic acid (NA) testing in research and clinical diagnostics is usually performed by use of labeled oligonucleotide probes. However, the use of target-specific fluorogenic probes increases the cost of analysis. Therefore, universal sequence-dependent (USD) NA detection methods have been developed to facilitate cost-effective target detection using standardized reagents.

2011

nach oben zur Jahresübersicht

A. Kloke, F. von Stetten, R. Zengerle, S. Kerzenmacher
Strategies for the Fabrication of Porous Platinum Electrodes
2011 Adv Mater, Band: 23, Seiten: 4976 - 5008
KurzfassungPorous platinum is of high technological importance due to its various applications in fuel cells, sensors, stimulation electrodes, mechanical actuators and catalysis in general. Based on a discussion of the general principles behind the reduction of platinum salts and corresponding deposition processes this article discusses techniques available for platinum electrode fabrication. The numerous, different strategies available to fabricate platinum electrodes are reviewed and discussed in the context of their tuning parameters, strengths and weaknesses. These strategies comprise bottomup approaches as well as top-down approaches. In bottom-up approaches nanoparticles are synthesized in a fi rst step by chemical, photochemical or sonochemical means followed by an electrode formation step by e.g. thin fi lm technology or network formation to create a contiguous and conducting solid electrode structure. In top-down approaches fabrication starts with an already conductive electrode substrate. Corresponding strategies enable the fabrication of substrate-based electrodes by e.g. electrodeposition or the fabrication of self-supporting electrodes by dealloying. As a further top-down strategy, this review describes methods to decorate porous metals other than platinum with a surface layer of platinum. This way, fabrication methods not performable with platinum can be applied to the fabrication of platinum electrodes with the special benefi t of low platinum consumption.

2010

nach oben zur Jahresübersicht

M. Focke, D. Kosse, C. Müller, H. Reinecke, R. Zengerle, F. von Stetten
Lab-on-a-Foil: microfluidics on thin and flexible films
2010 Lab Chip, Band: 10, Seiten: 1365 - 1386
KurzfassungFor the first time we demonstrate a self-sufficient lab-on-a-foil system for the fully automated analysis of nucleic acids which is based on the recently available isothermal recombinase polymerase amplification (RPA). The system consists of a novel, foil-based centrifugal microfluidic cartridge including prestored liquid and dry reagents, and a commercially available centrifugal analyzer for incubation at 37°C and real-time fluorescence detection. The system was characterized with an assay for the detection of the antibiotic resistance gene mecA of Staphylococcus aureus. The limit of detection was <10 copies and time-to-result was <20 min. Microfluidic unit operations comprise storage and release of liquid reagents, reconstitution of lyophilized reagents, aliquoting the sample into #30 independent reaction cavities, and mixing of reagents with the DNA samples. The foil-based cartridge was produced by blow-molding and sealed with a self-adhesive tape. The demonstrated system excels existing PCR based lab-on-a-chip platforms in terms of energy efficiency and time-to-result. Applications are suggested in the field of mobile point-of-care analysis, B-detection, or in combination with continuous monitoring systems.
D. Mark, S. Häberle, G. Roth, F. von Stetten, R. Zengerle
Microfluidic lab-on-a-chip platforms: requirements, characteristics and applications
2010 Chem Soc Rev, Band: 39, Seiten: 1153 - 1182
KurzfassungThis critical review summarizes developments in microfluidic platforms that enable the miniaturization, integration,automation and parallelization of (bio-)chemical assays (see S. Haeberle and R. Zengerle, Lab Chip, 2007, 7, 1094–1110, for an earlier review). In contrast to isolated application-specific solutions, a microfluidic platform provides a set of fluidic unit operations, which are designed for easy combination within a well-defined fabrication technology. This allows the easy, fast, and cost-efficient implementation of different application-specific (bio-)chemical processes. In our review we focus on recent developments from the last decade (2000s). We start with a brief introduction into technical advances, major market segments and promising applications. We continue with a detailed characterization of different microfluidic platforms, comprising a short definition, the functional principle, microfluidic unit operations,application examples as well as strengths and limitations of every platform. The microfluidic platforms in focus are lateral flow tests, linear actuated devices, pressure driven laminar flow, microfluidic large scale integration, segmented flow microfluidics, centrifugal microfluidics, electrokinetics, electrowetting, surface acoustic waves, and dedicated systems for massively parallel analysis. This review concludes with the attempt to provide a selection scheme for microfluidic platforms which is based on their characteristics according to key requirements of different applications and market segments. Applied selection criteria comprise portability, costs of instrument and disposability, sample throughput, number of parameters per sample, reagent consumption, precision, diversity of microfluidic unit operations and the flexibility in programming different liquid handling protocols (295 references).

2008

nach oben zur Jahresübersicht

S. Kerzenmacher, J. Ducrée, R. Zengerle, F. von Stetten
Energy Harvesting by Implantable Abiotically Catalyzed Glucose Fuel Cells
2008 J Power Sources, Band: 182, Nummer: 1, Seiten: 1 - 17
KurzfassungAbiotically catalyzed glucose fuel cells are a newly re-discovered approach to realize an autonomous energy supply for low power medical implants that solely relies on the electrochemical reaction of oxygen and glucose available from body fluids. The key advantage of a fuel cell driven power supply over conventional battery based approaches is the abundant availability of both reactants in body fluids, rendering the need for regular battery replacement or external charging mechanisms obsolete. Abiotic electrode catalysts, such as noble metals or activated carbon, exhibit favorable characteristics for long-term application in an implantable glucose fuel cell. In contrast to enzymes they are long-term stable and amenable to heat sterilization and corresponding fuel cells have already been developed in the late 1960s. However, the concept has drawn only little attention over the last decades, and research has mainly been focused on the development of enzymatic glucose fuel cells. This review therefore covers the development of implantable glucose fuel cells based on abiotic catalysts since the 1960s, with special regard to their applicability as sustainable micro power generators for implantable devices. The historical achievements of various academic and industrial research groups are critically reviewed, and different embodiment concepts are presented. While encouraging results have been achieved both in in-vitro and in preliminary in-vivo experiments, no further developments have been reported since the introduction of implantable lithium iodine batteries in the mid 1970s. In terms of design and fabrication of operational devices only limited information is documented in the literature, and further effort will be necessary to develop an understanding of the parameters influencing device performance and stability under in-vivo conditions.

2007

nach oben zur Jahresübersicht

Ducree,J., Haeberle,S., Lutz,S., Pausch,S., von Stetten,F., Zengerle,R.
The centrifugal microfluidic Bio-Disk platform
2007 Journal of Micromechanics and Microengineering, Band: 17, Seiten: S103 - S115

Monographien

Jahre: 2004 | 1994

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2004

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Books on Demand GmbH, Norderstedt, Germany, Seite: 197
FlowMap - Microfluidics Roadmap for the Life Sciences
ISBN: 3-8334-0744-1
Ducrée J, Zengerle R
KurzfassungThe report is based on a 15-month European project "FlowMap - Microfluidics Roadmap for the Life Sciences" lead by the Institute of Microsystem Technology (IMTEK). In the course of the project, present and emerging markets for microfluidic technologies in the life sciences have been investigated. Important market demands, major technology drivers and strategic issues are identified and analyzed in a global market research chapter as well as individual discovery, medicine and ecology. The present markets and expected growth rates are quantified to forecast the evolution of the market volume. A 19% annual growth rate starting from a 2002-turnover of 500 M€ and reaching 1.4 billion € in 2008 is estimated. The results are based on personal interviews and a questionnaire action involving more than 150 key experts in the life-science fields, representing end users, system suppliers and developers of unterlying microfluidic technologies. In addition, the report features an introduction into microfluidic technologies.

1994

nach oben zur Jahresübersicht

Shaker
Mikro-Membranpumpen als Komponenten für Mikro-Fluidsysteme (Dissertation)
ISBN: 3-8265-0216-7
Zengerle R

Buchbeiträge

Jahre: 2020 | 2018 | 2017 | 2016 | 2015 | 2014 | 2012 | 2010 | 2007 | 2006 | 2003

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2020

nach oben zur Jahresübersicht

A. Brunauer, H. Ceren Ates, C. Dincer, S. M. Früh
Integrated paper-based sensing devices for diagnostic applications
In: Comprehensive Analytical Chemistry
2020, Elsevier,
KurzfassungPaper-based sensing platforms are one of the most powerful tools for point-of-care diagnostics. The ease of use while ensuring low production costs of such devices is the key for paper-based technologies to find their way to a successful commercialization. Thus, all steps in the analytical process chain from sample interface, sample preparation, signal amplification to signal transduction and data analysis have to be integrated in a single diagnostic platform. In this chapter, we provide a comprehensive and critical overview on recent developments towards integrated paper-based platforms in academia and industry. Herein, innovative solutions are discussed with respect to their sampling methods such as invasive and non-invasive approaches. We also address the requirements and challenges for the sampling and analysis of the different body fluids. Finally, we present our views about the future perspectives, challenges, and opportunities of the integrated paper-based devices.

2018

nach oben zur Jahresübersicht

J. Riba, S. Zimmermann, P. Koltay
Technologies for Automated Single Cell Isolation
In: Handbook of Single Cell Technologies
2018, Springer Nature, T. S. Santra, F.-G. Tseng, T. S. Santra, F.-G. Tseng, ISBN: 978-981-10-4857-9
KurzfassungThe isolation of individual cells has gained tremendous importance with the advent of new methods for highly parallel single-cell analysis. A prerequisite for effective clonal cultivation or single-cell analysis is the efficient isolation of individual cells from liquid cell suspensions. This review provides an overview of technologies that are used to automate the isolation of single cells for subsequent cultivation or analysis. First, currently available technologies are classified based on their major technical characteristics. Then, the most prominent technologies such as limiting dilution, FACS, single-cell printing, hydrodynamic trapping, droplet microfluidics, and cell manipulation by external forces are described in detail. Furthermore, the individual features of each technology with focus on throughput, isolation efficiency, level of automation, flexibility in terms of cell types, and their suitability for specific downstream processing and analysis methods are discussed. In contrast to previous works, this review provides a classification approach for single-cell isolation technologies according to performance requirements, makes specific reference to methods for the isolation of microbial cells, and discusses sample input requirements, which is an important aspect in particular for diagnostic purposes.

2017

nach oben zur Jahresübersicht

A.G. Venkatesh, T. van Oordt, E. M. Schneider, R. Zengerle, F. von Stetten, J.H.T. Luong, S.K. Vashist
A Smartphone-Based Colorimetric Reader for Human C-Reactive Protein Immunoassay
In: Biosensors and Biodetection: Methods and Protocols Volume 1: Optical-Based Detectors, Methods in Molecular Biology, vol. 1571
2017, Springer, Avraham Rasooly and Ben Prickril, Seiten: 343 - 356, Avraham Rasooly and Ben Prickril,
KurzfassungA smartphone-based colorimetric reader (SBCR), comprising a Samsung Galaxy SIII mini, a gadget (iPAD mini, iPAD4, or iPhone 5s) and a custom-made dark hood and base holder assembly, is used for human Creactive protein (CRP) immunoassay. A 96-well microtiter plate (MTP) is positioned on the gadget’s screensaver to provide white light-based bottom illumination only in the specific regions corresponding to the well’s bottom. The images captured by the smartphone’s back camera are analyzed by a novel image processing algorithm. Based on one-step kinetics-based human C-reactive protein immunoassay (IA), SBCR is evaluated and compared with a commercial MTP reader (MTPR). For analysis of CRP spiked in diluted human whole blood and plasma as well as CRP in clinical plasma samples, SBCR exhibits the same precision, dynamic range, detection limit, and sensitivity as MTPR for the developed IA (DIA). Considering its compactness, low cost, advanced features and a remarkable computing power, SBCR is an ideal point-ofcare (POC) colorimetric detection device for the next-generation of cost-effective POC testing (POCT).

2016

nach oben zur Jahresübersicht

S. K. Vashist, A.G. Venkatesh, R. Zengerle, F. von Stetten, J.H.T. Luong
Smartphone-based in vitro diagnostic technologies for personalized healthcare monitoring and management
In: Nanobiosensors for personalized and onsite biomedical diagnosis
2016, The Institution of Engineering and Technology, UK, Pranjal Chandra, Seiten: 231 - 251, Pranjal Chandra, ISBN: 978-1-84919-950-6

2015

nach oben zur Jahresübersicht

M. Blazek, G. Roth, R. Zengerle, M. Meier
Microfluidic Proximity Ligation Assay for Profiling Signaling Networks with Single-Cell Resolution
In: Springer Protocol: Single Cell Protein Analysis
2015, Springer, Anup K. Singh, Aarthi Chandrasekaran, Seiten: 169 - 184, Anup K. Singh, Aarthi Chandrasekaran,
KurzfassungThe proximity ligation assay (PLA) is a technique that can be used to characterize proteins, protein–protein interactions, and protein modifications at the single-cell level. Image-based in situ detection of proteins using PLA is a quantitative method with a high degree of sensitivity and specificity. The miniaturization and parallelization of the PLA onto a microfluidic chip and concurrent use of an automated cell-culture system increase the throughput of this technology. Here, we describe the performance of PLA on a microfluidic chip. We provide protocols for on-chip cell culture, time-shifted cell stimulation and fixation, PLA implementation, and computational image analysis in order to achieve single-cell resolution. As a proof of concept, we studied the phosphorylation of Akt in response to stimulation with platelet-derived growth factor.
S.K. Vashist, A.G. Venkatesh, R. Zengerle, F. von Stetten, J.H.T. Luong
Smart-phone based Point-of-Care for mobile healthcare
In: Handbook of Biotechnology, Bioengineering and Biomedical Applications
2015, National Design and Research Forum, Gundu H. R. Rao and Dr. L.V. Muralikrishna Reddy, Seiten: 313 - 332, Gundu H. R. Rao and Dr. L.V. Muralikrishna Reddy,

2014

nach oben zur Jahresübersicht

D. Mark, F. von Stetten, R. Zengerle
Lab on a Chip: The Vision Becomes Reality
In: Smart Systems Integration for Micro- and Nanotechnologies
2014, goldenbogen, Seiten: 73 - 81, ISBN: 9783932434785
KurzfassungThis chapter elucidates the current socio-economical status of Lab-on-a-Chip (LOAC) technology. It starts from the original vision of LOAC to miniaturize and automate assays by microfluidic integration and then focusses on microfluidic Lab-on-a-Chip products in the field of point-of-care (POC)diagnostics. These are discussed in the light of their market impact, approval by the FDA (Food and Drug Administration), and their status of process integration and automation as categorized by the CLIA (Clinical Laboratory Improvement Amendments). Future requirements to strenghten the competiveness of microfluidic based POC products are seen in the implementation of a microfluidic platform based development approach, and foundry based manufacturing process.
S. Wadle, S. Rubenwolf, M. Lehnert, B. Faltin, M. Weidmann, F. Hufert, R. Zengerle, F. von Stetten
Mediator Probe PCR: Detection of Real-Time PCR by Label-Free Probes and a Universal Fluorogenic Reporter
In: Quantitative Real-Time PCR: Methods and Protocols
2014, Springer, R. Biassoni, A. Raso, HUMANA PRESS INC., Seiten: 55 - 73, R. Biassoni, A. Raso, HUMANA PRESS INC.,
KurzfassungMediator probe PCR (MP PCR) is a novel detection format for real-time nucleic acid analysis. Label-free mediator probes (MP) and fluorogenic universal reporter (UR) oligonucleotides are combined to accomplish signal generation. Compared to conventional hydrolysis probe PCRs costs can thus be saved by using the same fluorogenic UR for signal generation in different assays. This tutorial provides a practical guideline to MP and UR design. MP design rules are very similar to those of hydrolysis probes. The major difference is in the replacement of the fluorophore and quencher by one UR-specific sequence tag, the mediator. Further protocols for the setup of reactions, to detect either DNA or RNA targets with clinical diagnostic target detection as models, are explained. Ready to use designs for URs are suggested and guidelines for their de novo design are provided as well, including a protocol for UR signal generation characterization.

2012

nach oben zur Jahresübersicht

S. Haeberle, D. Mark, F. von Stetten, R. Zengerle
Microfluidic Platforms for Lab-on-a-Chip Applications
In: Microsystems and Nanotechnology
2012, Springer, Z. Zhou, Z. Wang, L. Lin, Seiten: 853 - 895, Z. Zhou, Z. Wang, L. Lin, ISBN: 978-3-642-18293-8

2010

nach oben zur Jahresübersicht

Mark D, Haeberle S, Roth G, Stetten von F, Zengerle R
Microfluidic Lab-on-a-Chip Platforms: Requirements, Characteristics and Applications
In: Microfluidic Based Microsystems: Fundamentals and Applications
2010, Springer Verlag, S. Kakac, B. Kosoy, D. Li, A. Pramuanjaroenkij, Seiten: 305 - 376, S. Kakac, B. Kosoy, D. Li, A. Pramuanjaroenkij, ISBN: 978-90-481-9031-7
KurzfassungThis review summarizes recent developments in microfluidic platform approaches. In contrast to isolated application-specific solutions, a microfluidic platform provides a set of fluidic unit operations, which are designed for easy combination within a well-defined fabrication technology. This allows the implementation of different application-specific (bio-)chemical processes, automated by microfluidic process integration [1]. A brief introduction into technical advances, major market segments and promising applications is followed by a detailed characterization of different microfluidic platforms, comprising a short definition, the functional principle, microfluidic unit operations, application examples as well as strengths and limitations. The microfluidic platforms in focus are lateral flow tests, linear actuated devices, pressure driven laminar flow, microfluidic large scale integration, segmented flow microfluidics, centrifugal microfluidics, electrokinetics, electrowetting, surface acoustic waves, and systems for massively parallel analysis. The review concludes with the attempt to provide a selection scheme for microfluidic platforms which is based on their characteristics according to key requirements of different applications and market segments. Applied selection criteria comprise portability, costs of instrument and disposable, sample throughput, number of parameters per sample, reagent consumption, precision, diversity of microfluidic unit operations and the flexibility in programming different liquid handling protocols.

2007

nach oben zur Jahresübersicht

Shoji,S., Sato,H., Zengerle,R.
Liquid Micropumps
In: Comprehensive Microsystems – Fundamentals, technology and applications
2007, Elsevier, Y. Gianchandani, O. Tabata, H. Zappe, Seiten: 301 - 322, Y. Gianchandani, O. Tabata, H. Zappe, ISBN: 0-444-52194-1
Zengerle,R., Ducree,J.
The Future of Microfluidics: Low-Cost Technologies and Microfluidic Platforms
In: Microsystems and Nanotechnology
2007, Springer, Seiten: 806 - 813,

2006

nach oben zur Jahresübersicht

Koltay P, Ducrée J, Zengerle R
Microfluidic Platforms
In: BioMEMS
2006, Springer Verlag, Gerald A. Urban, Seiten: 139 - 165, Gerald A. Urban, ISBN: 10 0-387-28731-0
Ducrée J, Koltay P, Zengerle R
Microfluidics
In: MEMS: A Practical Guide to Design, Analysis, and Applications
2006, William Andrew Publishing, Jan G. Korvink, Oliver Paul, Seiten: 667 - 727, Jan G. Korvink, Oliver Paul, ISBN: 0-8155-1497-2
Zengerle R
Mikrosystemtechnik und Nanotechnologie: Technologien im Kleinen mit enormen Impact
In: Festschrift „10 Jahre GMM“
2006, GMM Frankfurt, Seite: 87ff,

2003

nach oben zur Jahresübersicht

Koltay P, Ducrée J, Zengerle R
Nanoliter and Picoliter Liquid Handling
In: Lab-On-A-Chip: Miniaurized Systems for (Bio) Chemical Analysis and Synthesis
2003, Elsevier Science, Edwin Oosterbroek, Albert van den Berg, Seiten: 151 - 171, Edwin Oosterbroek, Albert van den Berg, ISBN: 0-444-51100-8

Kurzbeiträge

Jahre: 2018 | 2017 | 2016 | 2015 | 2012 | 2011 | 2008 | 2005 | 2000 | 1993

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2018

nach oben zur Jahresübersicht

J. Schemberg, M. Specht, M. Karle
Neue Wege in der Krebsdiagnostik - Mikrofluidische Strategien für die Medizin 4.0
2018 GIT-Laborfachzeitschrift, Band: 4, Seite: 16

2017

nach oben zur Jahresübersicht

N. Borst, F. von Stetten
Eine Technologieplattform für die digitale Nukleinsäureanalytik
2017 Management & Krankenhaus, Band: 2017-04, Seite: 37
J. Riba, S. Zimmermann, B. Steimle, A. Gross
Vereinzelung von prokaryotischen und eukaryotischen Zellen
2017 BIOspektrum, Band: 23, Seiten: 298 - 300

2016

nach oben zur Jahresübersicht

J. Merz
Große Hoffnung in kleinen Tröpfchen
2016 Laborjournal, Band: 11

2015

nach oben zur Jahresübersicht

F. Schuler, F. von Stetten
Tröpfchenschleuder
2015 Laborjournal, Band: 7-8, Seiten: 52 - 53

Datei herunterladen

2012

nach oben zur Jahresübersicht

B. Faltin, S. Wadle, G. Roth, S. Rubenwolf, M. Lehnert, R. Zengerle, F. von Stetten
Neuer Echtzeit-Nachweis von Nukleinsäuren
2012 Laborwelt, Band: 4, Seiten: 10 - 11

2011

nach oben zur Jahresübersicht

Daniel Mark, Günter Roth, Dominique Kosse, Nils Paust, Roland Zengerle, Felix von Stetten
Assay-Automatisierung als Dienstleistung - Mikrofluidische Integration von Laborprozessen durch den Lab-on-a-Chip Design- & Foundry-Service
2011 Labo, Band: April, Seiten: 10 - 13
D. Mark, G. Roth, R. Zengerle, F. von Stetten
Laborautomation - Die zentrifugal-mikrofluidische Plattform
2011 BIOspektrum, Nummer: 6, Seiten: 1 - 4
S. Spieth, S. Messner
Mikrodosiersysteme machen funktionellere Lösungen möglich
2011 MaschinenMarkt, Band: 42, Seiten: 26 - 29

2008

nach oben zur Jahresübersicht

Andreas Ernst, Peter Koltay
Auch Mikrotropfen besitzen "Fingerabdrücke"
2008 A&D Kompendium, Seiten: 191 - 194

2005

nach oben zur Jahresübersicht

Woias P, Manoli Y, Nann T, von Stetten F
Energy Harvesting for Autonomous Microsystems
2005 mst-news, Band: 4, Seiten: 42 - 45

2000

nach oben zur Jahresübersicht

Jens Ducrée, Bas de Heij, Hermann Sandmaier, Roland Zengerle; Fabrication of microarrays on an industrial, scale with TopSpot; mstnews; No 4/2000; September 2000
Fabrication of microarrays on an industrial scale with TopSpot
2000 mstnews; No 4/2000 (Sept. 2000), Seiten: 22 - 23

1993

nach oben zur Jahresübersicht

Zengerle R, Richter A
Mikropumpen als Komponenten für Mikrosysteme
1993 Physik in unserer Zeit, Band: 24, Nummer: 2, Seiten: 86 - 90

Vorträge

Jahre: 2024 | 2023 | 2022 | 2019 | 2018 | 2017 | 2016 | 2015 | 2014 | 2013 | 2012 | 2011 | 2009 | 2007 | 2006 | 2005 | 2004 | 2003 | 2001 | 1999

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2024

nach oben zur Jahresübersicht

E. Kipf, P. Jülg, F. Schlenker, M. Fillies, C. Kranig, M. Specht, S. Groeneveld-Krentz, S. Neumann, R. Zengerle, F. von Stetten, N. Borst, R. Kirschner-Schwabe, T. Hutzenlaub, M. Lehnert, C. Eckert
Messung des individuellen Therapieansprechens von akuten lymphoblastischen Leukämien (IRMA-4-ALL)
2024 Translationale Forschung in der Personalisierten Medizin – Chancen und Hürden, Netzwerkveranstaltung für geförderte Projekte der „Innovationen für die individualisierte Medizin“ und der „Translationsp

2023

nach oben zur Jahresübersicht

K. Seteiz, J. Häberlein, J. Disch, L. Bohn, P. Heizmann, S. Vierrath
Carbon black supported Ag NPs for CO2 reduction to CO
2023 29. Internes FMF-Kolloquium am FIT, Titisee, 10.10.2023
L. Bohn
Integrated reference electrodes for CO2 electrolysis cells
2023 29. Internes FMF-Kolloquium am FIT, Titisee, 10.10.2023

2022

nach oben zur Jahresübersicht

M. Elshamy, L. Metzler, S. Vierrath
Assessing the electronic and ionic conductivity of NiFe-LDH-based catalyst layers for AEMWEs
2022 Workshop on Ion Exchange Membranes for Energy Applications, Bad Zwischenahn, June 20 – 22, 2022
L. Metzler, S. Koch, M. Elshamy, S. Kilian, M. Breitwieser, S. Vierrath
Fully casted catalyst coated membranes for anion exchange membrane water electrolysis
2022 Workshop on Ion Exchange Membranes for Energy Applications, Bad Zwischenahn, June 20 – 22, 2022
J. Häberlein, K. Seteiz, P. Heizmann, J. Disch, S. Vierrath
Low loaded carbon supported Ag nanoparticles for CO2 to CO electrolysis showing high mass activities
2022 Symposium Nano-BW 2022 des Kompetenznetzes „Funktionelle Nanostrukturen“, Bad Herrenalb, December, 6-7, 2022
F. Pescher, M. von Holst
Particle Atomic Layer Deposited Overcoatings for Improving the Durability of Proton Exchange Membrane Fuel Cells
2022 Symposium Nano-BW 2022 des Kompetenznetzes „Funktionelle Nanostrukturen“, Bad Herrenalb, December, 6-7, 2022
M. von Holst, L. Pavko, J. Stiegeler, P. A. Heizmann, A. Salihi, M. Gatalo, N. Hodnik, C. Klose, S. Vierrath, M. Breitwieser
Reduced graphene oxide as durable carbon support for PtCo catalyst in proton exchange membrane fuel cells
2022 Symposium Nano-BW 2022 des Kompetenznetzes „Funktionelle Nanostrukturen“, Bad Herrenalb, December, 6-7, 2022

2019

nach oben zur Jahresübersicht

K. Mitsakakis
Converging Human, Animal, and Vector Diagnostics, together with Digital Technologies, towards a Holistic One Health Approach
2019 Molecular Diagnostics Europe, Lissabon/Portugal, 06. - 09.05.2019

2018

nach oben zur Jahresübersicht

S. Vierrath, M. Breitwieser, C. Klose, M. Klingele, S. Thiele
Novel approaches to tailor the PEM|electrode interface for fuel cells with increased power density
2018 innBW Wissenschaftlertreffen Stuttgart, 21.04.2018
M. Breitwieser, S. Vierrath
Neue Kompositmembranen und Mikrocharakterisierung: Die Gruppe „Elektrochemische Energiesysteme“ an IMTEK und Hahn-Schickard
2018 Brennstoffzellenallianz Duisburg, 26. - 27. Juni 2018
L. Becherer
Therapiebegleitende HIV- und HTLV-Diagnostik am Point-of-Care
2018 microTEC Südwest Clusterkonferenz 2018, 16. – 17.04.2018, Freiburg

2017

nach oben zur Jahresübersicht

F. Schuler, S. Wadle, N. Borst, M. Schulz, L. Becherer, J. Li, M. Specht, T. Hutzenlaub, N. Paust, R. Zengerle, F. von Stetten
A Technology Platform for Digital Nucleic Acid Diagnostics at the Point of Care (invited talk)
2017 3. Münchner point-of-care testing symposium, Deutsche Gesellschaft für Klinische Chemie und Laboratoriumsmedizin (DGKL), München, 13.-15. 3. 2017
F. von Stetten
A technology platform for digital nucleic acid testing at the point of need (invited talk)
2017 Potsdam Days on Bioanalysis 2017, Potsdam, 23.-24.11.2017
F. Schuler, N. Borst, S. Wadle, M. Schulz, M. Specht, J. Li, L. Becherer, T. Hutzenlaub, N. Paust, R. Zengerle, F. von Stetten
Centrifugal Step Emulsification Allows Miniaturized Digital Droplet-RPA,-LAMP and -PCR on the Centrifugal Microfluidic Platform (invited talk)
2017 9th Annual lab-on-a-chip & microfluidics Conference, Selectbio, Munich, 10.-11.5. 2017
P. Kocatürk Schumacher, J. Madjarov, P. Viwatthanasittiphong, S. Kerzenmacher
Increasing the energy efficiency of an AnMBR by using the membrane as microbial anode
2017 5. Workshop der Plattforminitiative Mikrobielle Bioelektrotechnologie, Rüsselsheim, 29.11.2017

2016

nach oben zur Jahresübersicht

F. von Stetten
Accelerated Development of Multiplex Real-Time PCR by Preloaded Fluorogenic Reporters and Label-Free Mediator Probes (talk)
2016 4th Point-of-Care Diagnostics & Global Health World Congress 2016, San Diego USA, 26.-28.09.2016
F. von Stetten
Accelerated development of multiplex real-time PCR by a fluorogenic mastermix (invited talk)
2016 4th qPCR and Digital PCR Congress, London / UK 20.-21.10.2016
F. von Stetten
Centrifugal Step Emulsification Allows Miniaturized Digital Droplet-RPA, -LAMP and -PCR on the Centrifugal Microfluidic Platform (talk)
2016 8th Lab-on-a-Chip, Microfluidics & Microarrays World Congress 2016, San Diego USA, 26.-28.09.2016
C. Klose, M. Breitwieser, L. Zielke, S. Vierrath, H. Cho, S. Thiele, J. Kerres, R. Zengerle
Long-life and high-power PEMFCs by combination of direct electrospinning and inkjet printing,
2016 Statusworkshop der Baden-Württemberg Stiftung, Bad Herrenalb, 2016
S. Thiele, S. Vierrath, R. Moroni, L. Zielke, R. Zengerle
Multiple scales and interfaces in PEMFCs - a tomographic study
2016 Electrocatalysis Workshop, Vancouver, February 2016.
F. von Stetten
Neue Ansätze zur nukleinsäurebasierten Vor-Ort-Diagnostik von Infektionskrankheiten (invited talk)
2016 Fachtagung Bio Medizin Technik: Innovationen in Diagnostik und Therapie von Infektionen, Hannover, 06.4.2016
M. Breitwieser, M. Klingele, B. Britton, S. Vierrath, R. Zengerle, S. Holdcroft, S. Thiele
Recent Progress in Low- and No- Pt loaded PEMFCs
2016 Electrocatalysis Workshop, Vancouver, February 2016
S. Vierrath, L. Zielke, R. Moroni, A. Mondon, R. Zengerle, S. Thiele
ZnO Contrasted Nano Tomographies of Fuel Cell and Battery Components
2016 MODVAL 13, Symposium for Fuel Cell and Battery Modeling and Experimental Validation, Lausanne, Schweiz (22.-23.03.2016)

2015

nach oben zur Jahresübersicht

F. von Stetten
Mediator probe PCR – label free probes and universal fluorogenic reporters for the detection of different RNA and DNA sequences (talk)
2015 Spring meeting, European Materials Research Society, Lille, France, 11.-15.05.2015
S. Vierrath, F. Güder, A. Menzel, M. Hagner, R. Zengerle, M. Zacharias, S. Thiele
Novel Approach in 3D-Reconstructions of PEMFC Catalyst Layers: Infiltration aided Segmentation
2015 ModVal 12, Munzingen, Deutschland, 26.-27. März 2015
L. Zielke, S. Vierrath, R. Moroni, R. Zengerle, S. Thiele
Transport, Degradation and Multi-Scale Morphology in X-ray Tomographic Reconstructions of Battery Electrodes
2015 Solid State Electrochemical Workshop 2015, Roggenburg, Germany, 06. – 09.09.2015
J. Eipper, A. Barske, K. Sturm-Richter, J. Gescher, S. Kerzenmacher
Using an enzyme secreting, genetically modified E. coli strain to supply Bilirubin Oxidase to a biofuel cell cathode
2015 Annual Conference 2015 of the Association for General and Applied Microbiology (VAAM) in Marburg, 01. - 04.03.2015

2014

nach oben zur Jahresübersicht

N. Lass, L. Riegger, R. Zengerle, P. Koltay
Direktes Drucken von metallischer Mikrostrukturen mit der StarJet Technologie
2014 Clusterkonferenz MicroTEC Südwest, Freiburg, 05.-06.05.2014
S. Kartmann, A. Ernst, R. Zengerle, P. Koltay
E-DosiS: Einweg-Dosiersystem mit intelligenter Sensorik
2014 Clusterkonferenz MicroTEC Südwest, Freiburg, 05.-06.05.2014
F. von Stetten
LabTube - a novel centrifugal microfluidic lab-on-a-chip platform for operation in standard laboratory centrifuges (invited key-note presentation)
2014 Biosensors 2014, Melbourne, Australia, 27.-30.05.2014
F. von Stetten
LabTube and LabDisk - prospective centrifugal microfluidic platforms for sample-to-answer point-of-care nucleic acid testing (invited key-note presentation)
2014 Lab‐on‐a‐Chip World Congress, San Diego/USA, 18. - 19. September 2014
F. von Stetten
LabTube – a novel "microfluidic app" for sample preparation and diagnostics operated in a laboratory centrifuge (invited talk)
2014 Lab-on-a-Chip European Congress, SelectBio, Berlin, 10.-11.03.2014
F. von Stetten
Mediator Probe PCR - Principle, Applications and Guidelines for Primer and Probe Design (invited talk)
2014 Advances in Biodetection & Biosensors, Berlin, 10.-11. 03.2014
S. Vierrath, F. Güder, A. Menzel, R. Zengerle, M. Zacharias, S. Thiele
Novel Approach in 3D-Reconstructions of PEMFC Catalyst Layer
2014 97th Canadian Chemistry Conference and Exhibition”, Vancouver, Kanada, 01. - 05. Juni 2014
S.K. Vashist, T. van Oordt, A. Kloke, F. Von Stetten, R. Zengerle
Smartphone-based colorimetric readers (SBCR) for bioanalytical applications and SBCR-based in vitro diagnostics for mobile healthcare
2014 Clusterkonferenz MicroTEC Südwest, Freiburg, 05.-06.05.2014
F. von Stetten
Universal reporters of mediator probe PCR as target-independent biosensors for detection of five different RNA and DNA sequences (invited key-note presentation)
2014 Biosensors 2014, Melbourne, Australia, 27.-30.05.2014

2013

nach oben zur Jahresübersicht

Lehnert M, Wadle S, Stetten F, Zengerle R
Mediator probe PCR as tool for personalized medicine
2013 BmbF
R. Zengerle, D. Mark, O. Strohmeier, D. Kosse, N. Paust, F. von Stetten, G. Czilwik, T. van Oordt, M. Keller, J. Drexler
LabDisk - a set of novel centrifugal microfluidc unit operations enables point of care sample-to-answer nucleic acid testing
2013 Gordon Research Conference on ”Physics and Chemistry of Microfluidics: Challenges, Advances and New Technologies for Diagnostics” in Lucca, Tuscany, Italy , 09. – 14.06.2013
F. von Stetten
LabDisk - a set of novel centrifugal microfluidc unit operations enables point of care sample-to-answer nucleic acid testing (talk)
2013 MicroTAS 2013, Freiburg, 27.-31.10.2013
F. von Stetten, A. Kloke, A. Fiebach, L. Drechsel, S. Zhang, N. Paust, J. Steigert, R. Zengerle
LabTube - a novel centrifugal microfluidic lab-on-a-chip platform for operation in standard laboratory centrifuges
2013 Gordon Research Conference on ”Physics and Chemistry of Microfluidics: Challenges, Advances and New Technologies for Diagnostics” in Lucca, Tuscany, Italy , 09. – 14.06.2013
F. von Stetten, B. Punnamoottil
Labor im Zentrifugenröhrchen zur dezentralen patientennahen Diagnostik (invited talk)
2013 Mobile Diagnostik am Point-of-Care, Deutsche Gesellschaft für Biomedizinische Technik, Düsseldorf, 13.11.2013
F. von Stetten
Physikalische und biologische Sensoren, fluidische Integration, und Fertigungstechnologie mit einem Anwendungsbeispiel zur Wasseranalytik (invited talk)
2013 Fachsymposium des Vereins HybridSensorNet, Karlsruhe, 29.11.2013

2012

nach oben zur Jahresübersicht

F. von Stetten
A functional blister-pack LabDisk system for point of care testing (invited talk)
2012 6th Workshop “Chemical and Biological Micro Laboratory Technology“, Ilmenau/Elgersburg, Germany, 2012
R. Zengerle, J. Hoffmann, G. Roth, D. Mark, F. von Stetten
Microfluidic Apps for off-the-shelf Instruments
2012 1st International POSTECH Biomedical Device Workshop 2012; Pohang, Korea , 19.07.2012- 20.07.2012
A. Gross, J. Schoendube, W. Streule, L. Riegger, R. Zengerle, P. Koltay 1 3
Non-contact, label-free printing of single, living cells
2012 IMTEK Poster Session, Okt. 2012, Freiburg

2011

nach oben zur Jahresübersicht

F. von Stetten
A functional blister-pack LabDisk system for rapid field testing of biological threats (invited talk)
2011 18th Annual Biodetection Technologies, Washington, 23.06.2011
F. von Stetten
Centrifugal Microfluidic Platform for Molecular Diagnostics (talk)
2011 19th IFCC-EFCC European Congress of Clinical Chemistry and Laboratory Medicine, Berlin, 15- 19.05.2011

2009

nach oben zur Jahresübersicht

F. von Stetten, M. Focke, S. Lutz, B. Faltin, J. Burger, P. Weber, C. Mueller, T. Metz, G. Roth, D. Mark, R. Zengerle
Miniaturisation, automation and integration of biochemical assays based on centrifugal microfluidics (talk)
2009 6. Deutschen BioSensor Symposiums, Freiburg, 2009

2007

nach oben zur Jahresübersicht

Zengerle R
Microfluidic Platforms for Miniaturization, Integration and Automation of Assays
2007 Proc. Transducers 2007, Lyon, France

2006

nach oben zur Jahresübersicht

Zengerle R
Microfluidics: From Application Specific Microfluidic Solutions to Integrated Microfluidic Platforms
2006 Micro Mechanics Europe (MME); 3-5th Sept 2006 in Southampton, UK
Zengerle R
Microfluidics: From Discrete Solutions to Integrated Microfluidic Platforms
2006 2nd International Symposium of Micro and Nano Technology (ISMNT-2); March 29-31, 2006 in Hsinchu, Taiwan

2005

nach oben zur Jahresübersicht

Zengerle R
Bio-Disk - A Versatile Centrifugal Microfluidic Platform for Point of Care Diagnostics
2005 "Lab-on-Microchip" Symposium at University of Siegen, Germany
Ducrée J, Grumann M, Brenner T, Zengerle R
Bio-Disk: A Flexible and Versatile Microfluidic Platform for Assay Automation
2005 Proc. BMT 2005; 39th Annual Congress of the German Society for Biomedical Engineering (DGMBT) within VDE; Nuremberg, Germany
Santer M, Moseler M, Cupelli C, Henrich B, Wonisch A, Glatzel T, Zengerle R
Dissipative Particle Dynamics as a practical Simulation Tool for Nanofluidic Applications
2005 Proc. "First International Nanofluidics Workshop"; Boekelo, the Netherlands
Niekrawietz R, Honstein W, Gutmann O, de Heij B, Zengerle R, Daub M
Integrated Process Control For Highly Parallel and Contact Free Microarray Printing
2005 Proc. "Statusseminar Chiptechnologien - Technologien und Anwendungen"; Dechema Haus, Frankfurt, Germany
Kohnle J, Schumacher A, Goettsche T, Messner S, Zengerle R
IntelliDrug - Intelligentes Medikamenten-Mikrodosiersystem für den Mundraum
2005 Proc. Mikrosystemtechnik-Kongress 2005, Freiburg, Germany

2004

nach oben zur Jahresübersicht

Zengerle R
Microfluidics & Highly Parallel Picoliter and Nanoliter Dispensing
2004 Industrial Forum at Kyoto University, Japan

2003

nach oben zur Jahresübersicht

Ducrée J, Zengerle R, Newman J, Ernst H, Riedmueller K, Messner S, Anrieux G, Provence M
FlowMap - Microfluidics Roadmap for the Life Sciences
2003 8th International Conference on the Commercialization of Micro and Nano Systems 2003; Amsterdam, The Netherlands
Grumann M, Dobmeier M, Schippers P, Brenner T, Zengerle R, Ducrée J, Kuhn C, Fritsche M
Hydrodynamic Creation of Monolayers for Parallel Readout of Bead-Based Assays
2003 NanoTec 2003; Montreux, Switzerland

2001

nach oben zur Jahresübersicht

Peter Koltay
A novel Fixed Volume Dispenser for the Massive Parallel Liquid Handling of Nanoliter Volumes. (EuroLabAutomation; 23-25 October 2001; London).
2001

1999

nach oben zur Jahresübersicht

Zengerle R
Nanoliter Liquid Handling
1999 IBC-conference Microfabrication and Microfluidics 99, San Francisco
Zengerle R
Nanoliter Liquid Handling
1999 IBC-conference BioChip Technologies, Edinburgh
Ducrée J
TopSpot
1999 Proc. Nanotechnologie, Montreux

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2025

nach oben zur Jahresübersicht

J. Sum, T. Truong, C. Mikloska, M. Oberländer, N. von Bubnoff, L. Christiansen, S. Tornow, S. Derer, F. Janke, H. Sültmann, S. Zeissig, M. Linnebacher, C. Schafmayer, I. Nazarenko, F. Scherer, H. Becker, M. Kalweit, M. Lehnert, T. Hutzenlaub, R. Zengerle, N. Paust, P. Juelg
Liquid Biopsy using Methylation Analysis-coupled digital PCR of Biomarkers to Detect Early-Onset Colorectal Cancer
2025 Kongress "Prevention of eoCRC" HARMONIZE des OUTLIVE Verbundes, Lübeck, 24. – 26.03.2025
C. Hensel, C. Kleber, J. N. Klatt, T. Hutzenlaub, F. von Stetten, J. C. Behrends, A. Schreiber
Protein Sample Preparation for Nanopore Recording
2025 Single Molecule Protein Sequencing (SMPS), Bolzano/Italy, January 18-24, 2025

2024

nach oben zur Jahresübersicht

K. Seteiz, H. Grammel, J. Häberlein, P. Heizmann, L. Metzler, M. Günthel, M. Knäbbeler-Buß, S. Vierrath, J. Disch
4-Aminothiophenol as anchoring agent for Ag/C catalysts in CO2 electrolysis to CO
2024 PSI Symposium, Villigen / Switzerland, 06.06.2024
T-T. Truong, Y. Kaku, J. Schlanderer, F. Schlenker, E. Kipf, E. Dazert, F. Axt, N. von Bubnoff, S. Kartmann, N. Borst, N. Paust, T. Hutzenlaub, P Juelg
A robotic microfluidic approach for rapid sample-to-answer analysis of cell-free DNA
2024 13th CNAPS International Symposium on Circulating Nucleic Acids in Plasma and Serum, Graz/Austria, 4-6 March 2024
L. Hagner, L. Metzler, S. Koch, M. Klingenhof, P. Strasser, R. Weber, M. Landrock, M. Sommer, S. Vierrath
AEM Water Electrolysis with Ni-based Catalysts and Tailored Poly(arylene piperidinium) Materials for Improved Stability
2024 245th ECS Meeting, San Francisco, CA, 26. -30.05.2024
L. Metzler, M. El Shamy, L. Hagner, K. Seteiz, J. Disch, S. Koch, S. Vierrath
Application of Anion Exchange Mambranes for AEMWE and CO2 Electrolysis
2024 EMEA 2024, Bad Zwischenahn, 16 -18 June, 2024
R. Voelckner, G. Miotto, R. Zengerle, S. Kartmann
Camera-based jet volume estimation using deep learning
2024 MFHS 2024 - The 5th Conference on Microfluidic Handling Systems, Munich, 21-23 February 2024
S. Koch, J. Disch, S. K. Kilian, M. Elshamy, L. Metzler, S. Vierrath
Catalyst Layer Engineering for Improved Water Management in Anion Exchange Membrane Water Electrolyzers
2024 37th ISE, Stresa / Italy, 9.-12.06.2024
J. Disch, K. Seteiz, J. Häberlein, F. Brendel, L. Bohn, S. Vierrath
Catalyst layer engineering and forward-bias bipolar membranes for the electrochemical reduction of CO2 to CO
2024 PSI Symposium, Villigen / Switzerland, 06.06.2024
N. Klatt, M. Hinrichs, T. Hutzenlaub
Centrifugal Microfluidic Automation of Proteomic Sample Preparation Techniques
2024 40th International Symposium on Microscale Separations and Bioanalysis 2024 (MSB 2024), Brno/Czech Republic, 19-22 May 2024
C. Schare, G. Titvinidze, E. Cruz Ortiz, N. Platenburg, M. Viviani, S. Vierrath, K.-D. Kreuer, C. Klose, A. Münchinger
Good Stability and Low Cross-Over Hydrocarbon Based Membrane for PEM Electrolysis
2024 37th ISE, Stresa / Italy, 9.-12.06.2024
H. Liepold, S. Vierrath, C. Klose, A. Münchinger
Hydrocarbon-Based Catalyst Layers: A Tradeoff Analysis for PEM Fuel Cells Under Low Humidity Conditions
2024 Gordon Research Conference, Bryant University, Smithfiled, Rhode Island / USA, 29.07. – 02.08.2024
E. Cruz Ortiz, M. Viviani, N. van Treel, S. Vierrath, M. Bühler
Hydrogen Crossover Measurements of Proton Exchange Membranes for Water Electrolysis with in-operando Conditions
2024 37th ISE, Stresa / Italy, 9.-12.06.2024
M. Neugebauer, S. Calabrese, A. Markl, L. Schumacher, T. Wolper, T-T. Truong, P. Juelg, N. Borst, T. Hutzenlaub, F. Scherer, F. von Stetten, M. Lehnert
Increasing digital PCR performance in liquid biopsy using reporter emission multiplexing
2024 13th CNAPS International Symposium on Circulating Nucleic Acids in Plasma and Serum, Graz/Austria, 4-6 March 2024
F. Brendel, L. Bohn, J. Häberlein, S. Vierrath, J. Disch
Investigating water management in bipolar membrane CO2-to-CO-electrolysis with high-resolution neutron imaging
2024 PSI Symposium, Villigen / Switzerland, 06.06.2024
D. Straubinger, Z. Khan, P. Koltay, R. Zengerle, S. Kartmann, Z. Shu
Investigation of metal jet printing for homogeneous lines with Starjet technology
2024 MFHS 2024 - The 5th Conference on Microfluidic Handling Systems, Munich, 21-23 February 2024
H. Gmoser, T. Groß, M. Ballweg, P. Sánchez-Martín, M. Lehnert, C. Jeney, A. Lux, P. Juelg, F. v. Stetten, N. Borst
Isothermal PICO Assay for One-Step Library Prep and Nanopore Readout
2024 nanodiag bw Innovative Retreat, Hohenfels, Bodensee, 30 September - 3 October 2024
H. Gmoser
Isothermal PICO Assay for One-Step Prep and Nanopore Readout
2024 nanodiag bw Innovative Retreat, Hohenfels, Bodensee, 30 September - 3 October 2024
J. Häberlein, K. Seteiz, P. Heizmann, J. Disch, S. Vierrath
Low loaded carbon supported Ag nanoparticles for CO2 electrolysis towards CO enabling high mass activities
2024 Renewable Energy: Solar Fuels, Gordon Research Conference; Ventura, California/United States, 4 - 9 Febraury 2024
J. Häberlein, K. Seteiz, P. Heizmann, J. Disch, S. Vierrath
Low loaded carbon supported Ag nanoparticles for CO2 electrolysis towards CO enabling high mass activities
2024 PSI Symposium, Villigen / Switzerland, 06.06.2024
J.F. Hess, J. Rüdiger, T. Hutzenlaub
Microfluidic Automation of Library Preparation for Nanopore Sequencing
2024 40th International Symposium on Microscale Separations and Bioanalysis 2024 (MSB 2024), Brno/Czech Republic, 19-22 May 2024
S. Calabrese, A. Markl, M. Neugebauer, L. Schumacher, N. Borst, F. Scherer, F. von Stetten, M. Lehnert
Reporter emission multiplexing (REM) Increases detection capacities of digital PCR devices leading to sensitive, precise and specific liquid biopsy assays
2024 EUDIP 2024 - European Digital PCR Symposium 2024, Gent/Belgium, 6-8 February 2024
L. Bohn
Sensing in Electrochemical CO₂ Reduction: Integrated reference electrodes for zero-gap CO₂ electrolysis cells
2024 ACHEMA, Frankfurt, 13.06.2024
Z. Khan, A. Saphala, D. Straubinger, S. Kartmann, P. Koltay, R. Zengerle, O. Amft, Z. Shu
Towards hybrid printing of intelligent devices: conductive traces from bulk metal for digital signals
2024 MFHS 2024 - The 5th Conference on Microfluidic Handling Systems, Munich, 21-23 February 2024
V. Zieger, D. Frejek, S. Zimmermann, P. Koltay, R. Zengerle, S. Kartmann
Transfer volume modeling for feedback-free, automated single spheroid deposition using droplet-generated microfluidic flow
2024 MFHS 2024 - The 5th Conference on Microfluidic Handling Systems, Munich, 21-23 February 2024
L. Bohn, J. Häberlein, F. Brendel, J. Disch, S. Vierrath
Water transport in CO2 electrolysis to CO during pulsed operation investigated by high-resolution neutron Imaging
2024 Renewable Energy: Solar Fuels, Gordon Research Conference; Ventura, California/United States, 4 - 9 Febraury 2024
L. Bohn, J. Häberlein, F. Brendel, S. Vierrath, J. Disch
Water transport in CO2 electrolysis to CO during pulsed operation investigated by high-resolution neutron imaging
2024 PSI Symposium, Villigen / Switzerland, 06.06.2024

2023

nach oben zur Jahresübersicht

V. Zieger, D. Frejek, S. Zimmermann, P. Koltay, R. Zengerle, S. Kartmann
A novel platform for automated and efficient handling of scaffold-free 3D cell-culture models enables well-controlled large-scale 3D in vitro drug screening
2023 SLAS 2023 Conference and Exhibition, San Diego, CA, USA, 25.02. - 01.03.2023
L. Metzler, S. Koch, M. Klingenhof, L. Hagner, M. Elshamy, L. Bohn, P. Strasser, S. Vierrath
Advances in AEM water electrolysis – Towards scalable production of iridium-free cells with high voltage efficiency
2023 EMEA 2023, Workshop on Ion Exchange Mambranes for Energy Applications, Bad Zwischenahn, 20.-22.06.2023
B. Breiner, D. Kainz, S. Wagner, M. Gavage, S. Sahakalkan, R. Marega, F. von Stetten, A. Klebes
Automated allergen sample preparation and detection via centrifugal microfluidic lateral flow assay
2023 Eurosensors 2023, Lecce, Italy, 10. - 13.09.2023
V. Zieger, E. Wöhr, S. Zimmermann, D. Frejek, P . Koltay, R. Zengerle, S. Kartmann
Automated large scale spheroid generation via hanging drop and efficient transfer into physiological mimicking microenvironment
2023 Transducers, Kyoto/Japan, May 25-29, 2023
Z. Shu, S. Hennig, P. Koltay, S. Kartmann, F. von Stetten, R. Zengerle
Automated sample preparation platform for protein diagnostics based on open microfluidics electrophoresis
2023 Black Forest Nanopore Meeting, Freiburg, 06.-09.11.2023
J. Disch, S. Ingenhoven, S. Vierrath
Bipolar membranes with porous anion exchange layers for the electrochemical reduction of CO2 to CO
2023 Carbon Capture, Utilization and Storage Gordon Research Conference, Les Diablerets, VD, Switzerland, 28.05. - 02.06.2023
K. Seteiz, J. Häberlein, P. Heizmann, J. Disch, S. Vierrath
Carbon black supported Ag nanoparticles for CO2 to CO electrolysis enabling high mass activities
2023 EFCF 2023, Low Temperature Fuel Cells, Electrolysers & H2 Processing Forum, Lucerne/Switzerland, July 4-7, 2023
Y.-K. Lai, J. F. Hess, N. Paust
Centrifugal gravity enables void-free priming of dead-end nanoliter cavities
2023 MicroTAS 2023, Katovice/Poland, 15.-19.10.2023
T.-T. Truong, K. Mikloska, N. Paust, T. Hutzenlaub, L. Kubetzko, S. Derer, N. von Bubnoff, P. Juelg
Comparison of DNA reference material for pre analytics : Nucleosomal plasma spike ins reveal true recovery efficiencies of circulating cell free DNA extractions
2023 ISMRC 2023 - 13th International Symposium on Minimal Residual Cancer, Hamburg, 02.-04.05.2023
N. van Treel, R. Qelibari, E. Cruz Ortiz, G. Titvinidze, C. Klose, A. Münchinger, S. Vierrath
Direct coating on PEEK reinforced sulfonated polyphenylensulfone membrane
2023 ECS Meeting, Gothenburg / Sweden, 8.-12.10.2023
Z. Khan, P. Koltay, R. Zengerle, S. Kartmann, Z. Shu
Direct conductive metal printing for one step fabrication of hybrid flexible electronics
2023 inno LAE 2023, Cambridge, UK, 21. – 23. Feb. 2023
E. Cruz Ortiz, M. Breitwieser, S. Vierrath, M. Bühler
Effect of compression on the membrane electrode assembly of polymer electrolyte electrolyzers
2023 EFCF 2023, Low Temperature Fuel Cells, Electrolysers & H2 Processing Forum, Lucerne/Switzerland, July 4-7, 2023
S. Koch, J. Disch, L. Bohn, L. Metzler, S. Vierrath
Electrode engineering for anion-exchange membrane electrolyzers
2023 SpinCat Workshop: "Interfacial Electrochemistry and Electrolysis”, Eindhoven / The Netherlands, 13.- 14.11.2023
S. Murad, M. Heyer, F. Lickert, J. Menges, S. Calabrese, T. Hutzenlaub, N. Paust, P. Juelg
Fast and bubble-free filling of nano-imprinted high-density picoliter well arrays for digital assays enabled by centrifugal microfluidics
2023 MicroTAS 2023, Katovice/Poland, 15.-19.10.2023
E. Mahmodi Arjmand, F. Schlenker, G. Grether, T. Tu Troung, T. Hutzenlaub, R. Zengerle, N. Paust, J. Lüddecke, P. Juelg
Gleichzeitige Extraktion von extrazellulären Vesikeln und zellfreier DNA aus einer einzigen Blutprobe durch zentrifugale Mikrofluidik
2023 Mikrosystemtechnik Kongress 2023, Dresden, 23.-25.10.2023
Z. Shu
Hybrid 3D printing of conductive metal and polymer for smart 3D electronics and sensors
2023 IVAM Hightech Summit 2023, Bochum, 03.-04.05.2023
Z. Khan, D. Gururajan, D. Straubinger, P. Koltay, S. Kartmann, R. Zengerle, Z. Shu
Hybrid 3D-printing of molten metal microdroplets and polymers for prototyping of printed circuit boards with integrated electrical energy storage systems
2023 Transducers, Kyoto/Japan, May 25-29, 2023
E. Cruz Ortiz, M. Viviani, N. van Treel, S. Vierrath, M. Bühler
Hydrogen Crossover Measurements of Proton Exchange Membranes for Water Electrolysis with in-operando Conditions
2023 ICE 2023, Sun City Resort, South Africa, 27.08. - 01.09.2023
H. Liepold, H. Nguyen, A. Muenchinger, S. Vierrath
Influence of ionomer chemistry on gas permeability in hydrocarbon-based proton-exchange membrane fuel cells
2023 EFCF 2023, Low Temperature Fuel Cells, Electrolysers & H2 Processing Forum, Lucerne/Switzerland, July 4-7, 2023
H. Liepold, H.Nguyen, A. Muenchinger, S. Vierrath
Influence of ionomer chemistry on gas permeability in hydrocarbon-based proton-exchange membrane fuel cells
2023 ECS Meeting, Gothenburg / Sweden, 8.-12.10.2023
B. Johannsen, D. Baumgartner, M. Karpíšek, D. Stejskal, N. Paust, R. Zengerle, K. Mitsakakis
Integration of a bead-based immunoassay on a commercial PCR-performing POC device
2023 Eurosensors 2023, Lecce, Italy, 10. - 13.09.2023 , Band: 97, Seite: 166
H. Gmoser, T. Groß, M. Ballweg, A. Lux, C. Jeney, M. Lehnert, F. v. Stetten, N. Borst
Isothermal Protein Interaction Coupling (PICO) Assay towards One-Step Library Prep and Nanopore Read-out
2023 Black Forest Nanopore Meeting, Freiburg, 06.-09.11.2023
N. Borst
Neue Technologien für die molekulare Diagnostik zuhause
2023 HomeDiagnostix Congress, Konstanz, July 5-7, 2023
F. Pescher, M. von Holst, P. Heizmann, S. Vierrath, M. Breitwieser
Novel Catalysts for Proton Exchange Membrane Fuel Cells via Fluidized Bed Atomic Layer Deposition
2023 EFCF 2023, Low Temperature Fuel Cells, Electrolysers & H2 Processing Forum, Lucerne/Switzerland, July 4-7, 2023
F. Pescher, M. von Holst, A. Salihi, J. Stiegeler, P. Heizmann, S. Vierrath, M. Breitwieser
Platinum Catalysts for Proton Exchange Membrane Fuel Cells via Fluidized Bed Atomic Layer Deposition
2023 ECS Meeting, Gothenburg / Sweden, 8.-12.10.2023
C. Engelmann, C. Kleber, Y. Kaku, T.-T. Truong, N. Klatt, P. Jülg, T. Ensslen, P. Jain, J. Schwaiger, S. Kartmann, T. Hutzenlaub, A. Schreiber
Protein Sample Preparation for Nanopore Technology
2023 Black Forest Nanopore Meeting, Freiburg, 06.-09.11.2023
T. Tu-Truong, Y. Kaku, S. ElGenk, M. Bösenberg, H. Sültmann, T. Gemoll, N. von Bubnoff, E. Dazert, L. Kubetzko, S. Derer, M. Oberländer, A. Katalinic, R. Deck, C. Sina, H. Busch, S. Kartmann, J. Lüddecke, T. Hutzenlaub, N. Paust, P. Juelg
Robotic centrifugal microfluidics: a novel automation platform for large sample volume applications demonstrated by cell-free DNA isolation
2023 MicroTAS 2023, Katovice/Poland, 15.-19.10.2023
V. Zieger, D. Frejek, S. Zimmermann, P. Koltay, R. Zengerle, S. Kartmann
Selective high-throughput deposition of single spheroids towards automated 3D in vitro cell culture
2023 3D Cell Culture 2023, Freiburg, 17. - 19.04.2023
L. Bohn, J. Disch, S. Vierrath
Separating loss mechanisms in CO2 electolyzers by utilizing reference electrodes
2023 EFCF 2023, Low Temperature Fuel Cells, Electrolysers & H2 Processing Forum, Lucerne/Switzerland, July 4-7, 2023
Z. Shu
StarJet Technology - Direct molten metal printing for printed, flexible, 3D electronic applications
2023 TechBlick, virtuell, 29.-30.03.2023
J. Schlanderer, J. Lüddecke, A. Golubov, W. Grasse, T. A. Kohl, C. Metzger-Boddien, S. Niemann, C. Pilloni, S. Plesnik, B. Raya, B. Shresta, R. Zengerle, M. Beutler, H. Hoffmann, N. Paust
Two-Stage Tuberculosis Diagnostics: Combining Centrifugal Microfluidics at the Point-of-Care with subsequent Antibiotic Resistance Profiling by Targeted NGS
2023 MicroTAS 2023, Katovice/Poland, 15.-19.10.2023
J. Schlanderer, M. Beutler, W. Grasse, T. A. Kohl, J. Lüddecke, S. Niemann, H. Hoffmann, N. Paust
Two-stage tuberculosis diagnostics: centrifugal microfluidics at the point of care with subsequent antibiotic resistance profiling by tNGS
2023 Eurosensors 2023, Lecce, Italy, 10. - 13.09.2023
S. Koch, J. Disch, S. Kilian, L. Metzler, S. Vierrath
Water Transport and Salt Precipitation in Anion-Exchange Membrane Electrolyzers
2023 ECS Meeting, Gothenburg / Sweden, 8.-12.10.2023

2022

nach oben zur Jahresübersicht

Z. Khan, R. Zengerle, P. Koltay, S. Kartmann, Z. Shu
3D printed single-layer functional PCB via digital hybrid printing of polymer and molten metal
2022 5th International Conference on 3D Printing & Bioprinting, ΑΙ, Digital and Additive Manufacturing (I3D22)
L. Riek, F. Koch, D. Frejek, L. Zausch, R. Zengerle, P. Koltay, S. Kartmann, S. Zimmermann
A Bioprinting Fidelity Imager (BioFI) for a standardized characterization of bioprinting processes
2022 SLAS Europe 2022 Conference and Exhibition, Dublin, Ireland, May 26, 2022
K. Seteiz, J. Disch, S. Vierrath
Cl doped Ag as highly porous nanoparticles for CO2 electrolysis to CO
2022 Gordons Solar Fuels, Lucca, Italy, May 8-13, 2022
C. Schwarz, F. Lombeck, H. Nguyen, F. Khan, D. Sultanova, K. Yildirim, M. Breitwieser
Development of roll-to-roll feasible, direct coating technique for membrane electrode assemblies
2022 Fuel Cells, Gordon Research Conference, Smithfield, RI, USA, July 24 - 29, 2022
Z. Khan, P. Koltay, R. Zengerle, S. Kartmann, Z. Shu
Direct printing of molten solder via StarJet technology in Flexible Hybrid Electronics
2022 Flex Conference & Expo, San Francisco, USA, July 11-14, 2022
E. Cruz Ortiz, M. Breitwieser, S. Vierrath, M. Bühler
Effect of compression on the membrane electrode assembly of polymer electrolyte electrolyzers
2022 ICE 2021, 3rd International Conference on Electrolysis 2021, Golden, Colorado USA, June 12-17, 2022
C. Schare, A. Münchinger, R. Qelibari, L. Metzler, G. Titvinidze, S. Vierrath, C. Klose
Enabling the large scale production of fluorine free electrode assemblies for proton exchange membrane water electrolysis
2022 ICE 2021, 3rd International Conference on Electrolysis 2021, Golden, Colorado USA, June 12-17, 2022
J. Disch, L. Bohn, S. Koch, M. Schulz, Y. Han, M. Breitwieser, S. Vierrath
High-resolution neutron imaging of carbonate precipitation and water transport in CO2 electrolysis to CO
2022 Swiss Electrochemistry Symposium, Aarau, Switzerland, May 11, 2022
J. Disch, L. Bohn, S. Koch, M. Schulz, Y. Han, M. Breitwieser, S. Vierrath
High-resolution neutron imaging of carbonate precipitation and water transport in CO2 electrolysis to CO
2022 Gordons Solar Fuels, Lucca, Italy, May 8-13, 2022
N. van Treel, E. Cruz Ortiz, S. Vierrath, M. Bühler
Influence of the gas diffusion layer on the performance of a PEM water electrolyzer
2022 ICE 2021, 3rd International Conference on Electrolysis 2021, Golden, Colorado USA, June 12-17, 2022
D. Kainz
Microthermoforming - enhancing Blister technology
2022 12th European Thermoforming Conference 2022, Vienna, Austria, 31st March - 1st April 2022
M. Trotter, A. Schreiber, D. Kleinknecht, N. Borst, M. Kuderer, K. Gläser, F. von Stetten
Mobile elektrochemische Plattform zur molekularen Diagnostik in der häuslichen Pflege
2022 5. Müchner Poit-of-Care Testing Symposium, Munich, September,27-29, 2022
F. von Stetten
Novel German innovation network “nanodiag BW” - nanopore diagnostics of epigenetic markers”
2022 SMPS3 (Single-molecule protein sequencing), Delft, The Netherlands, October, 27 - November, 3, 2022
H. Nguyen, D. Sultanova, F. Lombeck, C. Schwarz, P. A. Heizmann, C. Klose, S. Vierrath, M. Breitwieser
PEM fuel cells based on novel hydrocarbon ionomers: Approaching state-of-the-art performance
2022 Fuel Cells, Gordon Research Conference, Smithfield, RI, USA, July 24 - 29, 2022
J. Stiegeler, C. Schwarz, T. Mittermeier, T. Lehre, L. Tsikonis, S. Vierrath
Platinum catalyst stressor studies toward realistic accelerated durability tests for heavy-duty polymer electrolyte fuel cells
2022 Fuel Cells, Gordon Research Conference, Smithfield, RI, USA, July 24 - 29, 2022
M. von Holst, L. Pavko, J. Stiegeler, P. A. Heizmann, A. Salihi, M. Gatalo, N. Hodnik, C. Klose, S. Vierrath, M. Breitwieser
Reduced graphene oxide as durable carbon support for PtCo catalyst in proton exchange membrane fuel cells
2022 Fuel Cells, Gordon Research Conference, Smithfield, RI, USA, July 24 - 29, 2022
V. Zieger, D. Frejek, G. Miotto, L. Riek, S. Zimmermann, P. Koltay, R. Zengerle, S. Kartmann
Selective and automated high-throughput deposition of spheroids for scalable 3D-bioprinting
2022 Biofabrication 2022, Pisa, Italy, September, 25-28, 2022
V. Zieger, D. Frejek, L. Riek, R. Zengerle, S. Kartmann
Selective high-throughput deposition of microtumors for in vitro studies on 3D tumor models
2022 SLAS Europe 2022 Conference and Exhibition, Dublin, Ireland, May 26, 2022
T. Tu Truong, F. Schlenker, L. Karkossa, E. M. Arjmand, G. Grether, J. Lüddecke, U. A. Walker, S. Giaglis, N. Paust, T. Hutzenlaub, P. Juelg
Towards standardization of pre-analytics: Highly efficient platelet-poor-plasma generation for ccfmtDNA analysis on a centrifugal microfluidic platform
2022 EACR Liquid Biopsy, Bergamo, Italy, May 24-26, 2022
F. Koch, L. Riek, D. Frejek, L. Zausch, S. Zimmermann, S. Kartmann, R. Zengerle, A. Osorio-Madrazo, P. Koltay
Towards standardized characterization of droplet-based bioprinting processes
2022 Biofabrication 2022, Pisa, Italy, September, 25-28, 2022
T. Lange, T. Groß, Á. Jeney, J. Scherzinger, E. S. C. Niemöller, S. Zimmermann, P. Koltay, F. von Stetten, R. Zengerle, C. Jeney
Validation of scRNA-seq fold changes by single-cell reverse transcription digital PCR
2022 Single-Cell Genomics, Gordon Research Conference, Les Diablerets, VD, Switzerland, May 1- 6, 2022
S. Koch, S. K. Kilian, J. L. Disch, L. Metzler, P. A. Heizmann, Y. Han, M. Schulz, M. Breitwieser, S. Vierrath
Water management in anion-exchange membrane water electrolyzers under dry cathode operation
2022 GPR 2022, Golden, Colorado USA, June 12-17, 2022
S. Hennig, Z. Shu, L. Gutzweiler, P. Koltay, F. von Stetten, R. Zengerle, S. M. Früh
“Paper-based open microfluidics platform for automatic protein analysis
2022 SLAS Europe 2022 Conference and Exhibition, Dublin, Ireland, May 26, 2022

2021

nach oben zur Jahresübersicht

H. Nguyen, F. Lombeck, C. Schwarz, P. A. Heizmann, M. Adamski, H-F. Lee, B. Britton, S. Holdcroft, S. Vierrath, M. Breitwieser
A fluorine-free hydrocarbon-based proton exchange membrane fuel cell with state-of-the-art performance
2021 23rd European Fuel Cell Forum (EFCF), Lucerne, Switzerland (Online), 2.-5.07.2021
J.-N. Klatt, T.-L. Dinh, O. Schilling, R. Zengerle, F. Schmidt, T. Hutzenlaub, N. Paust
Automation of Solid Phase Extraction for Peptide Desalting by Centrifugal Microfluidics
2021 37th International Symposium on Microscale Separations and Bioanalysis 2021, Boston/USA (online), 12.-15.07.2021
J.-N. Klatt, T.J. Dinh, N. Paust, R. Zengerle, F. Schmidt, O.Schilling, T. Hutzenlaub
Automation of peptide desalting by centrifugal microfluidics
2021 MicroTAS 2021, Palm Springs/USA, 10.-14.10.2021, online
B. Johannsen, D. Baumgartner, L. Karkossa, L. Müller, N. Paust, M. Karpíšek, N. Bostanci, R. Zengerle, K. Mitsakakis
Detection of systemic and oral inflammation biomarkers through biochemical and microfluidic integration
2021 MicroTAS 2021, Palm Springs/USA, 10.-14.10.2021, online
D. Kainz, B. Breiner, R. Zengerle, N. Paust, T. Hutzenlaub, S. M. Früh
Determining binding kinetics of a PCT lateral flow assay during runtime
2021 MicroTAS 2021, Palm Springs/USA, 10.-14.10.2021, online
P. Juelg, E. Kipf, M. Specht, J. Menges, M. Fillies, C. Eckert, N. Paust, R. Zengerle, M. Lehnert, T. Hutzenlaub
Die MRD Disk: Automatisiertes Monitoring Minimaler Resterkrankung durch hochsensitive, zentrifugal-mikrofluidische Multiplex-qPCR / The MRD disk: automated minimal residual disease monitoring by highly sensitive centrifugal microfluidic multiplex qPCR
2021 MST
J. Weygant, F. Koch, K. Troendle, G. Finkenzeller, R. Zengerle, S. Kartmann, S. Zimmermann, P. Koltay
Drop-on-Demand Bioprinting Approach For Precise Alignment and Interaction Studies of Different Cell Types
2021 International Conference on Biofabrication, Australia, 27. – 29.09.2021 (online)
K. Tröndle, A. Itani, F. Koch, R. Zengerle, P. Koltay, S. Zimmermann
Drop-on-demand bioprinting solutions for the fabrication of 3D cell culture systems
2021 DECHEMA 3D Cell Culture Freiburg (online), 05.-07.05.2021
C. Schwarz, S. Vierrath, M. Breitwieser
Elucidating the impact of Pt-ink ageing on fuel cell performance in laboratory scale CCM production
2021 23rd European Fuel Cell Forum (EFCF), Lucerne, Switzerland (Online), 2.-5.07.2021
L. Niebling, S. Burger, N. Paust, A. R. Homann
Fast and on-site animal species identification in processed meat
2021 MicroTAS 2021, Palm Springs/USA, 10.-14.10.2021, online
C. Klose, T. Saatkamp, A. Münchinger, L. Bohn, G. Titvinidze, M. Breitwieser, S. Vierrath,
Fluorine-free membrane electrode assemblies for water electrolysis based on sulfonated polyphenylensulfone
2021 23rd European Fuel Cell Forum (EFCF), Lucerne, Switzerland (Online), 2.-5.07.2021
F. Schlenker, L. Karkossa, N. Paust, R. Zengerle, S. Giaglis, U. A. Walker, T. Hutzenlaub, P. Juelg
Generation of platelet poor plasma for circulating cell-free mitochondrial DNA analysis on a centrifugal microfluidic platform
2021 Micro and Nano Engineering Conference, Turin, Italy, 20. – 23.09.2021
M. Schulz, J. Ruediger, E. Landmann, M. Bakheit, S. Frischmann, D. Rassler, A. R. Homann, F. von Stetten, R. Zengerle, N.Paust
High dynamic range digital assay enabled by dual volume centrifugal step emulsification
2021 MST-Kongress, Ludwigsburg, 08.-10.11.2021
E. Ortiz, F. Lombeck, M. Kroschel, J. Hübner, L. Bohn, M. von Holst, M. Breitwieser, P. Strasser, S. Vierrath
Highly efficient low-loaded Ir-anodes proton exchange membrane water electrolysis: concepts to reduce in-plane resistance
2021 23rd European Fuel Cell Forum (EFCF), Lucerne, Switzerland (Online), 2.-5.07.2021
Z. Khan, Z. Shu, R. Zengerle, P. Koltay
Hybrid 3D printing of polymer and solder to create functional 3D electronics
2021 EPoSS Annual Forum 2021, Freiburg, 04.-07.10.2021
F. Koch, K. Tröndle, G. Finkenzeller, P. Rukavina, R. Zengerle, P. Koltay, S. Zimmermann
Hybrider 3D-Biodruck zur künstlichen Herstellung von Knochen / Using hybrid processes for 3D-bioprinting of artificial bone tissue
2021 MST-Kongress, Ludwigsburg, 08.-10.11.2021
S. Koch, S. K. Kilian, P. A. Heizmann, M. Breitwieser, S. Vierrath
Improving anion-exchange-membrane water electrolyzers by adjusting the ionomer content in the catalyst layers
2021 23rd European Fuel Cell Forum (EFCF), Lucerne, Switzerland (Online), 2.-5.07.2021
M. Trotter, D. Juric, Z. Bagherian, N. Borst, K. Gläser, F. von Stetten, A. Zimmermann
Integration of nanoporous gold electrodes in microfluidic chambers by inkjet-printing for biosensing applications
2021 MST-Kongress, Ludwigsburg, 08.-10.11.2021
J. Schlanderer, J. Lüddecke, R. Zengerle, N. Paust
Large sample volume management on centrifugal microfluidic cartridges
2021 Micro and Nano Engineering Conference, Turin, Italy, 20. – 23.09.2021
P. A. Heizmann, M. von Holst, H. Nguyen, F. Lombeck, C. Schwarz, C. Klose, M. Breitwieser, S. Vierrath
Linking morphological properties of Pt/C catalysts to electrochemical performances for improved catalysis in fuel cells
2021 23rd European Fuel Cell Forum (EFCF), Lucerne, Switzerland (Online), 2.-5.07.2021
D. Baumgartner, B. Johannsen, N. Paust, F. von Stetten, R. Zengerle, K. Mavridis, J. Vontas, K. Mitsakakis
Microfluidic-based molecular analysis of plant psts for insecticide resistance management (Superpests-Disk)
2021
A. Brunauer, A.-S. Kittel, R. D. Verboket, F. von Stetten, S. M. Früh
Multianalyte-Assays: Simultaneous detection of protein and nucleic acid biomarkers
2021 European Biosensor Symposium (EBS), online, 09.-12.03.2021
A.-S. Kittel, R. D. Verboket, F. von Stetten, S. M. Früh
Multianalyte-Assays: Simultaneous detection of protein and nucleic acid biomarkers
2021 European Biosensor Symposium (EBS), online, 09.-12.03.2021
Y.-T. Kao, S. Calabrese, N. Borst, M. Lehnert, Y.-K. Lai, F. Schlenker, R. Zengerle, P. Garstecki, F. von Stetten
One-step amplification-free bacteria detection by optimizes LNA/DNA molecular beacons in droplets
2021 MicroTAS 2021, Palm Springs/USA, 10.-14.10.2021, online
L. Becherer, J.F. Hess, S. Frischmann, M. Bakheit, H. Nitschko, S. Stinco, F. Zitz, H. Hofer, G. Porro, F. Hausladen, K. Stock, D. Drossart, H. Wurm, H. Kuhn, D. Huber, T. Hutzenlaub, N. Paust, M. Keller, O. Strohmeier, S. Wadle, N. Borst, R. Zengerle, F. von Stetten
Point-of-Care System for HTLV-1 Proviral Load Quantification by Digital Mediator Displacement LAMP
2021 MST-Kongress, Ludwigsburg, 08.-10.11.2021
P. A. Heizmann, C. Klose, M. Breitwieser, S. Vierrath
Quantitative STEM tomography for proton exchange membrane fuel cell apllications
2021 Symposium Nano-BW, Bad Herrenalb, online, 07.10.2021
A. Brunauer, R. D. Verboket, D. M. Kainz, F. von Stetten, S. M. Früh
Rapid nucleic acid lateral flow immunoassay for the detection of Pseudomonas aeruginosa
2021 Biosensors 2021, Haeundae-gu, South Korea, (online), 26. - 29.07.2021
K. Seteiz, B. Shanahan, P. A. Heizmann, S. Koch, J. Büttner, S. Ouardi, S. Vierrath, A. Fischer, M. Breitwieser
Rapid wet-chemical oxidative activation of graphite felt electrodes for vanadium redox flow batteries
2021 2nd Electrochemical Cell Concepts Colloquium (Virtual E3C), Oberhausen, Germany (Online), 6.5.2021
A. Klebes, A.-S. Kittel, R. D. Verboket, F. von Stetten, S. M. Früh
Simultaneous detection of protein and nucleic acid biomarkers via paper-based multianalyte sensor
2021 MicroTAS 2021, Palm Springs/USA, 10.-14.10.2021, online
D. Baumgartner, B. Johannsen, N. Paust, F. von Stetten, R. Zengerle, K. Mavridis, J. Vontas, K. Mitsakakis
SuperPests LabDisk: a microfluidic-based molecular diagnostic platform for detection of biotypes, resistance mutations and plant pathogens P3.021
2021 Biosensors, Haeundae-gu, South Korea (online), 26. – 29.07.2021
S. Vierrath, E. Cruz Ortiz, F. Hegge, T. Böhm, F. Lombeck, M. Breitwieser
Tackling durability and efficiency in polymer membrane fuel cells and electrolysis
2021 MRS Seattle/Washington, USA (online), 10. – 14.04.2021
P. A. Heizmann, M. von Holst, F. Lombeck, H. Nguyen, C. Klose, M. Breitwieser, S. Vierrath
Understanding the platinum carbon-support interaction for improved catalysis in hydrogen fuel cells
2021 9th NRW Nano Conference: Innovations in Materials and Applications, Münster, Germany (Online), 21.-23.04.2021
T. Härpfer, L. Becherer, M. Bakheit, S. Frischmann, S. Stinco, N. Borst, R. Zengerle, F. von Stetten
Universal multiplex mediator displacement LAMP Nr. P3.062 analytical and clinical validation on the example of HIV, Haemophilus ducreyi and Treponema pallidum
2021 Biosensors, , Haeundae-gu, South Korea (online) , 26. – 29.07.2021
E. Mahmodi Arjmand, G. Grether, R. Zengerle, N. Paust, J. Lüddecke
Waste liquid assisted flow-switching on a centrifugal microfluidic platform
2021 Micro and Nano Engineering Conference, Turin, Italy, 20. – 23.09.2021

2020

nach oben zur Jahresübersicht

A. Brunauer, B. Breiner, S. Hennig, D. Kainz, R. Verboket, B. Johannsen, D. Baumgartner, K. Mitsakakis, L. Gutzweiler, Z. Shu, P. Koltay, T. Hutzenlaub, N. Paust, R. Zengerle, F. von Stetten, S. M. Früh
Actuation principles for bioanalytical platforms to combat infectious diseases
2020 Virtual EMBL Conference: Microfluidics: Designing the Next Wave of Biological Inquiry 2020, 13.-15.07.2020
J. F. Hess, M. Kotrová, S. Calabrese, T. Hutzenlaub, R. Zengerle, M. Brüggemann, N. Paust
Automated library preparation for next generation sequencing of immunoglobulin gene rearrangements by centrifugal microfluidics
2020 MicroTAS 2020, 04.-09.10.2020, virtual
F. Schlenker, E. Kipf, N. Borst, T. Hutzenlaub, N. Paust, R. Zengerle, F. von Stetten, P. Juelg
Centrifugal microfluidic 4 Plex digital droplet PCR for quantification of circulating tumor DNA
2020 MicroTAS 2020, 04.-09.10.2020, virtual
F. Lombeck, F. Hegge, M. von Holst, C. Klose, S. Vierrath, M. Breitwieser
Ceramic Nanofibers: A versatile material class to improve Electrochemical Energy Applications
2020 71st International Society of Electrochemistry, Belgrad, Serbia (Online), 30.08. – 04.09.2020
K. Tröndle, A. Itani, F. Koch, R. Zengerle, S. Zimmermann, P. Koltay
Fabrication and fluidic integration of self-assembled cellular microtubules for nephron-on-chip applications
2020 MicroTAS 2020, 04.-09.10.2020, virtual
H. Nguyen, P. A. Heizmann, F. Lombeck, A. Belletti, B. Britton, S. Vierrath, M. Breitwieser
Improving the Performance of All-Hydrocarbon PEM Fuel Cells Based on Pemion™ Ionomer
2020 71st International Society of Electrochemistry, Belgrad, Serbia (Online), 30.08. – 04.09.2020
F. Schlenker, E. Kipf, M. Deuter, I. Hoeffkes, N. Borst, T. Hutzenlaub, R. Zengerle, F. von Stetten, N. von Bubnoff, P. Juelg
Low optimization effort for highly sensitive assays for point mutation quantification in CTDNA: the Mediator Probe digital PCR
2020 Liquid Biopsy Symposium, 30.10.2020, virtuell
P. Koch, O. Barth, M. Meyer, R. Streller, R. Zengerle, M. Rombach, M. Jehle
Microthermoforming: Enhancing blister technology to introduce microstructures in functional packaging
2020 12. European Thermoforming Conference, Geneva, Switzerland, 18.-20.03.2020
M. Breitwieser, S. Vierrath
One for all or one for each application? Recent advances in membrane & ionomer development for electrochemical energy converters
2020 E3C Electrochemical Cell Concepts Colloquium Fraunhofer UMSICHT, 14.05.2020
E. Cruz Ortiz, F. Hegge, M. Breitwieser, S. Vierrath
Performance Improvement of PEM Water Electrolyzer Anodes via a Bi-Functional Binder Polymer Blends for Ionic and Electrical Conduction
2020 71st International Society of Electrochemistry, Belgrad, Serbia (Online), 30.08. – 04.09.2020
M. Rombach, S. Hin, M. Specht, B. Johannsen, J. Lüddecke, N. Paust, R. Zengerle, K. Mitsakakis
RespiDisk: A Point-of-Care platform for fully automated detection of respiratory tract infection pathogens in clinical samples
2020 MicroTAS 2020, 04.-09.10.2020, virtual
S. Koch, C. Klose, B. Britton, M. Breitwieser, S. Vierrath
Towards stable catalyst layers for water electrolysis based on anion-exchange membranes
2020 71st International Society of Electrochemistry, Belgrad, Serbia (Online), 30.08. – 04.09.2020
B. Johannsen
id Diagnosis of Respiratory Tract Infections Using a Point-of-Care Platform Incorporating a Clinical Decision Support Algorithm
2020 pHealth2020, 14. – 16. 09. 2020

2019

nach oben zur Jahresübersicht

S. Kartmann, D. Kopp, M. Masoumi, R. Zengerle, H. Zappe, P. Koltay
Thermischer Einweg-Strömungssensor auf Basis einer flexiblen Polyimid-Folie
2019 MicroTEC Südwest Clusterkonferenz, Freiburg, 20.-21.03.2019
Kurzfassung---
M. Lehnert, E. Kipf, F. Schlenker, R. Zengerle, N. Borst, F. von Stetten
Multiplex Mediator Probe Real-Time PCR - Optimization and Guideline Development through Systematic Characterisation of Label Free Mediator Probes and Fluorogenic Universal Reporters
2019 9th Gene Quantification Event qPCR dPCR & NGS 2019, 18 - 22 March 2019, in Freising-Weihenstephan, Germany
KurzfassungMediator Probe PCR is a powerful and robust real-time PCR technology for multiplex DNA detection and quantification. It uses label free mediator probes, for molecular detection of nucleic acids during DNA amplification, in combination with fluorogenic universal reporters for signal generation. During PCR, target sequence specific mediator probes are cleaved by the polymerase and a generic sequence, the mediator, is set free. In the second step the mediator binds to the universal reporter, where it is extended by the polymerase. This generates a strong fluorescence signal increase. Due to the separation of DNA detection and signal generation many advantages arise. Mediator probes are not limited in their design by properties of the target sequence and a standard set of highly optimised fluorogenic universal reporters can be used for multiplex Mediator Probe PCR, right from the start.1 In the last years Mediator Probe PCR evolved from an innovative new method to an optimised and robust multiplexing technology. This was achieved by systematic characterisation of its molecular processes, which again was advantaged by the separation of DNA detection and signal generation. A DoE approach was used for the optimisation of Mediator Probes, focusing on their binding strengths.2 In parallel, a set of universal reporters with improved signal-to-noise ratios was established by successive testing over 40 molecular structures with different fluorophore-quencher labels and configurations.1 As a result, distinct guidelines exist, which enable fast adaption of new DNA targets and facilitate multiplex Mediator Probe PCR design. The capability of the technology was shown by highly sensitive, precise and specific multiplex Mediator Probe real-time PCRs in different areas of molecular diagnostics. These fields include monitoring of oncological disease, detection of pathogens or analysis of food samples.1,3
B. Shanahan, T. Böhm, B. Britton, S. Holdcroft, S. Vierrath, S. Thiele, M. Breitwieser
30 μm thin hexamethyl-p-terphenyl poly(benzimidazolium) anion exchange membrane for vanadium redox flow batteries
2019 The International Flow Battery Forum, Lyon/France, 09 - 11 July 2019
S. Nessler, S. Kartmann, L. Mutter, C. Grandauer, M. Marx, R. Zengerle, Y. Manoli
A Capacitive Readout Circuit for a Disposable Low-Cost Pressure and Flow Sensor with 200 Pa or 170 nl/s Resolution
2019 IEEE Sensors, 27. – 30. October 2019, Montreal / Canada
B. Johannsen, L. Müller, D. Baumgartner, L. Karkossa, S. M. Früh, N. Bostanci, M. Karpíšek, R. Zengerle, N. Paust, K. Mitsakakis
Automated pre-analytic processing of whole saliva on a centrifugal microfluidic platform for protein biomarker analysis
2019 MicroTAS, 27. – 31. October 2019, Basel/Switzerland
F. Schlenker, E. Kipf, S. Jenne, N. Borst, J. Lüddecke, K. Dormanns, T. Hutzenlaub, J. Steinert, N. Paust, R. Zengerle, F. von Stetten, P. Juelg
Doubling the order of color-multiplexing by photobleaching in Mediator Probe droplet digital PCR
2019 EACR-ESMO Joint Conference on Liquid Biopsies, Bergamo/Italien, 15. – 17. 05. 2019
C. Siber, L. Lautscham, J. Schoendube, P. Reichert, F. Stumpf, S. Zimmermann, R. Zengerle, P. Koltay
Effective acoustic field generation in diposable dispensing cartridges for acustophoretic particle focusing
2019 Transducers 2019, Berlin, 23.06. - 27.06.2019
J. Weisemann, G. B. Stevens, T. van Oordt, N. Krez, K. Dormanns, M. Karle, F. von Stetten, A. Rummel
Fast automatic detection of Botulinum neurotoxin by the BoNT LabDisk assay: results of a trans-european performance study
2019 Toxins 2019, Copenhagen/Denmark, 16. - 19.01.2019
KurzfassungBotulinum Neurotoxins (BoNT) are the most toxic naturally occurring substances for humans. After potential intoxication and occurrence of botulism symptoms, urgent detection of causative BoNT is highly desirable for successful medical treatment. The mouse bioassay (MBA) as gold standard requires a large number of mice, takes several days and is not suitable for point-of-care. Here, we developed an automatic in vitro assay to detect BoNT in complex biological matrices. The assay detects specific cleavage of SNARE proteins by BoNTs by fluorescent read out in a centrifugal microfluidic cartridge, termed BoNT LabDisk (BLD). The generic LabDisk comprises two different peptides able to distinguish between BoNT/ACE and BDF, respectively. The BLD prototype system was tested in a trans-European performance study by five naïve laboratories with expertise in BoNT detection to demonstrate practical applicability and performance of the BLD system. Eight blinded samples containing three complex biological matrices (human serum, bean juice, carrot juice) or buffer spiked with 10-1000 pM of BoNT/A and D were provided. Stability of samples was confirmed by mouse hemidiaphragm assay prior to shipment. The laboratories detected absence or presence of BoNT/A in 34 of the 40 samples correctly (85% accuracy). In three of ten bean juice or serum samples problems occurred due to high viscosity which requires improvement of sample preparation. In another three samples, signals close to background led to misinterpretation by experimentators. Altogether, the performance study showed that handling of the BLD assay is very easy, fast and practicable. The current detection limit is close to that of MBA. In conclusion, the BLD system allows the detection of functionally active BoNT in short assay times with low limits of detection within different matrices, without the need of animals or animal based reagents. The next step will be the adaption of the BLD assay for a direct serotyping of BoNT/A-F.
D. Kainz, S. M. Früh, T. Hutzenlaub, R. Zengerle, N. Paust
Flow profile through exposed porous media in centrifugal microfluidics
2019 MicroTAS, 27. – 31. October 2019, Basel/Switzerland
Z. Shu, B. Gerdes, M. Fechtig, R. Zengerle, P. Koltay
Highly conductive flexible and 3D metallization on flexible and textile substrates via StarJet Technology
2019 12th International Symposium on Flexible Organic Electronics (ISFOE19) 1-4 July 2019, Thessaloniki, Greece
KurzfassungHighly conductive metallizations are crucial for large area organic and printed electronics. State-of-the-art printing technologies such as inkjet printing and screen printing are still facing critical challenges regarding achieving high electrical conductivity and reducing the manufacturing costs. Moreover, additional post-processes such as thermal, photonic or laser sintering are either not compatible with the flexible substrates or expensive. On the contrary, the non-contact StarJet printing technology provides direct metallization from molten metal microdroplets and continuously Jet. It bases on a pneumatically driven printhead that features a heatable reservoir and an interchangeable nozzle chip with a star-shaped orifice geometry. Thanks to the pneumatic driven mechanism, materials with high melting temperature such as solder or aluminium alloys can be printed. Single-pass conductive features, printed via StarJet, exhibit high electrical conductance (7.5 Ω/m for 250 μm linewidth), high aspect ratio, i.e. high layer thickness (70 – 300 μm), and require no post-treatment. Examples of electrically functional, direct metallization were demonstrated on silicon solar cells and PCB boards. In this contribution, we demonstrate that the StarJet technology is also compatible with temperature sensitive flexible substrates such as polymer foils and textiles. The printed solder lines exhibit not only high electrical conductance but also high mechanical stability (i.e. adhesion) and high flexibility. The printed solder lines on polymer foils and textile can stand shear forces of up to 3000 mN and at the same time tolerate substrate bending at the radius of 5 mm. Furthermore, because the printed solder droplets fuse together, freestanding structures with different angles can also be printed via controlling process parameters. In summary, the StarJet technology shows high potential in direct metallization for large area flexible and wearable electronics and 3D electronic applications.
F. Hegge, E. Cruz Ortiz, S. Thiele, S. Vierrath
Improving the performance of low loaded PEMWE electrodes
2019 2nd International Conference on Electrolysis (ICE), Loen / Norway, 9. – 13. 06.2019
P. Juelg, M. Specht, M. Meyer, E. Kipf, F. Schlenker, F. Baensch, S. Neumann, F. von Stetten, R. Zengerle, N. Paust, M. Fillies, R. Kirschner-Schwabe, S. Groeneveld-Krentz, M. Lehnert, C. Eckert, T. Hutzenlaub
Individual Response Monitoring Assay (IRMA) – Standardization Of Personalized Multiplex Biomarker Quantification
2019 EACR-ESMO Joint Conference on Liquid Biopsies, Bergamo/Italien, 15. – 17.05. 2019
S. Burger, L. Drechsel, A. Homann, F. von Stetten, R. Zengerle, N. Paust
LabSlice XL – A centrifugal microfluidic cartridge for the automated bio-chemical processing of industrial process water
2019 Transducers, Berlin, 23. - 27. 06. 2019
M. Specht, J. Schemberg, T. Förster, S. Burger, M. Rombach, N. Paust, R. Zengerle, F. von Stetten, G. Gastrock, M. Karle
Microfluidic App for centrifugal separation and purification of lymphatic cancer cells from whole blood
2019 MST-Kongress, 28. - 30.Oktober 2019, Berlin
S. Hin, N. Paust, M. Rombach, J. Lueddecke, M. Specht, R. Zengerle, K. Mitsakakis
Minimizing ethanol carry-over in centrifugal microfluidic nucleic acid extraction by advanced bead handling and management of diffusive mass transfer
2019 Transducers 2019 - EUROSENSORS XXXIII, 23.-27. Juni 2019 - Berlin, Germany
KurzfassungWe present three concepts for centrifugal microfluidics reducing ethanol carry-over in magnetic bead-based nucleic acid (NA) extraction. Ethanol carry-over is critical regarding inhibition of downstream NA amplification. We identified two possible carry-over pathways: Liquid co-transport within bead-clusters and vapor diffusion. For the first time, we integrated magnetic bead handling in centrifugal microfluidics at continuous rotation aiming to avoid liquid co-transport within bead-clusters. Consequently, no significant contribution to ethanol carry-over could be assigned anymore to liquid cotransport. Major carry-over was attributed to diffusive transport of ethanol vapor. Countermeasures reduced this from 9.7 % (v/v) to 0.4 % (v/v), below the critical level for inhibition of downstream amplification reactions.
P. Holzapfel, M. Bühler, C. Pham, S. Thiele
Molybdenum sulphide based cathodes for PEM water electrolysis – catalyst synthesis and loading variation
2019 EFCD Conference 15.-18. September 2019, La Grande Motte, France
M. Bühler, P. Holzapfel, M. Bierling, S. Thiele
Porous transport electrodes for PEM water electrolysis: improved performance via studying materials interfaces
2019 ICE Conference 9.-13. Juni 2019, Loen, Norway
F. Koch, M. Wehrle, K. Tröndle, P. Koltay, G. Finkenzeller, R. Zengerle, S. Zimmermann
Rapid assessment of combined drop on demand and extrusion-based bioprinting with controlled shear stress and high shape fidelity
2019 Transducers 2019 - EUROSENSORS XXXIII 23. -27. Juni 2019 - Berlin, Germany
KurzfassungWe present a novel combination of drop on demand (DoD) and extrusion-based bioprinting to generate highprecision patterns of cells inside large hydrogel volumes. Extrusion-based bioprinting has the great advantage of enabling a fast deposition of high viscous cell-loaded hydrogel with reasonable precision. Compromises between high shape fidelity and cell viability, as well as short process times often require many iterations of optimizing process parameters and varying compositions of the hydrogel. To limit the multitude of parameters during extrusion-based bioprinting, a method for rapid process assessment was developed. This enables to define limits for printing temperature, flow rate and nozzle size from basic rheological measurements with regard to the biological and mechanical requirements. The combination of extrusion-based bioprinting with DoD bioprinting allows for precise deposition of low viscous cell suspension and adjustable concentrations of crosslinking agent. Together, the technologies were used to print a bone replacement model by using the predefined process parameters. Adiposed-derived stem cells (ASC) prone to osteogenic differentiation were homogenously extruded in a cuboid structure of 10x10x5 mm. Human umbilical vein endothelial cells (HUVEC) were printed as highly dense cell suspension lines inside the extruded hydrogel to allow a potential vascularization of the structure in vivo.
F. Koch, M. Wehrle, K. Tröndle, P. Koltay, G. Finkenzeller, R. Zengerle, S. Zimmermann
Rapid assessment of extrusion based bioprinting by controlling shear stresses on cells
2019 Transducers 2019, Berlin, 23.06. - 27.06.2019
T. Boehm, M. S. Mu’min, R. Moroni, S. Thiele, S. Vierrath, M. Breitwieser
Resolving structure and properties in ionomer composite membranes with Confocal Raman Microscopy
2019 Workshop on Ion Exchange Membranes for Energy Applications, Bad Zwischenahn, 25. -27.06. 2019
T. Boehm, M. S. Mu’min, R. Moroni, S. Thiele, S. Vierrath, M. Breitwieser
Resolving structure and properties in ionomer composite membranes with Confocal Raman Microscopy
2019 FDFC 2019 - 8th International Conference on Fundamentals and Development of Fuel Cells Nantes/France, 12. – 14.02.2019
A. Brunauer, F. von Stetten, S.M. Früh
Sensitive detection of Pseudomonas aeruginosa based on recombinase polymerase amplification combined with an immunological assay
2019 Molecular Diagnostics Europe, Lissabon/Portugal, 06. - 09.05.2019
P. Juelg, M. Specht, M. Meyer, E. Kipf, F. Schlenker, F. Bänsch, S. Neumann, F. von Stetten, R. Zengerle, N. Paust, M. Fillies, R. Kirschner-Schwabe, S. Groeneveld-Krentz, M. Lehnert, C. Eckert, T. Hutzenlaub
Standardization of Personalized Multiplex Biomarker Quantification: Individual Response Monitoring Assay (IRMA)
2019 MST-Kongress, 28. - 30.Oktober 2019, Berlin
B. Johannsen, L. Karkossa, D. Baumgartner, L. Müller, R. Zengerle, K. Mitsakakis
Storage of protein coated beads on point-of-care microfluidic cartridges for immunoassay applications
2019 MNE 2019, 23-26.09.2019, Rhodes/Greece
P. Trinke, B. Bensmann, C. Klose, S. Vierrath, S. Thiele, R. Hanke-Rauschenbach
System relevant Observation of Gas Crossover – Necessity of Mitigation Strategies
2019 international Conference on Electrolysis, Leon (Norway), 09. - 13. 06.2019
S. M. Früh, D. M. Kainz, T. Hutzenlaub, R. Zengerle, N. Paust
Tailor-made immunological reactions in lateral flow strips enables by total flow control
2019 Wissenschaftsforum Chemie, Aachen, 15. -18.09.2019
P. Koltay
Towards a generic 3D-Bioprinting Platform
2019 IS2M Annual Meeting, 3D & 4D printing in Upper Rhine Valley, Mulhouse/France, 06. - 07. 06. 2019
A. Brunauer, B. Breiner, D. Kainz, R. Verboket, F. von Stetten, R. Zengerle, N. Paust, T. Hutzenlaub, S. M. Früh
Towards digital diagnostic devices - From smart membrane cartridges to highly integrated test stripes
2019 Diagnostics-4-Future, 27. – 28. 11. 2019, Konstanz
M. Buehler, F. Hegge, P. Holzapfel, S. Thiele
Towards direct membrane deposition (DMD) for PEM water electrolyzers – development of innovative electrodes deposited directly on porous transport substrates
2019 f-cell Stuttgart, 18.- 19. September 2018
F. von Stetten
Universal microarray for voltammetric real-time detection of DNA-amplification by mediator displacement loop mediated isothermal amplification (MP LAMP)
2019 4th “NanoBio Surfaces and Interfaces in Healthcare and Science Workshop” 16.-17.5.2019, Potsdam

2018

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B. Shanahan, B. Britton, S. Holdcroft, R. Zengerle, S. Thiele, M. Breitwieser
30 μm thin, highly conductive PBI-based anion exchange membrane (AEM) for VRFB applications
2018 IFBF - The International Flow Battery Forum, Lausanne/Schweiz, 10. – 12.07.2018
C.-H. Tsai, D.- H. Kuan, S. Zimmermann, J. Schoendube, A. Gross, R. Zengerle, P. Koltay
A highliy parallel microbioreactor for cell line development based on a microtiter plate with functional microfluidic lid
2018 MicroTAS 2018, 11. -15. November 2018, Kaohsiung / Taiwan
Z. Bagheryan, M. Trotter, L. Becherer, N. Borst, F. von Stetten
A universal approach for electrochemically DNA detection based on mediator displacement LAMP
2018 9th Euro Biosensors & Bioelectronics Congress November 29-30, 2018 Dublin, Ireland
P. Juelg, M. Specht, E. Kipf, M. Lehnert, C. Eckert, N. Paust, F. von Stetten, R. Zengerle, T. Hutzenlaub
Automation of qPCR based Minimal Residual Disease Monitoring by Centrifugal Microfluidics
2018 11th Symposium on minimal residual cancer, 03. – 05.05.2018, Montpellier, Frankreich
K. Tröndle, S. Kartmann, L. Gutzweiler, R. Zengerle, P. Koltay, S. Zimmermann
Bioprinting with spheroids: Automated large-scale production and deposition
2018 3D Cell Culture 2018, 5. - 7. Juni 2018, Freiburg
J. F. Hess, S. Yazar, N. Paust, R. Zengerle, T. Hutzenlaub
Capillary Valve for Microfluidic Foil Chips Fabricated by Micro-Milled Metal Master Tools
2018 MicroTAS 2018, 11. -15. November 2018, Kaohsiung / Taiwan
F. Hegge, R. Moroni, E. Wright, J. Sharman, S. Thiele, S. Vierrath
Catalyst Support Ageing of Polymer Electrolyte Fuel Cells Investigated with Tomography
2018 69th Annual Meeting of the International Society of Electrochemistry (ISE), Bologna/Italy, 02. – 07.09.2018
N. Paust
Centrifugal Microfluidics:Unique operations enabled by artificial buoyancy
2018 Lab-on-a-Chip and Microfluidics Europe 2018, Rotterdam/Niederlande, 05. - 06.06.2018
N. Wipf, K. Mavridis, S. Hin, K. Mitsakakis, M. Specht, S. Medves, B. Carman, P. Müller, J. Vontas
Development of multiplex TaqMan assays for the LabDisk – an automated diagnostic platform for malaria vectors
2018 7th MIM Pan African Malaria Conference - Dakar, 18.04.2018
S. Hin, B. Lopez-Jimena, M.A. Bakheit, V. Klein, S. Stack, C. Fall, A.A. Sall, K. Enan, S. Frischmann, L. Gillies, M. Weidmann, S. Goethel, V. Rusu, O. Strohmeier, N. Paust, R. Zengerle, K. Mitsakakis
Differential diagnosis of fever in West- and East-Africa
2018 WHO Geneva Health Forum, 10. – 12.04.2018, Genf / Schweiz
Z. Shu, B. Gerdes, M. Fechtig, L. Riegger, R. Zengerle, P. Koltay
Direct Printing of Conductive Metal Lines from Molten Solder Jets via StarJet Technology on Thin, Flexible Polymer Substrates
2018 NIP & Digital Fabrication Conference, Printing for Fabrication 2018, Dresden, 23. – 27.09.2018 Society for Imaging Science and Technology.
Z. Shu, B. Gerdes, M. Fechtig, L. Riegger, R. Zengerle, P. Koltay
Direct Printing of Conductive Metal Lines from Molten Solder Jets via StarJet Technology on Thin, Flexible Polymer Substrates
2018 NIP & Digital Fabrication Conference, Printing for Fabrication 2018 Society for Imaging Science and Technology, Band: 2018, Nummer: 1, Seiten: 72 - 75
KurzfassungWe present the direct printing of thin (linewidth of 70 μm) conductive lines from molten solder on thin, flexible substrates. The lines are generated via the so-called StarJet technology that enables the printing of micro jets from molten metal. In this work, metal lines are printed for the first time on flexible substrates, possibly enabling applications in the field of printed electronics. The printed lines are evaluated regarding their mechanical and electrical properties. To the knowledge of the authors, this is the first time that direct printing of a functional metallization, requiring no further treatment, on a flexible polymer substrate was demonstrated. The lines exhibit a low ohmic resistance and can endure shear forces of up to 3.5 N on polyethylene terephthalate (PET) substrates.
K. Tröndle
Drop-on-Demand Bioprinting Process for Single-Spheroid Deposition and Immobilization
2018 International Conference on Biofabrication, Würzburg, 28. – 31.10.2018
C. Klose, L. Bohn, M. Klingele, S. Thiele, R. Zengerle, M. Breitwieser, S. Vierrath
Dynamic Quantification of Water Generation and Migration in Polymer Electrolyte Membrane Fuel Cells
2018 69th annual meeting of the International Society of Electrochemistry, Bologna (Italy), 02. - 07.09.2018.
C. Klose, L. Bohn, M. Klingele, S. Thiele, R. Zengerle, M. Breitwieser, S. Vierrath
Dynamic Quantification of Water Generation and Migration in Polymer Electrolyte Membrane Fuel Cells
2018 Gordon’s Research Conference on Fuel Cells, Smithfield (USA), 29.07. - 03.08.2018
L. Becherer, M. Bakheit, S. Frischmann, S. Stinco, N. Borst, R. Zengerle, F. von Stetten
Fluorogenic real-time detection of loop-mediated isothermal amplification by novel mediator displacement probes demonstrated for HIV-1 and HTLV-1
2018 International Biotech Innovation Days, 23 - 25 May 2018 / Senftenberg, Germany
M. Schulz, N. Borst, M. Specht, S. Calabrese, F. von Stetten, R. Zengerle, N. Paust
From nasal swab to digital answer: unit operations for antibiotic resistance screening on a single cell level
2018 MicroTAS 2018, 11. -15. November 2018, Kaohsiung / Taiwan
L. Becherer, M. Schulz, H. Kuhn, M. Bakheit, S. Frischmann, F. Zitz, N. Borst, R. Zengerle, F. von Stetten
HIV-1 and HTLV-1 multiplex detection by digital mediator displacement LAMP
2018 MicroTAS 2018, 11. -15. November 2018, Kaohsiung / Taiwan
C. Klose, L. Bohn, M. Klingele, M. Breitwieser, S. Vierrath
How engineering the PEM|CL interface influences the performance of PEMFCs
2018 69th Annual Meeting of the International Society of Electrochemistry (ISE), Bologna/Italy, 02. – 07.09.2018
C. Klose, L. Bohn, M. Klingele, M. Breitwieser, S. Vierrath
Influence of the PEM|CL interface on performance and water management
2018 Gordon Research Conference, Bryant University, Douglas Pike in Smithfield, RI, US., 29.07. – 03.08.2018
P. Juelg, M. Specht, E. Kipf, M. Lehnert, C. Eckert, N. Paust, R. Zengerle, T. Hutzenlaub
LabDisk for fully automated quantification of two leukemia associated gene targets
2018 MicroTAS 2018, 11. -15. November 2018, Kaohsiung / Taiwan
M. Trotter, N. Borst, F. von Stetten
Mediator probes for electrochemical DNA detection: Universal electrode functionalization for specific detection of different targets
2018 9th Euro Biosensors & Bioelectronics Congress November 29-30, 2018 Dublin, Ireland
M. Buehler, F. Hegge, P. Holzapfel, S. Thiele
Porous Transport Electrodes – The Influence of Depositing Electrodes on Porous Transport Layers on the Polarization Behaviour of PEM Water Electrolyzers
2018 69th Annual Meeting of the International Society of Electrochemistry (ISE), Bologna/Italy, 02. – 07.09. 2018
Kurzfassung69th Annual Meeting of the International Society of Electrochemistry (ISE), Bologna/Italy, 02. – 07.09. 2018
L. Becherer, N. Borst, R. Zengerle, F. von Stetten
Simultaneous detection of HIV and HTLV by mediator displacement loop-mediated isothermal amplification
2018 6th World Congress on Control and Prevention of HIV/AIDS, STDs & STIs, Zürich/Switzerland, 27. – 28.08.2018
Kurzfassung6th World Congress on Control and Prevention of HIV/AIDS, STDs & STIs, Zürich/Switzerland, 27. – 28.08.2018
T. A. Kohl, M. Beutler, M. Merker, T. Paprotka, K. Rönsch, M. Schmitt, W. Grasse, C. Metzger-Boddien, K. Dormanns, J. Lüddecke, N. Paust, J. Schlanderer, L. Delamotte, J. Schickedanz, M. Steinwand, S. Niemann, H. Hoffmann
TB-SeqDisK: A microfluidics platform in combination with next generation sequencing for ultra-fast notification of Mycobacterium tuberculosis and its resistance pattern
2018 39th Annual Congress of European Society of Mycobacteriology, Dresden, 01. – 04.07.2018
S. Vierrath, M. Klingele, S. Thiele, R. Zengerle, M. Breitwieser
Tailoring the membrane│electrode interface: a review and perspective of novel engineering approaches
2018 69th Annual Meeting of the International Society of Electrochemistry (ISE), Bologna/Italy, 02. – 07.09.2018
Kurzfassung69th Annual Meeting of the International Society of Electrochemistry (ISE), Bologna/Italy, 02. – 07.09.2018
D. Kainz, S. M. Früh, T. Hutzenlaub, R. Zengerle, N. Paust
Total flow control for lateral flow tests with centrifugal microfluidics
2018 MicroTAS 2018, 11. -15. November 2018, Kaohsiung / Taiwan
P. Juelg, M. Specht, E. Kipf, M. Lehnert, C. Eckert, N. Paust, F. von Stetten, R. Zengerle, T. Hutzenlaub
Towards Standardization of Molecular Diagnostic Workflows: Centrifugal Microfluidic Automation of qPCR for Cancer Monitoring
2018 6th International Molecular Diagnostics Europe, Lissabon / Portugal, 22. - 24. 05.2018
P. Koltay
Towards a generic 3D-Bioprinting Platform
2018 International Conference on Biofabrication, Würzburg, 28. – 31.10.2018
Kurzfassung; “”, (2018), International Conference on Biofabrication, Würzburg, 28. – 31.10.2018
M. Mu’min Solihul, T. Böhm, S. Thiele, M. Breitwieser
Towards more hydrophilic proton exchange membranes: adjusting the wetting properties by electrospinning PVDF-HFP/PVP blends
2018 ELEN Electrospinning for Energy, Montpellier / Fracne, 13. - 15.06.2018
C. Siber, F. Stumpf, J. Schöndube, S. Zimmermann, P. Koltay, L. Lautscham
Velocity field analysis of acoustophoretic focusing in a single-cell printing system
2018 Acoustofluidics, Lille/France, 29. – 31.08.2018

2017

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S. Zimmermann, J. Riba, R. Zengerle, P. Koltay
A single-cell printer as a versatile tool for cell line development and single-cell analysis
2017 LAPASO - Microfluidics for label-free particle sorting, Lund / Sweden, 05. - 06.09.2017
KurzfassungSingle-cell analysis emerged as a promising approach to decipher the heterogeneity of complex cell populations such as tumors. Furthermore, the proof of monoclonality is a regulatory requirement in cell line development, where a cell population producing a therapeutic protein in a bioreactor has to originate from a single cell. Within the advent of such diverse applications, a number of single-cell isolation technologies have been developed and adapted for different requirements [1]. Limitations of these technologies regarding the uniqueness and the integrity of the cells can be overcome by a single-cell printer (scp), a laboratory device developed by the University of Freiburg and commercialized by the spin-off company cytena.
J. Madjarov, P. Kocatürk Schumacher, S. Abdu, S. Kerzenmacher
Integration of a microbial fuel cell anode into membrane bioreactors treating synthetic brewery wastewater
2017 BW-Stiftung Forschungstag 2017, Stuttgart
KurzfassungMicrobial fuel cells (MFCs) are a promising new technology to directly convert wastewater’s chemically stored energy into electrical energy. Our work shows that a conductive membrane filter can simultaneously be used as anode of a MFC, so that the energy demand of the filtration unit of an anaerobic membrane bioreactor (AnMBR) can be partly supplied by the MFC. At the same time, COD (chemical oxygen demand) reduction is enhanced by the degradation of organic carbon to electricity and CO2 on the membrane.
M. Buehler, S. Vierrath, C. Klose, F. Hegge, S. Thiele
A Novel Fabrication Technique for Electrodes of PEM Water Electrolyzers
2017 232nd ECS MEETING Oct. 1-5, 2017 | National Harbor, MD (greater Washington, DC area)
KurzfassungIn this work the improvement of material interfaces at electrodes for proton exchange membrane (PEM) water electrolyzers is addressed by a novel fabrication technique. In this approach the electrode and the membrane are directly deposited on the porous transport layers (PTLs), which serve as substrate for the electrodes. The aim is to stabilize and increase the oxygen and hydrogen evolution rate at high current densities leading to a reduction of the noble metal loading of the electrodes – and additionally to develop a cost effective novel fabrication technique applicable for the large scale industrial fabrication of electrodes for PEM water electrolyzers. The innovative manufacturing technique is described in this transaction, and current challenges regarding the coating of porous substrates in terms of parameter control, reliability and homogeneity are pointed out.
S. Kartmann, F. Koch, A. Ernst, R. Zengerle, P. Koltay
A single-use in-line flow sensor fore closed-loop controlled precise non-contact liquid dispensing
2017 MFHS, Twente / The Netherlands, 04. - 06.10.2017
KurzfassungThis paper reports on a closed-loop controlled non-contact liquid dispensing system. The system employs a control algorithm and consists of a single-use in-line flow sensor and a disposable electromagnetic dispensing valve. By measuring the flow rate in real time, the system can control the opening time of the valve and is thus able to react to potential environmental influences such as pressure or temperature fluctuations. Furthermore, the system has the advantage that all fluid-carrying components can be exchanged after use, therefore cost intensive cleaning steps can be avoided. The precision of the system was demonstrated experimentally for different volumes in the range of 2:8 ml to 4:9 ml. The resulting coefficient of variation (CV) was below 2 %.
S. Vierrath, M. Breitwieser, M. Bühler, C. Klose, R. Zengerle, S. Thiele
Additive Fertigung für Brennstoffzellen und Elektrolyse
2017 MST Kongress, München, 23. - 25.10.2017
KurzfassungBei der Wasserstoff-Elektrolyse wird Wasser mit Hilfe von Strom in Wasserstoff umgewandelt, der dann als Energieträger gespeichert werden kann. Bei der Brennstoffzelle wird dieser Prozess umgekehrt und somit Strom erzeugt. Zusammen bilden diese Systeme die Grundlage der zukünftigen Wasserstoffwirtschaft, in der große Energiemengen, z.B. aus erneuerbaren Quellen, flexibel gespeichert und abgerufen werden können. Die Brennstoffzelle ermöglicht zudem eine emissionslose Mobilität ohne Reichweitenbegrenzung oder lange Ladezeiten. Die Membran-Elektroden-Einheit bildet das Herzstück der Brennstoffzelle und der Elektrolysezelle. Darin ist die Membran nur für Wasserstoffionen durchlässig und sorgt so für kontrollierte Reaktionen in den beidseitig aufgebrachten Elektroden. Die Qualität dieser Membran-Elektroden-Einheit entscheidet maßgeblich über die Leistung und Alterungsverhalten in der späteren Anwendung. Klassischerweise werden die Elektroden und die Membran getrennt betrachtet und hergestellt – dabei hat die Grenzschicht einen beachtlichen Einfluss auf das Leistungsverhalten. Wir gehen mit additiver Fertigungstechnik neue Wege in der Herstellung: Statt die Membran in Folienprozessierung und die Elektroden im Sprüh-Abzieh-Verfahren herzustellen, können wir die gesamte Membran-Elektroden-Einheit nacheinander in einem Sprühprozess herstellen (Abb.1) [1]. Neben der Vereinfachung des Prozesses bildet die aufgesprühte Membran eine dreidimensionale Grenzfläche mit den Elektroden, statt der herkömmlichen 2D-Grenzfläche der Membranfolie. Die vergrößerte Grenzschicht und der verbesserte ionische Kontakt sorgen für eine 40% höhere Maximalleistung (Abb. 2a) und besseres Wassermanagement bei großen Strömen [2]. Dank additiver Fertigung ist zudem die gezielte ortsaufgelöste Aufbringung der Materialien möglich. So kann Material eingespart und auch die Membran-Elektroden-Einheit lokal optimiert werden, z.B. durch Anpassung des Katalysator- oder Ionomergehalts an das Reaktionsprofil. Neben der Leistung und dem Herstellungsprozess ist auch das Alterungsverhalten ein wichtiger Aspekt. Durch die Integration von Nanofasern und Nanopartikeln kann die mechanische und chemische Stabilität erheblich gesteigert werden (Abb. 2b) [3]. Dazu werden Nanofasern direkt auf die Elektrode gesponnen und anschließend mit Ionomer besprüht um eine Kompositmembran zu erhalten [4]. Die Nanopartikel können gezielt in eine Schicht, z.B. als Radikalfänger in der Membran, integriert werden.
C.H. Tsai, S. Zimmermann, R. Zengerle, P. Koltay
An autonomous microbioreactor based on a functional lid in 96-well microplate format
2017 MFHS, Twente / The Netherlands, 04. - 06.10.2017
KurzfassungWe have developed an integrated microbioreactor (MBR) based on a disposable functional lid (FL) and a standard microtiter plate (MTP), which only requires one pressure source for parallel and reciprocal mixing of cells cultured in suspension in the MTP as a prerequisite in pharmaceutical cell line development (CLD). The mixing principle of the FL does not only allows for working with significantly smaller culture volumes (30 μl), but also reduces the requirements of external processing stations.
J. Riba, H. Becker, P. Koltay, R. Zengerle, S. Zimmermann
Assay miniaturization for the genetic analysis of individual cells enabled by single-cell printing and nanoliter liquid handling
2017 Keystone Symposia Conference – Single Cell Omics, Stockholm, Sweden, 26. -30.May 2017
KurzfassungAutomated single-cell isolation and low volume liquid handling for reagent cost reduction are needed to mature single-cell sequencing assays into routine clinical analysis methods. Here, we combine our single-cell printer (scp) for the isolation and deposition of individual cells with non-contact dispensing for reagent dosage in the nanoliter range. This enables us to downscale the reaction volumes of a single-cell whole-genome-amplification (WGA) assay from 50 µl to 2.5 µl using standard 384-well PCR plates.
Y. Zhao, V. Klein, K. Mitsakakis, G. Czilwik, R. Zengerle, N. Paust
Automated particle based C-reactive protein immunoassay with on-disk pre-stored reagents and centrifugo-pneumatic liquid control
2017 MST Kongress, München, 23. - 25.10.2017
KurzfassungRapid and highly sensitive immunoassays can be achieved using microparticles due to the large surface to volume ratio. Such assays automated in centrifugal microfluidics show great potential for point-of-care application. We present a fully automated centrifugal microfluidic concept for implementing particle based immunoassay. With all reagents pre-stored on a LabDisk, the automation is controlled exclusively by the spinning frequency and does not require any additional means.
S. Zimmermann, J. Schoendube, A. Gross, B. Steimle, L. Lautscham, K. Pfleghar, T. Christmann, B. Werdelmann, F. Koch, J. Riba, P. Koltay, R. Zengerle, M. Pirsch
Cell line development by single-cell printing and cell imaging
2017 Cell Line Development & Engineering, Amsterdam, 23.-25. April 2017
KurzfassungIn biopharmaceutical production the proof of monoclonality is a regulatory requirement for the development of clonal cell lines. A complementary approach based on a single-cell printer (scp, cytena GmbH) and a NYONE cell imager (SYNENTEC GmbH) is used to produce truly monoclonal cell lines and compared to standard single-cell isolation technologies like limited dilution and FACS. Different CHO cell lines were used on different microtiter plate types in addition to cell-equivalent beads for testing the system.
M. Specht, M. Keller, J. Naue, U. Schmidt, R. Zengerle, F. von Stetten
Centrifugal Microfluidic Tools for Forensic Nucleic Analysis
2017 1st International Caparica Conference in Translational Forensics, Caparica / Portugal, 20. - 23.11.2017
KurzfassungThe analysis of DNA by polymerase chain reaction (PCR) is a routinely applied method within most molecular biology laboratories, including forensic laboratories [1]. Especially within the fields of investigative genetics as forensic science and food analysis, the analysis of human and animal DNA is required and samples with degraded or a low amount of DNA are a commonly occurring problem to overcome. [1]. The different DNA analytic techniques require a lot of manual handling steps, which give rise to a high contamination risk. We develop centrifugal microfluidic Lab-on-a-Chip systems, which are able to automate the laboratory processing steps without the need of investing in expensive robots. One of our platforms, the LabDisk is able to perform DNA extraction with subsequent Realtime PCR [2]. It is processed in a small “Point of Care” device, the LabDiskPlayer. A second aproach is to design microfluidic disk slices for a standard PCR thermocycler. We have developed a microfluidic disk segment enabling an automated nested real-time PCR assay for identification of common European animal groups adapted to forensic standards [3]. The system was characterized with respect to assay sensitivity, specificity, risk of cross-contamination, and detection of minor components in mixtures. Altogether, augmentation of the standard real-time thermocycler with a self-contained centrifugal microfluidic disk segment resulted in an accelerated and automated analysis reducing hands-on time, and circumventing the risk of contamination associated with regular nested PCR protocols.
P. Juelg, M. Specht, E. Kipf, M. Lehnert, C. Eckert, S. Wadle, M. Keller, N. Paust, R. Zengerle, T. Hutzenlaub
Centrifugal microfluidic automation of dilution series for high dynamic range assays demonstrated for decadal dilutions up to 1:100,000
2017 MicroTAS 2017, Savannah /USA, 22.-26.10.2017
KurzfassungFor the first time we present the centrifugal microfluidic automation of an extensive dilution series that can cover all biochemically relevant dilution ranges. In contrast to existing methods, the new concept is based on iteration loops of individual dilution steps that can be easily combined in a theoretically unlimited fashion. Thus, any combination and range of dilutions can be implemented. The concept was demonstrated by generating a qPCR standard curve for cancer biomarker ETV6-RUNX1 up to 1:100,000. We achieved the following analytical performance characteristics: A high coefficient of determination of R²=98.9 %, equidistant quantification cycles of ΔCq=3.4±0.3 and low replicate variation coefficients of CV<3.5 %.
S. Abdu, J. Madjarov, M. Ade, S. Kerzenmacher
Developing stainless steel ultrafiltration membranes for filtering microbial fuel cells
2017 Baden-Württemberg Stiftung Forschungstag 2017, Stuttgart, 29.06.2017
KurzfassungIntegration of the anode of a microbial fuel cell (MFC) into membrane filtration in a compact configuration (Figure 1). This way, part of the electricity required for membrane bioreactor operation can be generated by the MFC [1]. To bring the concept into application, development of costeffective (<< 100 €/m²) electrically-conductive ultrafiltration membranes that also serve as MFC anode is required.
S. Abdu, J. Madjarov, M. Ade, S. Kerzenmacher
Developing stainless steel ultrafiltration membranes for filtering microbial fuel cells
2017 ICOM 2017, San Francisco / USA, 29.07. - 04.08 2017
KurzfassungIntegration of the anode of a microbial fuel cell (MFC) into membrane filtration in a compact configuration. This way, part of the electricity required for membrane bioreactor operation can be generated by the MFC. To bring the concept into application, development of costeffective (<< 100 €/m²) electrically-conductive ultrafiltration membranes that also serve as MFC anode is required.
C.H. Tsai, X.Y. Wu, S. Zimmermann, R. Zengerle, P. Koltay
Digital Hydraulic Drive For Microfluidic Large-scale Integration System Based On Shape Memory Alloy Actuators
2017 Transducers 2017, Kaohsiung/Taiwan, 18.-22.06.2017,
KurzfassungWe present a small size and low power Digital Hydraulic Drive (DHD) intended for use in miniaturized and portable control systems for microfluidic large-scale integration (mLSI) chips. The main components of a DHD are a pneumatic cylinder and a shape memory alloy (SMA) actuator. Depending on different types of SMA actuators, the DHD is not only able to provide digital hydraulic pulses (switching time smaller 1 s), but can maintain a steady state up to 24 hours. A single DHD enables to control 256 valves in parallel.
M. Breitwieser, S. Vierrath, C. Klose, M. Klingele, R. Zengerle, S. Thiele
Direct Membrane Deposition (DMD): A novel and versatile fabrication technique for high performance fuel cells
2017 7th International Conference on ”Fundamentals & Development of Fuel Cells” in Stuttgart, 31. Januar – 2. Februar 2017
KurzfassungIn the “Direct Membrane Deposition” (DMD) technique the conventional catalyst coated membrane (CCM) is replaced by two ionomer-coated gas diffusion electrodes (GDE). Assembling the ionomer-coated GDEs creates a fuel cell with a very thin membrane (12 μm) and improved interface between membrane and electrodes. Fuel cells fabricated with DMD showed record power densities of 4 W/cm² at 70°C, 300 kPa and with oxygen as fuel. The DMD approach also proved its suitability for medium temperature fuel cells: by incorporating TiO2 nanoparticles into the directly deposited membrane the fuel cell showed stable operation at 120°C with a power density of 2 W/cm² (300 kPa and oxygen at the cathode). Besides the increased power density, DMD bears the potential to simplify the membrane-electrode-assembly (MEA) fabrication process by successively spray-coating catalyst layer and membrane onto a gas diffusion layer. In very recent work, DMD was used to fabricate composite membranes by combining inkjet-printing of ionomer and with electrospun Poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) reinforcing nanofibers. These 12 μm thin composite membranes provided excellent thermal stability and high electrochemical performance up to 120 °C operation temperature. By anchoring CeO2 nanoparticles to the PVDF-HFP nanofibers, the open circuit voltage (OCV) degradation rate (0.39 mV/h) was found to be 3 times lower than that of a comparably thin reference Gore membrane in an OCV accelerated stress test. This poster provides an overview about our DMD activities, its future potential and gives detailed information about the possible MEA architectures feasible with DMD.
S. Vierrath, M. Breitwieser, C. Klose, M. Klingele, R. Zengerle, S. Thiele
Direct Membrane Deposition (DMD): Improved Power Density, Water Management and Stability
2017 7th International Conference on ”Fundamentals & Development of Fuel Cells” in Stuttgart, 31. Januar – 2. Februar 2017
KurzfassungKlingele et al. showed never reached high power fuel cells by applying direct membrane deposition (DMD), excelling the peak power of a catalyst coated membrane (CCM) by a factor of 2.3. To understand the underlying reasons for their high power, we identify the reasons and quantify their impact by employing electrochemical impedance spectroscopy. As a result we show, that the main reasons for the high power of DMD fuel cells are (i) a 50% reduced high frequency resistance (26 mΩcm²) due to a thinner membrane (12μm) compared to state-of-the-art and (ii) a factor 2.2 reduced mass transport losses (0.12 Ωcm²) due to increased water back diffusion through the thin membrane. A comparison of DMD vs. CCM fuel cells at the maximum power point of the CCM shows that 91% of the DMD’s improvement can be attributed to reduced mass transport losses and only 9% are caused by the reduction of the ohmic resistances.
S. Thiele, S. Vierrath, M. Breitwieser, M. Klingele, C. Klose, R. Moroni
Direct membrane deposition (DMD) – a new way in membrane electrode assembly manufacturing
2017 20th Topical Meeting of the International Society of Electrochemistry, Buenos Aires/Argentinien, 19-22 März 2017
KurzfassungThe membrane is one of the very central polymer electrolyte membrane fuel cell components. At the same time it must conduct protons and inhibit transport of electrons and cross-over of reactant gases. Additionally, degradation effects have to be small to ensure a long lifetime. While traditionally consisting of pure Nafion, up to date membranes contain nanofiber reinforcements and radical scavenger packages to decrease degradation effects. Thus, seminal membranes are multi-layer, multi-component structures. In the state of the art, membrane electrode assemblies (MEA) are manufactured as catalyst coated membranes (CCMs). To form a CCM, electrodes are deposited either by the decal method, or by another deposition method. In this talk we present a novel approach for MEA manufacturing. In the so called ‘direct membrane deposition’ (DMD) approach, liquid ionomer is deposited on the catalyst layers of two gas diffusion electrodes which are successively dried and pressed together to form an MEA. Interestingly, this approach enabled power densities more than two times higher than traditional CCM based approaches which are commercially available. Also this approach allows for a simple fabrication of thin multi-layer membranes and improves the water management. DMD applied to low Pt loading electrodes revealed very high power densities per gram Pt of up to 88 kW/g Pt. An analysis of the underlying reasons for the improved performance values revealed a small influence of membrane resistance but mainly an influence in mass transport and charge transfer phenomena. In this talk we highlight our latest developments in the field of DMD based manufacturing and give an insight on degradation and durability aspects.
M. Breitwieser, C. Klose, M. Klingele, S. Vierrath, R. Zengerle, S. Thiele
Direct membrane deposition (DMD): A versatile fabrication technique for PEMFC composite membranes
2017 WE-Heraeus-Seminar, Bad Honnef, 02. – 05.07.2017
KurzfassungThe conventional catalyst coated membrane (CCM) can be substituted by two ionomer-coated gas diffusion electrodes (GDE). Assembling the ionomer-coated GDEs creates a fuel cell with a very thin, directly deposited membrane (12 μm) and improved interface between membrane and electrodes. This interface has significant impact onto the fuel cell performance. Besides the increased power density, DMD bears the potential to simplify the membrane-electrode-assembly (MEA) fabrication process by successively spray-coating catalyst layer and membrane onto a gas diffusion layer. In recent work, DMD was used to fabricate composite membranes by combining inkjet-printing of ionomer and with electrospun Poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) reinforcing nanofibers [3,4]. The workflow for this type of novel composite membrane is graphically summarized in Figure 1. These 12 μm thin composite membranes provided high electrochemical performance up to 120 °C operation temperature. By anchoring CeO2 nanoparticles to the PVDF-HFP nanofibers, the OCV degradation rate (0.39 mV/h) was found to be 3 times lower than that of a comparably thin reference Gore membrane in an open circuit voltage accelerated stress test according to the US department of energy (DOE.
M. Breitwieser, M. Klingele, S. Vierrath, C. Klose, R. Zengerle, S. Thiele
Direct membrane deposition (DMD): A versatile technique for the production of novel fuel cell composite membranes
2017 Fuel Cells | Workshop EMEA 2017, Bad Zwischenahn, 26. - 28.06.2017
KurzfassungThe conventional catalyst coated membrane (CCM) can be substituted by two ionomer-coated gas diffusion electrodes (GDE). Assembling the ionomer-coated GDEs creates a fuel cell with a very thin, directly deposited membrane (12 µm) and improved interface between membrane and electrodes. Fuel cells fabricated with direct membrane deposition (DMD) showed record power densities of 4 W/cm² at 70°C, 300 kPa and with oxygen as fuel. Besides the increased power density, DMD bears the potential to simplify the membrane-electrode-assembly (MEA) fabrication process by successively spray-coating catalyst layer and membrane onto a gas diffusion layer. In recent work, DMD was used to fabricate composite membranes by combining inkjet-printing of ionomer and with electrospun Poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) reinforcing nanofibers. The workflow for this type of novel composite membrane is graphically summarized in Figure 1. These 12 µm thin composite membranes provided excellent thermal stability and high electrochemical performance up to 120 °C operation temperature. By anchoring CeO2 nanoparticles to the PVDF-HFP nanofibers, the open circuit voltage (OCV) degradation rate (0.39 mV/h) was found to be 3 times lower than that of a comparably thin reference Gore membrane in an open circuit voltage accelerated stress test according to the US department of energy (DOE).
C. Klose, M. Bühler, S. Vierrath, N. Baumann, T. Lickert, A. Fallisch, S. Thiele
Direct membrane deposition – a novel fabrication method for PEMWEs
2017 International Conference on Electrolysis 2017, Copenhagen/Denmark, 12. - 15.06.2017
B. Johannsen, R. Zengerle, N. Paust
Disk-integrated repeated dispensing of 200 nl volumes for the automation of pyrosequencing
2017 MicroTAS 2017, Savannah /USA, 22.-26.10.2017
KurzfassungFor the first time, we present a proof-of-concept of disk-integrated automation of pyrosequencing. In contrast to existing methods-[1][2], our presented workflow doesn’t require any external dispensers for adding the nucleotides (dNTPs): instead, centrifugo-pneumatic timing, metering, and valving is employed to repeatedly dose-200 nl-dNTP solution from four different disk-integrated reservoirs in any user-defined sequence. First results of a seven-time repeated usage of all four dispensers show a maximum volume deviation of 9% to target volume. Preliminary sequencing results demonstrate the successful detection of the subsequent integration of thymine and adenine. The new automation concept enables a fully closed sequencing system, which is attractive for a potential use at the point-of-care (PoC).
B. Gerdes, M. Jehle, M. Domke, R. Zengerle, P. Koltay, L. Riegger
Drop-on demand generation of aluminium alloy microdroplets at 950 °C using the Strarjet technology
2017 Transducers 2017, Kaohsiung/Taiwan, 18. – 22.06.2017
KurzfassungWe present the drop-on-demand generation of liquid microdroplets from aluminum alloy melts with minimum diameters of 235 μm. The so-called StarJet technology, used to generate the droplets features a pneumatically actuated printhead that has been used to print microdroplets from solder (Tmelt 220 °C) before. In this work a novel StarJet printhead is presented that can be operated at up to 950 °C and thus allows for printing of aluminum alloys. The printhead is compatible with chemically aggressive metal melts and can be operated in a standard laboratory environment. Experimental results regarding the generation of droplets and a printed aluminum structure are presented. To the knowledge of the authors this is the first time that aluminum alloy microdroplets of such small size (d = 235 μm) have been produced by drop-on-demand.
F. Schuler, N. Borst, S. Wadle, M. Schulz, M. Specht, J. Li, L. Becherer, T. Hutzenlaub, N. Paust, R. Zengerle, F. v. Stetten
Eine Technologieplattform für die digitale Nukleinsäurediagnostik vor Ort (A Technology Platform for Digital Nucleic Acid Diagnostics at the Point of Care)
2017 3. Münchner Point-of-Care-Testing Symposium der DGKL (Deutsche Gesellschaft für Klinische Chemie und Laboratoriumsmedizin e.V.) 13. – 15. März 2017, München
J. Riba, J. C. Niemöller, N. Renz, S. Bleul, J. M. Stosch, P. Koltay, R. Zengerle, R. Claus, H. Becker, S. Zimmermann
Genetic Analysis of Individual Cancer Cells Isolated via Single-Cell Printing
2017 Single-Cell Genomics Workshop Paris, Paris/France, 27. - 28.06.2017
KurzfassungSingle-cell genomics emerged as a promising tool to analyze the heterogeneity of complex cancer cell populations by characterizing the genome of each individual cell. In acute myeloid leukemia (AML), single-cell sequencing in addition to bulk next generation sequencing (NGS) is particularly useful for deciphering complex clonal architectures. Here, we present an efficient workflow based on an advanced Single-Cell Printer (scp) for the study of gene variants in single cancer cells. The ejection efficiency was 99.7% for fluorescent beads (n = 2304) and 98.7% for human cells (U-2OS or Kasumi-1 cancer cell line, or AML patient; n = 150). Per fluorescence microscopy, 98.8% of beads were correctly delivered into the wells. A subset of single cells (n = 81) was subjected to whole genome amplification (WGA), which was successful in all cells. On empty droplets, a PCR on LINE1 retrotransposons yielded no product after WGA, verifying the absence of free-floating DNA in SCP-generated droplets. Representative gene variants identified in bulk specimens were sequenced in single-cell WGA DNA. In U-2 OS, 22 of 25 cells yielded results for both an SLC34A2 and TET2 mutation site, including cells harboring the SLC34A2 but not the TET2 mutation. In one cell, the TET2 mutation analysis was inconclusive due to allelic dropout, as assessed via polymorphisms located close to the mutation. Of Kasumi-1, 23 of 33 cells with data on both the KIT and TP53 mutation site harbored both mutations. In the AML patient, 21 of 23 cells were informative for a TP53 variant; the identified alleles matched the loss of chromosome arm 17p. The advanced SCP allows efficient, precise and gentle isolation of individual cells for subsequent WGA and routine PCR/sequencing-based analyses of gene variants.
M. Frei, M. Bühler, J. Erben, J. Martin, S. Kerzenmacher
Hochporöses Platin auf Kohlenstoffnanofasern als neue Anode für die implantierbare Glukosebrennstoffzelle: Nachweis der Funktionalität in Blutserum über 30 Tage
2017 MST Kongress, München, 23. - 25.10.2017
KurzfassungImplantierbare Glukose-Brennstoffzellen auf Basis biokompatibler Platinelektroden sind ein vielversprechender Ansatz zur batterieunabhängigen Energieversorgung medizinischer Implantate [1,2]. Vorteilhaft sind insbesondere die kontinuierliche Art der Energiebereitstellung sowie eine theoretisch unendliche Lebensdauer. In echten oder realistisch angenäherten Gewebeflüssigkeiten ist die Lebensdauer dieser implantierbaren Glukose-Brennstoffzellen bislang allerdings auf wenige Tage beschränkt. Hauptursache hierfür ist eine Vergiftung der Anoden durch Komponenten der Gewebeflüssigkeit, wie beispielsweise Aminosäuren und Kreatinin [3,4]. Ein in diesem Zusammenhang vielversprechender Lösungsansatz ist die Erhöhung der spezifischen Reaktions-Oberfläche für die Glukose-Oxidation an der Anode. Wir zeigen nun einen neuen Ansatz zur Herstellung von Platinanoden mit deutlich erhöhter Reaktionsoberfläche und verbesserter Funktionalität in physiologischer Umgebung. Die Herstellung der neuen Elektroden basiert auf der elektrochemischen Abscheidung von hochporösem Platin auf dreidimensionalen elektrogesponnenen Kohlenstoffnanofasermatten. Mit diesem neuen Ansatz konnten Rauhigkeitsfaktoren (RF; Verhältnis aus tatsächlicher und geometrischer Oberfläche) von bis zu 16500 ± 2300 erreicht werden. Verglichen mit dem bisherigen Stand-der-Technik entspricht das in etwa einer Verbesserung um den Faktor drei [5]. Nach 30 Tagen kontinuierlichem Betrieb in Pferdeserum zeigen die neuen Anoden stabile Stromdichten von (7.2 ± 1.9) µA/cm2 bei einem Potential von -200 mV vs. SCE. Im Vergleich dazu erreichen Stand-der-Technik-Elektroden nur Stromdichten von (1.3 ± 0.1) µA/cm2 (Abb. 1). Bemerkenswert ist, dass die auf die tatsächliche Reaktionsoberfläche bezogenen Ströme der neuen Anoden ca. 2-mal höher sind als bei den bisherigen Anoden. Diese überproportionale Steigerung lässt sich mit einer verbesserten katalytischen Aktivität oder Vergiftungstoleranz der Glukoseoxidations-Anode bzw. einer Kombination beider Effekte erklären. Dies ist vermutlich auf die Mikro- und Nanostruktur des auf den Kohlenstofffasern abgeschiedenen Platins zurückzuführen. Zusammenfassend können wir zeigen, dass die Abscheidung von porösem Platin auf elektrogesponnenen Kohlenstoffnanofasern nicht nur eine geeignete Strategie zur Erhöhung der spezifischen Reaktionsoberfläche ist, sondern auch der Strom überproportional steigt, das vermutlich auf eine verbesserten katalytischen Aktivität oder Vergiftungstoleranz der Glukoseoxidations-Anode bzw. einer Kombination beider Effekte zurückzuführen ist. Die neue Herstellungsstrategie erlaubt nun erstmals den stabilen Betrieb unserer Platinanoden in echtem Pferdeserum über einen Zeitraum von mindestens 30 Tagen. In Kombination mit einer typischen Platinkathode, betrieben bei einem Potential von 100 mV vs. SCE [3], wären so Glukosebrennstoffzellen mit einer Leistungsdichte von etwa 2 µW/cm2 möglich. Eine nur wenige cm² große Brennstoffzelle wäre demnach bereits ausreichend zum Betrieb implantierbarer Sensoren oder eines Herzschrittmachers [6,7]. In zukünftigen Untersuchungen werden wir den Herstellungsprozess weiter optimieren. Zudem planen wir ausführliche in-vitro und in-vivo Studien mit kompletten Glukosebrennstoffzellen um die Anwendbarkeit unserer Technologie als batterieunabhängige Energieversorgung für medizinische Implantate auch über einen längeren Zeitraum zu demonstrieren.
J. Madjarov, S. Kerzenmacher
Increasing COD removal and energy efficiency of an AnMBR by using the membrane as microbial anode
2017 The 14th IWA Leading Edge Conference on Water and Wastewater Technologies, Florianópolis, Brazil, 29.05. - 02.06.2017
KurzfassungThis work reports on a novel concept for the integration of bioelectrochemical systems into AnMBRs. By operating a conductive filter membrane simultaneously as microbial anode, the significant COD degradation across the filtration membrane can be converted directly into electricity. In experiments conducted with a 0.1µm stainless steel membrane using Geobacter sulfurreducens in an acetate containing medium, current densities of 6 A/m² and a permeate flow of 9 lm-2h-1 after 18 days have been reached. During this period, COD degradation up to 200mg/l across the membrane was achieved. In an ongoing experiment, the system is tested with synthetic brewery wastewater and sewage sludge, yielding similar current densities in the range of 5 A/m² but achieving higher COD degradation rates of up to 450 mg/l across the membrane. This demonstrates the promising potential of our system to convert excess COD into electricity while increasing removal efficiencies of AnMBRs.
N. Borst
Innovative Diagnostikplattform zum Nachweis antibiotikaresistenter Erreger im Krankenhaus
2017 Innovation Forum Medizintechnik 2017, Tuttlingen, 19.10.2017
N. Borst, S. Wadle, K. Stock, M. Röder, E. Held-Föhn, A. Heiß, U. Götz, F. von Stetten
Innovative Diagnostikplattform zur Zuordnung von Krankenhauskeimen und deren Antibiotikaresistenzen
2017 microTEC Südwest Clusterkonferenz 2017, 27.-28. März 2017, Freiburg
N. Borst, M. Specht, M. Schulz, N. Paust, J. Li, S. Wadle, U. Götz, E. Held-Föhn, A. Heiß, F. Hausladen, R. Mader, K. Stock, M. Röder, A. Serr, G. Häcker, R. Zengerle, F. von Stetten
Integriertes System zur simultanen Detektion von Krankenhauskeimen und deren Antibiotikaresistenzen auf Einzelzellebene
2017 MST Kongress, München, 23. - 25.10.2017
KurzfassungBei Krankenhausinfektionen mit mehreren beteiligten Erregern ist die Zuordnung von Antibiotikaresistenzen zu den Erregern besonders wichtig um eine spezifische Therapie zu ermöglichen. Ein Projektkonsortium aus 6 Instituten der Innovationsallianz Baden Württemberg entwickelt im Projekt IDAK ein integriertes System das es künftig ermöglichen soll auf Einzelzellebene simultan die Spezies und die Resistenz aller Erreger in einer Probe zu bestimmen. Wir berichten von den aktuellen Forschungsarbeiten und ersten Ergebnissen. Diese umfassen: Entwicklung eines mikrofluidischen Testträgers zur Integration aller Prozessschritte; Überführung einzelner Bakterien eines Nasalabstriches in Tröpfchen; Bakterienlyse; digitaler multiplex-DNA Nachweis auf Basis einer isothermen Amplifikation; Multispektrale Fluoreszenzdetektion der Genotypen.
J.M. Stosch, A. Heumüller, S. Bleul, C. Niemöller, M. Rothenberg-Thurley, N. Renz, J. Riba, K. Szarc vel Szic, D. Pfeifer, S. Zimmermann, J. Duyster, M. Lübbert, J. Wehrle, K.H. Metzeler, R. Claus, H. Becker
MDS progression to AML associates with acquisition of single driver mutations with consequent changes in clonal architecture and occurrence of multiple clones with mutations in identical clones
2017 DGHO, Stuttgart 29.09. – 03.10. 2017
KurzfassungDevelopment of acute myeloid leukemia (AML) from myelodysplastic syndromes (MDS) associates with acquisition of genetic aberrations. Here, we studied serial samples of patients with MDS and subsequent AML in order to decipher changes in the mutation profiles and clonal evolution.
S. Vierrath, M. Breitwieser, C. Klose, M. Klingele, S. Thiele
Novel approaches to tailor the PEM|electrode interface for fuel cells with increased power density
2017 7th Bonn Humboldt Award Winners’ Forum “Fundamental Concepts and Principles of Chemical Energy Conversion” Bonn, 11 - 15 October 2017
A. B. Rodríguez-Martínez, N. Borst, E. Sarasola-Díez, M. Agirregabiria, J. M. Ruano-López, T. Codd, K. R. Ward, J. Bekacz, M. Gaboyard, M. J. García-Barcina
Novel ddPCR approach for NIPT rhesus genotyping
2017 European Human Genetics Conference, May 27–30, 2017, Copenhagen / Dänemark
J. Stosch, A. Heumüller, S. Bleul, C. Niemöller, M. Rothenberg-Thurley, N. Renz, J. Riba, K. Szarc vel Szic, D. Pfeifer, A. Nieters, S. Zimmermann, J. Duyster, M. Lübbert, J. Wehrle, K. Metzeler, R. Claus, H. Becker
Progression of MDS to AML features gain of single driver mutations with consequent changes in clonal composition and occurence of multiple clones with mutations in identical genes
2017 European Hematology Association (EHA), Madrid/Spain, 22.-25.06.2017
KurzfassungMutations in MDS are few in number, but enriched in genes involved in RNA-splicing or epigenetic regulation; gain of single driver mutations leads to clonal outgrowth and thus, AML. Subsequent treatment can change the mutational and clonal profile. Mutations in identical genes occur in different clones, as confirmed by single-cell analyses; this suggests a fertile ground (e.g. microenvironment) for such mutations in a patient and may lead to (a therapeutically exploitable) competition of clones.
S. Burger, J. Schemberg, T. Förster, M. Specht, M. Rombach, N. Paust, R. Zengerle, M. Karle
Separation of low-abundance cells as an App on standard laboratory centrifuge
2017 MicroTAS 2017, Savannah /USA, 22.-26.10.2017
KurzfassungA novel centrifugal microfluidic cell separation module is presented to extract target cells (KG-1) from buffy coat using antibody coated microbeads. All structures required for the target cell separation are monolithically integrated in the microfluidic cartridge including mixing under constant rotation using oxygen bubbles. Thus, the microfluidic cartridge processing can be done on a standard laboratory centrifuge lowering the monetary investment for the user. The entire process chain of the module is completed within 26 minutes and recovers approximately 90 % of the lympathic cells in the sample while only requiring few manual pipetting steps.
J. Madjarov, N.P. Kocatürk-Schumacher, S. Abdu, S. Kerzenmacher
Simultaneous use of a microbial anode as membrane filter shows high current densities and COD removal with synthetic brewery wastewater
2017 ISMET 6 2017, Lissabon / Portugal, 3. - 6.10.2017
KurzfassungWe report on a novel concept for the integration of bioelectrochemical systems into anaerobic membrane bioreactors (AnMBRs). By operating a conductive filtration membrane simultaneously as microbial anode, the significant COD degradation across the filtration membrane can be converted directly into electricity. In experiments conducted with a 0.1 μm stainless steel membrane using Geobacter sulfurreducens in an acetate containing medium, current densities of 6 A m-2 and a permeate flow rate of 9 L m-2 h-1 have been reached after 18 days. During this period, COD degradation up to 200 mg L-1 across the membrane was achieved. In ongoing experiments, the system is being tested with synthetic brewery wastewater and sewage sludge, yielding similar current densities in the range of 5 A m-2, but achieving higher COD degradation of up to 450 mg L-1 across the membrane. This demonstrates the promising potential of our system to convert excess COD into electricity while increasing removal efficiencies of AnMBRs.
S. Kartmann, F. Koch, R. Zengerle, P. Koltay, A. Ernst
Single-use flow sensor based on the differential pressure principle employing the radial expansion of a low-cost silicone tube
2017 Transducers 2017, Kaohsiung/Taiwan, 18. – 22.06.2017
KurzfassungFor the first time, we present a flow sensor consisting of low-cost consumable parts, to minimize the risk of cross-contamination in medical applications, for example. For our sensor, the consumable component consists of two simple silicone tubes and a capillary, which can be exchanged easily and cost-effectively after use. We characterized the flow sensor in the range from 0 up to 50 μL/s. The sensor showed a good consistency with the reference sensor, a linear correlation coefficient of minimal R(x,y) = 0.98 and a sensor resolution of 0.4 μL/s.
M. Breitwieser, M. Klingele, S. Vierrath, R. Zengerle, S. Thiele
Tailoring the membrane-electrode interface: A review and perspective of novel engineering approaches
2017 Fuel Cells | Workshop EMEA 2017, Bad Zwischenahn, 26. - 28.06.2017
KurzfassungThe interface between the catalyst layer (CL) and the polymer electrolyte membrane (PEM) in a fuel cell has significant impact onto its electrochemical performance. In consequence, in the past years there have been growing research activities to engineer this interface in order to improve the performance of polymer electrolyte membrane fuel cells (PEMFCs). This talk summarizes these approaches and compares the various techniques. Based on the available fuel cell data in literature we provide a quantitative comparison of relative improvements caused by specially 3D-engineered PEM|CL interfaces. This allows to draw several conclusions: We show that the similar improvements of relevant electrochemical properties such as improved high and low frequency resistances as well as higher peak power density can be achieved by 3D PEM|CL interface engineering techniques. As an example, regardless if patterned membrane surfaces, ionomer gradients in the catalyst layer or direct membrane deposition techniques are used, comparable improvements of the fuel cell characteristics were reported. Second, for patterned membranes surfaces it was found that feature sizes of about 1-10 µm on the membrane surface seem to result in the most significant power density improvement. Finally it is shown that a re-engineered PEM│CL interface can also contribute to extend the durability of the MEA due to enhanced adhesion and contact between both functional layers.
M. Breitwieser, M. Klingele, C. Klose, S. Vierrath, R. Zengerle, S. Thiele
Tailoring the membrane/electrode interface - novel engineering approaches
2017 EMEA Conference, Bad Zwischenahn, 26. - 28.06.2017
S. Hin, B. Lopez-Jimena, M. Bakheit, V. Klein, S. Stack, C. Fall, A. Sall, K. Enan, S. Frischmann, L. Gillies, M. Weidmann, S. Goethel, V. Rusu, O. Strohmeier, N. Paust, R. Zengerle, K. Mitsakakis
The FeverDisk: Multiplex detection of fever-causing pathogens for rapid diagnosis of tropical diseases
2017 MicroTAS 2017, Savannah /USA, 22.-26.10.2017
KurzfassungWe report the successful implementation of twelve assays for detecting a diverse panel of fever-causing pathogens based on a centrifugal microfluidic LabDisk platform (FeverDisk). The target panel was selected to diagnose tropical regions’ most prevalent endemic and epidemic fever-causing diseases. The FeverDisk was used by local scientific staff in two clinical settings (Dakar, Senegal & Khartoum, Sudan). It was able to detect single and double infections from real patient samples in less than 2 h without any user intervention. The FeverDisk may provide an important solution for differential diagnosis in cases of fever of unknown origin thus improving accurate diagnostics and reducing the burden of pathogen drug resistance.
M. Rombach, M. Keller, N. Paust, F. von Stetten, D. Mark, R. Zengerle, M. Karle
The LabCard – A new approach for centrifugal assay automation
2017 MST Kongress, München, 23. - 25.10.2017
KurzfassungWe present the LabCard, a new centrifugal microfluidic approach for simultaneous processing of multiple test carriers by arranging them in the vertical plane. As a proof-of-concept, we fluidically integrated an assay for isothermal nucleic acid analyses of respiratory pathogens with the microfluidic network comprising unit operations and processing chains[1] for thermal lysis of a patient sample (25–75 μL), release of pre-stored reagents, mixing of reagents, aliquoting and distribution into amplification wells, which was successfully demonstrated in 5/5 runs with an overall fluidic processing time of 10 min.
J. Erben, S. Kerzenmacher
The effect of oxygen traces on the current production of high performance electrospun anode materials for application with Shewanella oneidensis MR-1
2017 ISMET 6 2017, Lissabon / Portugal, 3. - 6.10.2017
KurzfassungShewanella oneidensis MR-1 is a well-studied electroactive model organism that can serve as chassis for production strains for, i.e., unbalanced fermentation (Flynn et al., mBio 1 (2010), e00190-10). To minimize unwanted side reactions, which would decrease production yields, strict anaerobic conditions are required. Under such strict anaerobic conditions (also indicated by absence of flavin production and planktonic cell growth in the bioreactor), high performance electrospun anode materials can yield up to 205 μA/cm2 at 200 mV vs. NHE, which is about 12 and 70 times higher than the commercial activated carbon cloth (C-Tex 13, MAST Carbon) and graphite felt (GFD 2, SGL Carbon), respectively. The average current production over the course of 2 weeks is up to 13-fold higher with respect to C-Tex 13 and about 150 times higher with respect to GFD 2. However, even traces of oxygen (<0.02% oxygen saturation) in a bioreactor, which can evolve from improper material of the N2 tubing (i.e. polyurethane), affect the current production drastically. With small traces of oxygen present, the currents increase for all tested materials, and with time the current production of the different materials converge. This is reflected in the average current production of the electrospun material being only 3-fold higher than with respect to C-Tex 13 and 6-fold higher with respect to GFD 2. In summary, our results highlight the importance of well controlled oxygen levels in order to accurately evaluate the performance of anode materials for Shewanella oneidensis MR-1. Furthermore, we can demonstrate that under the strict anaerobic conditions required for high yield bioproduction electrospun anode materials exhibit an order of magnitude better performance compared to commercial carbon materials.
F. Hegge, S. Vierrath, S. Ogawa, L. Zielke, M. Bühler, C. Klose, S. Litster, S. Thiele
Tomography Aided Development of Membrane Electrode Assemblies for PEM Water Electrolysis
2017 ECS Meeting, New Orleans/USA, 28.05. – 02.06.2017
KurzfassungIn polymer electrolyte membrane water electrolysis (PEMWE) the anode is crucial for the overall performance. State-of-the-art anodes comprise Ir, IrOx or IrRuOx, typically bound by an ionomer and can be TiOx supported [1]. Besides the material also the microstructure of the anode has an impact on the electrolyzer’s performance as it determines catalyst accessibility and species transport [2]. Optimizing the microstructure therefore offers a potential to increase cell efficiency. In our approach we use tomographic methods in order to establish a microstructure-performance relation for PEMWE anodes (see microstructure of a FuelCellsEtc PEMWE anode in Fig.1). We then apply our findings from the reconstructed anodes in order to develop improved membrane electrode assemblies (MEAs) for PEMWEs with novel manufacturing and design approaches. The experimental data will then be used as input for our theoretical models.
S. Hin, M. Loskyll, V. Klein, M. Keller, O. Strohmeier, F. von Stetten, R.Zengerle, K. Mitsakakis
User-friendly membrane-based sample inlet for the centrifugal microfluidic LabDisk platform
2017 MNE 2017, Braga / Portugal, 18. - 22.09.2017
KurzfassungWe present a sample inlet for whole blood consisting of a plasma separation membrane placed into the inlet chamber of a centrifugal-microfluidic LabDisk to take up the sample via capillary forces. This approach offers advantages regarding several aspects: • Compatibility with a vast range of blood transfer device • Safe, well-controlled and easy application of blood sample without the danger of spilling • Combination of sample inlet with state-of-the art plasma separation leading to reduced footprint of the cartridge
F. Koch, S. Kartmann, R. Zengerle, A. Ernst, P. Koltay
Viscosity determination by the in-line measurement of liquid flow time through a cylindrical tube
2017 MFHS, Twente / The Netherlands, 04. - 06.10.2017
KurzfassungThis paper demonstrates a novel in-line viscosity measurement concept, with reduced effort compared to common approaches. It determines the transition-time of a liquid/gas front to fill a well-defined capillary. In contrast to previous work [1] this paper measures the transition-time for the first time in a non-contact capacitive way. The method enables to determine the dynamic viscosity with a mean coefficient of variation (CV) of 8.4% for a measuring range between 1 and 20 mPa s and showed to be valuable as a fast viscosity calibration for flow sensors using the differential pressure principle.

2016

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D. Kosse, M. Keller, J. Obele, M. Specht, D. Baumann, P. Beckert, S. Feuerriegel, G. Roth, S. Niemann, R. Zengerle, D. Mark
Scalability of microthermoforming for Lab-on-a-Chip cartridges by the example of rapid diagnosis of antibiotic resistant tuberculosis
2016 20th International Conference on Miniaturized Systems for Chemistry and Life Sciences, µTAS 2016, Dublin / Irland, 09. – 13.10.2016
J. Danzer, A. Götze, S. Abdu, S. Kerzenmacher
A new concept for the integration of microbial fuel cells into membrane bioreactors
2016 The 13th IWA Leading Edge Conference on Water and Wastewater Technologies, Jerez de la Frontera, Spain, June 13, 2016
KurzfassungMicrobial fuel cells (MFC) are a promising new technology to directly convert wastewater’s chemically stored energy into electrical energy. Our work shows that a conductive membrane filter can simultaneously be used as anode of a MFC so that part of the needed energy for the filtration unit of a membrane bioreactor (MBR) can be supplied by the MFC.
S. Hin, N. Paust, M. Keller, O. Strohmeier, R. Zengerle, K. Mitsakakis
A novel approach for dead-volume-free rehydration and mixing of dry pre-stored reagents in non-terminal chambers on centrifugal microfluidic platforms
2016 20th International Conference on Miniaturized Systems for Chemistry and Life Sciences, µTAS 2016, Dublin / Irland, 09. – 13.10.2016
S. Hoda Moosavi, M. Kroener, M. Frei, F. Frick, S. Kerzenmacher, P. Woias
A thin silicon thermoelectric nanowire characterization platform (TNCP) equipped with nanoporous electrodes for electrical contact formation
2016 27th Micromechanics and Microsystems Europe (MME) workshop 28.-30.08.2016 Cork, Irland Journal of Physics: Conference Series, Band: 757
T. Gleichmann, B. Hamouda, L. Gutzweiler, M. A. Graewert, R. Zengerle, P. Koltay, L. Riegger
Analytical protein affinity chromatography in nl volumes in on-demand written liquid lines
2016 20th International Conference on Miniaturized Systems for Chemistry and Life Sciences, µTAS 2016, Dublin / Irland, 09. – 13.10.2016
J. Vontas, K. Mitsakakis, R. Zengerle, D. Yewhalaw, C. H. Sikaala, J. Etang, M. Fallani, B. Carman, P. Müller, M. Chouaïbou, M. Coleman
Automated innovative diagnostic, data management and communication tool, for improving malaria vector control in endemic settings
2016 pHealth 2016, 13th International Conference on Wearable, Micro & Nano Technologies for Personalized Health, 29-31 May, Heraklion, Crete, Greece Studies in Health Technology and Informatics, Band: 224, Seiten: 54 - 60
KurzfassungMalaria is a life-threatening disease that caused more than 400,000 deaths in sub-Saharan Africa in 2015. Mass prevention of the disease is best achieved by vector control which heavily relies on the use of insecticides. Monitoring mosquito vector populations is an integral component of control programs and a prerequisite for effective interventions. Several individual methods are used for this task; however, there are obstacles to their uptake, as well as challenges in organizing, interpreting and communicating vector population data. The Horizon 2020 project “DMC-MALVEC” consortium will develop a fully integrated and automated multiplex vector-diagnostic platform (LabDisk) for characterizing mosquito populations in terms of species composition, Plasmodium infections and biochemical insecticide resistance markers. The LabDisk will be interfaced with a Disease Data Management System (DDMS), a custom made data management software which will collate and manage data from routine entomological monitoring activities providing information in a timely fashion based on user needs and in a standardized way. The ResistanceSim, a serious game, a modern ICT platform that uses interactive ways of communicating guidelines and exemplifying good practices of optimal use of interventions in the health sector will also be a key element. The use of the tool will teach operational end users the value of quality data (relevant, timely and accurate) to make informed decisions. The integrated system (LabDisk, DDMS & ResistanceSim) will be evaluated in four malaria endemic countries, representative of the vector control challenges in sub-Saharan Africa, (Cameroon, Ivory Coast, Ethiopia and Zambia), highly representative of malaria settings with different levels of endemicity and vector control challenges, to support informed decision-making in vector control and disease management.
K. Mitsakakis, F. Stumpf, O. Strohmeier, V. Klein, D. Mark, F. von Stetten, J. R. Peham, C. Herz, P.N. Tawakoli, F. Wegehaupt, T. Attin, N. Bostanci, K. Bao, G.N. Belibasakis, J.P. Hays, G. Elshout, R.C. Huisman, S. Klein, A.P. Stubbs, L. Doms, A. Wolf, V. Rusu, S. Goethel, T. Binsl, A. Michie, J. Jancovicova, V. Kolar, M. Kostka, J. Smutny, M. Karpisek, C. Estephan, C. Cocaud, R. Zengerle
Chair/bedside diagnosis of oral and respiratory tract infections, and identification of antibiotic resistances for personalised monitoring and treatment
2016 pHealth 2016, 13th International Conference on Wearable, Micro & Nano Technologies for Personalized Health, 29-31 May, FORTH, Heraklion, Crete, Greece Studies in Health Technology and Informatics, Band: 224, Seiten: 61 - 66
KurzfassungGlobal healthcare systems are struggling with the enormous burden associated with infectious diseases, as well as the incessant rise of antimicrobial resistance. In order to adequately address these issues, there is an urgent need for rapid and accurate infectious disease diagnostics. The H2020 project DIAGORAS aims at diagnosing oral and respiratory tract infections using a fully integrated, automated and user-friendly platform for physicians’ offices, schools, elderly care units, community settings, etc. Oral diseases (periodontitis, dental caries) will be detected via multiplexed, quantitative analysis of salivary markers (bacterial DNA and host response proteins) for early prevention and personalised monitoring. Respiratory Tract Infections will be diagnosed by means of DNA/RNA differentiation so as to identify their bacterial or viral nature. Together with antibiotic resistance screening on the same platform, a more efficient treatment management is expected at the point-of-care. At the heart of DIAGORAS lies a centrifugal microfluidic platform (LabDisk and associated processing device) integrating all components and assays for a fully automated analysis. The project involves an interface with a clinical algorithm for the comprehensive presentation of results to end-users, thereby increasing the platform’s clinical utility. DIAGORAS’ performance will be validated at clinical settings and compared with gold standards.
M. Clemenz, M. Kegel, S. Herrlich, S. da Luz, J. Kalla, S. Baumeister, M. Trächtler, R. Zengerle
Dermaject - A Novel, Convenient Intradermal Injection Device for Highly Precise, Safe, Standardized and Reproducible Intracutaneous Injections of Small and Larger Volumes with Guided Needle Insertion Mechanism Mimicking the Mantoux Method and with Protection Against Needlestick Injuries
2016 14th CIMT Annual Meeting 2016, May 10-12, Mainz
KurzfassungWe present Dermaject, a novel, convenient intradermal injection device suitable for injection of liquid drugs into the top layer of the skin (intradermal route) and for drug targeting of the skin, immune and lymphatic system. The newly developed and patented cannula insertion mechanism in combination with microneedle technology enables easy, safe, precise, fast, standardized, reproducible and leakproof intradermal injections of larger than previously injectable volumes.
F. Schuler, C. Siber, S. Hin, S. Wadle, N. Paust, R. Zengerle, F. von Stetten
Digital droplet loop-mediated isothermal amplification (ddLAMP) on a microscope slide
2016 Biosensors 2016, Goeteborg, 25. - 27.05.2016
M. Breitwieser, M. Klingele, C. Klose, S. Vierrath, K. Holdcroft, S. M. Lyth, T. Bayer, B. Britton, S. Holdcroft, R. Zengerle, S. Thiele
Direct membrane deposition (DMD): How to fabricate a high power DMD fuel cell in your lab
2016 Gordon’s Research Conference on Fuel Cells, Stonehill College (USA), 07. - 12.08.2016
M. Breitwieser, M. Klingele, S. Vierrath, R. Zengerle, S. Thiele
Direkte Membrandeposition und 3D-Rekonstruktion elektro-chemischer Systeme: Aktivitäten der Porous Media Group
2016 Fuel Cell Workshop Duisburg: „9. Workshop AiF-Brennstoffzellenallianz 2016“, Zentrum für Brennstoffzellentechnik Duisburg, 21. Juni 2016
C. Klose, M. Breitwieser, M. Klingele, S. Vierrath, H. Cho, J. Kerres, R. Zengerle, S. Thiele
Enhancing the ionic conductivity of directly deposited sulfonated poly(ether ketone)-Nafion composite membranes
2016 Gordon’s Research Conference on Fuel Cells, Stonehill College (USA), 07.-12.08.2016.
S. Zimmermann, J. Schoendube, A. Gross, B. Steimle, T. Christmann, B. Werdelmann, P. Koltay, M. Pirsch
Establishing clonal cell lines by single-cell printing and cell imaging
2016 Cell Line Development & Engineering, Wien (AU), 11. - 13.04.2016
KurzfassungThe proof of monoclonality is a regulatory requirement for the development of clonal cell lines for biopharmaceutical production. Here we describe a complementary approach based on a single-cell printer (SCP, cytena GmbH) and a NyONE cell imager (SynenTec GmbH) to produce truly monoclonal cell lines derived from CHO-K1 cell progenitors with high efficiencies.
M. Kokko, V. Vazhnik, S. Kerzenmacher
Granular activated carbon improves current densities and COD removal at microbial anodes treating industrial wastewater
2016 The 13th IWA Leading Edge Conference on Water and Wastewater Technologies, Jerez de la Frontera, Spain, June 13, 2016
KurzfassungFor microbial electrochemical systems to be feasible, the anodic current densities with real wastewaters need to be increased. One approach for achieving higher current densities is to use fluidized granular activated carbon (GAC) at the anode. In this study, current densities from real industrial wastewater were increased at the highest by 2.3-fold by adding GAC particles to the anode compartment.
M. Frei, L. Dietel, F. Wiedenmann, Ch. Köhler, S. Kerzenmacher
Highly Porous Electro-Deposited Pt-Ru, Pt-Pd, and Pt-Au Electrodes for the Electro-Oxidation of Methanol, Formic Acid, and Glucose
2016 19th Topical Meeting of the ISE, Auckland, New Zealand, 17. – 20.04.2016
KurzfassungWe present an electro-deposition process for the fabrication of highly porous Pt-Ru, Pt-Pd and Pt-Au electrodes. The process is based on our previous works where Pt and Cu have been co-deposited from an aqueous electrolyte. Upon subsequent selective Cu dissolution at an oxidative potential a highly porous Pt electrode can be obtained [1, 2]. In the present work, a second noble metal was added to the electrolyte. The specific surface area and the electrochemical properties of various combinations of platinum and a second noble metal are compared for their applicability in methanol, formic acid and glucose fuel cells. We can show that the combination of two metals can enhance the electro-oxidation properties of the electrode. In contrast to the previous work [2], an electrolyte containing also a second noble metal (Ru, Pd, or Au) in addition to platinum and copper was used for electrode fabrication. The molar ratios of the metals in the Pt-Pd and Pt-Au electrolytes were 4:1, 1:1, and 1:4; for Pt-Ru electrolytes ratios of 1:1, 1:10, and 1:20 were used. To yield mechanically stable deposits, only 600 instead of 1200 deposition pulses were applied. Despite the same number of deposition pulses, the electrode roughness factors (RF, ratio between specific and geometrical area) vary from about 500 (Pt-Ru(1:20)) to 4700 (Pt-Pd(4:1)). For comparison, the previous state-of-the-art platinum electrodes (1200 pulses) yielded RFs of 6500 ± 700 [2]. The concentration of the second noble metal in the electrolyte has a distinct influence on microstructure, as shown exemplarily for Pt-Au in Fig. 1. Energy-dispersive X-ray spectroscopy reveals that the ratio of the metals in the electrolyte does not correspond to the ratio of the metals deposited on the electrode. Regarding the electro-oxidation of methanol, Pt-Ru(1:1) electrodes exhibit current densities of 11 ± 2 mA/cm2 at a potential of 355 mV vs SCE after 30 min. The other Pt-Ru electrodes show lower current densities in the same range as the various Pt-Pd and Pt-Au electrodes. In formic acid, all of the Pt-Pd electrodes and Pt-Ru(1:1) reach more than 30 mA/cm2 at 400 mV vs SCE after 30 min. The other Pt- Ru and all of the Pt-Au electrodes exhibit only between 8 and 24 mA/cm2. Since glucose oxidation anodes are subject to significant poisoning, their long-term performance at -200 mV vs SCE has been evaluated after 8 days of continuous operation in phosphate buffered saline containing 3 mM glucose. Here, the Pt-Au(1:4) electrodes with a RF of 2904 ± 627 show 16 ± 14 µA/cm2. This value corresponds to the previous state-of-the-art electrode with a much higher RF of 6500 ±700 [2]. It is therefore expected, that Pt-Au(1:4) electrodes with increased RF will show better performance. However, these electrodes also exhibit a large variation, presumably due to a not yet well controlled parameter in the fabrication process. Future work will thus be focused to optimize the fabrication process and also to yield mechanically stable electrodes with increased specific surface area.
J. Madjarov, F. Wiedenmann, J. Erben, A. Götze, S. Kerzenmacher
How the uncompensated resistance and double layer capacitance can influence your polarization data
2016 The 3rd European Meeting of the International Society for Microbial Electrochemistry and Technology, Rome (Italy), 26-28 September 2016
X. Wu, N. Schneider, R. Zengerle, M. Meier
Human Adipose-Derived Stems Cell Differentiation And Lipid Analysis Under Controlled Microenvironment On Chip
2016 20th International Conference on Miniaturized Systems for Chemistry and Life Sciences, µTAS 2016, Dublin / Irland, 09. – 13.10.2016
M. Frei, M. Bühler, J. Erben, S. Kerzenmacher
Improved platinum anodes for the operation of implantable glucose fuel cells in real physiological fluids
2016 XLIII Annual Congress of the European Society for Artificial Organs, 14.-17.08.2016, Warschau, Polen
S. Hin, M. Loskyll, V. Klein, O. Strohmeier, F. von Stetten, R. Zengerle, K. Mitsakakis
Membrane-based sample inlet for pathogen-containing whole blood on a centrifugal microfluidic platform (LabDisk)
2016 Biosensors 2016, Goeteborg, 25. - 27.05.2016
M. Frei, J. Erben, J. Martin, S. Kerzenmacher
Neue Platinanoden für implantierbare Glukosebrennstoffzellen ermöglichen technisch nutzbare Stromdichten in Serum
2016 1. Jahrestagung der Fachgruppe Chemie und Energie 6. – 7. Oktober 2016 · Jena
KurzfassungImplantierbare Glukosebrennstoffzellen auf Basis von Platinelektroden sind ein vielversprechender Ansatz zur batterieunabhängigen Elektrizitätsversorgung medizinischer Implantate [1,2]. Durch die dauerhafte Verfügbarkeit von Blutzucker und Sauerstoff aus der Körperflüssigkeit ist die Lebensdauer dieser Systeme theoretisch unbegrenzt. In der Praxis wird jedoch die katalytische Aktivität der zur Glukoseoxidation verwendeten Platinanode durch die Adsorption körpereigener Aminosäuren drastisch herabgesetzt. Entsprechend ist die Lebensdauer dieser Brennstoffzellen bislang auf wenige Tage beschränkt [3,4]. Ein Verbesserungsansatz ist die massive Erhöhung der für die Glukoseoxidation zur Verfügung stehenden Reaktionsoberfläche der Platinanode. Dazu verwenden wir elektrogesponnene Kohlenstoffnanofasern als Substrat für die galvanische Abscheidung [5] hochporöser Platinanoden. Mit diesem neuen Ansatz können Platinanoden mit einem im Vergleich zu den bisherigen Anoden [4] nahezu 3-fach erhöhten Rauhigkeitsfaktor (RF; Verhältnis von tatsächlicher Oberfläche zu geometrischer Grundfläche der Elektrode) von 15440 ± 2160 hergestellt werden. Die neuen Anoden wurden über einen Zeitraum von 15 Tagen kontinuierlich bei einem für die Anwendung typischen Potential von -200 mV vs. SCE in Blutserum (Pferde-serum) betrieben. Dabei wurde im Vergleich zu den bisher verwendeten Anoden [4] eine sechsfach höhere stabile Stromdichte von (8.5 ± 1.7) μA/cm2 erreicht. Unsere Ergebnisse zeigen somit, dass mit den neuen Platinanoden in Serum technisch nutzbare Stromdichten erreicht werden können. In Verbindung mit einer bei 0 mV vs. SCE betriebenen Platinkathode ergäbe sich daraus theoretisch bereits eine Leistungsdichte von etwa 2 μW/cm² – ausreichend, um medizinische Implantate wie z. B. Herzschrittmacher oder Vitalsensoren batterielos zu betreiben. Bislang ungeklärt ist der Grund für die verbesserte Leistungsfähigkeit der neuen Platinanoden, die sich nicht allein durch deren erhöhte spezifische Oberfläche erklären lässt. Hier kommen sowohl eine verbesserte katalytische Aktivität hinsichtlich der Oxidation von Glukose und den Bestandteilen der Körperflüssigkeit als auch eine verringerte Adsorption vergiftender Substanzen in Betracht.
L. Gutzweiler, T. Gleichmann, P. Koltay, R. Zengerle, L. Riegger
Open Microfluidics for Lab-on-a-Chip Applications
2016 2016 International Conference of Microfluidics, Nanofluidics and Lab-on-a--Chip, Dalian/China, June 10-12, 2016
KurzfassungIn this work we introduce bioanalytical applications previously realized on lab-on-chip devices that have been successfully transferred to the field of open microfluidics (OM). Open microfluidic systems are microfluidic networks on planar substrates without being enclosed by solid interfaces and thus not having rigid boundaries [1]. Applications in open microfluidic systems can be conducted on-demand with often less amounts of reagents required. Furthermore, time consuming & cost intensive fabrication of microchips can be omitted using planar low-cost polymer substrates. In this work, we present DNA and protein electrophoresis as well as microbatch protein crystallization in an open microfluidic environment.
I. Schwarz, D. Kosse, F. Schwemmer, R. Zengerle, N. Paust
Parallel robust hydraulic resistance aliquoting for equal reaction conditions on the centrifugal microfluidic platform
2016 20th International Conference on Miniaturized Systems for Chemistry and Life Sciences, µTAS 2016, Dublin / Irland, 09. – 13.10.2016
T. van Oordt, O. Strohmeier, K. Mitsakakis, S. Hin, R. Zengerle, F. von Stetten
Point-of-Need Detection of Biological Threats
2016 15th MEDICAL BIODEFENSE CONFERENCE, Munich, 26 - 29 April 2016 , Band: JP20, Seite: 58
KurzfassungThe state-of-the-art for detection of biological threats often requires complex stationary devices and experts, thus, limiting the capability for a fast and efficient response. A novel portable platform , designated "LabDisk" has been developed . The versatile analytical platform allows automated and easy-to-use detection of biological threats at the point-ofneed. lt consists of a centrifugal device and disposable disks for the detection of various toxins and pathogens.
S. Vierrath, M. Breitwieser, M. Klingele, C. Klose, N. Wehkamp, R. Moroni, R. Zengerle, S. Thiele
Polymer Electrolyte Fuel Cells Fabricated with Direct Membrane Deposition (DMD)
2016 Prime 2016, Honolulu / Hawaii, 2-7 October 2016
S. Vierrath, M. Breitwieser, M. Klingele, R. Zengerle, S. Thiele
Reasons for the High Power Density of Direct Membrane Deposition Fuel Cells Revealed by Impedance Spectroscopy
2016 MODVAL 13, Symposium for Fuel Cell and Battery Modeling and Experimental Validation, Lausanne, Schweiz (22.-23.03.2016) , Seite: 145
KurzfassungKlingele et al. showed never reached high power fuel cells by applying direct membrane deposition (DMD), excelling the peak power of a catalyst coated membrane (CCM) by a factor of 2.3. [1] To understand the underlying reasons for their high power, we identify the reasons and quantify their impact by employing electrochemical impedance spectroscopy. As a result we show, that the main reasons for the high power of DMD fuel cells are (i) a 50% reduced high frequency resistance (26 mΩcm²) due to a thinner membrane (12µm) compared to state-of-the-art and (ii) a factor 2.2 reduced mass transport losses (0.12 Ωcm²) due to increased water back diffusion through the thin membrane (Figure 1a). A comparison of DMD vs. CCM fuel cells at the maximum power point of the CCM shows that 91% of the DMD’s improvement can be attributed to reduced mass transport losses and only 9% are caused by the reduction of the ohmic resistances (Figure 1b).
C. Klose, M. Breitwieser, M. Klingele, S. Vierrath, H. Cho, J. Kerres, R. Zengerle, S. Thiele
Simple fuel cell membrane fabrication by direct electrospinning and inkjet-printing
2016 ELEN (Electrospinning for Energy), Montpellier (France), 22. - 24.06.2016
J. Riba, J.C. Niemöller, J. Schoendube, A. Gross, S. Bleul, R. Claus, J. Duyster, H. Becker, P. Koltay, R. Zengerle, S. Zimmermann
Single-Cell Printing for the genomic analysis of eukaryotic and prokaryotic cells
2016 Single Cell Biology, Hinxton, UK, 8-10 March 2016
KurzfassungSingle-cell genomics emerged as a promising tool to analyze the heterogeneity of complex cell populations by characterizing the genome of each individual cell. Prerequisite for precise single-cell genomic analysis is an efficient cell isolation. Conventional isolation workflows or instruments are often not able to isolate both eukaryotic and prokaryotic cells or require complex and cost-intensive devices. We previously demonstrated that the Single-Cell Printer (SCP) allows for isolating and depositing individual mammalian cells with high viability rates for monoclonal culturing. Similar to an inkjet printer, the SCP uses a piezo-driven dispenser chip to generate free-flying micro-droplets. A camera system coupled with computer-assisted image processing enables the detection of cells in the chip nozzle and the printing of droplets containing exactly one cell. Here, we demonstrate an advanced SCP that is capable of isolating individual eukaryotic and prokaryotic cells down to 1 µm in size for subsequent single-cell genomic analysis. Using a commercially available whole-genome amplification (WGA) kit (Qiagen REPLI-gTM) with reduced reaction volumes, the genomes of 25 individually printed mammalian cancer cells (U2OS osteosarcoma cell line) were amplified with 100 % success rate as quantified with a QubitTM assay. Eight representative WGA samples were analyzed by Sanger sequencing revealing the U2OS-specific mutations in the SLC34A2 (c.1538G>T) and TET2 (c.1394C>T) genes. We further amplified the genome of 14 individual bacteria cells (E.coli and E.faecalis) with 93 % success rate. Finally, we sequenced part of the 16S rRNA gene of individual bacteria cells enabling the successful taxonomic classification on a phylum level. In conclusion, we show that the SCP allows for efficient and highly automated single-cell deposition of both eukaryotic and prokaryotic cells. Furthermore, the data demonstrate the applicability of the SCP for the analysis of genetic aberrations in single cancer cells at the base pair level and for 16S rRNA-based taxonomic classification of individual microorganisms.
M. Rombach, M. Keller, N. Paust, F. von Stetten, D. Mark, R. Zengerle, M. Karle
The LabCard – A new approach for centrifugal assay automation”
2016 20th International Conference on Miniaturized Systems for Chemistry and Life Sciences, µTAS 2016, Dublin / Irland, 09. – 13.10.2016
L. Zielke, A. Fallisch, M. Zedda, R. Zengerle, S. Thiele
Tomographic Screening of Flow Field Current Collectors for Water Electrolysis
2016 MODVAL 13, Symposium for Fuel Cell and Battery Modeling and Experimental Validation, Lausanne, Schweiz (22.-23.03.2016) , Seite: 55
KurzfassungFor the production of pure hydrogen, PEM electrolysis is suited.1 Water splitting at room temperature demands at least 1.48 V of thermoneutral voltage.2 In our system this is facilitated by a combination of a light focusing Fresnel lens and a III-V tandem solar cell, providing the electrolyser with voltages of >2V. A key component in our system is the porous titanium mesh, which functions both as a current collector and a flow field (FF/CC).3 In order to maximize the performance of the system and simultaneously minimize the costs, a suited candidate must be found. In this study we present simple yet important transport parameters of multiple candidates and show correlations between these transport parameters. The hydraulic resistance, calculated in our 3D X-ray reconstruction, will also be validated by a simple flow experiment. Figure

2015

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J. Riba, T. Gleichmann, P. Koltay, R. Zengerle, S. Zimmermann
A new tool for label-free isolation and deposition of single bacteria cells
2015 New Approaches and Concepts in Microbiology, EMBL Heidelberg, Germany, 11.-14. October 2015
KurzfassungIncreasing interest in single-cell analysis throughout life sciences and industry has aroused demand for technologies to separate and handle individual cells. We previously demonstrated that the Single-Cell Printer (SCP) can be used to sort and deposit single mammalian cells onto various substrates for subsequent monoclonal culturing and single-cell genomics. The SCP exploits drop-on-demand printing and automatic image recognition to print 35-200 pl droplets containing single-cells. Compared to other technologies like FACS systems the SCP can address various substrates with high precision and employs a disposable cartridge to prevent cross-contamination. Here, we present an advanced version of the instrument with high-resolution optical detection that has been developed with the aim to detect and deposit bacterial cells. For the first time, we show label-free deposition of single bacterial cells using the SCP. By printing single-cell arrays of GFP expressing E. coli we found that the single-cell printing efficiency of our first prototype yields 78 %. We further demonstrate that the instrument can be used to separate individual cells from a heterogeneous sample followed by clonal culturing. Therefore, we deposit arrays of 100 individual cells from a mixture of E. faecalis and E. coli directly on agar plates for subsequent incubation overnight. After 10 hours we count on average 66 clearly visible clonal cultures. Using light microscopy we show that the two strains were evenly printed and resulted in clonal colonies. In the future we aim to apply the technology to enable highly automated single-cell genomics for phylogenetic studies of environmental samples and to finger-printing of rare bacterial species from clinical samples via mass spectroscopy.
E. Kipf, D. Morse, T. Messinger, S. Sané, S. Kerzenmacher
An air-breathing enzymatic cathode with extended lifetime by continuous Laccase supply
2015 European Fuel Cell Technology & Applications Conference - Piero Lunghi Conference December 16-18, 2015, Naples, Italy
F. Stumpf, F. Schwemmer, T. Hutzenlaub, O. Strohmeier, F. von Stetten, R. Zengerle, D. Mark
Automated sample-to-answer nucleic acid testing with frequency controlled reagent release from cartridge integrated stickpacks
2015 18th International Conference on Solid-State Sensors, Actuators and Microsystems (Transducers 2015), Anchorage, Alaska, 21. – 25.06.2015 IEEE, Seiten: 743 - 746
KurzfassungFor the first time we demonstrate an automated centrifugal Lab-on-a-Disk system for sample-to-answer point-of-care testing of multiple nucleic acid targets that features pre-storage of all required liquid reagents for nucleic acid extraction as well as primers and probes and magnetic beads. Highly wetting and thus hardly controllable liquid buffers were pre-stored in stickpacks with frequency controlled on-demand reagent release enabling automated addition of binding buffer after sample lysis. The self-contained Lab-on-a-Disk system automates all necessary assay steps for PCR-based pathogen detection: RNA extraction, aliquoting of the RNA and geometrically multiplexed real-time RT-PCR. As a proof-of-principle, we demonstrated detection of as little as 15 plaque forming units (pfu) of RNA bacteriophage MS2 in a 200 µL sample in 3.5 hours.
G. Czilwik, T. van Oordt, F. von Stetten, R. Zengerle, D. Mark
Automation of a magnetic immuno-PCR on a centrifugal point-of-care analyzer
2015 19th International Conference on Miniaturized Systems for Chemistry and Life Sciences October 25-29, 2015, Gyeongju, KOREA
F. Stumpf, F. Schwemmer, T. Hutzenlaub, O. Strohmeier, F. von Stetten, R. Zengerle, D. Mark
Automatisierte Nukleinsäurediagnostik in der LabDisk mittels frequenzgesteuerter Freisetzung vorgelagerter Reagenzien
2015 6. Mikrosystemtechnik Kongress (MST Kongress 2015), Karlsruhe, 26. – 28.10.2015
KurzfassungPräsentiert wird ein neues Verfahren zur automatisierten Sample-to-answer Point-of-Care Diagnostik auf der zentrifugal-mikrofluidischen LabDisk Plattform. Hochbenetzende und fluidisch schwer handhabbare Flüssigreagenzien für die Nukleinsäure-Extraktion werden in Stick-packs vorgelagert und können drehfrequenzgesteuert freigesetzt werden. Magnetische Beads, Primer und Fluoreszenzsonden werden durch Eintrocknung vorgelagert. Die LabDisk Plattform ermöglicht die Automatisierung aller erforderlichen Assayschritte der Pathogendetektion: RNA Extraktion und Aufreinigung, Aliquotieren der RNA sowie multiplex real-time RT-PCR. 15 PFU (plaque forming units) RNA-phage MS2 in einem 200 μL Sample werden in weniger als 3 Stunden detektiert.
F. Schuler, M. Trotter, S. Wadle, F. Schwemmer, R. Zengerle, F. von Stetten, N. Paust
Centrifugal microfluidic step emulsification for digital droplet recombinase polymerase amplification
2015 19th International Conference on Miniaturized Systems for Chemistry and Life Sciences October 25-29, 2015, Gyeongju, KOREA
KurzfassungFor the first time we show centrifugal step emulsification. It enables the fast and easy production of monodispers w/o droplets with minimal handling effort (3 pipetting steps). In contrast to previously presented centrifugal emulsification systems [1], homogenous droplets with pre-selectable diameters were generated with zero run-in time and zero dead volume. The centrifugal microfluidic step emulsification was used to perform the first digital droplet recombinase polymerase amplification (ddRPA). Compared to digital droplet PCR, the amplification time was reduced by a factor of 4 from 2 hours to 30 minutes.
M. Keller, A. Drzyzga, F. Schwemmer, R. Zengerle, F. von Stetten
Centrifugo-thermopneumatic wax valve for centrifugal microfluidic platforms
2015 19th International Conference on Miniaturized Systems for Chemistry and Life Sciences October 25-29, 2015, Gyeongju, KOREA
L. Zielke, C. Barchasz, S. Waluś, F. Alloin, J.-C. Leprêtre, R. Bouchet, A. Spettl, V. Schmidt, A. Hilger, I. Manke, J. Banhart, R. Zengerle, S. Thiele
Degradation of LSB Electrodes investigated with X-ray Phase Contrast Tomography
2015 Lithium Battery Discussion (LIBD) 2015, 21.-26.06.2015, Arcachon, France
A. Balakrishnan, M. Frei, S. Kerzenmacher, H. Reinecke, C. Mueller
Design and fabrication of miniaturized PEM fuel cell combined microreactor with self-regulated hydrogen mechanism
2015 PowerMEMS 2015, Boston, Massachusetts, 1.-4.12.2015
KurzfassungAbstract. In this work we present the design and fabrication of the miniaturized PEM fuel cell combined microreactor system with hydrogen regulation mechanism and testing of prototype microreactor. The system consists of two components (i) fuel cell component and (ii) microreactor component. The fuel cell component represents the miniaturized PEM fuel cell system (combination of screen printed fuel cell assembly and an on-board hydrogen storage medium). Hydrogen production based on catalytic hydrolysis of chemical hydride takes place in the microreactor component. The self-regulated hydrogen mechanism based on the gaseous hydrogen produced from the catalytic hydrolysis of sodium borohydride (NaBH4) gets accumulated as bubbles at the vicinity of the hydrophobic coated hydrogen exhaust holes. When the built up hydrogen bubbles pressure exceeds the burst pressure at the hydrogen exhaust holes the bubble collapses. This collapse causes a surge of fresh NaBH4 solution onto the catalyst surface leading to the removal of the reaction by-products formed at the active sites of the catalyst. The catalyst used in the system is platinum deposited on a base substrate. Nickel foam, carbon porous medium (CPM) and ceramic plate were selected as candidates for base substrate for developing a robust catalyst surface. For the first time the platinum layer fabricated by pulsed electrodeposition and dealloying (EPDD) technique is used for hydrolysis of NaBH4. The major advantages of such platinum catalyst layers are its high surface area and their mechanical stability. Prototype microreactor system with self-regulated hydrogen mechanism is demonstrated.
A. Balakrishnan, M. Frei, S. Kerzenmacher, H. Reinecke, C. Mueller
Design and fabrication of miniaturized PEM fuel cell combined microreactor with self-regulated hydrogen mechanism
2015 PowerMEMS 2015, Boston, Massachusetts, 1.-4.12.2015
KurzfassungIn this work we present the design and fabrication of the miniaturized PEM fuel cell combined microreactor system with hydrogen regulation mechanism and testing of prototype microreactor. The system consists of two components (i) fuel cell component and (ii) microreactor component. The fuel cell component represents the miniaturized PEM fuel cell system (combination of screen printed fuel cell assembly and an on-board hydrogen storage medium). Hydrogen production based on catalytic hydrolysis of chemical hydride takes place in the microreactor component. The self-regulated hydrogen mechanism based on the gaseous hydrogen produced from the catalytic hydrolysis of sodium borohydride (NaBH4) gets accumulated as bubbles at the vicinity of the hydrophobic coated hydrogen exhaust holes. When the built up hydrogen bubbles pressure exceeds the burst pressure at the hydrogen exhaust holes the bubble collapses. This collapse causes a surge of fresh NaBH4 solution onto the catalyst surface leading to the removal of the reaction by-products formed at the active sites of the catalyst. The catalyst used in the system is platinum deposited on a base substrate. Nickel foam, carbon porous medium (CPM) and ceramic plate were selected as candidates for base substrate for developing a robust catalyst surface. For the first time the platinum layer fabricated by pulsed electrodeposition and dealloying (EPDD) technique is used for hydrolysis of NaBH4. The major advantages of such platinum catalyst layers are its high surface area and their mechanical stability. Prototype microreactor system with self-regulated hydrogen mechanism is demonstrated.
M. Klingele, M. Breitwieser, N. Wehkamp, R. Zengerle, S. Thiele
Direct membrane deposition
2015 EMEA Conference, Bad Zwischenahn (Germany), 22. - 24.06.2015
M. Breitwieser, M. Klingele, R. Zengerle, S. Thiele
Direct membrane deposition for high performance hydrogen fuel cells
2015 ModVal, 12th Symposium on Fuel Cell and Battery Modeling and Experimental Validation. Munzingen (Germany), 26. - 27.03.2015
B. Gerdes, N. Lass, M. Jehle, L. Riegger, R. Zengerle, P. Koltay
Direct printing of molten metal lines using the StarJet technology
2015 Swiss ePrint, Neuchatel, Switzerland, 01. - 02. October 2015

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M. Pospischil, M. Kuchler, M. Klawitter, C. Rodríguez, M. Padilla, R. Efinger, M. Linse, A. Padilla, H. Gentischer, M. König, M. Hörteis, L. Wende, O. Doll, R. Zengerle, F. Clement, D. Biro
Dispensing Technology on the Route to an Industrial Metallization Process
2015 Energy Procedia, Band: 67, Seiten: 138 - 146
M. Frei, J. Erben, S. Kerzenmacher
Fabrication of platinum electrodes with high roughness factor using a 3D-support
2015 66th Annual Meeting of the ISE, Taipei, Taiwan, 04. – 09.10.2015
J. Danzer, A. Götze, S. Kerzenmacher
Filtering with an MFC Anode: A new concept for the integration of microbial fuel cells into membrane bioreactors
2015 ISMET 5, Tempe, Arizona, USA, 01.– 04.10.2015
KurzfassungMembrane bioreactors (MBRs) are a spreading alternative to conventional wastewater treatment plants. By separating the biomass from the treated water with membrane filtration instead of sedimentation, MBRs achieve higher degradation capacities with lower space requirements and a germ free outflow. The disadvantage is a high energy demand up to 10kWh/m³ [1] compared to 0,35kWh/m³ [2]. To lower the energy footprint, the combination of energy consuming MBRs with energy delivering microbial fuel cells (MFCs) has gained raising attention.
D. Baumann, S. Hin, F. Stumpf, V. Klein, K. Mitsakakis, D. Kosse, F. von Stetten, R. Zengerle, D. Mark
Fully automated stick-packaging for precise liquid reagent pre-storage and release in lab-on-a-chip disposables
2015 19th International Conference on Miniaturized Systems for Chemistry and Life Sciences October 25-29, 2015, Gyeongju, KOREA
N. Lass, B. Gerdes, M. Jehle, L. Riegger, R. Zengerle, P. Koltay
Generation of High Aspect Ratio Metal Microstructures Exhibiting Low Surface Roughness by Drop-wise Printing of Liquid Metal
2015 Eurosensors 2015, Freiburg, 06.- 09.09.2015 Procedia Engineering, Band: 120, Seiten: 1103 - 1106
KurzfassungThis paper presents the results of parameter studies for the drop-wise generation of metal microstructures from liquid metal. In this context, thin walls (170 μm---180 μm thickness) featuring aspect ratios of over 50 are printed from solder droplets to identify the correlation between printing parameters and resulting material properties. Droplet spacing as well as substrate temperature are varied and the resulting surface quality in terms of roughness is evaluated. Best results, for given boundary conditions, are achieved with a relative droplet spacing of 0.65 in combination with a substrate temperature of 140 °C. Based on printing with droplets of 170 m diameter a printed area surface roughness of 9.35 m is achieved.
K. Lehmann, O. Yurchenko, S. Vierrath, S. Thiele, G. Urban
High Surface Carbon Nanostructures with Improved Accessibility for Energy Applications
2015 PacificChem, Honolulu, Hawaii, USA December 15 - 20, 2015
M. Breitwieser, M. Klingele, B. Britton, S. Holdcroft, R. Zengerle, S. Thiele
High power fuel cells with direct membrane deposition via ionomer spray-coating
2015 EMEA Conference, Bad Zwischenahn (Germany), 22. - 24.06.2015
S. Kartmann, P. Koltay, R. Steger, R. Zengerle, A. Ernst
Injection-molded, consumable, non-contact dispensing valve applicable for 96-well plate processing
2015 SLAS 2015, 4th Annual Conference and Exhibition in Washington, DC, USA, 07.-11.02.2015
KurzfassungThe presented work focusses on the fabrication by an injection molding process of a cost-effective, disposable, non-contact dispensing valve for cross-contamination free applications. The valve allows a super silent multi-channel processing of well plates in standard 96-well format. The implementation of a design capable for the fabrication in injection molding could be realized with performance improvements concerning reproducibility and with enhanced handling properties. The requirements of industry and research on the dispensing performance of liquid handling systems in terms of minimal dosing volume, precision and accuracy as well as throughput and analysis costs are increasingly growing. Also the risk of cross-contamination implies the demand of disposable components and non-contact technologies. Since such systems are hardly available on market, we focus on the implementation of a system providing a comprehensive solution for the entire set of industrial specifications. The developed functional model of the valve presented in [1] was fabricated by a 3D printing process to approach the given requirements. This valve revealed several disadvantages, like it’s large outer diameter with an overall size of 16 mm, the huge temperature coupling into the fluid induced by required high coil currents (I = 10 A) which affects the viscosity of the fluid and leakage problems of the two-part valve body assembly for actuation pressures above 1.5 bar. To enable a multichannel application for parallel filling of 96-well plates, the dimensions of the valve were optimized to fit in a 9 mm pitch. Therefore, the outer diameter of the valve including external actuating coil was reduced from 16 mm to 8.5 mm. The smaller dimensions allowed a reduction of the actuation current by 60%. Consequently, the heat transfer, thus the effect on the dispensing performance, could be reduced enormously. In contrast to the functional model, the novel valve consists of a one-part valve body, which solves the previous leakage problem. An inserted stopper defines the maximum plunger movement. The entire valve design is adapted to the fabrication by an injection molding process in polypropylene to implement cost effectivity and the compatibility to medical applications. It is now possible to dispense target volumes with CV’s less than 2% for a volume range between 230 nL and 2 µL and CV < 1% for a volume range between 2 µL and 20 µL. Furthermore, we were able to adjust the desired volume range and flow rate by using nozzles with different dimensions. In conclusion, the performance is very comparable to similar commercially available systems with the advantage, that the material costs stay under 1 €. The reduced size and the standard Luer-Lock interface make the dispensing valve compatible to a wide range of applications in biomedical technology.
J. Riba, T. Gleichmann, R. Zengerle, P. Koltay
Label-free sorting and deposition of single bacterial cells using the Single-Cell Printer technology
2015 6th International conference on analysis of microbial cells at the single cell level, Retz/Austria, 19. - 22. Juli 2015
KurzfassungWe present a modified Single-Cell Printer (SCP) for sorting and deposition of individual bacterial cells by: •Label-free optical cell detection •Confinement of single cells in 35 picoliter droplets •Non-contact drop-on-demand deposition onto a variety of substrates We show that Escherichia coli cells can be deposited with a single cell printing efficiency of 78 %. Further, we deposited individual cells from a heterogeneous sample directly onto agar plates for subsequent clonal culturing.
M. Rombach, S. Zehnle, N. Paust, M. Weil, Ö. Sogukpinar, R. Zengerle, M. Karle
Microfluidic App for buffy coat extraction from large peripheral blood samples for low-abundance living-cell analysis
2015 19th International Conference on Miniaturized Systems for Chemistry and Life Sciences October 25-29, 2015, Gyeongju, KOREA
L. Zielke, R. Moroni, T. Hutzenlaub, D.R. Wheeler, I. Manke, T. Arlt, N. Paust, R. Zengerle, S. Thiele
Modeling the missing carbon phase in X-ray tomographic reconstructions of a metal-based battery cathode
2015 ModVal, 12th Symposium on Fuel Cell and Battery Modeling and Experimental Validation. Munzingen (Germany), 26. - 27.03.2015
R. Moroni, M. Börner, L. Zielke, M. Schroeder, M. Winter, I. Manke, R. Zengerle, S. Thiele
Multi-scale Correlative Tomography of Li-Ion Battery Cathode Morphology
2015 12th Symposium on Fuel Cell and Battery Modelling and Experimental Validation – ModVal 12, Freiburg, 26.-27.03.2015
S.K. Vashist, F. von Stetten, R. Zengerle, J.H.T. Luong
One-step antibody immobilization-based high sensitivity immunoassay procedure for potential in vitro diagnostics
2015 6. Mikrosystemtechnik Kongress (MST Kongress 2015), Karlsruhe, 26. – 28.10.2015
T. Gleichmann, J. Kottmeier, P. Koltay, R. Zengerle, L. Riegger
Open Surface Batch Crystallization of Proteins on an Automated Non-Contact nL-Dispenser Setup
2015 19th International Conference on Miniaturized Systems for Chemistry and Life Sciences October 25-29, 2015, Gyeongju, KOREA
T. Silva Santisteban, R. Zengerle, M. Meier
Optical clearance of spheroids on chip
2015 19th International Conference on Miniaturized Systems for Chemistry and Life Sciences October 25-29, 2015, Gyeongju, KOREA
S. Kartmann, P. Koltay, R. Zengerle, A. Ernst
Pressure transducer for medical applications
2015 BMT 2015 (49. Jahrestagung der Deutschen Gesellschaft für Biomedizinische Technik (DGBMT) im VDE), 16.-18. September, Lübeck
KurzfassungParticularly in the field of medical applications, full- or partly disposable pressure sensors are needed to implement cross-contamination-free monitoring solutions e.g. for infusion systems or process control for in vitro diagnostic (IVD) applications. The demand for reliable, single-use technologies increases rapidly, driving forward the investigation of innovative measuring principles.
S. Kartmann, P. Koltay, R. Zengerle, A. Ernst
Pressure transducer for medical applications employing radial expansion of a low-cost polymer tube
2015 Eurosensors 2015, Freiburg, 06.- 09.09.2015 Procedia Engineering, Band: 120, Seiten: 1213 - 1216
KurzfassungWe present a low-cost pressure transducer for medical applications. It’s based on the radial expansion of a liquid filled elastic tube, which is detected by a capacitive measuring principle in a non-contact manner. For optimization we investigated the influence of the number and arrangement of the measurement electrodes, their length as well as the gap separating them. The optimized electrode geometry features a sensitivity of 0.195 fF/103 Pa and a corresponding mean coefficient of variation (CV) of 6.4% considering three individual transducer assemblies. The transducer performance was investigated applying pressures up to 50 x 103 Pa. Due to a viscoelastic behavior of silicone material we determined a hysteresis effect which implied a maximum error of 1.13 fF implying a pressure error of 5.8 x 103 Pa.
S. Vierrath, M. Breitwieser, M. Klingele, R. Zengerle, S. Thiele
Properties of a direct deposited membrane (DDM) Investigating the reasons for its high performance
2015 EMEA Conference, Bad Zwischenahn (Germany), 22. - 24.06.2015
F. von Stetten
Risk and cost reduction by outsourcing design and fabrication of microfluidic chips – A service provider’s perspective
2015 19th International Conference on Miniaturized Systems for Chemistry and Life Sciences, Gyeongju, KOREA, 25.-29.10.2015
J. Riba, J. C. Niemöller, S. Zimmermann, J. Schoendube, S. Bleul, P. Koltay, R. Zengerle, R. Claus, H. Becker, A. Gross
Single-cell printing for the genetic analysis of cancer cells
2015 Single cell genomics 2015, Utrecht, The Netherlands, 16. – 18. September 2015
KurzfassungWe present a workflow for the isolation and genetic analysis of single cancer cells based on a Single-Cell Printer (SCP): • Printing of single cells from the osteosarcoma cell line U2OS in wells of a 384-well microtiter plate (MTP) • Whole genome amplification (WGA) of single-cell DNA at reduced reagent volumes • Multiplex PCR on LINE1 retrotransposons • Analysis of U2OS-specific mutations Following this workflow, a single-cell printing efficiency of 98% and uniform DNA yields after WGA were achieved. LINE1 retrotransposons could be detected in all WGA samples, and mutations in the TET2 and the SLC34A2 gene, respectively.
A.G. Venkatesh, F. von Stetten, R. Zengerle, S.K. Vashist
Smartphone EasyELISA – A point-of-care platform for cost-effective and easy-to-use in vitro diagnostics
2015 6. Mikrosystemtechnik Kongress (MST Kongress 2015), Karlsruhe, 26. – 28.10.2015
A.G. Venkatesh, T. van Oordt, F. von Stetten, R. Zengerle, S.K. Vashist
Smartphone-based colorimetric readers for cost-effective in vitro diagnostics
2015 6. Mikrosystemtechnik Kongress (MST Kongress 2015), Karlsruhe, 26. – 28.10.2015
A. G. Venkatesh, F. von Stetten, R. Zengerle, S. K. Vashist
Smartphone-based immunoassay for human fetuin A
2015 6. Mikrosystemtechnik Kongress (MST Kongress 2015), Karlsruhe, 26. – 28.10.2015
M. Breitwieser, R. Moroni, J. Schock, M. Schulz, B. Schillinger, F. Pfeiffer, R. Zengerle, S. Thiele
Studying the water evolution in direct membrane deposition PEM fuel cells via in-situ neutron imaging
2015 ModVal, 12th Symposium on Fuel Cell and Battery Modeling and Experimental Validation. Munzingen (Germany), 26. - 27.03.2015
C. Scheuerlein, M. Di Michiel, A. Rack, M. Hagner, S. Vierrath, L. Zielke, S. Thiele, R. Zengerle
Tomographic characterisation of superconductors
2015 Materials and Mechanisms of Superconductivity Conference, Geneva, 23.-28.08.2015
S. Wadle, M. Lehnert, F. Schuler, R. Zengerle, F. von Stetten
Universelle Reporter der Mediatorsonden PCR als Zielsequenz-unabhängige Biosensoren zur Detektion fünf verschiedener RNA- und DNA-Sequenzen
2015 9. Deutsches BioSensor Symposium 11.–13. März 2015, München
KurzfassungIn der Molekulardiagnostik werden meist sogenannte Hydrolysesonden (hydrolysis probe, HP) zur Echtzeitdetektion von Nukleinsäuren verwendet. Hierbei ist für jede zu detektierende Zielsequenz die Synthese einer spezifischen dual-markierten HP notwendig. Deren Anschaffung ist sehr kostenintensiv, vor allem beim Bedarf nur geringer Bestellmengen. Zudem müssen HP bei jeder neu zu detektierenden Zielsequenz individuell bezüglich der Signalgenerierungseffizienz optimiert werden. Ein von uns publiziertes neuartiges Verfahren, die Mediatorsonden PCR (mediator probe PCR, MP PCR) [1, Abb.1] löst diese Probleme durch Verwendung eines dual-markierten Universellen Reporter Oligonukleotids (UR). Dieser Biosensor erzeugt unabhängig der zu detektierenden Zielsequenz ein Signal, initiiert durch die Interaktion mit nicht-markierten und somit kostengünstigen sequenzspezifischen Mediatorsonden. Im Vergleich zu [1] wurde die Fluoreszenz-Quenchingeffizienz am UR und die Reaktionszusammensetzung der MP (RT-)PCR Assays verbessert, um fünf verschiedene DNA und auch RNA Sequenzen von Atemwegsinfektion-verursachenden Viren zu detekieren. Die Detektionsreaktionen wurden mit HP-basierten Assays als Referenz verglichen, bei denen fünf verschiedene dual-markierte Sonden benötigt werden.
T. van Oordt, G.B. Stevens, A. Rummel, O. Strohmeier, G. Urban, R. Zengerle, F. von Stetten
Vollintegrierte zentrifugale Mikrofluidik für die Vor-Ort-Analyse
2015 9. Deutsches BioSensor Symposium 2015, München, 11. - 13. 03. 2015 , Seite: P71
O. Strohmeier, D. Mark, D. Kosse, R. Zengerle, F. von Stetten
Zentrifugale Mikrofluidik für die DNA Analytik
2015 Forschungstag der Baden-Württemberg Stiftung, Stuttgart, 22.07.2015
KurzfassungIm Rahmen des von der Baden-Württembergstiftung geförderten Projektes „Amplidisk“ wurden verschiedene Applikationen aus dem Bereich der molekularbiologischen Diagnostik mit Hilfe zentrifugal-mikrofluidischer Testträger „LabDisks“ automatisiert. Diese können in tragbaren Geräten prozessiert werden und bieten durch den hohen Automatisierungsgrad eine ideale Lösung für die zukünftige Diagnostik am Point-of-Care. Zunächst wurde im Rahmen des Projektes eine Methode zum Transport magnetischer Partikel zwischen verschiedenen, flüssigkeitsgefüllten Kammern auf einer LabDisk entwickelt [1]. Mit Hilfe dieser Methode konnte ein Prozess zur automatisierten und disk-integrierten DNA Extraktion implementiert werden wobei silica beschichtete Magnetpartikel als Festphase dienten [2]. In weiteren Arbeiten wurden LabDisks für den Nachweis von KRAS -Mutationen aus Tumorzell-DNA entwickelt die bis zu 7 gängige DNA - Mutationen in etwa 2 Stunden detektieren können während das Goldstandardverfahren, die Sequenzierung, hierzu bis zu 20 Stunden benötigt. Kenntnisse über den Mutationsstatus sind zwingend zur Einleitung einer spezifischen Therapie erforderlich [3]. Für ein zweites Anwendungsfeld konnte eine Disk zum qualitativen und quantitativen Nachweis von sechs typischen Lebensmittelpathogenen wie Listerien, Salmonellen oder EHEC entwickelt werden. [4] Die entwickelten Module wurden in weiteren Projekten erfolgreich gemeinsam auf einer Disk kombiniert um die gesamte Analyse zu integrieren.

2014

nach oben zur Jahresübersicht

L. Riegger, A. Ernst, P. Koltay
A dispensing system for sedimenting metal microparticle solutions based on a circulation mixer method
2014 2nd MFHS Conference 2014, Freiburg, 08 - 10.Okt. 2014 , Seiten: 81 - 83
KurzfassungWe present a novel method for the ejection of sedimenting microparticle solutions by a non-contact drop-on-demand dispensing system with integrated mixing technology. The system enables the generation of single liquid droplets in the nanoliter range containing similar amounts of solids. The system is evaluated for a process time of more than 4 h and is applied to produce particle layers with homogeneous layer thicknesses in the micrometer range.
S. Kartmann, A. Ernst, R. Zengerle, P. Koltay
A disposable, dispensing valve for non-contact microliter applications in 96-well plate format
2014 2nd MFHS Conference 2014, Freiburg, 08 - 10.Okt. 2014 , Seiten: 65 - 68
KurzfassungWe present a miniaturized, disposable dispensing valve for the microliter range, applicable as consumable to process 96-well plates. The new valve design is adapted to fit into a 9 mm grid and derives from the miniaturization study of a previous functional model [1]. The outer diameter of the valve, including actuating coil, was reduced from 16 mm to 8.5 mm without performance restrictions, thus made compatible for 96-well plate processing. Also the actuation current was reduced from 10 A to 5 A. The valve enables the dosage of target volumes in the range between 230 nL and 5 μL with coefficients of variation (CVs) below 2%. The current performance coincides with similar commercially available systems with the decisive advantage of material costs below 1 €.
F. Stumpf, L. Gutzweiler, L. Tanguy, P. Koltay, R. Zengerle, L. Riegger
A flexible method for rapid-prototyping of PDMS microfluidic chips for droplet based applications using direct-written polymer master structures
2014 Biosensors 2014, Melbourne, Australia, 27.05.2014 – 30.05.2014
S.K. Vashist, F. von Stetten, R. Zengerle
A highly-sensitive rapid sandwich immunoassay for human fetuin A using the one/step antibody immobilization procedure
2014 Biosensors 2014, Melbourne, Australia, 27.05.2014 – 30.05.2014
J. Riba, L. Gutzweiler, L. Riegger, P. Koltay, R. Zengerle, A. Gross
A picoliter dispenser with disposable cartridges for precise and contact-free injection of DNA into open microfluidic structures
2014 2nd MFHS Conference 2014, Freiburg, 08 - 10.Okt. 2014 , Seiten: 84 - 87
KurzfassungWe present a new disposable liquid handling system addressing the lower picoliter volume range and allowing for precise and contact-free injection of biopolymer samples into open microfluidic structures. Droplet placement precision of single stranded DNA (ssDNA) solutions up to 50 μM and a DNA reference ladder is investigated by high resolution optical monitoring. We present three different sample injection methods that account for evaporation protection of picoliter samples. Finally, we show the applicability of the dispenser by a successful electrophoretic separation via injecting ~70 pL of a DNA solution into a 200-300 μm wide gel line.
R. Zengerle, D. Mark, N. Paust, F. von Stetten
Advanced centrifugal microfluidics and Microfluidic Apps
2014 EMBL Conference Series Microfluidics, Heidelberg, 23. - 25.07.2014
E. Kipf, T. Messinge, S. Sané, S. Kerzenmacher
An air-breathing cathode based on buckypaper electrodes with reversibly adsorbed laccase
2014 2nd European International Society for Microbial Electrochemistry and Technology Meeting, Alcala, Spain, 03.-05-09.2014
KurzfassungPreviously, we presented buckypaper electrodes with reversibly adsorbed laccase as promising cathodes for biofuel cell applications [1]. This concept is particularly advantageous, since the periodic exchange of the enzyme solution against fresh enzymes can help to overcome the limited lifetime caused by denaturation of the enzymatic biocatalyst. Here, we present the development of a corresponding air-breathing cathode, which enables passive operation without energy-intensive aeration of the catholyte. Thereto, buckypaper electrodes [2] were equipped with a 0.5 mm thin silicone membrane as diffusion layer which enables sufficient oxygen supply but prevents salt crust formation and electrolyte leakage [3]. As catholyte 0.1 M Na-acetate buffer (pH 5) containing 3.6 U/mL laccase from T. versicolor (Sigma-Aldrich, Germany) was used in two different configurations. The setup with 20 mL catholyte volume was operated in batch mode, similar to previous experiments with active aeration. In addition, a thin flat-plate configuration with minimized ohmic resistance and a small catholyte volume of only 0.29 mL was investigated in batch and continuous mode. The batch-type air-breathing cathode with 20 mL volume yielded ~78 µA/cm² at 0.4 V vs. SCE, which is in the same range as corresponding electrodes in actively aerated laccase solution [1]. In comparison, the flat-plate cathode with smaller catholyte volume yielded only ~12 µA/cm² in batch-mode. This indicates that not enough laccase was supplied to the electrode to sustain higher current densities. However, by applying a continuous laccase flow through the catholyte chamber (HRT: 3.5h), the current density could be increased to ~53 µA/cm2 at 0.4 V vs. SCE. This underlines that the performance is governed by the amount of enzymes available for adsorption. In the next step, optimum flow-rates for the advantageous flat-plate configuration will be identified, and the long-term stability of the air-breathing cathode with continuous supply of fresh laccase will be investigated.
M. Blazek, X. Wu, R. Zengerle, M. Meier
Analysis of fast protein phosphorylation kinetics in single cells on a microfluidic chip
2014 MicroTAS 2014, San Antonio, USA, 26. – 30.10.2014 , Seiten: 267 - 269
KurzfassungWe present a microfluidic large-scale integration chip (mLSI) for characterizing the sequential activation of protein kinases within mammalian growth signaling pathways on a single cell level. The polydimethylsiloxane (PDMS) chip integrates automated cell culturing, stimulation and Proximity Ligation Assay (PLA) for protein analytics in 128 individually addressable microchambers. Design and fluidic operations on this chip generation are optimized for fast reagent exchange in order to resolve protein phosphorylation kinetics in a time regime of seconds. In an experimental series we monitored the protein phosphorylation kinetics of the Akt kinase leading to its activation. Long term activated Akt is a pivotal hallmark of several human cancer types. On chip PLA results with fibroblast cells revealed a consistent temporal order for the phosphorylation of Akt at the residues Ser-473 and Thr-308 upon stimulation with platelet derived growth factor (PDGF) and insulin-like growth factor (IGF-1).
G. Czilwik, V. Klein, O. Strohmeier, G. Roth, F. von Stetten, R. Zengerle, S.K. Vashist, D. Mark
Automated detection of human C-reactive protein on centrifugal microfluidics-based LabDisk platform
2014 Biosensors 2014, Melbourne, Australia, 27.05.2014 – 30.05.2014
G. Czilwik, T. Messinger, O. Strohmeier, F. von Stetten, R. Zengerle, P. Saarinen, J. Niittymäki, K. McAllister, J. O´Leary, D. Mark
Automated point-of-care diagnosis of neonatal sepsis from a 200 µL serum sample based on a LabDisk with integrated DNA extraction, pre-amplification, and real-time PCR detection
2014 SepsEast 2014, Budapest, Ungarn, 18-20 September, 2014
KurzfassungSepsis remains among the major causes of infant death worldwide and management of patient sepsis is challenged by short-comings in current diagnostics. The diagnostic gold standard is blood culture that requires 1-3 days to attain a conclusive result. The immune system of a neonate is relatively immature compared to adults and progression of neonatal sepsis disease can be extremely fast. As a consequence intensive-care units administer broad-spectrum antibiotics when neonatal sepsis is only suspected and before the causative pathogen has been identified. Therefore, a rapid diagnostic tool for identification of causative pathogens is of major interest to give clinicians facts-based treatment options as early as possible. In this context, we developed a fully automated centrifugal microfluidic `LabDisk` system for highly sensitive detection of neonatal sepsis pathogens in human serum samples within 4 hours. All necessary assay steps are integrated on a single test carrier: DNA extraction, PCR pre-amplification and geometrically multiplexed realtime PCR. The reagents for the PCRs are already prestored in a dry format on the test carrier. Therefore, processing solely requires loading of the sample and DNA extraction reagents. Afterwards the entire process is automated using a rotational protocol in a mobile processing device. We demonstrate detection down to 3 colony-forming-units (cfu) of Staphylococcus warneri, 150 cfu of Streptococcus agalactiae, 5 cfu of Escherichia coli and 18 cfu of Haemophilus influenzae in 200 µL of serum. The system has the potential to reduce neonatal mortality and ensure appropriate treatment of newborn sepsis patients. Further development will include an adaptation of the LabDisk to process whole blood instead of serum, reduction of the analysis time and adding additional bacterial targets to the panel.
Y. Zhao, F. Schwemmer, S. Zehnle, F. von Stetten, R. Zengerle, N. Paust
Centrifugo-pneumatic handling of microparticles without external actuation as a new unit operation for centrifugal microfluidics
2014 MicroTAS 2014, San Antonio, USA, 26. – 30.10.2014 , Seiten: 21 - 23
KurzfassungFor the first time we present a microfluidic method for handling of microparticles that requires neither surface treatment of chambers and channels nor external actuators such as magnets. Thus it is not limited to handling of magnetic particles. Using centrifugal forces and temporary storage of pneumatic energy, only, we demonstrate 1) liquid mediated microparticle loading, 2) re-suspension of microparticles by shake mode at low centrifugation; sedimentation of microparticles and afterwards exchange of liquids with particle loss below 2% and supernatant removal efficiency of more than 99.5%, 3) re-suspension and subsequent transport of microparticles together with liquid reagent with particle loss of 6% or less.
L. Zielke, T. Hutzenlaub, D. R. Wheeler, I. Manke, T. Arlt, N. Paust, R. Zengerle, S. Thiele
Combining X-ray tomography with virtual design in LiCoO2 electrodes
2014 Gordon Research Seminar Batteries, Ventura/CA March 09.-14.03.2014
M. Keller, P. Beckert, S. Feuerriegel, M. Merker, E. Bruske, M. Frank, S. Niemann
Development of a molecular Lab-on-a-Disk test system to rapidly detect antibiotic resistant Mycobacterium tuberculosis complex isolates
2014 DZIF Jahrestagung, Braunschweig, 26. - 28.11.2014
KurzfassungTuberculosis (TB) is still a fatal disease. According to the WHO, in 2012 approx. 8.6 million people were newly infected and 1.3 million died from TB. An increasing number of patients infected with drug resistant, multi drug resistant (MDR), and extensively drug resistant (XDR) isolates can be observed with, usually curable, TB caused by Mycobacterium tuberculosis complex (MTBC). MDR MTBC isolates are resistant to at least the two most effective drugs isoniazid (INH) and rifampicin (RIF), XDR strains carry additional resistance to at least one fluoroquinolone and one injectable drug. Drug resistances are acquired by mutations, mainly single nucleotide polymorphisms (SNPs), in resistance mediating genes. For the first line antibiotics, resistance mediating genes are known: INH [katG, inhA], RIF [rpoB], ethambutol (EMB) [embB], and pyrazinamide (PZA) [pncA]. To ensure effective treatment and prevent further spreading of TB, rapid detection of drug resistances is crucial. Thus, we present a molecular Lab-on-a-Disk test system to rapidly detect antibiotic resistant MTBC isolates. The Lab-on-a-Disk test system consists of a disposable centrifugal microfluidic cartridge comprising pre-stored primer and probes of antibiotic resistant assays that can be processed in an off-the-shelf Rotor-Gene (QIAGEN GmbH, Hilden, Germany). The cartridge features a geometric multiplex of an initial sample into eight reaction volumes allowing to perform eight parallel singleplex Real-Time-PCRs. Required assays for resistance mediating SNPs in katG, inhA, rpoB (FRET-probes) and embB (SimpleProbes (TIB MOLBIOL, Berlin, Germany)) were first established in tube. To cover the RIF resistance determining region in rpoB, two assays with different probes were developed. Finally, all single assays were optimized to run at a harmonized temperature protocol. To distinguish wild type isolates from mutants, the PCR is followed by a melting curve analysis. Analyses of drug susceptible wild type and drug resistant isolates, with known resistance mediating mutations, with the assays, revealed distinct melting points for all five assays (INH [katG, inhA), RIF [rpoB[1], rpoB[2]), and EMB [embB]) in tube and for the first four assays, which are implemented up to this point, in the Lab-on-a-Disk test system. The mutated isolates can be clearly distinguished from wild type strains by the melting points. We developed Real-Time-PCR based assays for implementation into a Lab-on-a-Disk test system. The system allows rapid detection of resistance mediating SNPs in katG, inhA, rpoB and embB. Due to the geometric multiplex of the system, the easy implementation or exchange of (further) assays allows the development of region-specific detection systems. Next steps include implementation and optimization of (further) assays and trials in the DZIF African Partner Site at the Albert-Schweitzer Hospital in Lambaréné, Gabon.
D. Czurratis, T. Brettschneider, Y. Beyl, S. Zinober, R. Zengerle, F. Lärmer
Direct on-chip storage and release of liquid reagents for diagnostic lab-on-a-chip devices
2014 Lab-on-a-Chip European Congress, Berlin, 10.-11.03.2014
K. Mitsakakis, S. Hin, V. Klein, O. Strohmeier, D. Mark, F. von Stetten, R. Zengerle
Disc-shaped Point-of-Care platform for infectious disease diagnosis
2014 NN14 Nanotexnology, 08.-11.07.2014, Thessaloniki, Greece
S. Vierrath, F. Güder, A. Menzel, M. Hagner, R. Zengerle, M. Zacharias, S. Thiele
Enhanced FIB-SEM Reconstruction of PEMFC Catalysts Layers by Filling via Atomic Layer Deposition
2014 Gordon’s Research Conference „Fuel Cells“, Bryant University Smithfield, RI, August 3-8, 2014.
KurzfassungThe bottleneck of FIB-SEM reconstruction of PEMFC catalyst layers is the segmentation, i.e. the physical interpretation of the raw SEM images. It is either extremely time-consuming when done manually, or incorrect when applying a threshold, as commonly done. We propose filling the catalyst layer via ALD prior to FIB-SEM reconstruction. In combination with threshold segmentation it is significantly faster and yields a more accurate reconstruction than state-of-the-art methods.
J. Erben, S. Kerzenmacher, S. Thiele
Fabrication of high surface area carbon electrodes with tunable and well defined properties by electrospinning
2014 2nd European International Society for Microbial Electrochemistry and Technology Meeting, Alcala, Spain, 03.-05-09.2014
KurzfassungRecent studies showed that the anodic current production with Shewanella oneidensis MR-1 can be improved with high surface area anode materials such as knitted activated carbon [1] and electrospun carbon fiber mats [2]. The current generation of such varies strongly with the material properties, e.g. electrochemically active surface area (ECSA) or electrical conductivity [3]. To obtain reproducible results it is therefore mandatory to precisely control the material properties. Therefore, we present an according electrode fabrication process that comprises electrospinning with a custom hot-air assisted apparatus and subsequent carbonization. Our process enables to tune carbon fiber diameters between 120 nm ± 78% and 1072 nm ± 13% by adjusting the polymer concentration (Polyacrylonitrile). The area density of the obtained fiber mats is not uniform along the axis of the rotating collector. The fiber deposition patterns on the collector for three polymer concentrations were analyzed in order to quantify material inhomogeneities. Area density variations 9 cm around the center of the collector are always smaller than 7%. The variations increase towards the edges of the collector to values as high as 55%. For same fiber diameters, the sheet resistance varies between 2.40 Ω ± 5% and 2.76 Ω ± 20%. The ECSA (estimated by cyclic voltammetry [3,4]) depends strongly on the fiber diameter. The variation within the samples of one fiber diameter is between 11% and 16%. Normalized to the area density the variations drop to about 5%. Our results show that the electrospinning fabrication process is subject to high variations. This underlines the need to optimize the process chain in order to fabricate electrodes with precisely controlled and tunable properties. In future work, these optimized electrodes will be subject to bio-electrochemical characterization.
M. Keller, C. Nuese, P. Papireddy Vinayaka, R. Zengerle, F. von Stetten
Fluidic structure for temperature measurement under rotation in centrifugal microfluidics
2014 MicroTAS 2014, San Antonio, USA, 26. – 30.10.2014 , Seiten: 1416 - 1418
KurzfassungWe present a novel fluidic temperature measurement system (FTMS), which allows measurement under rotation at arbitrary positions. Temperature determination and control is of high importance for many biochemical applications integrated into centrifugal microfluidic (CM) cartridges while the integration of electronic temperature sensors into processing devices remains a challenge. By enclosing a well-defined air volume inside a fluidic chamber, temperature-induced volume expansion is utilized to displace fluorescent liquid into a detection chamber. Results of a proof-of-concept are in good accordance with temperatures of a commercially available thermocycler (Rotor-Gene Q, QIAGEN GmbH, Germany).
G. Czilwik, T. Messinger, O. Strohmeier, F. von Stetten, R. Zengerle, P. Saarinen, J. Niittymäki, K. McAllister, O.Sheils, D. Mark
Fully integrated PCR detection of pathogens for fast diagnosis of neonatal sepsis on LabDisk
2014 MicroTAS 2014, San Antonio, USA, 26. – 30.10.2014 , Seiten: 2528 - 2529
KurzfassungWe developed a fully automated centrifugal microfluidic `LabDisk` system for highly sensitive detection of neonatal sepsis pathogens in human serum samples within 4 hours. All necessary assay steps are integrated on a single test carrier: DNA extraction, pre-amplification and geometrically multiplexed realtime PCR. Processing solely requires loading of the sample and extraction reagents. Afterwards the entire process is automated using a rotational protocol in a mobile processing device. We demonstrate detection down to 3 colony-forming-units (cfu) of Staphylococcus warneri, 150 cfu of Streptococcus agalactiae, 5 cfu of Escherichia coli and 18 cfu of Haemophilus influenzae in 200 μL of serum.
A. Madjarov, W. Streule, B. Schaub, R. Zengerle, P. Koltay, A. Ernst
Going low Volume – A Nanoliter Dispensing Module for Standard Liquid Handling Robots
2014 Advances in Automation & Robotics (Co-located to 4th European Lab Automation Exhibition), Barcelona, Spain, 13. - 15.05.2014
KurzfassungThe dispensing system implements a wireless eight channel nanoliter dispenser. It is built at a footprint of just a standard SBS well plate, thus can be placed on available deck-tray positions of existing pipetting workstations as an add-on component. By extending their volume range to the lower end, completely new prospects for high-throughput-screening, miniaturized assays and other applications arise. The droplet ejection method is based a piezo-driven piston squeezing a disposable dispensing tube to eject free flying droplets. This dispensing Technology is called PipeJetTM and to make it ready for automated handling, novel dosage elements (PipeJet-Tip) were developed. These PipeJet-Tips are compatible to standard pipetting interfaces and injection molded including the 650 µm dispensing tube and the reservoir. A new tip generation is completely molded in polypropylene and therefore, a very low cost disposable dispensing element. The plug-in system is able to address eight individual dispensing channels to imprint custom droplet patterns with single droplet volumes down to 20 nl (CV < 5%). Rechargeable batteries as power supply and wireless communication housed inside the system enable the autonomous working principle and therefore easy integrate ability of the dispensing module.
S. Vierrath, J. Haußmann, H. Markötter, I. Manke, J. Scholta, R. Zengerle, S. Thiele
Improving segmentation of PEMFC x-ray tomographies
2014 ModVal 11, Winterthur, Schweiz, 17.-19. März 2014
KurzfassungProton exchange membrane fuel cell (PEMFC) performance strongly depends on morphology. Within the past years analysis by tomographic approaches has emerged as a valuable tool to assess morphology. Segmentation, the physical interpretation of 3D images, is a crucial step of tomography. In this study we compare different methods for segmentation of a gas diffusion layer/micro porous layer compound. We find that a mere threshold leads to erroneous segmentation and present a combined approach to overcome this problem.
O. Strohmeier, G. Czilwik, T. van Oordt, M. Keller, D. Mark, R. Zengerle, F. von Stetten
LabDisk: Zentrifugale Mikrofluidik zur voll-integrierten Automatisierung von Laborabläufen
2014 17. Heiligenstädter Kolloquium, Heiligenstadt, 22. - 24.09.2014 , Seiten: 139 - 146
KurzfassungZentrifugale Mikrofluidik auf preiswerten, CD-ähnlichen Einweg-Testträgern, sog. „LabDisks“, kann erfolgreich zur vollintegrierten Automatisierung von Laborabläufen in einem portablen Analysegerät, dem „LabDisk Player“ eingesetzt werden. Das Potential der LabDisk wird anhand von zwei Anwendungen demonstriert: (1) dem integrierten Nachweis von Biokampfstoffen auf DNA Ebene und (2) dem Nachweis von Botulinum Neurotoxin.
N. Paust, A. R. Fiebach, L. Drechsel, S. Zhang, R. Zengerle, F. von Stetten
LabTube - a novel centrifugal microfluidic lab-on-a-chip platform for operation in standard laboratory centrifuges
2014 IFCC WorldLab Istanbul, 22.-26-06-2014, Istanbul, Türkei
KurzfassungThe “LabTube” is a novel centrifugal lab-on-a-chip platform that uses a standard laboratory centrifuge as processing device. It automates multistep protocols such as nucleic acid extraction or protein purification, decreasing the hands-on-time from > 6 to 1 minute per extraction. Future applications will include point-ofcare sample-to-answer nucleic acid analysis. The LabTube approach lowers the market entry barrier for microfluidics as the user only requires to purchase disposable parts without the need to invest in specialized processing devices.
F. von Stetten, A. Kloke, A.R. Fiebach, J. Steigert, M. Hoehl, R. Zengerle, N. Paust
LabTube - a novel centrifugal microfluidic lab-on-a-chip platform for operation in standard laboratory centrifuges
2014 Biosensors 2014, Melbourne, Australia, 27.05.2014 – 30.05.2014
F. von Stetten
LabTube and LabDisk - prospective centrifugal microfluidic platforms for sample-to-answer point-of-care nucleic acid testing
2014 Lab‐on‐a‐Chip World Congress, San Diego/USA, 18. - 19. September 2014
F. von Stetten
LabTube – a novel "microfluidic app" for sample preparation and diagnostics operated in a laboratory centrifuge
2014 Lab-on-a-Chip European Congress, Berlin, 10.-11.03.2014
KurzfassungThe LabTube is a novel lab-on-a-chip cartridge processed by a laboratory centrifuge. Not requiring specialized processing devices this "microfluidic app" has low market entry barriers. Fully automated DNA-extraction and protein purification are demonstrated. The LabTube is amenable to sample-to-answer diagnostics.
J. Schoendube, A. Gross, R. Zengerle, P. Koltay
Label-free Isolation of Single Cells by Inkjet-like Printing
2014 Single Cell Analysis Europe 2014, Berlin, 10.-11.03.2014
KurzfassungSeparation and manipulation of individual living cells for single cell analysis remains challenging for many life science applications, including single cell genomics, isolation of circulating tumor cells (CTC) and clonal cell line production. In order to provide a platform technology to feed single living cells into such applications, we have developed a liquid handling instrument termed Single Cell Printer. It is able to print single living cells confined in free flying droplets in an ink-jet like manner into well plates, into microfluidic chips or other substrates for subsequent single cell applications. A machine vision system detects single cells in proximity of the nozzle before droplet ejection. Droplets, predicted to contain no cell or more than one cell, are deflected by a pneumatic shutter system. Only droplets with exactly one single cell are printed onto the substrate.
S. Sané, A. König, R. Gminski, S. Kerzenmacher
Laccase from Trametes versicolor can help to improve the performance of microbial fuel cells and to efficiently degrade micropollutants from wastewater
2014 2nd European International Society for Microbial Electrochemistry and Technology Meeting, Alcala, Spain, 03.-05-09.2014
KurzfassungCurrent challenges in wastewater treatment are both, the reduction of energy consumption and the efficient removal of micropollutants. To meet these, we envision a new concept in which the enzyme laccase is used to improve the cathode reaction of a microbial fuel cell [1] and to achieve the degradation of micropollutants [2]. As a first step, we show that the laccase producing fungus T. versicolor can be cultivated on synthetic wastewater (according to DIN EN 11733 ). Furthermore, we demonstrate that the enzyme-containing supernatant can be directly used to degrade the model micropollutant 17β-estradiol (Sigma-Aldrich, Germany) and to catalyze cathodic oxygen reduction at pH 6. For T. versicolor grown on synthetic wastewater (SW), laccase activity in the supernatant was increased from 0.006 UmL-1 to 0.022 UmL-1 with the addition of lignin (LSW). Used in triplicate at a buckypaper cathode, the corresponding current densities at pH 6 amounted to 9 ± 1 μAcm-2 and 14 ± 2 μAcm-2 at 0.644 V vs. NHE, respectively. For comparison, significantly higher values of 1.234 UmL-1 and 121 ± 8 μAcm-2 were achieved with synthetic complete laccase medium, indicating that laccase production has to be improved to achieve higher current densities. Despite the comparably low laccase activities achieved in SW and LSW, in first experiments already 72% (SW) and 96% (LSW) of synthetic wastewater spiked with 17β-estradiol (0.025 μg/L) were removed from these supernatants during 24 h of incubation. Our results are a promising step towards the use of the laccase- secreting T. versicolor to improve both, the performance of microbial fuel cell cathodes and the removal of estrogen from domestic waste water. Further work will focus on the optimization of laccase production, the removal of further micropollutants from wastewater, and the combination of a microbial anode with the enzymatic cathode presented here.
F. von Stetten
Mediator Probe PCR - Principle, Applications and Guidelines for Primer and Probe Design
2014 Advances in Biodetection & Biosensors, Berlin, 10. - 11. 03.2014
KurzfassungMediator probe PCR is an alternative to establish sequence-specific fluorogenic probe based real-time PCRs. Detection relies on label-free primary probes and secondary universal fluorogenic reporters that can be synthesized at drecreased cost. Guidelines for probe design and applications for detection of HPV18, influenza B virus, and HAdV B7 are presented.
S. Wadle
Mediator probe qPCR and dPCR
2014 qPCR and digital PCR Congress, London / UK, 20. - 21.10.2014
P. Koltay
Metrological Methods for Low Volume Liquid Handling in Drug Delivery and In-Vitro Diagnostics
2014 8th Workshop Low Flows in Medical Technology, Lübeck, 23. - 24.09-2014
R. Zengerle
Microfluidic Platforms, Microfluidic Apps and Microfluidic Foundry Services
2014 Micronano System Workshop in Uppsala, Sweden, 15. - 16. 05. 2014
K. Mitsakakis, S. Hin, V. Klein, O. Strohmeier, D. Mark, F. von Stetten, R. Zengerle
Multi-pathogen identification on a centrifugal microfluidic platform
2014 CLINAM - European Foundation for Clinical Nanomedicine, 23. - 25. 06.2014, Basel/CH
F. Stumpf, J. Schöndube, A. Gross, G. Roth, R. Zengerle, P. Koltay
Non-contact single cell printing for single cell real-time PCR
2014 Biosensors 2014, Melbourne, Australia, 27.05.2014 – 30.05.2014
S.K. Vashist, F. von Stetten, R. Zengerle
One-step kinetics based immunoassay for the detection of human fetuin A in 30 min
2014 Biosensors 2014, Melbourne, Australia, 27.05.2014 – 30.05.2014
M. Trotter, F. Stumpf, F. von Stetten, J. Hoffmann, R. Zengerle, G. Roth
One-step single cell solid-phase PCR
2014 5th annual conference for advances in qPCR & dPCR , Barcelona, Spain, 14. - 15. 05.2014
A. Schumacher, M. Götz, G. Kattinger, J. Merz, S. Spieth, R. Zengerle
Peristaltic MicroPump with Active Damping (PMP-AD)
2014 Smart Systems Integration 2014, Wien, Austria, 26. - 27.03.2014
KurzfassungA novel peristaltic micropump with active damping for medical or biotechnological applications is presented. The modular pump concept is based on a reusable actuator unit with a low-cost disposable fluidic pump chip and enables the easy and cost-effective exchange of all components being in contact with the liquid to be pumped. The peristaltic micropump is driven by three piezo stack actuators. Active pulsation damping is implemented by measuring the flow pulsations with an integrated pressure sensor and an additional piezo stack actuator whose movement is controlled in real-time in a closed-loop. The pump rate of water is proportional to the operation frequency and reaches 1 mL/min at 30 Hz. From 0 to 200 kPa backpressure, the pump rate varies less than ±10 %. With active damping, flow pulsations can be reduced by 80 to 90 % (related to the undamped flow).
A. Schumacher, M. Götz, G. Kattinger, J. Merz, S. Herrlich, S. Spieth, R. Zengerle
Peristaltic micropump with integrated active damping
2014 2nd European International Society for Microbial Electrochemistry and Technology Meeting, Alcala, Spain, 03.-05-09.2014 , Seiten: 25 - 28
KurzfassungWe present a novel peristaltic micropump with active damping for biotechnological or medical applications. The modular concept of the pump is based on a low-cost disposable fluidic pump chip and a reusable actuator unit. The disposable pump chip enables the cost-effective and easy exchange of all components being in contact with the liquid to be pumped. The reusable actuator unit consists of three piezo stack actuators that form an undamped peristaltic micropump. With an integrated pressure sensor measuring the flow pulsations and an additional piezo stack actuator whose movement is controlled in real-time in a closed-loop, active pulsation damping is implemented. The pump rate of water is proportional to the operation frequency and reaches 1 mL/min at 30 Hz. From 0 to 200 kPa backpressure, the pump rate varies less than ±10 %. With active damping, flow pulsations can be reduced by 80 to 90 %, compared to the undamped flow.
M. Rombach, S. Hin, O. Strohmeier, F. von Stetten, R. Zengerle, D. Mark
Pre-storage and release of purification reagents for full “hands-off” integration of DNA/RNA assays on the LabDisk platform
2014 MicroTAS 2014, San Antonio, USA, 26. – 30.10.2014 , Seiten: 1169 - 1171
KurzfassungFor the first time we demonstrate complete integration and pre-storage of all required compo-nents for nucleic acid extraction and purification on the centrifugal microfluidic LabDisk platform. On the one hand pre-storage of large volume liquid reagents from 200-–-550 μL is realized in stick-packs, that are stacked to decrease the footprint consumption on the LabDisk and are released au-tomatically during the run using centrifugal pressure (pcent-=-1 bar). On the other hand magnetic beads are mixed with PEG8000 (ratio 2:1) and air dried into the final cavity over 12 h. PEG8000 allows stable pre-storage and does not influence the extraction yield.
S. K. Vashist
Rapid In Vitro Diagnostic Procedures and Platforms for Point-of-Care Diagnostics
2014 MicroTAS 2014, San Antonio, USA, 26. – 30.10.2014
KurzfassungTaking into account the immense need for rapid in vitro diagnostic (IVD) procedures and platforms for point-of-care diagnostics (POCD), we have developed rapid and highly-sensitive IVD procedures based on one-step kinetics-based immunoassays (IA) for the detection of several diabetic and inflammatory biomarkers. They have the same precision but many-fold reduced IA duration (<30 min) in comparison to conventional IA format, and employ our proprietary leach-proof and highly simplified antibody immobilization chemistries for enhanced bioanalytical performance. Additionally, we have developed the EasyELISA platforms as a very simple and easy-to use IVD format for POCD; centrifugal microfluidics-based LabDisk platform for fully-automated and rapid analyte detection; and, cost-effective smartphone-based colorimetric readers for the developed IVD formats. Our current research is focussed at the development of miniaturized smart systems for the personalized healthcare monitoring and management of prediabetes, metabolic and psychiatric disorders.
I. Schwarz, S. Zehnle, G. Czilwik, T. Hutzenlaub, F. von Stetten, D. Mark, R. Zengerle, N. Paust
Rapid development of centrifugal microfluidic assay automation by network-simulation based fluidic design
2014 Biosensors 2014, Melbourne, Australia, 27.05.2014 – 30.05.2014
S.K. Vashist, T. van Oordt, F. von Stetten, R. Zengerle
Rapid in vitro diagnostic procedures and platforms for point-of-care diagnostics
2014 MicroTAS 2014, San Antonio, USA, 26. – 30.10.2014
K.G. Kraiczek, G.P. Rozing, R.Zengerle
Relation between chromatographic resolution and limit of detection in spectrophotometric HPLC detection
2014 30th International Symposium on Chromatography (ISC), Salzburg/Austria, 14. - 18.09.2014
L. Gutzweiler, T. Gleichmann, P. Koltay, R. Zengerle, L. Riegger
Semi-contact writing technology & applications
2014 2nd MFHS Conference 2014, Freiburg, 08 - 10.Okt. 2014 , Seiten: 96 - 99
KurzfassungWe present an adaption of a direct ink writing approach to facilitate prevalent standard applications like fabricating masters for PDMS casting, conducting path structuring and generation of open microfluidic structures towards gel electrophoresis. In all presented applications, flexibility is increased and standard structuring processes can be substituted offering the ability for low-cost fabrication with less required expertise. In contrast to existing approaches low to medium viscous liquids are applied due to passive capillary forces.
S. Kartmann, M. Kellermann, R. Zengerle, P. Koltay, A. Ernst
Simulation study of a novel capacitive pressure sensor concept based on the geometrical deformation of an elastic measuring cell
2014 2nd MFHS Conference 2014, Freiburg, 08 - 10.Okt. 2014 , Seiten: 118 - 121
KurzfassungWe present the simulative investigation of design rules for a novel pressure transducer to realize a disposable pressure sensor for medical applications. The presented simulation study is based on a threedimensional CFD-ACE+ model, which describes the expansion behavior of tubular, elastic measuring cells at varying inner hydrostatic pressures for and different boundary conditions like material properties or size. The elastic measuring cell is exposed to an electric field which is sensitive to the implied geometrical deformation, thus transduces a pressure change to a change in capacitance.
T. Gleichmann, L. Gutzweiler, R. Zengerle, P. Koltay, L. Riegger
Smart open microfluidics: an automated platform for the dynamic generation of fluidic structures down to the sub nl-range
2014 2nd MFHS Conference 2014, Freiburg, 08 - 10.Okt. 2014 , Seiten: 161 - 164
KurzfassungWe developed an open microfluidic (OM) [1] platform for the computer-assisted generation of fluidic structures virtually on demand. On using a set of piezo-driven dispenser modules, namely PipeJetTM [2] and Nano-Jet [3] (BioFluidix GmbH, Freiburg, Germany), and a peristaltic pump as well the system enables handling of liquids from the mL- down to the pL-range covering up to nine orders of magnitude in volume. The integration of multiple structuring methods like semi-contact writing (SCW) or non-contact dispensing allows for processing droplet arrays or continuous geometries of desired dimension, using low to medium viscous fluids and a number of different substrate materials.
S.K. Vashist, T. van Oordt, E.M. Schneider, F. von Stetten, R. Zengerle
Smartphone and tablet-based point-of-care in vitro diagnostics and devices for mobile healthcare
2014 12th Psychoimmunology Expert Meeting, Guenzberg, Germany, 06.-09.03.2014 Neurology, Psychiatry and Brain Research (2014), Band: 2014, Seiten: 25 - 26
S. K. Vashist
Smartphone-based C-reactive protein immunoassay
2014 Biosensors 2014, 27. – 30.05.2014, Melbourne, Australien
S.K. Vashist, T. van Oordt, F. von Stetten, R. Zengerle
Smartphone-based colorimetric reader for bioanalytical applications using tablet's/smartphone's screen-based bottom illumination
2014 Biosensors 2014, Melbourne, Australia, 27.05.2014 – 30.05.2014
V. Alagarswamy Govindaraj, J. Jin, F. von Stetten, R. Zengerle, S. K. Vashist
Smartphone-based immunoassay for the highly-sensitive point-of-care detection of human C-reactive protein in whole blood and serum
2014 Biosensors 2014, Melbourne, Australia, 27.05.2014 – 30.05.2014
F. von Stetten
Smartphone-based immunoassay for the highly-sensitive point-of-care detection of human C-reactive protein in whole blood and serum
2014 Biosensors 2014, Melbourne, Australia, 27-30.05.2014
S. Wadle, M. Follo, M. Lehnert, F. Schuler, N. von Bubnoff, R. Zengerle, F. von Stetten
Specific SNP detection by mediator probe digital droplet PCR
2014 Advances in dPCR & qPCR, Barcelona, Spain, 14. – 15. Mai 2014
KurzfassungMediator probe digital droplet PCR (MP ddPCR) was used to detect single nucleotide polymorphisms (SNP) at the cKit V559D gene locus, a gastrointestinal cancer biomarker [1]. In comparison to conventional PCR with dual-labelled hydrolysis probes (HP) the MP PCR combines label-free mediator probes with universal fluorogenic reporters [2]. In the presented experiment, specificity of the MP-based SNP detection was as high as SNP detection using HPs with locked-nucleic acid (LNA) modified nucleotides.
B. Gerdes, N. Lass, L. Riegger, R. Zengerle, P. Koltay
StarJet-based, pneumatically actuated liquid metal droplet printing at up to 500 °C
2014 2nd MFHS Conference 2014, Freiburg, 08 - 10.Okt. 2014 , Seiten: 57 - 60
KurzfassungIn this work, we present a novel generation of pneumatically actuated printheads based on the StarJet technology which have been successfully applied for the direct non-contact printing of droplets from molten metal [1, 2]. This paper reports the technological advances of the newly designed printhead V3 which for the first time has been fabricated by selective laser melting (SLM). The StarJet technology features an inert rinse gas that surrounds the droplets inside the nozzle. V3 features an integrated heating for rinse gas which prevents the droplets from fast solidification and oxidation after ejection, as they are surrounded by hot nitrogen gas. The feasibility of the StarJet technology is demonstrated for printing at temperatures up to 500 °C. Moreover, the angular deviation of the droplets’ flight path has been investigated. A maximum angular deviation of 0.89° has been evaluated. The droplets’ velocity after ejection and the influence of the different pressures on this parameter have been investigated.
S. Hin, K. Mitsakakis, V. Klein, O. Strohmeier, M. Keller, D. Kosse, R. Zengerle, F. von Stetten, D. Mark
The Lab-on-a-Chip Design & Foundry Service
2014 2nd MFHS Conference 2014, Freiburg, 08 - 10.Okt. 2014 , Seiten: 195 - 198
KurzfassungThe Lab-on-a-Chip Design & Foundry Service offers the rapid development of point-of-care systems, which automate diagnostic assays delivered by the customer. The automation is done on a centrifugal microfluidic lab-on-a-chip platform, the LabDisk. The customer profits from the utilization of unit operations in the development process. Those unit operations apply standard rules for the design and production of the cartridges. Unit operations are combined to form process chains for the translation of a manual laboratory protocol into a fully automated analysis. Thus, risk, time, and costs are reduced during the development process, because a wellestablished production technology is used and existing developments can be re-used. To describe that development process, in this paper the example of a unit operation for liquid reagent release is implemented into a LabDisk for the EU-FP7 project DiscoGnosis. The liquid release is needed in a fluidic structure for nucleic acid extraction from pathogens out of a whole blood sample (50 μl). To implement this unit operation, five different buffer solutions are filled into stickpacks. For each buffer, a research-scale batch of 100 stickpacks is produced. It is demonstrated for all buffers that 4 out of 4 stickpacks release their content in the planned time in the protocol. The time effort for this first design iteration was two weeks, including specification phase, CAD, fabrication, and fluidic validation.
J. Danzer, A. Prokhorova, K. Dolch, J. Gescher, S. Kerzenmacher
The performance of microbial anodes in municipal waste water: pre-grown multispecies biofilm vs. natural inocula
2014 2nd European International Society for Microbial Electrochemistry and Technology Meeting, Alcala, Spain, 03.-05-09.2014
KurzfassungA comparison of inoculation strategies shows, that anodes running only with municipal wastewater will produce (75 ± 10) μA cm-2 at 0 V vs. NHE already after 4 days in a continuously fed system without any inoculation. Surprisingly, anodes with a pre-grown exoelectrogenic biofilm or inoculated with sewage sludge do not show a significant improvement in anode performance under the applied experimental conditions.
G. B. Stevens, T. Binz, W. Römer, T. van Oordt, G. A. Urban, R. Zengerle, F. von Stetten
Towards a full-function molecular-based assay for botulinum neurotoxin
2014 World Congress on Alternatives and Animal Use, Prague, 24. - 28. August 2014 Altex-altern Anim Ex, Band: 3, Nummer: 1/14, Seite: V-4-593
KurzfassungThousands of mice are used annually for potency testing of an ever growing number of products that use Botulinum Neurotoxin as the active ingredient. Here we present a first step in the development of a molecular-based assay to detect binding and translocation of Botulinum Neurotoxin type A (BoNT/A). It consists of a liposome (Giant Unilammelar Vesicles, GUVs) with a BoNT/A receptor (GT1b) on the surface. We demonstrate binding of BoNT/A to the GUVs using a fusion protein (eGFP-HcA) consisting of the BoNT/A binding domain (HcA) and Green Fluorescent Protein (GFP). Microscope images of prepared GUVs with HcA-eGFP show binding to vesicles containing GT1b. GUVs prepared without GT1b did not produce the same objects, so GT1b was necessary for binding of the eGFP-HcA. The next step is to demonstrate binding of a construct containing the BoNT/A translocation domain, in addition to the binding domain, to open the way for high-resolution confocal microscopy studies of translocation.When used with an automated sensitive luciferase reporter assay for the detection of BoNT/A proteolytic activity (van Oordt et al., 2013),the developed system has the potential to replace the mouse bioassay,measuring both the translocation and the enzymatic activity of the toxin.
S. Wadle, M. Lehnert, F. Schuler, R. Zengerle, F. von Stetten
Universal reporters of mediator probe PCR as target-independent biosensors
2014 IFCC WorldLab Istanbul, 22.-26.06.2014, Istanbul, Türkei
KurzfassungMolecular diagnostics often uses hydrolysis probes (HP) for real-time nucleic acid sensing. However, each target sequence requires synthesis of specific dual-labelled HPs, which are expensive, especially when used at low batch sizes. Also, HPs must be individually optimized for signal generation efficiencies for each target sequence to be detected. We have published a novel approach, the mediator probe PCR (MP PCR) [B. Faltin et al.: Clin Chem, vol. 58, pp. 1546-1556, 2012] which overcomes these issues by using a labelled but universal reporter oligonucleotide (UR) as a biosensor for target-independent signal generation. It is triggered by unlabelled and thus cost-effective sequence-specific mediator probes. Compared to [Faltin 2012] we improved UR quenching efficiencies and reaction setup of MP PCRs to detect 5 different DNA and also RNA target sequences of viruses causing respiratory tract infections. HP based assays, which required 5 different dual-labelled probes were run as references. MPs and the UR designs were adapted from [Faltin 2012] with the sequence-specific MP section equal to corresponding HP sequences. Nucleic acid standards from human adenovirus (hAdV), influenza virus A&B (InfA & B), human metapneumovirus (hMPV), and respiratory syncytial virus (RSV) were serially diluted enabling efficiency calculation and detection limit determination. Reaction efficiencies and the correlation of input- with back-calculated output concentrations were better for MP RT-PCRs than for HP RT-PCRs. 95 % detection limits were: hAdV 7 / 7 copies per reaction (MP / HP (RT-)PCR), InfA 4 / 18, InfB 10 / 14, hMPV 11 / 29, RSV 14 / 22. These correspond well to commercially available assays [L. Van Wesenbeeck et al.: J. Clin Microbiol., vol. 51, pp. 2977-2985, 2013]. As conclusion, one UR was used for sensing 5 different DNA and RNA targets by MP (RT-) PCR. Even higher reaction efficiencies and lower detection limits as with the more expensive HP (RT-) PCRs could be reached. The method is especially recommended if many different target-specific probes are required at low batch sizes. In future, multiplexing degrees shall be increased using UR-microarrays.
S. Wadle, M. Lehnert, R. Zengerle, F. von Stetten
Universal reporters of mediator probe PCR as target-independent biosensors for detection of five different RNA and DNA sequences
2014 Biosensors 2014, Melbourne, Australia, 27.05.2014 – 30.05.2014
S. Sané, J. Eipper, N. J. Matschke, K. Richter, J. Gescher, S. Kerzenmacher
Using Crude Culture supernatant of Escherichia coli to Supply Copper Efflux Oxidase at a Biofuel Cell Cathode
2014 14th Topical Meeting of the International Society of Electrochemistry, 29.03. - 01.04 2014, Nanjing, China
KurzfassungWe demonstrate the possibility to use crude culture supernatant of a copper efflux oxidase (CueO) exporting recombinant E. coli strain to supply this redox enzyme as oxygen reducing catalyst to a biofuel cell cathode. We observed that the crude extracellular protein extract exhibits significant catalytic differences if oxidation rates with the synthetic substrate ABTS and electron abstracting activity at a biofuel cell cathode are compared. While the supernatant’s activity with ABTS was 0.018 x 10-3 U ml-1 at pH 5.0, no activity was observed at pH 7.4. In contrast, a significant electro-catalytic activity prevailed under both conditions. Here current densities of 119 ± 23 μA cm-2 and 11 ± 4 μA cm-2 at 0.400 V vs. NHE were obtained at pH 5.0 and pH 7.4, respectively. The corresponding control experiments yielded no current at 0.400 V vs. NHE. The CueO-containing supernatant enables similar current densities as laccase containing supernatant of the fungus Trametes versicolor at pH 5.0, which we have studied in earlier work [1]. However, the electrode potential of CueO is by approx. 300 mV lower due to its more positive redox potential [2]. In summary, our results help to circumvent expensive and time-consuming enzyme purification procedures and open possibilities towards easy-to-operate enzymatic biofuel cells. In future work, we will explore the possibilities to extend the electrode lifetime by regularly supplying fresh E. coli culture supernatant, as already successfully demonstrated for T. versicolor [1]. Furthermore, the genetic engineering of CueO towards higher redox potentials may be a promising optimization strategy [2].

2013

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Mitsakakis K, Hin S, Stetten F, Zengerle R
Disc-shaped Point-of-Care Platform for Infectious Disease Diagnosis
2013 The 7th Annual Concertation and Consultation Workshop on Micro-Nano-Bio Convergence Systems (MNBS 2013), Cork, Ireland, 24-25 September 2013
KurzfassungMalaria and infectious diseases of similar clinical symptoms are one of the primary causes of death in endemic areas of the world where numbers denote the extent of the problem (from WHO, 2010): 174 million malaria cases, 80 % of which in Africa, leading to 600 000 deaths. Patients often suffer from different disease than malaria but exhibit similar clinical symptoms, resulting in wrong diagnosis and subsequent maltreatment. The current “gold standard” diagnostic methods are microscopy smear tests, applicable only to malaria, and Rapid Diagnostic Tests (RDTs), available for other infectious diseases too. The latter are often preferred due to their low cost-per-test. On the other hand, each test detects only one disease; therefore, if the patient is found negative to malaria, more than one (disease-specific) RDTs need to be employed, which significantly increases the cost-per-patient. DiscoGnosis aims at developing a fully-automated diagnostic platform for point-of-care use, keeping the cost-per-patient close to RDTs’ level. The platform is based on a disc-shaped microfluidic cartridge (LabDisk), wherein the fluids are transported by centrifugal forces using a dedicated LabDisk reader, the latter performing the detection too.
D. Kosse, F. Schwemmer, D. Buselmeier, R. Zengerle, F. von Stetten
3D microfluidic cartridges by gas pressure assisted thermal bonding of microthermoformed films
2013 Transducers 2013, Barcelona, Spain, 16. – 18.06.2013 , Seiten: 1318 - 1321
KurzfassungMicrothermoforming of film substrates is an emerging technology to form thin-walled microfluidic Lab-on-a-Chip cartridges. We present a process chain to fabricate thin-walled 3D microfluidic cartridges by thermally bonding a stack of microthermoformed polymer layers. The three layer bond stack comprises an upper and a lower microthermoformed film substrate separated by a flat intermediate film layer. For thermal bonding the films are pressed together by gas pressure, eliminating the need for any structure dependent tools. The capabilities of the process chain are demonstrated by bonding a complex microfluidic LabDisk demanding two stacked fluidic layers on top of each other.
S. Thiele, T. Hutzenlaub, R. Zengerle
A 3D water model in a tomographic reconstruction of a PEMFC cathode catalyst layer
2013 Hydrogen + Fuel Cell Conference 2013 (HFC 2013) in Vancouver, Canada, 16. - 19.06.2013
KurzfassungThe cathode catalyst layer (CCL) of a polymer electrolyte membrane fuel cell (PEMFC), where the oxygen reduction reaction takes place, is still considered a major source for performance losses [1]. As transport processes within a CCL strongly depend on the morphology of the layer we introduced 3D PEMFC CCL reconstruction by Focused Ion Beam / Scanning Electron Tomography tomography (SEMt) in the past [3]. However, imaging the microstructure is only the first step towards understanding transport processes within the CCL. Water management is also a major factor influencing the PEMFC CCL performance [4]. We present a 3D water model in a CCL reconstruction of a commercial MEA that is able to depict hydrophilic and hydrophobic water distributions. We further show how this influences diffusion and active surface area. This can be considered as a first step towards understanding the influence of water management on performance.
S. Bammesberger, I. Malki, A. Ernst, L. Tanguy, P. Koltay, R. Zengerle
A Calibration-free, Disposable, Non-contact Reagent Dosing Cartridge for the Sub-μl Range
2013 SLAS 2013, Orlando, Florida/USA, Jan. 12 - 16 2013
J. Danzer, B. Bierer, S. Kerzenmacher
A comparison of dynamic and static polarization for the characterization of anode performance in microbial fuel cells
2013 4th International Microbial Fuel Cell Conference, Cairns, Australia, 01. – 04.09.2013 , Seiten: 44 - 45
L. Gutzweiler, F. Stumpf, L. Riegger, P. Koltay, R. Zengerle, L. Tanguy
A flexible method for rapid-prototyping of PDMS microfluidic chips using direct-written polymer-master-structures
2013 MicroTAS 2013, Freiburg, 27.10.- 31.10.2013 , Seiten: 1409 - 1411
S. Sané, C. Kräß, S. Rubenwolf, S. Kerzenmacher
A simple mediator-less enzymatic biofuel cell based on unpurified fungus culture supernatant
2013 12th ISE topical meeting and 22th International Symposium on Bioelectrochemistry and Bioenergetics, Bochum, Germany, March 17-21, 2013,190
E. Kipf, D. Thissen, S. Kerzenmacher
Air-breathing cathodes for microbial fuel cells based on activated carbon cloth and spin-coated PDMS membranes as hydrophobic diffusion layer
2013 4th International Microbial Fuel Cell Conference, Cairns, Australia, 01. – 04.09.2013 , Seiten: 58 - 59
G.Czilwik, O.Strohmeier, I. Schwarz, N.Paust, S. Zehnle, M.Kräft, F. von Stetten, R. Zengerle, D. Mark
An Integrated Centrifugal Lab-on-a-Chip System for fully automated detection of pathogens via Real-time PCR
2013 Lab-on-a-Chip European Congress, Barcelona 2013,05.03.2013 – 06.03.2013
G. Czilwik, O. Strohmeier, I. Schwarz, N. Paust, S. Zehnle, F. von Stetten, R. Zengerle, D. Mark
An integrated Lab-on-a-Chip system with DNA extraction, pre- and main PCR amplification for automated detection of low concentrated pathogens
2013 MicroTAS 2013, Freiburg, 27.-31.10.2013 , Seiten: 1607 - 1609
C. Köhler, L. Bleck, S. Kerzenmacher
Application-oriented investigation of amino acid poisoning at highly porous platinum electrodes for glucose oxidation
2013 223rd ECS Meeting, Toronto/Canada, 12.-17.05.2013
T. van Oordt, O. Strohmeier, S.K. Vashist, R. Zengerle, F. von Stetten
Automated detection of biological threats with a centrifugal lab-on-a-chip system
2013 2nd International Conference and Exhibition on Biosensors & Bioelectronics, Chicago, USA, 17 June 2013 , Band: 4, Nummer: 3, Seite: 56
L. Drechsel, M. Schulz, F. von Stetten, R. Zengerle, N. Paust
Automated on-site detection of organophosphorous pesticides in real food samples
2013 MicroTAS 2013, Freiburg, 27.-31.10.2013 , Seiten: 1923 - 1925
M. C. Weil, W. Hauser, D. Kosse, O. Strohmeier, F. von Stetten, R. Zengerle, D. Mark
Automatic Foodpathogen detection on a centrifugal microfluidic cartridge in a commercially available PCR thermocycler
2013 MicroTAS 2013, Freiburg, 27.-31.10.2013 , Seiten: 626 - 628
T. van Oordt, G. Stevens, S. Vashist, G. Urban, R. Zengerle, F. von Stetten
Automatisierte Vor-Ort-Detektion von Botulinum Toxin auf der LabDisk Plattform
2013 Microsystemtechnik (MST) Kongress 2013, Aachen, 14. - 16.10.2013 , Seiten: 376 - 379
KurzfassungDie LabDisk Plattform ist ein portables, universell einsetzbares System bestehend aus einem zentrifugalen Analysegerät und Einweg-Disks für die Detektion von diversen Pathogenen [1]. Erstmals konnte eine LabDisk zur vollautomatisierten Detektion von Botulinum Neurotoxin (BoNT) Typ A entwickelt und validiert werden. In einem Konzentrationsbereich von 8 – 2000 pM wurde sowohl die leichte Kette (LC) als auch das komplexe BoNT in Pufferlösung und Vollmilch nachgewiesen. Der Nachweis hat eine signifikante Bedeutung für schnelle Vor-Ort-Analysen im Falle eines terroristischen Anschlages.
S. Wadle, O. Strohmeier, M. Rombach, D. Mark, R. Zengerle, F. von Stetten
Automatisierung der DNA Extraktion aus Vollblut unter Verwendung magnetischer Partikel auf der LabDisk Plattform
2013 Microsystemtechnik (MST) Kongress 2013, Aachen, 14. - 16.10.2013 , Seiten: 403 - 405
KurzfassungDie Integration der Probenvorbereitung spielt eine Schlüsselrolle in der Entwicklung von point-of-care Diagnostik- Systemen. Wir demonstrieren die Integration einer Magnetpartikel-basierten DNA Extraktion aus 200 μl Vollblut in eine zentrifugal-mikrofluidische LabDisk. Die mithilfe der LabDisk extrahierte DNA (vier unabhängige Extraktionen aus einer Blutprobe) wurde auf ihre Qualität geprüft. Als Referenz wurden dabei kommerziell verfügbare Säulen mit Silicamembranen als Goldstandard der DNA-Extraktion verwendet. Es konnten gleich gute Ausbeuten einer Wachstumsfaktor-Gensequenz – bestimmt mithilfe qPCR – (c1:10 LabDisk = 4,6 +/- 0,7 ng/μl gg. c1:10 Aufreinigungssäulen = 4,1 +/- 0,4 ng/μl) sowie Reinheiten (A260/A280 ~ 1,8 +/- 0,1) erzielt werden. Im Fall der LabDisk-extrahierten DNA lag eine leicht erhöhte Ethanol-Konzentration (5,9 +/- 2,4) % im Vergleich zu (3,3 +/- 0,2) % bei Aufreinigungssäulen vor. Die integierte und vollautomatiserte LabDisk-basierte DNA-Extraktion kann für weitere Anwendungen empfohlen werden.
L. Tanguy, S. Bammesberger, A. Ernst, R. Zengerle, P. Koltay
Autonomously compensated pressure controlled and driven dispenser for the IVD industry
2013 European Lab Automation 2013 (ELA2013), Hamburg, 06. – 07.06.2013
KurzfassungThe presented system is a novel, sensor controlled, non-contact fluid dispenser applicable down to the sub-microliter domain. A disposable syringe is filled with fluid and connected through a T-connector to a pressure sensor, which is separated from the liquid by an enclosed and defined gas volume. The other end of the T-connector is linked to a normally-closed solenoid dispensing valve. By displacement of the syringe plunger a defined pressure inside the enclosed gas volume can be established and controlled by the pressure sensor’s signal. The valve is opened to release a pressure driven liquid jet until a certain, pressure-dependent value A is reached. The ejected volume is linearly dependent on A and the dispensed volumes can be estimated with the pressure difference, before and after the dispensing. Thus the influence of temperature and viscosity variations can be compensated autonomously and in-between each dispense. The system was tested and used with several fluids exhibiting different viscosities in the sub-microliter domain with viscosities varying from 1 mPas to 16.69 mPas. Volumes range covered was from 500 nanoliter to 10 microliter. The standard deviations measured were 1.1% for water at 500 nanoliter and 0,8% for mixture water/glycerol 66 %wt at 1 microliter.
M. Karle, J. Wöhrle, F. von Stetten, R. Zengerle, D. Mark
Axial centrifugal filtration – A novel approach for rapid bacterial concentration from a large volume
2013 Transducers 2013, Barcelona, Spain, 16. – 18.06.2013 , Seiten: 1235 - 1238
KurzfassungA novel approach for filtration on a centrifugal microfluidic platform is presented for the first time. This approach is intended to concentrate bacteria from a large volume. In axial centrifugal filtration the filter is oriented perpendicular to the axis of rotation. This feature allows for integration of dead-end filtration while the filter cake is continuously removed from the filter by centrifugation. This prevents clogging of the filter. Furthermore, a continuous sample feed enables processing of large samples on one disk. Especially for analyzing drinking water large volumes have to be processed and solutions for rapid bacterial concentration are highly appreciated.
D. Liang, J. Zhang, M. T.Govindaiah, L. Tanguy, A. Ernst, R. Zengerle, P. Koltay
Benchmark of seven calibration technologies for non-contact micro liquid handling devices
2013 European Lab Automation 2013 (ELA2013), Hamburg, 06. – 07.06.2013
KurzfassungThe miniaturization of liquid handling devices is facing demanding requirement of accurate and standardized calibration methods for smaller volume range. For the first time seven different calibration technologies with the potential to be new standards in the nano-liter and sub-µl range have been benchmarked. In order to compare their efficiency on the same liquid aliquot, a novel, fully automated and multiple principles integrated calibration system has been developed. Single liquid aliquots in the range from pl to µl from a non-contact dispenser are characterized simultaneously with four online methods (the imaging, the flow sensing, the capacitive sensing and the optical sensing method) and one of the three offline methods (the dual-dye photometric, the gravimetric regression and the quartz crystal microbalance (QCM) method). Besides quantitative comparison all these methods are also benchmarked in a qualitative manner in concerning of working range, readability, user-friendliness, liquid suitability, integration size, tractability, cost of equipment and single calibration as well as handling steps etc. This comprehensive work provides the researchers and engineers in the liquid handling field the best overview of different calibration technologies and could support to establish a universal low volume liquid calibration standard for everyday lab situations.
T. Hutzenlaub, A. Asthana, J. Becker, D.R. Wheeler, R. Zengerle, S. Thiele
Calculation of tortuosity in a Li-ion battery cathode based on FIB/SEM tomography
2013 Advances in Electrochemical Materials Science and Manufacturing; Pretoria, South Africa, 07. – 10.04.2013
M. Hoehl, M. Weißert, N. Paust, R. Zengerle, A. H. Slocum, J. Steigert
Centrifugal LabTube for fully automated DNA extraction & lamp assay based on an integrated, low-cost heating system
2013 MicroTAS 2013, Freiburg, 27.-31.10.2013 , Seiten: 1276 - 1278
M. Keller, M. Focke, O. Strohmeier, P. Reith, G. Roth, D. Mark, R. Zengerle, F. von Stetten
Centrifugo-thermopneumatic aliquoting on LabDisk for DNA-based detection of different bacteria
2013 Microsystemtechnik (MST) Kongress 2013, Aachen, 14. - 16.10.2013 , Seiten: 31 - 34
KurzfassungWe present the automation of an aliquoting process in an unmodified commercially available real-time PCR thermocycler (Rotor-Gene, QIAGEN, Germany) by integration of a centrifugal microfluidic LabDisk. With the help of a new centrifugo-thermopneumatic actuation principle we demonstrate the splitting of a DNA sample into 8 times 20 μl aliquots. Each aliquot serves for separate bacteria detection by real-time PCR. For demonstration purposes, DNA of the bacteria Corynebacterium glutamicum and Escherichia coli are automatically detected using pre-stored PCR master mixes inside the reaction cavities. The presented work is an example of how so-called Microfluidic Apps can increase the degree of automation of standard laboratory instruments through the microfluidic integration of workflows. In contrast to conventional automation via pipetting robots Microfluidic Apps do not require fixed costs.
K. Mutschler, L. Tanguy, N. Weber, A. Ernst, R. Zengerle, P. Koltay
Characterization of liquid jet injection into tissue based on optical coherence tomography
2013 Transducers 2013, Barcelona, Spain, 16. – 18.06.2013 , Seiten: 1675 - 1678
KurzfassungWe present the combination of high speed video monitoring, force measurement and Optical Coherence Tomography (OCT) as a new method for the characterization of liquid jets for needle-free tissue injection applications. It is well known that physical parameters, such as jet velocity and jet diameter determine the penetration characteristics of liquid micro-jets into a specific tissue [1]. The optimum injection parameters vary significantly for different types of tissues. Therefore, we have used high speed video monitoring and force sensor measurements to characterize the liquid jet. The penetration into the tissue is then analyzed by Optical Coherence Tomography (OCT) [2]. This enables the general description of the specific jet’s physical properties as well as the penetration characteristics with respect to a specific tissue. In the experimental study, jets with diameters of 100 μm and jet lengths from 6 to 18 ms (~ 2 to 9 μl) have been injected into colon tissue from pigs.
S. Wadle, S. Rubenwolf, M. Lehnert, B. Faltin, R. Zengerle, F. von Stetten
Cost-effective geometric multiplex mediator probe PCR
2013 7. Senftenberger Innovationsforum Multiparameteranalytik, 18. - 19.04.2013
KurzfassungProbe-based real-time PCR is used in molecular diagnostics due to its superior specificity and clinical sensitivity. High synthesis costs for sequence-specific dual-labelled detection probes are still one reason why researchers are reluctant when larger numbers of probes need to be ordered. In order to reduce costs we suggested a novel real time PCR method, the mediator probe PCR [1, 2]. It replaces fluorescently labeled hydrolysis probes by sequence-specific label free mediator probes (MP). Cleavage of the MP during amplification results in release of a mediator which is detected by a universal fluorogenic reporter (UR) oligonucleotide. The key to cost savings is that the same UR can be used for all assays and therefore can be ordered in large scale. This way oligonucleotide synthesis costs can be reduced to less than 40 % compared to the synthesis costs in hydrolysis probe based assays. In this work, performance characteristics of mediator probe PCR (MP PCR) were compared to hydrolysis probe PCR (HP PCR).
S. Wadle, S. Rubenwolf, M. Lehnert, B. Faltin, R. Zengerle, F. von Stetten
Cost-effective real-time analysis by mediator probe (RT-)PCR
2013 qPCR & NGS 2013 Symposium, 18th -20th March 2013, Technical University of Munich, Freising, Germany
L. Gutzweiler, L. Riegger, P. Koltay, R. Zengerle, L. Tanguy
DNA Gelelektrophorese in offenen mikrofluidischen Systemen
2013 Microsystemtechnik (MST) Kongress 2013, Aachen, 14. - 16.10.2013 , Seiten: 380 - 383
KurzfassungIn diesem Beitrag wird die elektrophoretische Trennung von DNA in digital gedruckten offenen mikrofluidischen Linien präsentiert. Im Gegensatz zur gängigen, Chip-basierten Kapillarelektrophorese in mikrostrukturierten Glas-Chips, kommen bei diesem Ansatz mit Platin-Elektroden versehene, planare Polyimid-Substrate zum Einsatz. Eine mittels Teilkontaktverfahren generierte 200 μm breite Gellinie verbindet die Elektroden und fungiert als Trennkanal, in wel-chen kontaktfrei 500 pL der zu untersuchenden Probe dosiert werden. Um Verdunstungseffekte zu unterbinden wird das Gel bis zum Taupunkt gekühlt und mit Mineralöl überschichtet. Durch das Anlegen eines elektrischen Feldes an den Elektroden für 80 s konnte die Trennung der DNA-Fragmente (56 bp-Cy5 und 112 bp-Cy5, 10 μM) erfolgreich gezeigt werden.
M. Pospischil, M. Klawitter, M. Kuchler, J. Specht, H. Gentischer, R. Efinger, M. König, M. Hörteis, C. Mohr, L. Wende, J. Lossen, M. Weiss, O. Doll, I. Köhler, R. Zengerle, F. Clement, D. Biro
Development of a High-Throughput Fine Line Metallization Process using CFD-Simulation
2013 Photovoltaic Specialists Conference (PVSC), 2013 IEEE 39th, Tampa, FL, USA , 16-21 June 2013 IEEEXplore, Seiten: 2250 - 2253
KurzfassungIn order to enhance dispensing technology towards an industrial application in Silicon Photovoltaics, in particular throughput rate has to be increased. For this reason, a novel parallel high precision fine line dispensing unit is currently being developed at Fraunhofer ISE providing one nozzle per contact finger and a central Paste supply. In order to ensure a homogeneous paste distribution to all nozzles, the influence of paste rheology on the flow profile of the dispensing nozzles was analyzed. An analytical comparison of two different dispensing pastes with water gave a good insight on the influence of paste rheology on flow patterns inside the dispensing nozzles. Furthermore, numerical CFD-simulation (CFD: Computational Fluid Dynamics) was used to investigate different nozzle geometries and finally print head designs. In various iteration steps, the influence of fabrication tolerances especially concerning the nozzle geometry was isolated and print head designs were optimized based on CFD towards maximum process stability. In the meantime, process optimization using a single nozzle approach led to an average finger width below 35 μm, confirmed by several characterization methods.
Mitsakakis K, Hin S, Stetten F, Zengerle R
Disc-shaped Point-of-Care Platform for Infectious Disease Diagnosis
2013 European Summit on Clinical Nanomedicine (CLINAM), Basel, Switzerland, 23. – 26.06.2013
Mitsakakis K, Stetten F, Zengerle R
Disc-shaped Point-of-Care Platform for Infectious Disease Diagnosis
2013 10th International Conference on Nanosciences & Nanotechnologies (NN13), Thessaloniki, Greece, 09-12 July 2013
KurzfassungAbstract: Infectious diseases are a huge threat, not only in developing countries, but globally. An estimated 220 million people get infected by malaria every year; 650.000 cases lead to death, 20% of which are within small children. The clinical symptom is mostly acute fever, but a reliable diagnosis is very difficult because in malaria-endemic areas there are several other diseases with the same symptom (Salmonella typhi/paratyphi bacteria or dengue and chikungunya viruses, all of which, like malaria, are transmitted by mosquitos). Within this context, DiscoGnosis aims to develop a platform for the detection of malaria and similar pathogenic diseases in a rapid, multiplexed, highly specific way at the point-of-need. Using centrifugal forces, a disc-shaped chip will handle the injected blood sample and distribute it among integrated microfluidic chambers for processing till the final detection step. Main technical objectives are: (i) Fully automated and integrated analysis from blood (“sample-to-answer”) where several unit operations are integrated on the disc for self-handling of fluid. All necessary (bio)chemical components will be pre-stored on the disc. (ii) Multiplexed detection, by means of quantum dots and magnetic beads acting as pathogen-specific identification codes in an array configuration on disc. (iii) Both nucleic acid and protein based analysis so as to achieve maximum reliability and cross-checked results and to monitor a broader diagnostic window of the diseases. (iv) Scalable fabrication technology based on the microthermoforming of polymer foils, in order to have a low-cost and high-throughput production of diagnostic kits. Clinical trials will be done in Africa for system validation. Acknowledgement: DiscoGnosis is supported by the European Commission through the objective FP7 ICT-2011.3.2 and under Grant Agreement No. 318408.
A. Kloke, S. Niekrawietz, A.R. Fiebach, J. Bernhardt, R. Kneusel, K. Schemel, J. Ritzel, F. von Stetten, R. Zengerle, N. Paust
Disposable LabTube cartridges for automated protein purification in standard lab centrifuges
2013 MicroTAS 2013, Freiburg, 27.-31.10.2013 , Seiten: 1628 - 1630
KurzfassungThe protein purification process is often the bottleneck for the efficient production of a large number of different proteins. Automation of these procedures is often the crux of the matter and is frequently a trade-off between efficiency and cost. Using our novel disposable LabTube cartridges we demonstrate how the process of His-tagged protein purification can be automated in standard laboratory centrifuges. LabTube cartridges include prestored reagents which are sequentially applied to a Ni-NTA purification matrix by an integrated ballpen mechanism actuated by acceleration changes of the centrifuge. Fully automated runs demonstrated similar yield and purity compared to manual purifications with sample addition as the only manual handling step. Thus, the user is available for parallel tasks during 95 % of the overall process time (33 min). In contrast manual processing requires the user to be present for 18 minutes out of the 33 minute overall process time. Since LabTube automation requires no investment in a special lab automation device, this platform lowers the market entry barrier for lab automation.
D. Kosse, F. Schwemmer, D. Buselmeier, R. Zengerle, F. von Stetten
Druckluftunterstützes Thermodiffusionsbonden zur Herstellung dünnwandiger Lab-on-a-Chip Kartuschen mit zwei fluidischen Ebenen
2013 Microsystemtechnik (MST) Kongress 2013, Aachen, 14. - 16.10.2013 , Seiten: 697 - 700
KurzfassungMikrothermoformen von Folienmaterialien ist eine neue sowie attraktive Technologie zur Herstellung dünnwandiger Lab-on-a-Chip Testträger. Der hier vorgestellte Prozess erlaubt das thermische Verbinden mehrerer mikrothermogeformter Folien zur Herstellung dünnwandiger mikrofluidischer 3D-Strukturen. Unter Verwendung von Druckluft wird der Folienstapel bestehend aus zwei mikrothermogeformten Folien außen und einer unstrukturierten Mittelfolie zusammengepresst. Diese Vorgehensweise ermöglicht den Verzicht auf aufwendig strukturierte Siegelwerkzeuge und garantiert eine gleichmäßige und Geometrie-unabhängige Einleitung der Siegelkraft. Die Herstellbarkeit dünnwandiger Testträger mit zwei fluidischen Ebenen wird anhand einer LabDisk demonstriert.
O. Strohmeier, M. Rombach, D. Mark, R. Zengerle, G. Roth, F. von Stetten
Erzeugung von Verdünnungsreihen auf einer Laborzentrifuge
2013 Microsystemtechnik (MST) Kongress 2013, Aachen, 14. - 16.10.2013 , Seiten: 353 - 356
KurzfassungVorgestellt wird ein neuartiges Verfahren zur automatischen Erzeugung von Verdünnungsreihen auf einer mikrofluidischen Kartusche. Die fluidische Prozessierung erfolgt lediglich durch definierte Rotation der Kartusche in einer Standard-Laborzentrifuge. Integrierte, aktiv gesteuerte Ventile sind hierbei nicht erforderlich. Das Verdünnungs-verhältnis wird lediglich durch das Volumen der zu verdünnenden Flüssigkeit bestimmt. Als Anwendungsbeispiel wird die Erzeugung von 5 Verdünnungsstufen aus Fluorescein in PBS Puffer in den Verhältnissen 1:3 und 1:5 gezeigt und anschließend die Reproduzierbarkeit mittels Fluoreszenzmessung gezeigt.
A. Gross, R. Zengerle, P. Koltay
Exploitation and Commercialization within the EU FP7 Project PASCA
2013 10th International Conference on Wearable Micro and Nano Technologies for Personalized Health. Tallin, 26.-28.06.2013 IOS Press, B. Blobel, Seiten: 167 - 178
K. Mitsakakis, S. Hin, O. Strohmeier, D. Mark, F. von Stetten, R. Zengerle
Fully-automated point-of-care detection of malaria and other infectious diseases with a disc-shaped diagnostic platform
2013 Second WHO Global Forum on Medical Devices Duration, Geneva, Switzerland, 22-24 November 2013
KurzfassungMalaria is one of the highest mortality rate infectious diseases globally, mainly prevalent in sub-saharan Africa. Other diseases like dengue, pneumonia, typhoid fever are also present in the same areas, and, although they emerge from different pathogenic agents, they exhibit the same clinical symptom (acute fever). This makes reliable diagnosis extremely challenging especially due to the low resource nature of the endemic regions. Under these circumstances, existing diagnostic methods are often not efficient enough and unable to provide a generic solution: (i) blood smear microscopy is only malaria-specific; (ii) lateral flow Rapid Diagnostic Tests (RDTs) are cheap but single-target specific; (iii) existing molecular methods (e.g., PCR, ELISA) and/or pathogen cultivation require expensive equipment, well-trained users and long time-to-result. The presently suggested technology aims to provide a true point-of-care diagnostic platform, by addressing key application-oriented needs: (i) Portability and autonomous use, based on a disc-shaped plastic disposable cartridge (LabDisk) capable of handling liquid sample (blood) via centrifugal forces operated by a CD-player-like device (LabDisk Player). (ii) Full automation from sample collection to result, via a simple blood transfer device (patient-to-system interface) and on-disc integration of all biochemical components needed for the blood-based pathogen identification (e.g., molecular probes, buffers, etc). (iii) Rapid analysis, by using time-saving analytical protocols based on immunoassays and isothermal nucleic acid amplification (LAMP, instead of PCR). (iv) Multiplexity, by combining a broad diagnostic panel on the same disc (parasites, viruses, bacteria). The panel is flexible and can be tailored to the geographic-specific diseases. (v) Low-cost fabrication technology based on microthermoforming of thin polymer foils, adaptable from pharmaceutical and food package production. This work is part of the EU FP7 project DiscoGnosis, financed by the European Commission which is acknowledged, as well as all the consortium members for their contribution.
N. Losleben, J. Spinke, R. Zengerle, N. Oranth
Herausforderungen für die Anwendung von kontaktfreien Dosiertechniken in in-vitro Diagnostik (IVD) Analysesystemen
2013 Microsystemtechnik (MST) Kongress 2013, Aachen, 14. - 16.10.2013 , Seiten: 349 - 352
G. Czilwik, J. Jin, G. Roth, S. K. Vashist, T. van Oordt, O. Strohmeier, F. von Stetten, R. Zengerle, D. Mark
Immunoassay auf der LabDisk Plattform auf Basis einer Grundoperation zum Transfer magnetischer Partikel
2013 Microsystemtechnik (MST) Kongress 2013, Aachen, 14. - 16.10.2013 , Seiten: 406 - 408
KurzfassungWe present a novel technology for automated processing of immunoassays on our centrifugal-microfluidic LabDisk platform. Here, magnetic beads acting as a mobile phase are subsequently transported through liquid buffers by inter-play of magnetic- and centrifugal forces. Compared to state of the art technologies, the main advantage are short pro-cessing times, assay automation in a portable point-of-care player (LabDisk Player prototype) and a modular microflu-idic design. For demonstration of the automated processing scheme, we chose a magnetic immunoassay for quantifica-tion of human c-reactive protein (h-CRP). Due to a 1-step kinetics reaction of all immunoassay reagents and by only applying two successive washing steps the process time was only 20 minutes. Therefore the test fulfills the require-ments for rapid point-of-care diagnostics.
J. Erben, A. Sido, E. Kipf, S. Thiele, S. Kerzenmacher
Improving current production of Shewanella oneidensis MR-1 with electrospun anode materials
2013 4th International Microbial Fuel Cell Conference, Cairns, Australia, 01.09.2013 – 04.09.2013 , Seiten: 188 - 189
T. Brettschneider, C. Dorrer, H. Suy, T. Braun, E. Jung, R. Hoofman, M. Bründel, R. Zengerle, F. Lärmer
Integration of CMOS Biosensor into a Polymeric Lab-on-a-Chip System
2013 International Conference on Microfluidics and Nanofluidics (ICMN) 2013, Venice, Aug 15-16, 2013 Int. J. Electrical, Electronic Science and Engineering, Band: 7, Nummer: 8, Seiten: 174 - 178
KurzfassungWe present an integration approach of a CMOS biosensor into a polymer based microfluidic environment suitable for mass production. It consists of a wafer-level-package for the silicon die and laser bonding process promoted by an intermediate hot melt foil to attach the sensor package to the microfluidic chip, without the need for dispensing of glues or underfiller. A very good condition of the sensing area was obtained after introducing a protection layer during packaging. A microfluidic flow cell was fabricated and shown to withstand pressures up to Δp = 780 kPa without leakage. The employed biosensors were electrically characterized in a dry environment.
S. Herrlich, R. Nouna, S. Spieth, R. Zengerle
Klinische Erprobung eines intraoralen Medikamentendosiersystems mit telemedizinischem Therapiemonitoring
2013 Microsystemtechnik (MST) Kongress 2013, Aachen, 14. - 16.10.2013 , Seiten: 165 - 168
M. Keller, G. Czilwik, T. van Oordt, O. Strohmeier, J. Drexler, D. Mark, D. Kosse, N. Paust, R. Zengerle, F. von Stetten
LabDisk – novel centrifugal microfluidic unit operations for sample-to-answer analysis and Microfluidic Apps
2013 9. Jahrestagung des Arbeitskreises Mikrosysteme für Biotechnologie und Lifesciences e.V, Jena, 18. - 20.06.2013
A.R. Fiebach, S. Zhang, L. Drechsel, A. Kloke, N. Fritzemeier, D. Wulff, J. Steigert, R. Zengerle, F. von Stetten, N. Paust
LabTube – an innovative platform for assay automation in laboratory centrifuges
2013 Microsystemtechnik (MST) Kongress 2013, Aachen, 14. - 16.10.2013 , Seiten: 27 - 30
KurzfassungIn this paper we present the innovative LabTube platform: A fully automated, easy to handle and cost-effective system that automatizes diverse assays on standard laboratory centrifuges and thus offers a reasonable alternative to existing lab-on-a-chip systems. The LabTube has the size of a 50 ml centrifuge tube and is composed of three stacked revolvers that are operated by a centrifuge-triggered ball-pen mechanism. The upper revolver provides the reagent pre-storage, the middle revolver comprises the assay-specific fluidic unit operations and the lower revolver functions as a unit for the collection and separation of the processed reagents. To demonstrate the functionality of the LabTube on the basis of a frequently used assay, a DNA extraction was performed. The fully automated DNA extraction from rapeseed lysate in the LabTube resulted in a DNA yield of 17,7 +/- 8,1 ng μl -1 in comparison to a manual reference with 14,8 +/- 1,5 ng μl -1. Thus, the hands-on time was reduced from 15 minutes to 1 minute by employing the LabTube, without the need for special training or special laboratory equipment. Currently, the LabTube is also under investigation for protein analysis and for point-of-care diagnostic.
M. Hoehl, E. Schulte Bocholt, N. Karippai, R Zengerle, J. Steigert, A. Slocum
Low-cost bacterial detection system for food safety based on automated DNA extraction, amplification and readout
2013 MicroTAS 2013, Freiburg, 27. - 31.10.2013 , Seiten: 1302 - 1304
M. Keller, J. Naue, P. Papireddy Vinayaka, O. Strohmeier, D. Mark, U. Schmidt, R. Zengerle, F. von Stetten
Microfluidic APP featuring nested PCR for forensic screening assay on off-the-shelf thermocycler
2013 MicroTAS 2013, Freiburg, 27.-31.10.2013 , Seiten: 320 - 322
S. Herrlich, U. Haffa, A. Wolff, S. Spieth, R. Zengerle
Mikrosystemintegration im herausnehmbaren Zahnersatz
2013 Dreiländertagung der Deutschen, Schweizerischen und Österreichischen Gesellschaft für Biomedizinische Technik (BMT 2013) 19.-21. September 2013, Graz, Österreich Biomed Tech, Band: 58, Nummer: SI-1, Seite: 4p
KurzfassungFür ein miniaturisiertes osmotisches Medikamentendosiersystem, das als austauschbare Kartusche in einer Zahnteilprothese getragen wird, wurden mögliche Einbauverfahren evaluiert, welche sich durch die Vermessung und Betrachtung des verfügbaren Platzes im Prothesenkörper in 200 Zahnpatientenfällen ergaben. Hierbei wurde berücksichtigt, dass einerseits der Wirkstoff in ausreichender Menge in der Kartusche gespeichert werden kann, andererseits die ursprünglichen Funktionsfähigkeiten der Prothese, d.h. die Stabilität, Langlebigkeit und Okklusion erhalten bleiben. In Abhängigkeit der Einbauhöhe zwischen Kieferkamm- Mitte und der tiefsten Stelle der Zentralfissur des entsprechenden Zahnes, kann die Kartusche entweder bei ausreichenden Platzverhältnissen in einem standardisierten Einbaukasten oder bei unzureichenden Platzverhältnissen in einer individuell gefertigte Prothese in 183 der 200 betrachteten Fälle eingebaut werden.
J. Liebeskind, A. Kloke, A. R. Fiebach, F. von Stetten, R. Zengerle, N. Paust
Mixing by on-chip generated gas bubbles for assay automation in standard laboratory centrifuges
2013 MicroTAS 2013, Freiburg, 27.-31.10.2013 , Seiten: 967 - 969
S. Thiele, T. Hutzenlaub, R. Zengerle
Multi-scale tomography of nano-porous hydrogen fuel cell catalyst layers
2013 5th International Conference on Porous Media & Annual Meeting in Prague, Tschechien, 21.-24.05.2013
S. Thiele, T. Hutzenlaub, R. Zengerle
Multi-scale tomography to understand mass transport limitations in the cathode catalyst layer of a PEMFC
2013 Hydrogen + Fuel Cell Conference 2013 (HFC 2013) in Vancouver, Canada, 16. - 19.06.2013
KurzfassungThe cathode catalyst layer (CCL) of a polymer electrolyte membrane fuel cell (PEMFC ), where the oxygen reduction reaction occurs, has a major influence on PEMFC performance [1]. Optimizing transport of all reactants to reaction centers is central in the high current density regime where mass transport limitations occur [2]. In the past, we demonstrated that the pore structure in the CCL can be reconstructed using Focused Ion Beam / Scanning Electron Tomography tomography (SEMt) approaches [3]. SEMt resolution is however not high enough to image Pt catalyst morphologies. We developed an approach to combine SEMt with a Transmission Electron Microscopy tomographic (TEMt) approach within the same geometry. Thereby we include information from two different scales and two different tomographic techniques. For the first time we present results on diffusion time and electron transport time through the pore space to all imaged active centers. This is an important step to understand mass transport limitations in the CCL.
O. Strohmeier, S. Laßmann, B. Riedel, D. Mark, G. Roth, M. Werner, R. Zengerle, F. von Stetten
Multiplex SNP Genotyping of Tumorcell DNA for KRAS mutations by allele specific real-time PCR on a centrifugal microfluidic disk segment “GeneSlice”
2013 7. Senftenberger Innovationsforum Multiparameteranalytik, 18. - 19.04.2013
KurzfassungPoint Mutations (SNP) on the KRAS oncogene have been identified as an important predictive biomarker for response to EGFR-targeted therapy of colorectal carcinomas. Since KRAS mutations are prevalent in up to 40% of all colorectal carcinomas, routinely conducted KRAS genotyping is becoming mandatory to predict therapy success and to reduce therapy costs by avoiding ineffective treatment. We demonstrate a low-cost, disposable centrifugal microfluidic cartridge “GeneSlice” for the parallel detection of the seven most relevant KRAS point mutations by allele-specific real-time PCR, a recently discussed cost effective alternative technique to dideoxy-sequencing. Microfluidic processing of the GeneSlices as well as allele-specific amplification and real-time detection are conducted in a slightly modified, commercially available PCR thermocycler, requiring only minor hands on time. Intra-chip standard deviation of Cq values on the GeneSlices was negligible. In 23/24 experiments, DNA from 6 cancer cell lines (n = 4 per cell line) was genotyped correctly and concordant with dd-sequencing. Additionally, DNA derived from microdissected formalin-fixed and paraffin embedded colorectal carcinomas of two cases was genotyped correctly and reproducibly (n = 3 per patient; 1 GeneSlice excluded from evaluation). The GeneSlice therefore clearly demonstrates the potential to become a valuable tool for routine diagnostics of KRAS mutations by reducing costs and hands-on time.
O. Strohmeier, S. Laßmann, B. Riedel, M. Werner, D. Mark, R. Zengerle, F. von Stetten
Multiplex detection of KRAS point mutations from tumor cell DNA on a centrifugal microfluidic cartridge (GeneSlice) for choice of personalized cancer therapy
2013 MicroTAS 2013, Freiburg, 27.-31.10.2013 , Seiten: 1815 - 1817
S. Kerzenmacher, J. Danzer, E. Kipf, A. Kloke, C. Köhler, S. Sané, R. Zengerle
Neue Materialien und Konzepte für Biobrennstoffzellen
2013 Microsystemtechnik (MST) Kongress 2013, Aachen, 14. - 16.10.2013 , Seiten: 626 - 629
KurzfassungBiobrennstoffzellen sind ein vielversprechender Ansatz zur autarken Energieversorgung verteilter Systeme, wie z.B. medizinische Implantate oder verteilte Sensoren. In unserem Beitrag stellen wir neue Materialien und Konzepte vor, um die Leistung und Langzeitstabilität dieser Systeme zu verbessern.
D. Liang, J. Zhang, T. G. Muniyogeshbabu, L. Tanguy, A. Ernst, P. Koltay, R. Zengerle
Novel automated multi-principle volume calibration system for non-contact micro and nano liter liquid handling devices
2013 Society for Laboratory Automation & Screening (SLAS) 2013: 2nd annual Conference & Exhibition in Orlando, FL, USA, 12.01. – 16.01.2013
L. Tanguy, L. Gutzweiler, P. Koltay, R. Zengerle, L. Riegger
On-demand electrophoretic separation of DNA in written gel lines on planar substrates
2013 Transducers 2013, Barcelona, Spain, 16. – 18.06.2013 , Seiten: 1223 - 1226
KurzfassungWe report a new approach to perform on-demand electrophoretic separation of DNA. In contrast to standard chip-based capillary electrophoresis in micromachined glass chips, we apply a planar polyimide substrate, write 200 μm wide gel lines bridging two Pt-electrodes and inject 500 pl sample volumes in non-contact manner. The gel is covered with mineral oil to inhibit evaporation. Subsequently, an electrical field is applied for 80 s and the separation of the DNA molecules (56 bp-Cy5 and 112 bp-Cy5, 10 μM) is successfully demonstrated.
M. Pospischil, M. Klawitter, M. Kuchler, J. Specht, H. Gentischer, R. Efinger, C. Kroner, M. Luegmair, M. König, M. Hoerteis, C. Mohr, L. Wende, J. Lossen, M. Weiß, O. Doll, I. Koehler, R. Zengerle, F. Clement, D. Biro
Process Development for a High-Throughput Fine Line Metallization Approach Based on Dispensing Technology
2013 4th Workshop on Metallization for Crystalline Silicon Solar Cells, Konstanz, Germany , 07. – 08.05.2013 Energy Procedia, Band: 43, Seiten: 111 - 116
M. Blazek, R. Zengerle, M. Meier
Proximity ligation assay for high content profiling of cell signaling pathways on a microfluidic chip
2013 MicroTAS 2013, Freiburg, 27.-31.10.2013 , Seiten: 293 - 295
S.K. Vashist, G. Czilwik, F. von Stetten, R. Zengerle
Rapid Immunodiagnostic Kits based on proprietary 1-step chemistry for covalent and leach-proof antibody immobilization
2013 Microsystemtechnik (MST) Kongress 2013, Aachen, 14. - 16.10.2013 , Seiten: 384 - 387
KurzfassungWe have developed a novel chemistry for the 1-step immobilization of antibodies on solid-substrate bioanalytical platforms. It enables the development of rapid immunodiagnostic (ID) kits that are analytically superior to the commercial ID kits using conventional antibody immobilization procedure. The developed chemistry is low-cost as it simply involves the dilution of capture antibodies in a particular concentration of 3-aminopropyltriethoxysilane (APTES), which is in fact cheaper than the phosphate buffered saline. It enables the leach-proof covalent binding of capture antibodies in just 30 min, which is >20-fold and >4-fold more rapid than the conventional (used in commercial ID kits) and our previously developed immobilization procedures, respectively. The immobilization chemistry was employed for the developed of rapid ID kit, based on sandwich enzyme-linked immunosorbent immunoassay (ELISA), to detect human Creactive protein (hCRP) in the dynamic range of 15.6-4000 pg/mL. The developed ID was very highly-sensitive and can detect the entire pathophysiological range of CRP in human serum after appropriate sample dilution. The developed chemistry has very high commercial potential as it will enable the development of very highly-sensitive ID kits for clinical, industrial and bioanalytical applications.
L. Tanguy, S. Bammesberger, A. Ernst, R. Zengerle, P. Koltay
Smart pressure driven and regulated dispenser for the nanoliter and microliter range
2013 Society for Laboratory Automation & Screening (SLAS) 2013: 2nd annual Conference & Exhibition in Orlando, FL, USA, 12.01. – 16.01.2013
A. Kloke, L. Drechsel, S. Zhang, A.R. Fiebach, N. Paust, R. Zengerle, F. von Stetten
The LabTube Platform – Disposable Cartridges For Automated Processing Of Biochemical Assays In Standard Laboratory Centrifuges
2013 21st annual international BIODETECTION TECHNOLOGIES, Washington, DC, USA, 18-19.6. 2013
KurzfassungA laboratory centrifuge can be applied to automate biochemical assays for point-of-care diagnostics or sample preparation such as DNA or protein extraction. Key innovation is integration of liquid handling into a 50 ml centrifuge tube. This "LabTube" harbors three revolvers which are stepwise rotated against each other by a g-force operated ball pen mechanics. The first revolver sequentially releases pre-stored reagents into the second revolver which is equipped with a mixing chamber and a solid phase column. Fractions of processed liquids are collected by the third revolver. Automated LabTube based DNA-extractions showed comparable yields to manual reference extractions.
K. G. Kraiczek, R. Bonjour, Y. Salavdé, R. Zengerle
Ultra high flexible UV-VIS radiation source and novel detection schemes for spectrophotometric HPLC detection
2013 MicroTAS 2013, Freiburg, 27. - 31.10.2013 , Seiten: 1977 - 1979
S. Thiele, J. Erben, T.Hutzenlaub, R. Zengerle
Virtuelles Design nano- und mikroporöser Materialien für Energieanwendungen
2013 Microsystemtechnik (MST) Kongress 2013, Aachen, 14. - 16.10.2013 , Seiten: 857 - 859
KurzfassungPoröse Schichten sind zentrale Elemente zukunftsträchtiger Technologien, wie Batterien, Brennstoffzellen und organi-schen Solarzellen. Die komplexen nano-porösen Strukturen, die in diesen Materialien auftreten, erschwerten in der Ver-gangenheit fundierte Untersuchungen. Wir zeigen anhand einer Wasserstoffbrennstoffzellenkathode ein tomographi-sches Verfahren dass es ermöglicht 3D Informationen von verschiedenen Skalen miteinander zu kombinieren. Basie-rend auf diesen Daten zeigen wir neuartige Simulationsansätze in porösen Medien auf. Die Kombination von 3D Infor-mationen und neuartigen Modellierungsansätzen ermöglicht es das Verbesserungspotential solcher Schichten zu evalu-ieren.
A. Madjarov, W. Streule, B. Schaub, A. Ernst, R. Zengerle, P. Koltay
Wireless Eight Channel Printhead for Non-Contact Nanoliter Droplet Ejection
2013 European Lab Automation 2013 (ELA2013), Hamburg, 06. – 07.06.2013
KurzfassungThe new developed system is based on a highly integrated actuator which implements an eight channel nanoliter dispenser. It is built at a footprint of a standard SBS well plate, thus can be placed on available deck-tray positions of existing liquid handling platforms to extend their volume range to the lower end. Considering the application of the presented dispensing device, completely new prospects for high-throughput-screening, miniaturized assays and other applications using standard liquid handling platforms arise. The droplet ejection method is based on the PipeJetTM-technology. This method uses a piezo-driven piston squeezing a disposable dispensing tube to eject free flying droplets. To make this technology ready for automated handling, novel dosage elements (PipeJet-Tip) were developed. These PipeJet-Tips are compatible to standard pipetting interfaces and are molded in polypropylene including the 650 µm dispensing tube and the reservoir. Therefore, a low cost disposable dispensing element is implemented enabling the ejection of single droplets with volumes down to 20 nl (CV < 5%). The new actuator is able to address eight individual dispensing channels to imprint custom droplet patterns. Rechargeable batteries as power supply and wireless communication housed inside the system enable the autonomous working principle of the dispensing module.

2012

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T. van Oordt, O. Strohmeier, D. Mark, R. Zengerle, M. Eberhard, J. Drexler, P. Patel, M. Weidmann, A. Zgaga-Griesz, W. Bessler, F. von Stetten
The LabDisk - A Fully Automated Centrifugal Lab-on-a-Chip System for the Detection of Biological Threats
2012 7th Security Research Conference, Future Security 2012, Bonn, Germany , Seiten: 220 - 223
D. Mark, T. van Oordt, O. Strohmeier, G. Roth, N. Paust, D. Kosse, J. Drexler, M. Eberhard, F. von Stetten, R. Zengerle
A Functional Blister-Pack LabDisk System for Point of Care Testing
2012 Forum Biotechnologie Baden-Württemberg 19. September 2012, Freiburg
T. van Oordt, O. Strohmeier, D. Mark, D. Kosse, G. Roth, K. Achazi, P. Patel, S. Linke, N. Paust, M. Weidmann, J. Drexler, F. Hufert, R. Zengerle, M. Eberhard, M. Niedrig, F. von Stetten
A Functional Blister-Pack LabDisk System for Point of Care Testing
2012 64th Annual Meeting of the German-Society-for-Hygiene-and-Microbiology (DGHM) Location: Hamburg, GERMANY Date: SEP 30-OCT 03, 2012 Int. J. of Med. Microbiol., Band: 302, Ergänzungsband: 1, Seite: 7-7
S. Bammesberger, A. Ernst, L. Tanguy, R. Zengerle, P. Koltay
A calibration-free, disposable, non-contact reagent dosing cartridge for the sub-µl range
2012 Microfluidic Handling Systems, MFHS 2012, Enschede, The Netherlands, 10.10. – 12.10.2012 , Seiten: 54 - 57
S.K. Vashist
A label-free and real-time surface plasmon resonance-based immunoassay for the highly sensitive detection of human fetuin A in 15 minutes
2012 Label-free Technologies 2012; Amsterdam, The Netherlands, 01.11. – 03.11.2012
S. Bammesberger, S. Kartmann, L. Tanguy, D. Liang, K. Mutschler, A. Ernst, P. Koltay, R. Zengerle
A low-cost, normally closed, solenoid valve for non-contact dispensing in the sub-µL range
2012 1st International Conference on Microfluidic Handling Systems, October 2012, Enschede, The Netherlands , Seiten: 156 - 159
A. Madjarov, W. Streule, P. Prokopp, R. Zengerle, P. Koltay
A novel technology for automated liquid handling with disposable tips for the sub microliter range
2012 SLAS 2012, San Diego, USA, February 4-8, 2012
D. Mark, T. van Oordt, O. Strohmeier, G. Roth, J. Drexler, M. Eberhard, M. Niedrig, P. Patel, A. Zgaga-Griesz, W. Bessler, M. Weidmann, F. Hufert, R. Zengerle, F. von Stetten
Automated and miniaturized detection of biological threats with a centrifugal microfluidic system
2012 Smart Biomedical and Physiological Sensor Technology IX Baltimore, Maryland, USA | April 23, 2012 Proc. SPIE 8367
J. Schoendube, D. Wright, A. Yusof, R. Zengerle, P. Koltay
CellJet: Label-Free Cell Printing via Real-Time Impedance Flow Cytometry for Single Cell Analysis
2012 MicroTAS 2012, Okinawa/Japan, 28.10. - 01.11.2012 , Seiten: 419 - 421
M. Pospischil, J. Specht, H. Gentischer, M. König, M. Hoerteis, C. Mohr, R. Zengerle, F. Clement, D. Biro
Correlations between finger geometry and dispensing paste rheology
2012 EU-PVSEC in Frankfurt, 24.09.2012 – 27.09.2012 , Seiten: 1773 - 1776
O. Strohmeier, B. Kanat, D. Bär, P. Patel, J. Drexler, T. van Oordt, G. Roth, D. Mark, R. Zengerle, F. von Stetten
DNA based sample-to-answer analysis on a centrifugal microfluidic foil cartridge
2012 MicroTAS 2012, Okinawa/Japan, 28.10. - 01.11.2012 , Seiten: 779 - 781
P. Patel, M. Weidmann, K. Achazi, S. Linke, O. Strohmeier, D. Mark, T. van Oordt, J. Drexler, M. Eberhard, F. von Stetten, M. Niedrig
Development of Rapid Diagnostic Platform for Detection of Category A Biothreat Pathogens in the Field
2012 ASM Biodefense & Emerging Diseases, Washington, MD, USA, February. 26-29, 2012
KurzfassungIncreased threat of infectious diseases and bioterrorist incidents pose danger to the human population. As a preparedness of such incidents, a rapid detection system for identification of biothreat agents is needed. The S.O.N.D.E. project intends to develop a suitcase size platform for the detection of category A biothreat pathogens by nucleic acid and antigen detection. One subproject is dealing with the development of molecular methods such as enrichment of pathogens and nucleic acid isolation. These assays are designed to be used in an integrated bio-analytical system being developed by our S.O.N.D.E. project partners for rapid detection of a number of pathogens and toxins. To concentrate enveloped and non-enveloped viruses from large volume biological samples, an enrichment method based on polymer was developed. Viruses captured by polymer were successfully analyzed for nucleic acid detection, virus infectivity assay and electron microscopy. Also the nucleic acid purification using paramagnetic beads was successfully developed and tested on different model pathogens (gram+ and gram- bacteria, RNA and DNA viruses). Purified nucleic acid was detected by real-time PCR and an isothermal amplification method for different pathogens in spiked samples and the limit of detections was 10-100 genome copies/ml. Centrifugal microfluidic platform and portable device have been developed by our project partners for the detection of biothreat pathogens in automated “sample to answer”-platform. Developed methods like nucleic acid isolation and isothermal amplification were integrated into this platform. Furthermore, this platform is going to be evaluated and compared with conventional laboratory methods as well as commercial available rapid diagnostic platforms.
Y. Abbas, J. Miwa, R. Zengerle, F. von Stetten
Development of an active micromixer using an external mechanical actuator array
2012 1st International Conference on Microfluidic Handling Systems, October 2012, Enschede, The Netherlands , Seiten: 34 - 37
KurzfassungWe present an active continuous-flow micromixer based on channel-wall deflection in a polydimethylsiloxane (PDMS) chip using Braille display pins. The chip design comprises a main microchannel connected to a series of side channels with dead ends aligned on the Braille pins. Computercontrolled deflection of the side-channel walls induces chaotic advection in the main-channel, which substantially accelerates mixing in low-Reynolds number flow. Several influencing parameters such as the number of cross-channels, actuation frequency, side-channel width, actuation sequence, and flow rate velocities have been investigated. Sufficient mixing of fluids could be achieved within seconds (~500 ms). Finally, continuous dilution of yeast cell sample by a ratio down to 1:10 is successfully demonstrated.
L. Tanguy, D. Liang, R. Zengerle, P. Koltay
Droplet generation at the critical Weber numbers
2012 65th Annual Meeting of the American Physical Society Division of Fluid Dynamics, 2012, San Diego, California USA, 18th - 20th November 2012
KurzfassungThe ejection of liquid droplets from a nozzle is highly important for physics of fluid. The Weber number describes how much kinetic energy is needed to overcome the surface tension and create a free-flying droplet. According to literature Weber numbers above 12 assure the creation and safe break up of a liquid droplet. However, even when this number goes down below 8, it is still possible to observe droplet break-up but with particular effects. We present here experimental results and CFD simulations for droplet break-up at low Weber number where the droplet is generated with negative kinetic energy. Such droplet generation is characterized by the droplet breaking up and then returning back into the nozzle. This is due to the fact that during the droplet formation the surface tension begins to slow down the flow velocity inside the droplet and then finally inverts the flow direction, while the droplet tail still breaks off from the nozzle. Thus after the break up the droplet momentum is oriented toward the nozzle. It is therefore possible to observe the droplet returning into the bulk fluid. High-speed images of this particular phenomenon are shown and simulation results are presented to illustrate the break up dynamics and the local velocities in the droplet.
Simon Herrlich, Sven Spieth, Hans Gerstmann, Astrid Virnich, Thorsten Goettsche, Peter Osypka, Roland Zengerle
Drug Release Mechanisms from Steroid Eluting Rings in Cardiac Pacemaker Lead Electrodes
2012 IEEE-EMBC 2012, San Diego, Kalifornien, USA, 28.08.- 01.09.2012
S.K. Vashist, M. Saraswat
Effect of 3-aminopropyltriethoxysilane-based antibody immobilization chemistries on the performance of surface plasmon resonance-based human fetuin A immunoassay
2012 Label-free Technologies 2012; Amsterdam, The Netherlands, 01.11. – 03.11.2012
K. Mutschler, W. Kunert, R. Ingenpaß, K. E. Grund, L. Tanguy, A. Ernst, R. Zengerle, P. Koltay
EndoMediskop: Trans-Endoscopic Microinjection for Flexible Endoscopy
2012 BMT 2012 - Biomedical Technology Congress in Jena, Germany, 16.09. – 19.09.2012 Biomed Tech, Band: 57, Ergänzungsband: 1, Seiten: 361 - 364
N. Lass, L. Riegger, A. Ernst, R. Zengerle, P. Koltay
Enhanced liquid metal micro droplet generation by pneumatic actuation based on the StarJet Method
2012 1st International Conference on Microfluidic Handling Systems, October 2012, Enschede, The Netherlands , Seiten: 38 - 41
J. Hoffmann, S. Hin, F. von Stetten, R. Zengerle, G. Roth
Fabricating DNA Microarrays By Copying A Next Generation Sequencing Chip
2012 MicroTAS 2012, Okinawa/Japan, 28.10. - 01.11.2012 , Seiten: 1528 - 1530
M. Vosseler, T. Botzelmann, P. Schilling, S. Spieth, S. Messner, V. Mayer, M. Schmelz, H. Kück, R. Zengerle
In vivo and ex vivo intradermal infusion and injection experiments with microneedles
2012 Microneedles 2012, Cork, Ireland, May 13-15, 2012
F Stumpf, D Mark, G Roth, R Zengerle, F von Stetten
Lab-on-a-chip disposable cartridges for DNA purification and genotyping processed in standard laboratory instruments
2012 Biosensors 2012; Cancun, Mexico , Seite: P2.62
S. Wadle, O. Strohmeier, M. Rombach, D. Mark, R. Zengerle, F. von Stetten
LabDisk integrated DNA Extraction from Whole Blood using Magnetic Particles
2012 MicroTAS 2012, Okinawa/Japan, 28.10. - 01.11.2012 , Seiten: 1381 - 1383
T. Brettschneider, C. Dorrer, R. Zengerle, M. Daub
Laser welded microfluidic plasma separation unit with on-chip pressure conversion
2012 Lab-on-a-Chip European Congress, Edinburgh, UK, March 28-29, 2012
M. Trotter, F. von Stetten, G. Roth, R. Zengerle, J. Hoffmann
Massively-parallel digital solid-phase PCR for the in-situ generation of a sequencing-ready picowell array circumventing emPCR
2012 Digital PCR Conference, San Diego, USA, 15.10. – 16.10.2012
R. Zengerle, J. Hoffmann, G. Roth, O. Strohmeier, A. R. Fiebach, L. Drechsel, S. Zhang, A. Kloke, N. Paust, D. Mark, F. von Stetten
Microfluidic Apps on standard Lab-instruments
2012 MicroTAS, Okinawa, Japan, 28. Okt. - 01. Nov. 2012 , Seiten: 239 - 241
KurzfassungHere we promote a new way of thinking: Designing microfluidic chips that can be processed on standard instruments which are already present in typical laboratory setups. Those instruments could be standard lab centrifuges, real-time PCR cyclers or even second generation sequencers. We call this approach the Microfluidic App approach
S. Zehnle, M. Rombach, F. von Stetten, R. Zengerle, N. Paust
Microfluidic centrifugo-pneumatic siphon enables fast blood plasma extraction with high yield and purity
2012 MicroTAS 2012, Okinawa/Japan, 28.10. - 01.11.2012 , Seiten: 869 - 871
J. Burger, O. Stoevesandt, J. Hoffmann, F. von Stetten, R. Zengerle, G. Roth, F Stumpf
Microfluidic hand-helds for DNA to protein microarray replication by cell-free systems
2012 Biosensors 2012; Cancun, Mexico , Seite: P3.141
D. Liang, J. Zhang, T. G. Muniyogeshbabu, S. Bammesberger, L. Tanguy, A. Ernst, P. Koltay, R.Zengerle
Multi-principle droplet calibration technology
2012 MicroTEC Südwest Clusterkonferenz 2012, Stuttgart, Germany, 14. - 15. May 2012
A. Madjarov, W. Streule, P. Prokopp, A. Ernst, R. Zengerle, P. Koltay
Nanoliter Dispensing on Pipetting Workstations by Disposable PipeJet-Tips
2012 Actuator 2012, Bremen, Germany, June 18-20 , Seiten: 430 - 433
D. Liang, J. Zhang, L. Tanguy, A. Ernst, P. Koltay, R. Zengerle
Nanoliter droplet characterization using vibrating crystal sensor with surface-attachedpolymer hydrogel coating
2012 Eurosensors XXVI, Krakow/Poland, 09. - 12. September 2012 Procedia Engineering, Band: 47, Seiten: 1017 - 1020
J. Schöndube, F. Stumpf, A. Gross, R. Zengerle, G. Roth, P. Koltay
Non-Contact Single Cell Printing For Single Cell Real-time PCR
2012 EMBL Conference Microfluidics 2012, Heidelberg, Germany, July 25-27 , Seite: p185
P. Koltay
Non-contact micro dispensing technologies for science and industry
2012 Actuator 2012, Messe Bremen, Germany, June 18 - 20, 2012
D. Liang, L. Tanguy, A. Ernst, R. Zengerle, P. Koltay
Novel gravimetric calibration method for nanoliter liquid handling devices
2012 1st International Conference on Microfluidic Handling Systems, October 2012, Enschede, The Netherlands , Seiten: 144 - 147
M. Salzer, S. Thiele, R. Zengerle, V. Schmidt
On automatic segmentation of FIB-SEM images
2012 Forum Bildverarbeitung, Regensburg, 29.-30. Nov. 2012
D. Liang, T.G. Muniyogeshbabu, L. Tanguy, A. Ernst, R. Zengerle, P. Koltay
Online liquid calibration technologies
2012 1st International Conference on Microfluidic Handling Systems, October 2012, Enschede, The Netherlands , Seiten: 95 - 98
G.B. Stevens, D. Silver, T. van Oordt, S.K. Vashist, G.A. Urban, M. Krueger
Optimizing the luciferase release assay for the automated detection of Botulunim Neurotoxin type A
2012 IBRCC 2012 - 49th Annual Meeting of the Interagency Botulism Research Coordinating Committee, Baltimore, MD, USA, September 4-7, 2012
J. Schöndube, A. Yusof, D. Wright, K. Kalkandjiev, R. Zengerle, P. Koltay
Picoliter Droplet Dispenser with Integrated Impedance Detector for Single-cell Printing
2012 Actuator 2012, Bremen, Germany, June 18-20 , Seiten: 418 - 421
L. Tanguy, A. Ernst, S. Bammesberger, R. Zengerle, P. Koltay
Pressure driven and regulated dispenser for the microliter range
2012 Microfluidic Handling Systems, MFHS 2012, Enschede, The Netherlands, 10.10. – 12.10.2012 , Seiten: 50 - 53
T. Hutzenlaub, R. Zengerle, S. Thiele
Reconstruction of the active material, binder and pore space of a LiCoO2 Li-ion battery cathode
2012 221st ECS Meeting Seattle, WA | May 6-10, 2012 , Seite: Nr. 547
F. Schwemmer, S. Zehnle, N. Paust, C. Blanchet, M. Rössle, F. v. Stetten, R. Zengerle, D. Mark
SAXS-LabDisk: A centrifugal microfluidic screening platform for protein structure analysis
2012 MicroTAS 2012, Okinawa/Japan, 28.10. - 01.11.2012 , Seite: p186
F. Schwemmer, S. Zehnle, N. Paust, C. Blanchet, D. Svergun, F. v. Stetten, R. Zengerle, D. Mark, M. Rössle
SAXS-LabDisk: A centrifugal microfluidic screening platform for protein structure analysis
2012 SAS Conference, Sydney, Autralia, Nov. 18 - 23, 2012
KurzfassungA small angle x-ray scattering (SAXS) screening platform for protein structure analysis based on centrifugal microfluidics is presented. SAXS can be used to reconstruct low-resolution structures of macromolecules directly from solution scattering. This enables screening for conformational changes of proteins due to different environmental conditions. However, for state-of-the art techniques, consumption of the protein samples is still at least 6 µl per condition and the time per measurement is at best 3 min. In most cases this still renders multi-parameter screening impractical. We present a centrifugal microfluidic platform capable of decreasing both, time per measurement and consumed protein volumes in small angle scattering screenings by more than one order of magnitude. During an automated rotational protocol the presented compact disk prepares 20 different screening conditions for each protein using 2 µl protein solution, 3 µl buffer and 3 µl screening solution. The three input solutions are split into 40 nl aliquots, the aliquots are then combined at predefined ratios, mixed and can be measured on chip. Up to seven independent protein screenings can be performed on one chip. Protein solution (2 µl), screening reagent (3 µl) and buffer solution (3 µl) are pipetted in the disk. During an automated rotational protocol the liquids are split into 120 aliquots of 40 nl each. Then 6 of these aliquots are combined, respectively. This results in 20 mixtures of different predefined ratios. One disk has enough space for seven dilution matrices or 140 experiments, which can be performed on chip within a SAXS beamline. Including positioning within the beam, the expected time per measurement is less than 5 s. The SAXS-LabDisk will enable routine SAXS screening of minute protein volumes. The performance of the SAXS-LabDisk for protein structure determination will be evaluated at the beamline PETRA-III at EMBL Hamburg, Germany later this year.
F. Schwemmer, S. Zehnle, N. Paust, C. Blanchet, D. Svergun, F. von Stetten, R. Zengerle, D. Mark, M. Rössle
SAXS-LabDisk: A centrifugal microfluidic screening platform for protein structure analysis
2012 EMBL Conference Microfluidics 2012, Heidelberg, Germany, July 25-27 , Seite: 186
KurzfassungA small angle x-ray scattering (SAXS) screening platform for protein structure analysis based on centrifugal microfluidics is presented. SAXS can be used to reconstruct low-resolution structures of macromolecules directly from solution scattering. This enables screening for conformational changes of proteins due to different environmental conditions. However, for state-of-the art techniques, consumption of the protein samples is still at least 6 µl per condition and the time per measurement is at best 3 min. In most cases this still renders multi-parameter screening impractical. We present a centrifugal microfluidic platform capable of decreasing both, time per measurement and consumed protein volumes in small angle scattering screenings by more than one order of magnitude. During an automated rotational protocol the presented compact disk prepares 20 different screening conditions for each protein using 2 µl protein solution, 3 µl buffer and 3 µl screening solution. The three input solutions are split into 40 nl aliquots, the aliquots are then combined at predefined ratios, mixed and can be measured on chip. Up to seven independent protein screenings can be performed on one chip. Protein solution (2 µl), screening reagent (3 µl) and buffer solution (3 µl) are pipetted in the disk. During an automated rotational protocol the liquids are split into 120 aliquots of 40 nl each. Then 6 of these aliquots are combined, respectively. This results in 20 mixtures of different predefined ratios. One disk has enough space for seven dilution matrices or 140 experiments, which can be performed on chip within a SAXS beamline. Including positioning within the beam, the expected time per measurement is less than 5 s. The SAXS-LabDisk will, for the first time, enable routine SAXS screening of minute protein volumes. The performance of the SAXS-LabDisk for protein structure determination will be evaluated at the beamline PETRA-III at EMBL Hamburg, Germany later this year.
M. Rombach, S. Lutz, C. Dumschat, A. Witt, S. Hensel, S. Frenzel, F. Aßmann, F. Gehring, T. Reiner, H. Drechsel, P. Szallies, D. Mark, G. Roth, R. Zengerle, F. von Stetten
Sample-to-Answer LabDisk for Point-of-care Analysis of Total Cholesterol from Whole Blood
2012 MicroTAS 2012, Okinawa/Japan, 28.10. - 01.11.2012 , Seiten: 782 - 784
E. Kipf, J. Koch, B. Geiger, S. Kerzenmacher
Systematic comparison of anode materials for microbial fuel cells
2012 7. EU-ISMET 2012 in Ghent, Belgium, 27.09. – 28.09.2012 Comm. Appl. Biol. Sci, Ghent University, 77/2, 2012, Seite: 128
T. van Oordt, O. Strohmeier, D. Mark, R. Zengerle, M. Eberhard, J. Drexler, F. von Stetten
The LabDisk – a fully automated point-of-care system for the detection of biological threats
2012 7. Lab-on-a-Chip World Congress in San Diego, USA, 25.09. – 26.09.2012
D. Mark, O. Strohmeier, T. van Oordt, G. Roth, D. Kosse, R. Zengerle, Felix von Stetten
The centrifugal microfluidic LabDisk platform for the automation of nucleic acid analysis and immunoassays
2012 EMBL Conference Microfluidics 2012, Heidelberg, Germany, July 25-27 , Seite: 66
J. Danzer, B. Bierer, S. Kerzenmacher
The effect of electrical load variations on the performance of different anode materials for microbial fuel cells
2012 7. EU-ISMET 2012 in Ghent, Belgium, 27.09. – 28.09.2012 Comm. Appl. Biol. Sci, Ghent University, 77/2, 2012, Seite: 126
S. Sané, S. Rubenwolf, C. Jolivalt, S. Kerzenmacher
Using fungi to produce electricity- Towards a self-regenerating enzymatic biofuel cell
2012 the 63rd Annual Meeting of the International Society of Electrochemistry, Prague, Czech Republic, August 19-24 , Seite: 40
S. Sané, S. Rubenwolf, C. Jolivalt, S. Kerzenmacher
Using microorganisms to extend the lifetime of an enzymatic biofuel cell cathode
2012 7. EU-ISMET 2012 in Ghent, Belgium, 27.09. – 28.09.2012 Comm. Appl. Biol. Sci, Ghent University, 77/2, 2012, Seite: 20
S. Sané, S. Rubenwolf, C. Jolivalt, S. Kerzenmacher
Using yeast and fungi to produce electricity - Towards a self-regenerating enzymatic biofuel cell cathode
2012 Biospektrum Tagungsband zur VAAM Jahrestagung, Tübingen, Deutschland, March 18-21, 2012, 135
A. Yusof, K. Kankandjiev, J. Schöndube, R. Zengerle, P. Koltay
Wafer Level Fabrication of an Integrated Microdispenser with Electrical Impedance Detection for Single-cell Printing
2012 Proc. Of Smart Systems Integration, Zürich, Switzerland, March 21-22, 2012 , Band: paper 99, Seite: 4pp

2011

nach oben zur Jahresübersicht

N. Lass, A. Tropmann, L. Riegger, R. Zengerle, P. Koltay
3D Rapid-Prototyping durch Drucken von flüssigem Metall unter Verwendung der StarJet Technologie
2011 Mikrosystemtechnik-Kongress, Darmstadt, Deutschland, October 10-12 , Seiten: 193 - 196
KurzfassungIn dieser Arbeit präsentieren wir einen neuen Ansatz für das direkte 3D-Prototyping von Metallstrukturen basierend auf der StarJet Technologie [1]. Im Gegensatz zu dem früheren Funktionsmuster (V0) verfügt die neue Version des Druckkopfs (V1) über hitzebeständigere Komponenten, die es erlaubt den Dispenser bei Temperaturen bis Tmax = 500°C zu betreiben (früher Tmax =_250°C). Dies ermöglicht das Dispensieren einzelner Tropfen aus Metall wie z.B. ZAMAK (Schmelztemperatur Tmelt = 450°C). Gleichzeitig wurde das Design und der Herstellungsprozess der sternförmigen Düsenchips optimiert. Die maximale Dosierfrequenz konnte somit um einen Faktor 10 auf fmax_=_4_kHz erhöht werden. Darüberhinaus konnte die Abweichung der Tropfenflugbahn von der Symetrieachse des Düsenchips auf unter deg_=_0,28° minimiert werden. In diesem Artikel berichten wir über die Ergebnisse der ersten experimentellen Versuche und präsentieren verschiedene 3D Metallstrukturen die damit gedruckt wurden.
Jürgen Burger, David Lämmle, Felix von Stetten, Oda Stoevesandt, Michael J Taussig, Roland Zengerle, Günter Roth
A hand-held DNA to protein microarray translation system
2011 Book of Abstracts of Functional Genomics, Frankfurt am Main, 03.-04.02.2011 , Seiten: 14 - 16
Jürgen Burger, David Lämmle, Felix von Stetten, Oda Stoevesandt, Michael J Taussig, Roland Zengerle, Günter Roth
A hand-held device to copy DNA to protein microarrays
2011 Proceedings of 2011 International Conference on Microtechnologies in Medicine and Biology Lucerne, Switzerland, 4-6 May , Seiten: 127 - 128
KurzfassungThe DNA Array to Protein Array (DAPA) system presented in 2008 by He et al. [1,2] allows to replicate protein microarrays from one master DNA microarray by cell-free expression and diffusion. We improved the basic idea by designing a hand-held microfluidic device replacing the porous membrane used in [1,2] by a microfluidic gap of ~50 μm in height. Hence any mechanical damage inflicted by the membrane is prevented as only the cell free system is in physical contact with the microarrays. The capillary priming of the microfluidic gap leads to a defined protein expression start. Protein translation and microarray formation only needs 30 minutes at 25 °C, the amount of cell free system needed is reduced significantly. The DNA master array can be re-used for multiple protein expressions.
A. Gross, J. Schöndube, S. Rubenwolf, A. Yusof, G. Roth, R. Zengerle, P. Koltay
Automatic Single Cell Printing for Tissue Engineering and Stem Cell Research
2011 45. Deutschen Gesellschaft für Biomedizinische Technik (DGBMT), September 27-30, Freiburg
KurzfassungWe present a novel method for automatic non-contact printing living single cells currently being developed within the PASCA project (www.pasca.eu). A microfluidic dispenser [1] with optical feedback prints single cells confined in free flying droplets of only hundreds of picoliter volume onto arbitrary substrates. Single yeast, cancer (HeLa) and stem cells (fibroblasts, keratinocytes) have been successfully printed with this method at viabilities of up to 95 %. Apart from applications in research and diagnostics the technology can also be used for tissue engineering. To show the feasibility an extra cellular matrix comprised of collagen and alginate has been printed.
J. Schöndube, A. Yusof, A. Gross, S. Rubenwolf, D. Liang, G. Roth, R. Zengerle, P. Koltay
Automatisiertes Drucken einzelner Zellen mittels eines kontaktfreien Druckverfahrens im Picoliterbereich
2011 Mikrosystemtechnik-Kongress, Darmstadt, Deutschland, October 10-12 , Seiten: 902 - 905
KurzfassungWir präsentieren einen Einzelzellmanipulator (EZM) zum automatisierten Drucken und Sortieren von Zellen. Der EZM ist Teil eines Projekts zur Realisierung einer „Platform for Advanced Single Cell-Manipulation and Analysis“ (PASCA, www.pasca.eu). Zellen werden in einem mikrofluidischen Tropfenerzeuger (NanoJet-Chip, [1]) von einer Kamera erkannt und mit hohen Überlebensraten einzeln in Pikoliter großen Tropfen auf beliebige Substrate kontaktfrei gedruckt [2]. Im Rahmen dieser Arbeit wurden Hefe-Zellen, Krebszellen (HeLa-Zellen) und Stammzellen (Fibroblasten, Keratinozyten) gedruckt. Zusätzlich wurden Überlebensraten von bis zu 95% und Einzelzellraten von bis zu 84% experimentell bestimmt.
S. Kerzenmacher, J. Danzer, E. Kipf, A. Kloke, C. Köhler, S. Rubenwolf, S. Sané, R. Zengerle, J. Gescher
Biobrennstoffzellen zur Energieversorgung von Mikrosystemen: vom energieautarken Implantat hin zum dezentralen Umwelt-Monitoring
2011 Mikrosystemtechnik-Kongress, Darmstadt, Deutschland, October 10-12 , Seiten: 375 - 378
KurzfassungBiobrennstoffzellen sind ein vielversprechender „Energy Harvesting“-Ansatz, bei dem die chemische Energie eines in der Umgebung verfügbaren Substrats in direkt nutzbare Elektrizität umgewandelt wird. In unserem Beitrag werden die verschiedenen Biobrennstoffzellenkonzepte vorgestellt und die zukünftigen Herausforderungen und Chancen der Tech-nologie an Hand von typischen Anwendungsbeispielen diskutiert.
H. Hoefemann, N. Bakhtina, S. Wadle, V. Kondrashov, N. Wangler, R. Zengerle
Bubble-Jet actuated cell sorting
2011 15th International Conference on Miniaturized Systems for Chemistry and Life Sciences (µTAS), October 2-6, 2011, Seattle, Washington, USA , Seiten: 2040 - 2042
KurzfassungWe present cell sorting based on Bubble-Jet actuation. 35 x 35 μm² heaters for bubble generation are fabricated on transparent Borofloat® wafer substrates and embedded into microfluidic channels in PDMS. The chips are assembled onto customized printed circuit boards (PCBs) in standard microscopy slide format of 76 x 26 mm². Hydrodynamically focused L929 mouse fibroblast cells are flowing with velocities in the order of 500 μm/s inside a channel (120 x 45 μm²). Cells of interest are selectively deflected about 60 μm from their original streamline by Bubble-Jet actuation to flow into a collector outlet.
K. Mutschler, A. Ernst, N. Paust, R. Zengerle, P. Koltay
Capacitive detection of nanoliter droplets on the fly - investigation of electric field during droplet formation using CFD-simulation
2011 16th International Solid-State Sensors, Actuators and Microsystems Conference (TRANSDUCERS), 5-9 June 2011, Beijing China , Seiten: 430 - 433
KurzfassungRecently we presented a capacitive droplet sensor that enables the characterization of volume and velocity of dispensed nanoliter liquid droplets on the fly in a contact free manner [1]. In this work we perform a multi-physics simulation study to understand the physical effects behind the sensor signal. We combine a two-phase fluid dynamics model for droplet generation and droplet flight with an electrostatic model for analyzing the electric field distribution inside an open plate capacitor while the droplet is passing through. Beside droplet volume and velocity, also droplet tear-off point as well as droplet oscillations are reflected in the electric field distribution. The characteristic negative dip of the transient sensor signal which was observed in experiments can be explained by capacitive coupling of the liquid column with the sensor and is correctly reflected by the model. The detected changes in charge on the sensor capacitor, are in the range of 2 – 28 fC and correspond to droplet volumes in the range of 5 nl < Vdrop < 100 nl. This is in good agreement with experimental findings and analytical approximations.
S. Lutz, D. Mark, G. Roth, R. Zengerle, F. von Stetten
Centrifugal microfluidic platforms for molecular diagnostics
2011 EuroMedLab Ber lin 2011 – Berlin, 15-19 May 2011 Clinical Chemistry and Laboratory Medicine, Band: 49, Ergänzungsband: 1, Seiten: 608 - 608
M. Focke, O. Strohmeier, P. Reith, G. Roth, D. Mark, R. Zengerle, F. von Stetten
Centrifugo-thermopneumatic liquid actuation for microfluidic genotyping of nucleic acids
2011 15th International Conference on Miniaturized Systems for Chemistry and Life Sciences (µTAS), October 2-6, 2011, Seattle, Washington, USA , Seiten: 659 - 661
KurzfassungWe report a novel principle to actuate liquids based on centrifugo-thermopneumatic effects. This approach enables us to reliably realize temperature-controlled valves and aliquoting structures on the centrifugal microfluidic platform. We present special geometries that force liquids to generate gas entrapments when exposed to a centrifugal field. The gas entrapments expand (or contract) when heated (or cooled) thus displacing the liquid volumes. Successful implementation of this principle is demonstrated by a microfluidic chip for automated real-time PCR based genotyping of nucleic acids.
S. Bammesberger, A. Ernst, D. Liang, S. Kartman, L. Tanguy, R. Zengerle, P. Koltay
Characterization of Dispensing Technologies in the sub-µl range
2011 MicroTEC Südwest Clusterkonferenz 2011, Karlsruhe, Germany, July 5 and 6, 2011:
M. Karle, G. Czilwik, J. Miwa, N. Paust, G. Roth, R. Zengerle, F. von Stetten
Continuous microfluidic DNA purification for online monitoring and process control
2011 Proceedings of 2011 International Conference on Microtechnologies in Medicine and Biology Lucerne, Switzerland, 4-6 May , Seiten: 197 - 198
KurzfassungWe demonstrate the first continuous microfluidic platform for flow-through DNA purification from cell lysate. Using superparamagnetic beads, DNA is continuously transported across interfaces between co-flowing laminar streams of extraction reagents. In on-chip experiments DNA was continuously purified over a time period of 110 min. After the on-chip purification, DNA content and purity of the eluate sampled at different stages of the continuous extraction experiment was analyzed off-chip via qPCR. Results show successful flow-through purification with constant output over almost the complete duration of the experiment. Possible applications are seen in biological safety and environmental monitoring or bioprocess control.
T. van Oordt, D. Mark, R. Zengerle, M. Eberhard, M. Niedrig, F. von Stetten
Development of a Fully Automated Centrifugal Lab-on-a-Chip System for Rapid Field Testing of Biological Threats
2011 Proc. of Future Security 2011, Berlin, Germany, September 5-7
KurzfassungThe world’s growing mobility, mass tourism and the threat of terrorism increase the risk of the fast spread of infectious microorganisms and toxins. Today’s procedures for pathogen detection involve complex, stationary devices. Their use is often too time consuming for a rapid and effective response. Therefore a robust and mobile diagnostic system is required. We are presenting a microstructured Lab-on-a-Chip test carrier which performs complex biochemical analysis and a mobile centrifugal microfluidic device to process this test carrier. This hand-held system will allow rapid automated detection of biological threats at the point of need.
Fabian Stumpf, Junichi Miwa, Nils Paust, Felix von Stetten, Roland Zengerle, Günter Roth
Development of segmented-flow microfluidic operations for single-cell nucleic acid analysis
2011 45. Deutschen Gesellschaft für Biomedizinische Technik (DGBMT), September 27-30, Freiburg
KurzfassungThe importance of single cell analysis is rapidly growing especially in the fields of biological and medical research. A cost- and time-efficient technology for handling and analyzing individual cells instead of averaging whole culture popu-lations is extremely attractive for applications like drug development, pathological screening, cancer development and many others. Segmented-flow microfluidics is thought to be highly suitable for this purpose, considering the ability to handle a series of minute reaction compartments at moderate-to-high throughputs. Our on-going development of segmented-flow microfluidic devices aims for the realization of an integrated, automated single-cell nucleic acid analysis system with complete sample preparation capabilities. Although some of the required unit operations such as droplet mixing and thermocycling are already fairly established in this field, key procedures such as accurate single-cell encapsulation and nucleic acid purification are still missing.
Stefanie Rubenwolf, Sonja Niekrawietz, Jonas Schöndube, André Gross, Azmi Yusof, Dong Liang, Peter Koltay, Roland Zengerle, Günter Roth
Digitaler Druck einer Hydrogelmatrix für das Einbetten von Zellen in künstlichen Zellverbänden
2011 Mikrosystemtechnik-Kongress, Darmstadt, Deutschland, October 10-12 , Seiten: 879 - 882
KurzfassungRapid Prototyping Verfahren auf Basis der Tintenstrahl-Drucktechnologie sind vielversprechende Ansätze zur Erzeu-gung dreidimensionaler heterogener Zellverbände als Organmodelle. Mit Hilfe der PipeJet™-Technologie konnte eine mehrschichtige Costruktur aus Collagen und Alginat gedruckt werden, die als Hydrogelmatrix zum Einbetten von Zellkulturen geeignet ist. Die hierzu aufgebaute automatisierte Plattform erlaubt steriles Arbeiten für synchrones Drucken von Zellen und Hydrogelmatrix zu künstlichen Zellverbänden.
Dominique Kosse, Dirk Buselmeier, Claas Müller, Roland Zengerle, Felix von Stetten
Druckluft-unterstütztes thermisches Deckeln folienbasierter Lab-on-a-Chip Kartuschen
2011 Mikrosystemtechnik-Kongress 2011, Darmstadt, Deutschland, October 10-12, 2011 , Seiten: 579 - 582
KurzfassungPräsentiert wird ein druckluft-unterstütztes thermisches Bondverfahren zum Deckeln dünnwandiger folienbasierter Lab-on-a-Chip Kartuschen (Lab-on-a-Foil) [1-3]. Das Verfahren verzichtet auf eine aufwendige Siegelaufnahme zur Siegelkrafteinleitung und ermöglicht eine auch unter thermischer Belastung stabile Deckelung von Lab-on-a-Foil Kartuschen. Besonders variotherme mikrofluidische Anwendungen mit schnellen Temperaturwechseln (z.B. Polymerase-Kettenreaktion) [4] profitieren von den dünnen Wandstärken und der temperaturstabilen Deckelung. Die Herstellung der Lab-on-a-Foil Kartuschen erfolgt durch Mikrothermoformen von Foliensubstraten, die anschließend gedeckelt werden. Die vorgestellte Deckelungsmethode nutzt Druckluft zur Einleitung der benötigten Siegelkraft. Als Siegelfolie wird eine co-extrudierte COC-Folie eingesetzt. Diese besteht aus einer Temperatur stabilen COC 6013-Trägerschicht und einer nieder-schmelzenden COC 8007 Siegelschicht. Experimentell konnte eine Druckstabilität der Siegelverbindung bis 500 kPa bei Raumtemperatur und bis zu 150 kPa unter Temperaturbelastung von 95°C gezeigt werden.
J. Hoffmann, S. Hin, F. von Stetten, R. Zengerle, G. Roth
Enabling DNA-microarrays in polymeric lab-on-a-chip substrates for multiplexed target analysis via solid-phase PCR
2011 15th International Conference on Miniaturized Systems for Chemistry and Life Sciences (µTAS), October 2-6, 2011, Seattle, Washington, USA , Seiten: 1840 - 1842
KurzfassungA novel universal protocol is demonstrated for covalent grafting of solid-phase PCR primers oriented onto glass and various polymers (COP, PP, COC, PDMS) relevant for Lab-on-a-chip (LoaC) applications. Primers immobilized in a DNAmicroarray format feature spots with high homogeneity and integrity. PCR compatibility of the novel immobilization protocol was confirmed by applying such arrays to solid-phase PCR (SP-PCR), improving previously reported “enhanced SPPCR” [1] in terms of factorial signal increase from 9.9 to 86.8 and specificity from 11.7 to 45.9. Our method also enables to directly integrate DNA-microarrays amenable for SP-PCR into microfluidic LoaC cartridges of various materials circumventing the need of hybrid assemblies.
Artur Tropmann, Nils Lass, Nils Paust, Christoph Ziegler, Roland Zengerle, Peter Koltay
Erzeugung monodisperser Mikropartikel aus wässrigen Lösungen Monodisperse Microparticle Generation from Aqueous Solutions
2011 Mikrosystemtechnik-Kongress, Darmstadt, Deutschland, October 10-12 , Seiten: 941 - 944
O. Strohmeier, M. Rombach, D. Mark, R. Zengerle, G. Roth, F. von Stetten
Fully integrated dilution series generation on a laboratory centrifuge
2011 16th International Solid-State Sensors, Actuators and Microsystems Conference (TRANSDUCERS), 5-9 June 2011, Beijing China , Seiten: 2952 - 2955
KurzfassungWe present a novel approach for the fully automated generation of dilution series using a disposable microfluidic cartridge. Fluids are metered, mixed and routed without active valving by defined rotational speed only. As a processing device, a standard lab centrifuge can be used. The dilution ratio can be freely choosen by loading the corresponding volume of sample into the cartridge without the need for changes in the microfluidic layout. Dilution series of Fluorescein in PBS buffer with ratios of 1:3 and 1:5 are shown with each dilution series comprising 5 single dilution steps. Reproducibility was determined by fluorescence measurement.
A. Kloke, C. Köhler, R. Zengerle, S. Kerzenmacher
Galvanische Abscheidung von hochporösen Platin-Elektroden mit einstellbarer spezifischer Oberfläche für die implantierbare Glukose-Brennstoffzelle
2011 Mikrosystemtechnik-Kongress, Darmstadt, Deutschland, October 10-12
KurzfassungPräsentiert wird ein neuartiger Prozess zur Herstellung von hochporösen Platin-Elektroden auf der Basis von zyklischer Voltammetrie. Die galvanische Abscheidung erfolgt aus einer schwefelsauren Lösung von Platin- und Kupfer-Ionen, wobei sich in einem 2-stufigen Prozess die (1) Abscheidung einer Platin-Kupfer-Legierung und das (2) Herauslösen des Kupfers abwechseln. Durch die Wiederholung dieses zyklischen Ablaufs kann die spezifische Oberfläche der Elektrode bis zu einem Rauhigkeitsfaktor (RF) von 2031 ± 218 eingestellt werden. Voraussetzung für diesen Herstellungsprozess ist lediglich ein leitfähiges Substrat, wodurch diese Methode für Anwendungen wie z.B. Mikrobrennstoffzellen, Sensor– oder Stimulationselektroden zur Verfügung steht. Am Beispiel der implantierbaren Glukose-Brennstoffzelle konnte gezeigt werden, dass mit dem neuen Verfahren im Vergleich zu bisher eingesetzten Raney-Platin-Elektroden eine höhere Leistungsdichte (5,1 ± 0,1 μW cm-2) mit einem vereinfachten Herstellungsprozess erreicht werden kann.
T. Boretius, T. Jurzinsky, C. Köhler, S. Kerzenmacher, H. Hillebrecht, T. Stieglitz
High-Porous Platinum Electrodes for Functional Electrical Stimulation
2011 33rd Annual International IEEE EMBS Conference, August 30 - September 3, Boston USA , Seiten: 5404 - 5407
KurzfassungThis paper is about the preparation and characterization of highly porous platinum electrodes for functional electrical stimulation. Thin-film platinum electrodes were roughened by electrochemical deposition of platinum-copper alloys and subsequent removal of copper using cyclic voltammetry (CV). Prepared samples were characterized by electrochemical impedance spectroscopies (EIS), CVs and long-term pulse testing. The electrodes exhibited an increased porosity by a factor of ~238 when compared to sputtered platinum electrodes. EIS measurements showed a decreased impedance of about 85% and pulse tests suggested a stable coating over at least 250M pulses.
J. Burger, André Gross, Daniel Mark, Felix von Stetten, Roland Zengerle, Günter Roth
IR thermocycler for centrifugal microfluidic platform wit direkt on-disk wireless temperature measurement system
2011 Mikrosystemtechnik-Kongress 2011, Darmstadt, Deutschland, October 10-12, 2011 , Seiten: 916 - 918
KurzfassungWe present a novel infrared (IR) thermocycler for centrifugal microfluidic platforms [1]. It allows to directly heat liquids in reaction containers within microfluidic polymer film disks [2] for polymerase chain reactions (PCR) with average heating gradients of up to 4 K/s. This thermocycler mainly consists of an IR ring-heater, a direct on-disk wireless temperature measurement system with a resolution of 0.1 K and an embedded adaptive PID controller. That enables to precisely control the temperature of the liquid even at variant conditions e.g. manufacturing tolerances, different cavity locations, ambient temperature changes, whereas state-of-the-art thermocyclers with in-direct air temperature measurement are inflexible due to static thermal energy flow models. Hence our system has the potential for a higher efficiency, accuracy and robustness, thus for a better PCR reproducibility.
J. Burger, A. Gross, D. Mark, F. von Stetten, R. Zengerle, G. Roth
IR thermocycler for centrifugal microfluidic platform with direct on-disk wireless temperature measurement system
2011 16th International Solid-State Sensors, Actuators and Microsystems Conference (TRANSDUCERS), 5-9 June 2011, Beijing China , Seiten: 2867 - 2870
KurzfassungWe present an infrared (IR) thermocycler with closed loop temperature control for performing fast polymerase chain reactions (PCR) in centrifugal microfluidics [1]. It consists of an IR ring heater and an on-disk wireless temperature sensor module with a resolution of 0.1 K [2]. The closed loop system enables to precisely control the temperature of the reagents even at varying conditions e.g. manufacturing tolerances of the polymer film disks [3], different locations of the cavities, ambient temperature changes. Due to the direct heating of the reagents by IR absorption we achieve fast average heating gradients of up to 4 K/s. Average cooling gradients so far are limited to 1.3 K/s. Our system is superior in terms of energy efficiency, temperature accuracy and overall reproducibility and robustness.
J. Burger, A. Gross, D. Mark, G. Roth, F. von Stetten, R. Zengerle
IR thermocycler for centrifugal microfluidic platform with direct ondisk wireless temperature measurement system
2011 Smart Sensors, Actuators, and MEMS V, 18th April 2011, Prague, Czech Republic , Seite: p. 80661X
KurzfassungThe direct on-disk wireless temperature measurement system [1,2] presented at μTAS 2010 was further improved in its robustness. We apply it to an IR thermocycler as part of a centrifugal microfluidic analyzer for polymerase chain reactions (PCR). This IR thermocycler allows the very efficient direct heating of aqueous liquids in microfluidic cavities by an IR radiation source. The efficiency factor of this IR heating system depends on several parameters. First there is the efficiency of the IR radiator considering the transformation of electrical energy into radiation energy. This radiation energy needs to be focused by a reflector to the center of the cavity. Both, the reflectors shape and the quality of the reflecting layer affect the efficiency. On the way to the center of the cavity the radiation energy will be diminished by absorption in the surrounding air/humidity and especially in the cavity lid of the microfluidic disk. The transmission spectrum of the lid material and its thickness is of significant impact. We chose a COC polymer film with a thickness of 150 μm. At a peak frequency of the IR radiator of ~2 μm approximately 85 % of the incoming radiation energy passes the lid and is absorbed within the first 1.5 mm depth of liquid in the cavity. As we perform the thermocycling for a PCR, after heating to the denaturation temperature of ~ 92 °C we need to cool down rapidly to the primer annealing temperature of ~ 55 °C. Cooling is realized by 3 ventilators venting air of room temperature into the disk chamber. Due to the air flow itself and an additional rotation of the centrifugal microfluidic disk the PCR reagents in the cavities are cooled by forced air convection. Simulation studies based upon analogous electrical models enable to optimize the disk geometry and the optical path. Both the IR heater and the ventilators are controlled by the digital PID controller HAPRO 0135 [3]. The sampling frequency is set to 2 Hz. It could be further increased up to a maximum value being permitted by the wireless temperature data transmission system. As we are controlling a significantly non-linear process the controller parameters need to be optimized for all temperatures relevant for the PCR thermocycling process. Such we get a dynamic system for both, the heating and the cooling process. Heating rates up to 5 K/s with our IR heater (100 W electrical power) could be achieved. Cooling rates of instantly 1.3 K/s at 20 Hz rotation frequency could be even further increased by higher rotation frequencies, faster air circulation, optimization of the controller parameters or an active air cooling unit. Keywords: lab-on-a-chip, centrifugal microfluidics, PCR, Immunoassay, thermocycling, IR radiator, thermistor, wireless temperature measurement system
D. Liang, A. Gross, J. Schöndube, S. Rubenwolf, A. Yusof, A. Ernst, R. Zengerle, G. Roth, P. Koltay
Improved Machine Vision for Single Cell Printing
2011 Mikrosystemtechnik-Kongress, Darmstadt, Deutschland, October 10-12 , Seiten: 891 - 894
KurzfassungWe present an improved application of novel machine vision in single cell printing. Biological cells are optically im-aged inside a microfluidic dispenser chip by a monochrome smart camera with digital signal processor (DSP) for real-time processing. Coaxial illumination and parallel image acquisition make high speed cell selection possible. In our first experiment the maximal selection rate reached 125Hz, which is about 16 times faster than previous work [1]. The successful selection rate in the first experiment reaches 89%.
J. Schöndube, A. Gross, S. Rubenwolf, S. Niekrawitz, P. Koltay, R. Zengerle, G. Roth
Integrated Instrument for Printing Single Cells and Hydrogel Matrices for Future Tissue Engineering
2011 NanoBioTech 2011, Montreux, Switzerland, November 14-16
T. Brettschneider, C. Dorrer, D. Czurratis, R. Zengerle, M. Daub
Integration von Metallfolien in Polymerschichtsysteme mittels Laserdurchstrahlschweißens
2011 Mikrosystemtechnik-Kongress, Darmstadt, Deutschland, October 10-12 , Seiten: 535 - 538
KurzfassungDie direkte Metallisierung von Polymeren eröffnet vielfältige Möglichkeiten, nicht nur in Form von Leiterbahnen, sondern auch für eigenständige Funktionen in einem polymeren Bauteil. Hier stellen wir ein laserbasiertes Aufbaukonzept zur Herstellung metallisierter Polymerschichtsysteme vor, welches zur Einbindung neuer Funktionen, beispielsweise bei Labs-on-a-Chip Implementierungen, verwendet werden kann. Als wesentliche Schritte des Prozesses wurden die Verbindung sowie die Strukturierung der Metallfolie mittels Schältests und 3D-Mikroskopie untersucht. Dabei wurden Schälfestigkeiten von 1 N/mm erreicht und minimal realisierbare Strukturgrößen von ca. 20 µm ermittelt. Als Anwendung wird ein Thermoelement Typ T in einem polymeren Schichtaufbau vorgestellt.
A. Ernst, R. Zengerle, P. Koltay
Kontaktfreie quantitative Volumenbestimmung dispensierter Nanolitertropfen mittels eines kapazitiven Tropfensensors
2011 Mikrosystemtechnik-Kongress, Darmstadt, Deutschland, October 10-12 , Seiten: 799 - 802
Kiril Kalkandjiev, Ludwig Gutzweiler, Roland Zengerle, Peter Koltay
Kostengünstige Fertigung großflächiger Druckköpfe durch Lamination von Trockenlacken auf vorstrukturierte Polymersubstrate
2011 Mikrosystemtechnik-Kongress, Darmstadt, Deutschland, October 10-12 , Seiten: 883 - 886
KurzfassungIn diesem Beitrag wird ein mikrofluidischer Kunststoff-Druckkopf als Alternative zu seinem etablierten Silizium/Glas-Äquivalent beschrieben. Der Druckkopf wurde durch die Kombination spanabhebender und lithographischer Verfahren hergestellt, welche für großflächige Bauteile mit mikrostrukturierten Durchgangsöffnungen besonders geeignet sind. Er beinhaltet 24 Düsen mit einem Durchmesser von 50 μm, die über mikrofluidische Kanäle mit jeweils einem Reservoir verbunden sind. Alle Mikrostrukturen wurden im Trockenlack TMMF strukturiert, das Druckkopfinterface besteht aus PMMA. Die verhältnismäßig große Grundfläche von 36 x 18 mm wird durch die standardisierte Anordnung der Reser-voire im Rastermaß der 384er Mikrotiterplatte und die notwendige Interaktion mit einem externen Piezoaktor vorgege-ben. Grundlegende Anforderungen wie die leckagefreie Verbindung zwischen den Reservoiren und den entsprechenden Düsen, die Realisierung eines gedeckelten mikrofluidischen Kanalsystems sowie die Durchgängigkeit und Homogenität der Düsen wurden reproduzierbar umgesetzt. Durch entsprechende Nachbehandlung wurden die mikrofluidischen Strukturen mit entsprechenden Oberflächenfunktionalitäten versehen, die eine kapillare Befüllung der Düsen und den parallelen Ausstoß von Einzeltropfen nach dem etablierten TopSpot® Verfahren ermöglichen.
Strohmeier O., Mark D., Focke S., Lutz S., Burger J., Riegger L., Hoffmann J., Zengerle R., von Stetten F.
Lab-on-a-Chip solutions designed for being operated on standard laboratory instruments
2011 45. Deutschen Gesellschaft für Biomedizinische Technik (DGBMT), September 27-30, Freiburg
KurzfassungWe report lab-on-a-chip solutions that can be operated on standard laboratory instruments. Although disposable labchips can be produced at low cost, market penetration can be hindered by initial invests for instrumentation. Therefore, we upgrade standard laboratory instruments by microfluidic disposables for process automation. This could significantly increase the acceptance of lab-chips. We present: 1. Microfluidic disks for DNA pre-amplification, aliquoting and real-time PCR, operated on a Qiagen thermocycler with < 10 copy sensitivity. 2. Fully automated hematocrit measurement in a DVD ROM drive from <10 μL of whole blood.
Maximilian Focke, Daniel Mark, Fabian Stumpf, Martina Müller, Günter Roth, Roland Zengerle, Felix von Stetten
Microfluidic cartridges for DNA purification and genotyping processed in standard laboratory instruments
2011 Smart Systems Integration 2011, Dresden, 22 – 23 March 2011 , Seite: P 40 (6pp)
KurzfassungWe present two disposable microfluidic cartridges intended for upgrading standard laboratory instruments with automated liquid handling capability by use of centrifugal forces. Both cartridges integrate and automate laboratory protocols for analysis of nucleic acids. The first microfluidic cartridge enables purification of DNA from human whole blood and is operated in a standard laboratory centrifuge. The second microfluidic cartridge enables genotyping of pathogens by geometrically multiplexed real-time PCR. It is operated in a slightly modified off-the-shelf thermal cycler. Both solutions aim at smart and cost-efficient ways to automate work flows in laboratories.
M. Focke, D. Mark, F. Stumpf, M. Müller, G. Roth, R. Zengerle, F. von Stetten
Microfluidic cartridges for DNA purification and genotyping processed in standard laboratory instruments
2011 Smart Sensors, Actuators, and MEMS V, 18th April 2011, Prague, Czech Republic , Band: 8066, Seite: Art80660G
KurzfassungTwo microfluidic cartridges intended for upgrading standard laboratory instruments with automated liquid handling capability by use of centrifugal forces are presented. The first microfluidic cartridge enables purification of DNA from human whole blood and is operated in a standard laboratory centrifuge. The second microfluidic catridge enables genotyping of pathogens by geometrically multiplexed real-time PCR. It is operated in a slightly modified off-the-shelf thermal cycler. Both solutions aim at smart and cost-efficient ways to automate work flows in laboratories. The DNA purification cartridge automates all liquid handling steps starting from a lysed blood sample to PCR ready DNA. The cartridge contains two manually crushable glass ampoules with liquid reagents. The DNA yield extracted from a 32 μl blood sample is 192 ± 30 ng which corresponds to 53 ± 8% of a reference extraction. The genotyping cartridge is applied to analyse isolates of the multi-resistant Staphyloccus aureus (MRSA) by real-time PCR. The wells contain pre-stored dry reagents such as primers and probes. Evaluation of the system with 44 genotyping assays showed a 100% specificity and agreement with the reference assays in standard tubes. The lower limit of detection was well below 10 copies of DNA per reaction. Keywords: lab-on-a-chip, lab-on-a-foil, centrifugal microfluidics, DNA purification, DNA genotyping
M. Karle, G. Czilwik, J. Miwa, N. Paust, G. Roth, R. Zengerle, F. von Stetten
Microfluidic flow-through DNA purification for continuous monitoring applications
2011 EuroMedLab Berlin 2011 – Berlin, 15-19 May 2011 Clin Chem Lab Med, Band: 49, Ergänzungsband: 1, Seiten: S607 - S607
R. Zengerle, D. Mark, D. Kosse, G. Roth, F. von Stetten
Microfluidic solutions for miniaturization, integration, automation and parallelization of tests on commercially available instruments
2011 16th International Solid-State Sensors, Actuators and Microsystems Conference (TRANSDUCERS), 5-9 June 2011, Beijing China , Seiten: 12 - 15
KurzfassungWe demonstrate that Lab-on-a-Chip implementations can be designed for operation in common commercialized instruments like laboratory centrifuges, DVD drives, or real-time PCR cyclers. On the one hand this approach could render the expensive development of tailor-made instruments superfluous and could significantly reduce market entry barriers for developing Lab-on-a-Chip solutions. On the other hand this provides instrument companies with the opportunity to upgrade their devices e.g. by integrating complex sample preparation protocols prior to the detection for which the instruments are designed. We demonstrate this approach for the following applications: • automated DNA-purification operated on a standard laboratory centrifuges with 50% yield compared to gold standards, • DNA pre-amplification, aliquoting, and real-time PCR operated on a slightly modified real-time thermocycler (Rotor-Gene) with < 10 copy sensitivity, • isothermal DNA amplification by recombinase polymerase amplification with < 20 copy sensitivity and a time-to-result of less than 15 minutes, also operated on the Rotor-Gene platform, • hematocrit measurement of less than 10 μL of whole blood in a DVD drive.
Simon Wadle, Vitaliy Kondrashov, Henning Hoefemann, Natalia Bakhtina, Nicolai Wangler, Roland Zengerle
Microheater-mediated mechanical single-cell lysis
2011 15th International Conference on Miniaturized Systems for Chemistry and Life Sciences (µTAS), October 2-6, 2011, Seattle, Washington, USA , Seiten: 1044 - 1046
KurzfassungWe demonstrate the first mechanical single-cell lysis via on-chip integrated microheaters. The chip combines an electrical layer with embedded microheaters and a fluidic layer, fabricated by soft lithography. Vapor bubbles can be generated above the microheaters resulting in fast fluid displacement and therefore in mechanical cell lysis by pushing the cell against the wall or the ceiling of the microfluidic channel. Single-cell lysis was analyzed with Calcein AM stained mouse fibroblasts via monitoring the exclusion of the live cell stain after bubble formation. 27 of 27 cells were lysed, even in a distance of up to 37 μm away from the heater. KEYWORDS: Bubble Jet, cell lysis, single-cell analysis
D. Kosse, M. Focke, C. Müller, F. Von Stetten, R. Zengerle
Microthermoforming and Sealing of COP Films to Form Thin Walled Lab-On-A-Chip Cartridges
2011 8th International Conference on Multi Material Micro Manufacture, Stuttgart, Germany, November 08-10 , Seiten: 187 - 190
KurzfassungThis paper describes a process chain to form and seal thermoplastic films to obtain enclosed microfluidic cartridges with thin walls. Especially applications requiring fast thermocycling such as polymerase chain reaction (PCR) highly benefit from this lab-on-a-foil approach, due to an improved heat transfer. The cartridge fabrication is a two-step process comprising microthermoforming by soft lithography followed by a novel gas pressure assisted thermal sealing. As film material a 188 μm thick cyclic olefin polymer (COP) is used, which is microthermoformed over a male Polydimethylsiloxane (PDMS) mold to shape the intended thin walled microstructures. The process parameters have been optimized and feature sizes in the range of a few micrometers to millimeters with aspect ratios up to three are replicated. The forming of the thermoplastic film is caused by heating the film above glass transition temperature (Tg) and applying a gas pressure of 310 kPa. After cooling and demolding the COP structures are thermally sealed with a special coextruded COC film. The coextruded film consists of a temperature stable TOPAS COC 6013 (Tg ~ 135 °C) layer and a thin layer of TOPAS COC 8007 (Tg ~ 79 °C) acting like hot melt. An additional mold for bond support, which is commonly needed for positive thermoformed structures, has been eliminated by a gas pressure assisted bonding approach. The processes enable fast and flexible prototyping of thin walled microfluidic cartridges within 8 – 10 hours.
G. Roth, S. Lutz, G. Welte, D. Mark, R. Zengerle, F. von Stetten
Mikrofluidisches Lab-on-a-Chip System zur Prozessierung von Immunoassays mit integrierter Probenvorbereitung
2011 Mikrosystemtechnik-Kongress 2011, Darmstadt, Deutschland, October 10-12, 2011 , Seiten: 457 - 460
KurzfassungEs wird eine Plattform zur Prozessierung von kompetitiven und Sandwich-Immunoassays präsentiert. Die Plattform be-steht aus einer spritzgegossenen mikrofluidischen Kartusche und einem Prozessierungs-Gerät mit Detektionseinheit. Die Kontrolle der Fluide erfolgt unter gezielter Kombination von Zentrifugal- und Kapillarkräften durch rein passive Elemente wie z.B. Siphons, sowie hydrophile und hydrophobe Beschichtungen. Die Kartusche ermöglicht die Separati-on von 4 µL Blutplasma aus 10 – 15 µL Vollblut, sowie Mischprozesse, Inkubations- und Waschschritte und verfügt über einen integrierten Flüssigabfallbehälter zur Vermeidung von Kontaminationen. Beispielhaft werden ein Sandwich- Immunoassay zur Analyse von IL8 und ein kompetitiver Immunoassay zur Analyse von Estradiol demonstriert. Die Detektion unter Rotation erfolgt mittels Chemilumineszenz.
Thomas van Oordt, Yannick Barb, Roland Zengerle, Felix von Stetten
Miniature stick-packaging – an industrial technology for pre-storage and release of reagents in lab-on- a-chip systems
2011 15th International Conference on Miniaturized Systems for Chemistry and Life Sciences (µTAS), October 2-6, 2011, Seattle, Washington, USA , Seiten: 437 - 439
KurzfassungStick-packaging of goods in tubular shaped composite-foil pouches has become a popular technology for food packaging. We miniaturized stick-packaging for use in Lab-on-a-Chip (LOAC) systems to pre-store and release liquid and dry reagents in a volume range of 80 – 500 μl. A frangible seal integrated in the package allows for the pressure-controlled release of reagents, reducing the number of downstream valves required for liquid control. The frangible seal is fabricated by ultrasonic welding, enabling adjustment of burst pressures from 20 to 100 kPa, and allowing for packaging of temperature sensitive reagents. As an additional advantage, stick-packaging is also a scalable technology suitable for both rapid prototyping and low-cost mass production. KEYWORDS: reagent pre-storage, stick-packaging, centrifugal lab-on-a-chip
A. Tropmann, N. Lass, N. Paust, C. Ziegler, R. Zengerle, P. Koltay
Monodisperse microparticle generation from aqueous solutions
2011 Proc. of 16th International Solid-State Sensors, Actuators and Microsystems Conference (TRANSDUCERS), 5-9 June 2011, Beijing China , Seiten: 1460 - 1463
KurzfassungWe present a new approach for the generation of monodispersed droplets and tailor-made microparticles of complex liquids from a star-shaped nozzle that precisely defines the dispensed droplet sizes. From two aqueous polymer solutions: 30w% Polyvinylpyrrolidone (PVP) (viscosity η ≈ 105 mPas) and 40w% PVP (η ≈ 490 mPas) droplet volumes of 3.9 nl and 3.2 nl respectively were generated employing a star-shaped silicon nozzle with a diameter of 183 μm. From 1w% Mannitol (η ≈ 1 mPas) droplets (100 pl) and particles (22 μm) were generated from a 59 μm nozzle. These results show for the first time particle generation with the StarJet method that could be applicable for the generation of monodispersed powders for use in healthcare, food and home care products.
Boretius T., Jurzinsky T., Köhler Ch., Kerzenmacher S., Stieglitz T.
Raney-platinum electrodes for functional electrical stimulation
2011 45. Deutschen Gesellschaft für Biomedizinische Technik (DGBMT), September 27-30, Freiiburg
KurzfassungThis abstract is about the fabrication of platinum thin-film electrodes with defined roughness and microporosity. This is achieved through surface modification of a sputtered platinum layer on a polyimide substrate via deposition, annealing and subsequent etching of an aluminium layer. The electrochemical properties of the resulting layers were characterized by cyclo-voltammetry (CV), pulse testing and electrochemical impedance spectroscopy (EIS).
N. Lass, A. Tropmann, A. Ernst, R. Zengerle, P. Koltay
Rapid prototyping of 3D microstructures by direct printing of liquid metal at temperatures up to 500°C using the starjet technology
2011 16th International Solid-State Sensors, Actuators and Microsystems Conference (TRANSDUCERS), 5-9 June 2011, Beijing China , Seiten: 1452 - 1455
KurzfassungWe present a novel approach for 3D-prototyping of porous metal structures by direct non-contact liquid metal printing, based on the StarJet technology [1]. In contrast to our previous work, the presented droplet generator features an improved nozzle chip design and actuator housing that allows operation at temperatures up to Tmax = 500°C (formerly Tmax = 250°C). This enables the ejection of single droplets of metals with higher melting points like for example magnesium or zinc alloys like ZAMAK. The droplet generation frequency could be increased by a factor of 10 to fmax = 4 kHz. Furthermore, deviations of the droplet trajectory from the symmetry axis of the nozzle are reduced to Δdeg = 0.28° by the new design. This paper reports on experimental results obtained with the improved device and presents 3D metal structures with various porosities.
Oliver Strohmeier, Nico Marquart, Daniel Mark, Günter Roth, Roland Zengerle, Felix von Stetten
Real-time PCR based food pathogen detection on a centrifugal microfluidic foil disk including positive- and no-template-controls
2011 15th International Conference on Miniaturized Systems for Chemistry and Life Sciences (µTAS), October 2-6, 2011, Seattle, Washington, USA , Seiten: 506 - 508
KurzfassungWe designed and evaluated a novel microfluidic structure for the real-time PCR based detection of six common food pathogens on a centrifugal microfluidic foil disk, including onboard positive- and no-template-controls for each of the targets. The microfluidic design enables for geometric multiplexed PCR in a standard centrifugal real-time PCR thermocycler. The limit of detection was 0.1 pg target DNA what corresponds to 17-56 DNA copies per PCR reaction. KEYWORDS: Lab-on-a-Chip, Centrifugal microfluidics, PCR on a chip, Food pathogen testing
J. Hoffmann, M. Trotter, F. von Stetten, R. Zengerle, G. Roth
Single-Molecule PCR in a Picowell Array Simultaneously Immobilizing PCR Products to a PDMS Coverslide
2011 15th International Conference on Miniaturized Systems for Chemistry and Life Sciences (µTAS), October 2-6, 2011, Seattle, Washington, USA , Seiten: 900 - 902
KurzfassungFor the first time, we amplified single DNA-molecules (“Digital PCR”) randomly distributed in a picowell array and simultaneously immobilized the generated PCR-products to the surface of a PDMS coverslide (“solid-phase PCR”) which was used as sealing of the picowells during PCR. First, by this unprecedented technique PCR-products can be recovered for both, further reactions/analysis and counting the number of initial DNA-molecules from digital signals with a good signal to noise ratio of 10. Second, our experiments demonstrate the currently smallest low-volume on-chip PCR in an array of 18.5 pL wells. This may enable single-cell PCR experiments by filling PCR microreactors with truly single-cells due to geometrical constriction. KEYWORDS: Digital PCR, solid-phase PCR, parallelization
T. van Oordt, J. Smetana, R. Zengerle, F. von Stetten
Stickpacks zur langzeitstabilen Vorlagerung von Reagenzien in Lab-on-a-Chip-Systemen
2011 Mikrosystemtechnik-Kongress 2011, Darmstadt, Deutschland, October 10-12 2011 , Seiten: 555 - 558
KurzfassungStickpacks sind eine in der Lebensmittelindustrie etablierte Methode zur Verpackung. Wir zeigen, dass diese nach einer Miniaturisierung auch zur Speicherung kleinster Flüssigkeitsvolumina (80 – 500 µl) verwendet werden können und demonstrieren dies am Beispiel einer langzeitstabilen Vorlagerung von Flüssigreagenzien in Lab-on-a-Chip-Systemen. Durch einen einstellbaren Berstdruck lassen sich die Reagenzien in den Stickpacks automatisiert freisetzen und können somit kontaktierungsfrei in zentrifugale Lab-on-a-Chip-Systeme integriert werden. Die Öffnungsdrücke sind im Bereich von 200 - 1200 mbar variierbar und die Stickpacks entleeren sich zentrifugal nahezu vollständig (99 % ± 1 %, ab Δp = 400 mbar). Die Eignung für eine langzeitstabile Lagerung konnte in beschleunigten Lager-Tests nachgewiesen werden.
E. Kipf, J. Koch, S. Kerzenmacher
Systematic comparison of anode materials for microbial fuel cells
2011 Marine Resources and Beyond, Bremerhaven, Germany, September 5-7 , Seite: 95
KurzfassungWe present a systematic comparison of anode materials for microbial fuel cells (MFCs). Therein the anodes are assembled as half-cells and galvanostatic polarization curves are recorded against a reference electrode. This approach led to the identification of activated carbon cloth (ACC) as superior anode material compared to graphite felt (GF), which at present is predominantly used in microbial fuel cells.
Azmi Yusof, Roland Zengerle, Peter Koltay
TMMF dry film resist as masking layer in deep etching of Pyrex-glass for microfluidic chip fabrication
2011 Proc. Eurosensors XXV, September 4-7, Athens, Greece, Volume 25 , Seiten: 827 - 830
KurzfassungWe present the application of dry film resist (TMMF) as new masking technology to process glass wafers using standard wet etching. The considered microfluidic chip features patterned metal electrodes for impedance sensing and hydraulic access holes fabricated on a Pyrex wafer. Therefore, deep etching of through holes, while protecting the deposited metal structures on the Pyrex glass wafer, is required. To achieve this, amorphous silicon (a-Si) was used as masking layer on one side and unexposed TMMF dry film resist was used as mask on the other side of the wafer. The a-Si and TMMF are excellent masking layers in deep-wet etching for Pyrex wafers with etch duration more than 1 hour in 49% hydrofluoric (HF) acid.
A. Yusof, R. Zengerle, P. Koltay
Towards a microfluidic dispenser chip for printing of single cells
2011 24th IEEE International Conference on Micro Electro Mechanical Systems.IEEE MEMS 2011 Conference - January 23 - 27, 2011 - Cancun, MEXICO
C. Köhler, C. Bentler, A. Kloke, J. Oudenhoven, V. Pop, B. Op het Veld, S. Kerzenmacher
Towards implantable autonomous systems; A low-power transducer platform powered by a glucose fuel cell
2011 PowerMEMS 2011, Seoul, Korea, November 15-18 , Seite: 19
S. Sané, S. Rubenwolf, R. Zengerle, C. Jolivalt, S. Kerzenmacher
Using microorganisms to harvest electricity-Towards a self-regenerating enzymatic cathode
2011 Proc. 3rd MicrobialFuelCell Conference, Leeuwaarden, Netherlands, June 5-8, 2011,, 81
O. Strohmeier, G. Czilwik, A. Emperle, M. Focke, G. Roth, D. Mark, R. Zengerle, F. von Stetten
Verfahren zur DNA Aufreinigung mit magnetischen Partikeln auf einer zentrifugal-mikrofluidischen Einweg-Foliendisk
2011 Mikrosystemtechnik-Kongress 2011, Darmstadt, Deutschland, October 10-12, 2011 , Seiten: 66 - 69
KurzfassungVorgestellt wird ein neues Verfahren zur integrierten DNA Aufreinigung mit Hilfe magnetischer Partikel auf einer zentrifugal-mikrofluidischen Foliendisk. Wesentliche Vorteile gegenüber dem Stand der Technik [1-4] sind kurze Prozesszeiten und Ausbeuten von annähernd 100% (verglichen mit der manuell durchgeführten Referenzextraktion), automatischer Betrieb bei niedrigen Rotationsfrequenzen (< 8 Hz) und ein modulares Design der mikrofluidischen Kammern. Der Transport der magnetischen Partikel zwischen den einzelnen Kavitäten erfolgt durch ein Zusammenspiel magnetischer und zentrifugaler Kräfte. Mit dem vorgestellten System konnte vollautomatisch DNA in PCR Qualität aus 3 Verdünnungen (1,5 • 104 Kolonie bildende Einheiten (KbE); 1,5 • 106 KbE und 1,5 • 108 KbE pro Probe) eines Escherichia coli Lysats in ~ 6 min extrahiert werden.
K. Kalkandjiev, A. Yusof, J. Schöndube, R. Zengerle, P. Koltay
Wafer-Level Fabrication of Microfluidic Sensors for Impedance Spectroscopy with Integrated Opposing Electrodes
2011 Proc. Eurosensors XXV, September 4-7, Athens, Greece , Seite: ID 1202
KurzfassungWe present the fabrication of microfluidic sensors with opposing electrodes for impedance spectroscopy. The sensors are fabricated by sandwiching TMMF dry photopolymer between two substrates, each with one electrode patterned on its fluid-contacting side. In this configuration, TMMF becomes a permanent part of the microfluidic device and has a twofold purpose: it defines the microfluidic network, and it is used as a patterned adhesive for low-temperature full-wafer silicon to glass bonding. According to the requirements of single cell dispensing, the opposing electrodes are placed between a hydrodynamic flow focusing for aligning the cells in a single file and a dispensing nozzle for printing the detected cells.
M. Focke, M. Müller, G. Roth, R. Zengerle, F. von Stetten, D. Mark, F. Stumpf
Zwei Lab-on-a-Chip-Einweg-Kartuschen zur DNA-Aufreinigung bzw. Genotypisierung in leicht modifizierten Standard-Laborgeräten
2011 Mikrosystemtechnik-Kongress 2011, Darmstadt, Deutschland, October 10-12, 2011 , Seiten: 914 - 915
KurzfassungWir präsentieren zwei unabhängige Lab-on-a-Chip-Systeme, die zum „Upgrade“ von geringfügig modifizierten kommerziellen Standard-Laborgeräten dienen. Beide Systeme erlauben die automatisierte Prozessierung von gängigen Laborprotokollen zur Extraktion beziehungsweise Analyse von Nukleinsäuren (DNA) und erweitern dadurch das Nutzungsspektrum dieser Geräte. Das erste System besteht aus einer mikrofluidischen Kartusche, die in einer programmierbaren Laborzentrifuge (Sigma 1-15, Sigma GmbH) betrieben wird und die Aufreinigung von DNA aus humanem Vollblut ermöglicht (Abb. 1). Das zweite System ist eine mikrofluidische Kartusche, die in einem leicht modifizierten Thermocycler (Rotor-Gene 2000, Corbett Research Ltd., mittlerweile Qiagen GmbH, Abb. 2) betrieben wird und ein geometrisches Multiplexing sowie anschließende Genotypisierung mittels Real-Time PCR ermöglicht. Beide Systeme sind aus Kunststoff gefertigt und sollen häufige Arbeitsabläufe in Laboren kosten-effizient automatisieren.

2010

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A. Yusof, L. Riegger, N. Paust, A. Ernst, R. Zengerle, P. Koltay
A Non-Invasive Single Cell Dispensing Approach for 2-Dimensional Micro-Patterning
2010 Actuator 2010, Bremen, Germany, 14.-16. June , Seiten: 1033 - 1036
KurzfassungWe present a computer vision-based approach for detection of micro-beads and cells combined with a noncontact liquid dispensing system to pattern single polystyrene-beads and yeast cells in a 2-dimensional array. A so called NanoJet dispenser for dispensing liquid borne particles features the average droplet volume of 150pL to 950pL and a reproducibility of (CV) < 3%. The computer vision set-up consists of a CCD camera coupled with a magnifying lens, which was employed to detect the micro-beads close to the dispenser’s orifice prior to dispensing. A real-time sequential image analysis was carried out by using a simple temporal differencing detection algorithm to identify single cells or particles in the proximity of the orifice that would be ejected with the subsequent dispense. Using this process arrays of polystyrene-beads and yeast cells were deposited onto glass slides attached to a programmable motorized stage. The overall deposition efficiency obtained was 70% with 58% of the spots contained single polystyrene-beads or cell respectively. Keywords: single-cell, computer vision based detection, non-contact droplet dispensing, cell printing
N. Wangler, M. Welsche, G. Roth, N. Paust, R. Zengerle
A disposable discrete-agent-release cartridge for flexible endoscopes
2010 Proc. of the 14th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS), Groningen, The Netherlands, October 3 – 10 , Seiten: 1205 - 1207
KurzfassungWe present a disposable four-channel-cartridge as a new tool for flexible endoscopes to release adjustable and precisely defined agent volumes. The agent volumes are generated by externally triggered (0 – 11 kHz) release of discrete droplets (Vdroplet = 8 pl) with flow rates up to 88 nl/s in each channel. The miniaturized cartridge (l × w × h = 9 mm × 1.2 mm × 1.4 mm) can be inserted into working channels of standard flexible endoscopes (Øworking channel = 2 – 3 mm). Up to four different agents are stored in separate integrated reservoirs (Vreservoir = 1 μl). Each channel is equipped with a bubble jet actuator which allows for addressing the single reagents individually. To prevent any diffusion based agent leakage a diffusion barrier is realized by forming a stable phase separation via capturing an air bubble in front of the dispenser’s nozzle orifices. KEYWORDS: multi channel discrete agent release, bubble jet actuator, minimal invasive surgery, phase gap
Kiril Kalkandjiev, Ludwig Gutzweiler, Mathias Welsche, Roland Zengerle, Peter Koltay
A novel approach for the fabrication of all-polymer microfluidic devices
2010 roc. of IEEE-MEMS, Hong-Kong, China, January 24-28 , Seiten: 1079 - 1082
KurzfassungThis paper describes a process sequence for the fabrication of all-polymer microfluidic chips based on the multilayer lamination of TMMF dry resist (TOK, Japan) on a pre-patterned PMMA substrate. The sequence provides a simple way to meet major microfluidic requirements like the fabrication of embedded microchannels, nozzles and intercon-necting vias as well as their accurate integration into a chip-interface without additional materials and bonding procedures. We demonstrate the appli-cability of the sequence by manufacturing and test-ing a 24-channel TopSpot printhead. Additionally, non-cytotoxicity of TMMF was confirmed in cell culture experiments and different methods for sur¬face modification were investigated.
Sven Kerzenmacher, Stefanie Rubenwolf, Arne Kloke, Roland Zengerle, Johannes Gescher
Biofuel cells for the energy supply of distributed systems: State-of-the-Art and applications
2010 Sensoren und Messsysteme, Nürnberg,Germany, 18.+19. May , Seiten: 562 - 565
KurzfassungBiofuel cells are an attractive possibility to generate electricity for energy-autonomous distributed devices. These fuel cells can tap into a variety of chemical energies available in environments such as the human body, fauna, or aquatic systems. The different biofuel cell concepts can be classified according to the catalyst system that is employed to enable the electrochemical reactions at the electrodes. Here abiotic catalysts (e.g. noble metals), isolated enzymes, or the enzy-matic system of whole living microorganisms are used. In our contribution the different approaches and their specific challenges are discussed, and present and future application scenarios are highlighted.
Dennis Trebbels, Christof Hübner, Rolf Becker, Roland Zengerle
Digital low-cost Time Domain Reflectometer circuit optimized for use in field applications
2010 Proc. of Aquametry 2010 - First European Conference on Moisture Measurement, Weimar, Germany, October 5-7 , Seiten: 174 - 181
KurzfassungTime Domain Reflectometry is a well-established method for measuring moisture profiles. In addition to special transmission lines this measurement principle requires a Time Domain Reflectometer. In the laboratory there are several state-of-the-art measurement devices available (e.g. Tektronix 1502B/C), but due to the high cost, the size and the power consumption they are often not suitable for field measurement applications. This article presents a new digital circuit design concept dedicated for developing cheap Time Domain Reflectometers especially suited for self-sustaining outdoor applications such as long-term field measurements.
Jürgen Burger, Thomas Jäger, André Gross, Anton Lastochkin, Daniel Mark, Günter Roth, Felix von Stetten, Roland Zengerle, Leo Reindl
Direct on-disk wireless temperature measurement for centrifugal microfluidic platforms
2010 Proc. of the 14th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS), Groningen, The Netherlands, October 3 – 10 , Seiten: 1502 - 1504
KurzfassungFor the first time we present an on-disk wireless temperature measurement system (Fig.1) for centrifugal microfluidic platforms[1]. Tiny thermistors with a volume of 54nl allow the direct temperature measurement in almost any of cavity (Fig.2) of microfluidic chips with a resolution of 0.1 K. A rotating radio module transfers digitalized data to a stationary receiver with D/A converter being connected to a temperature controller. The total response time of the temperature measurement system is 9.6 ms. The rotating electronic elements are powered by inductive coupling with up to 2W. The radio transmission of sensor data can be parameterized by any commercial PC via USB port. This system enables to precisely measure the temperature of fluids in centrifugal microfluidic systems and hence allows closed-loop control of direct heating systems e.g. IR radiators for fast Polymerase Chain Reaction (PCR) thermocycling processes. KEYWORDS: Lab-on-a-Chip, Microfluidic, PCR, Thermocycling, wireless temperature measurement
M. Karle, G. Czilwik, J. Miwa, N. Paust, G. Roth, R. Zengerle, F. von Stetten, Felix von Stetten
High-performance flow-through DNA purification on a microfluidic chip
2010 Proc. of the 14th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS), Groningen, The Netherlands, October 3 – 10 , Seiten: 106 - 108
KurzfassungWe present a significant increase in performance for flow-through purification of nucleic acids by continuous microfluidic processing. After binding to superparamagnetic beads the nucleic acids are sequentially transported across the phase-interface of co-flowing laminar streams of purification reagents. The entire purification procedure is performed within only 2 minutes. Compared to classical batch-wise purification in test tubes, 150  50 % of total DNA have been recovered in on-chip purifications over a DNA concentration range of 7 orders of magnitude. With appropriate surface modification of the magnetic beads the chip is also suggested for the implementation of other continuous biomolecular purification tasks. KEYWORDS: Nucleic Acids Purification, Magnetophoresis, Continuous Processing, Flow-Through Assay
Kiril Kalkandjiev, Roland Zengerle, Peter Koltay
Hybrid fabrication of microfluidic chips based on COC, silicon and TMMT dry resist
2010 Proc. of IEEE-MEMS, Hong-Kong, China, January 24-28 , Seiten: 400 - 403
KurzfassungWe describe the hybrid fabrication of silicon-plastic microfluidic chips based on machining of Cyclic Olefin Copolymer (COC), standard silicon process-ing and TMMF lithography. The combination of different processes enables an individual material selection leading to significant reduction of the manufacturing costs. We demonstrate the potential of the hybrid technology by manufacturing and testing a 24-channel TopSpot dispenser [1] which consists of an intermediate silicon layer, a COC interface and a TMMF sealing lid. Characterization studies show that TMMF lamination is ideally suited for the sealing of silicon microchannels showing numerous advantages over adhesive-based approaches, thermal and anodic bonding.
D. Mark, S. Lutz, M. Focke, M. Müller, G. Roth, R. Zengerle, F. von Stetten
Integrierte Analytik und Diagnostik auf der zentrifugal-mikrofluidischen Bio-Disk Plattform
2010 Tagungsband des 15. Heiligenstädter Kolloquiums, 27.-29.09 2010, Heiligenstadt , Seiten: 285 - 290
KurzfassungIn der modernen Medizin gewinnen hochspezifische und sensitive Verfahren wie Nukleinsäurediagnostik oder Immunoassays zunehmend an Bedeutung. Diese beinhalten eine Vielzahl von aufwendigen Prozessierungsschritten. Sie werden daher entweder durch hochqualifiziertes Personal in langwierigen Verfahren manuell durchgeführt oder in Großlabors mit großem apparativen Aufwand automatisiert. Entsprechend lange sind die Antwortzeiten nach der Probennahme, da die aufwendige Laborarbeit bzw. das Verschicken von Proben Stunden bis Tage in Anspruch nimmt. Für eine schnelle, patientennahe Diagnose sind daher kompakte, automatisierte Geräte wünschenswert, die vor Ort mit geringem Schulungsaufwand eingesetzt werden können. Mikrofluidische Systeme sind dabei vielversprechende Kanditaten [1]. Die zentrifugale Mikrofluidik ist eine solche Entwicklungsplattform zur Miniaturisierung, Integration und Automatisierung biochemischer Analyseprotokolle [2]. Sie beruht auf der kontrollierten Prozessierung kleinster Flüssigkeitsmengen in einem zentrifugalen Beschleunigungsfeld und kann so Analyseprotokolle automatisieren. Auf Grundlage der zentrifugalmikrofluidischen Bio-Disk Plattform [2] zeigen wir die Integration grundlegender Laborprotokolle der Analytik und Diagnostik: Nukleinsäure- Aufreinigung, Nachweise basierend auf Polymerase-Kettenreaktion (PCR), sowie isotherme Amplifikationsverfahren und Immunoassays.
T. Preis, D. Mark, N. Paust, C. Ziegler, G. Roth, R. Zengerle, F. v. Stetten
Lab-on-a-Chip Design- und Foundry-Service: Implementierung und Miniaturisierung biochemischer Assays auf Grundlage einer Bibliothek validierter mikrofluidischer Grundoperationen
2010 Tagungsband des 15. Heiligenstädter Kolloquiums , Seiten: 123 - 132
D. Mark, M. Focke, S. Lutz, J. Burger, M. Müller, L. Riegger, M. Rombach, J. Hoffmann, G. Roth, O. Piepenburg, Y. Park, R. Zengerle, F. von Stetten
Lab-on-a-chip solutions designed for being operated on standard laboratory instruments
2010 Eurosensors XXIV, September 5-8, Linz, Austria , Seiten: 444 - 447
KurzfassungIn this paper, we propose the development of microfluidic disposables that can be processed with standard laboratory instruments. The use of prevalent processing devices could significantly reduce existing market entry barriers for lab-on-a-chip solutions and support the market uptake of microfluidic products. We demonstrate the concept with the following applications: - microfluidic chips for DNA-purification operated on a standard laboratory centrifuge with 42% yield compared to gold standards (QIAamp, Qiagen GmbH) - microfluidic foil disk for DNA pre-amplification, aliquoting, and real-time PCR operated on a slightly modified Corbett Life Science thermocycler (now Qiagen) with < 10 copy sensitivity - microfluidic disposable for isothermal DNA amplification by recombinase polymerase amplification also operated on a Corbett Life Science (now Qiagen) thermocycler with < 10 copy sensitivity and a time-to-result of < 15 minutes. - fully automated hematocrit measurement in a DVD ROM drive from < 10 μL of whole blood.
O. Strohmeier, A. Emperle, M. Focke, G. Roth, D. Mark, R. Zengerle, F. von Stetten
Magnetic bead based DNA purification on a disposable centrifugal microfluidic foil cartridge
2010 Proc. of the 14th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS), Groningen, The Netherlands, October 3 – 10 , Seiten: 402 - 404
Gregor Welte, Sascha Lutz, Berit Cleven, Hero Brahms, Claudia Gärtner, Günter Roth, Daniel Mark, Roland Zengerle, Felix von Stetten
Microfluidic lab-on-a-chip system with integrated sample preparation for processing immunoassays
2010 Proc. of the 14th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS), Groningen, The Netherlands, October 3 – 10 , Seiten: 818 - 820
KurzfassungWe present an advanced, injection molded microfluidic lab-on-a-chip cartridge to process immunoassays with unit operations for sample preparation, metering, mixing, incubation, washing, chemiluminescence detection and waste handling. A newly developed readout device is capable of recording data points under rotation. Latest assay results feature a lower average standard deviation (7 % of maximum signal) in contrast to previously achieved 27 % [1]. A competitive chemiluminescent Estradiol immunoassay is demonstrated on-chip with a series of different Estradiol concentrations. A lower limit of detection of 60 pg/mL is established with a time-to-result of 45 min compared to 60 min in a microtiterplate.
Stephan Messner, Axel Schumacher, Michael Vosseler, Simon Herrlich, Rainer Günzler, Roland Zengerle
Mikrotechnische Systeme zur Selbstverabreichung von Medikamenten – MEMS based systems for self-medication
2010 3. Deutscher AAL-Kongress, Berlin, 26.-27. Januar , Seite: P 1.4
KurzfassungDer zunehmende Kostendruck im Gesundheitswesen und die sich kontinuierlich verschlechternde medizinische Versor-gung in ländlichen Gebieten erfordern u. a. neue medizintechnische Hilfsmittel, die durch die Patienten selbst oder durch Pflegepersonal bedient werden können. In diesem Beitrag werden Konzepte zur Verabreichung von Medikamenten vor-gestellt, die sich aufgrund des unkritischen Zugangs zum Körper besonders zur Anwendung durch den Patienten selbst oder durch Pflegepersonal eignen. Das intraorale Medikamentendosiersystem IntelliDrug wird im Mundraum platziert und gibt Medikamente direkt an die Backenschleimhaut ab. In einer ersten klinischen Studie konnte anhand des Wirk-stoffs Naltrexon die prinzipielle Funktionalität des Systems nachgewiesen werden. Ferner wurde gezeigt, dass die Bio-verfügbarkeit (Wirkstoffkonzentration im Blut) bei der Verabreichung mit dem IntelliDrug System bis zu 25-fach höher ist als bei der Einnahme des gleichen Wirkstoffes über den Magen-Darm-Trakt. In weiterführenden Arbeiten wird der-zeit eine vereinfachte Variante (BuccalDose) entwickelt, die auf die Behandlung von Parkinsonpatienten abzielt. Das Wirkstoffpflaster ChronopaDD verabreicht Medikamente in die Haut (intradermal) über Mikronadeln. Das System ist als kostengünstiger Einmalartikel konzipiert. Der zum Wirkstofftransport integrierte Pumpmechanismus arbeitet ohne elekt-rische Energie und ist mit einer integrierten Zeitverzögerung ausgestattet, so dass die Wirkstoffabgabe 4 – 6 h nach der Aktivierung erfolgt.
S. Spieth, A. Schumacher, C. Kallenbach, S. Messner, R. Zengerle
Neuromedicator – A disposable drug delivery system with silicon microprobes for neural research
2010 Proc. of IEEE-MEMS, Hong-Kong, China, January 24-28 , Seiten: 983 - 986
KurzfassungWe report on a novel disposable drug delivery system for neural research which allows to infuse 16 discrete liquid portions of 0.25 μL directly into neural cell tissue. The system comprises an 11×14.5×3 mm³ fluidic chip with a pluggable electrical micro connector and two 8-mm-long micromachined silicon fluidic microprobes with a cross-sectional area of 250×250 μm². A pearl chain-like fluidic structure with spherical segments was developed which stores and predefines the required drug liquid portions for the whole time of operation. The micropump principle for liquid delivery is based on the local, irreversible thermal expansion of microspheres embedded into polydimethylsiloxane (PDMS).
Martina Müller, Daniel Mark, Markus Rombach, Günter Roth, Jochen Hoffmann, Roland Zengerle, Felix von Stetten
On the way to a fully integrated DNA-purification system on a standard laboratory centrifuge
2010 Proc. of the 14th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS), Groningen, The Netherlands, October 3 – 10 , Seiten: 405 - 408
KurzfassungFor the first time, we combine liquid reagent storage in glass capillaries [1], time-controlled reagent release [2], and a novel solution for unidirectional centrifugal routing, paving the way to a fully integrated DNA extraction on a standard laboratory centrifuge. The average yield of the extraction is 192 ± 30 ng DNA out of 32 μl blood, corresponding to 53 ± 8 % of a reference extraction. The overall processing time of ~66 minutes can be reduced to ~8 minutes after optimization of the burst-valves. This novel approach demonstrates a convenient way for fully automated DNAextraction on a standard laboratory centrifuge. KEYWORDS: Microfluidics, centrifugal routing, DNA extraction, time-controlled release, liquid reagent storage
F. Trenkle, M. Mayer, S. Haeberle, S. Messner, R. Zengerle
PMP-NC² - A Bi-Directional, Normally-Closed and Backpressure Independent Micropump
2010 Actuator 2010, Bremen, Germany, 14.-16. June , Seiten: 234 - 237
KurzfassungAbstract: This paper presents a novel Peristaltic MicroPump with a twofold intrinsic Normally-Closed mechanism (PMP-NC2). It is based on a modular concept with a low cost disposable microfluidic chip and a re-usable actuator unit. The normally-closed mechanism prevents fluid flow without power consumption in the stand-by mode for pressures up to 150 kPa. Together with the backpressure independent pumping performance up to 80 kPa this results in a fail-safe and precise micropump. The addressed range of pump rates is up to 100 μL/min. Due to the symmetrical setup, bi-directional pumping is possible and also air bubble tolerance is demonstrated. This results from the very low dead volume per pump chamber of only 230 nL, which leads to a complete transport of the air bubbles through the pump. Keywords: Microfluidics, Micropump, Microvalve, Normally-closed, Modular, Piezostack
T. van Oordt, D. Mark, M. Focke, S. Lutz, F. von Stetten, R. Zengerle
Rapid Field Testing of Biological Threats with Lab-on-a-Chip Systems
2010 5th Security Research Conference, Berlin, 07-09 September 2010 , Seiten: 256 - 257
KurzfassungThe world’s increasing mobility, mass tourism but also possible terrorist activities increase the risk of a fast distribution of infections and toxins. Today’s procedures for pathogen detection involve complex, stationary devices and may be too time consuming for a rapid and effective response. A robust, mobile field diagnostic system is required. A microfluidic system that includes a mobile centrifugal platform and a disposable test carrier enabling complex biochemical analysis is currently being developed within the BMBF funded project SONDE.
Arne Kloke, Christian Köhler, Roland Zengerle, Sven Kerzenmacher, Felix von Stetten
Reaction-specific platinum electrodes for implantable glucose fuel cells:Versatile fabrication by cyclic electrodeposition
2010 Proc. of PowerMEMS, Leuven, Belgium, December 1–3 , Seiten: 73 - 76
KurzfassungWe present a new versatile method for the generation of ultra porous noble metal electrodes based on cyclic Pt-Cu electrodeposition and anodic Cu dissolution. Performing this method, electrodes with tailored roughness factors (RF exceeding up to 2031) and thus reaction-specificity can be fabricated. Applied in implantable glucose fuel cells, the novel process enables a by 14 % increased power density compared to state of the art, at significantly reduced platinum consumption and substantially facilitated fabrication.
Dennis Trebbels, Michael Jugl, Roland Zengerle
Real-Time Cannula Navigation in Biological Tissue with high temporal and spatial resolution based on Impedance Spectroscopy
2010 32nd Annual International Conference of the IEEE EMBS Buenos Aires, Argentina, August 31 - September 4 , Seiten: 1886 - 1889
KurzfassungIn many medical applications a well-directed positioning of a cannula in body tissue is mandatory. Especially the accurate placing of the cannula tip in the tissue is important for efficient drug delivery or for accessing blood vessels and nerves. This paper presents a new approach for a universal cannula navigation system based on tissue classification on the cannula tip by impedance spectroscopy. The cannula serves as coaxial, open ended waveguide which is connected to remote measurement equipment. Objective of the new system is to reach a high spatial and temporal resolution for dynamic cannula guidance. Therefore the proposed coaxial cannula design has been analyzed by Finite Element Simulation to investigate the sensitivity of the cannula tip. For fast tissue impedance spectrum measurement the Time-Domain- Reflectometry method is used in order to achieve a high temporal resolution. Measurement data derived in the laboratory is analyzed and interpreted using the general Cole- Cole model for tissue. Based on the results we propose to use a chirp signal for impedance measurement in order to improve the sensitivity of the system towards specific tissue properties.
Phillip Kuhn, Nils Paust, Roland Zengerle, Felix von Stetten, Günter Roth
Smaller Structures Taking the Lead - Analysis and Simulation of Structure Size Influences on Binding Kinetics Down to the Single Molecule Level
2010 Proc. of IEEE-MEMS, Hong-Kong, China, January 24-28 , Seiten: 919 - 922
KurzfassungThis paper describes a method for the quantitative detection of biochemical binding events onto mi-crostructured and functional surfaces on a truly single molecular level. The classic Streptavidin-biotin system is used to provide the last detection step and the binding is visualized via gold-nanoparticles in a SEM. We showed that this allows a spatial resolution down to the nanometer scale. It also allowed us to proof the spot size dependence of binding kinetics according to the theorem of Ekins in one single experiment. The method allows to analyze any binding event on a planar surface and is enabling to measure surface densities of func-tional groups like the amount of BSA molecules on a blocked glass surface.
S. Thiele, R. Zengerle, C. Ziegler
Three dimensional Reconstruction of PEFC Catalyst Layers
2010 Proc. of MMM 2010, Microstructure Modeling, Freiburg, Germany, October 4 – 8 , Seiten: 564 - 567
KurzfassungThe introduction of hybrid electric vehicles has prepared the complete replacement of gasoline systems by systems based on batteries or polymer-electrolyte fuel cells. One of the main sources for performance losses, degradation problems and cost are the catalyst layers. Therefore there is a great need for detailed insight into catalyst layer materials to exploit their potential. In order to solve this problem we define a threefold aim: The first step is to develop a new method for morphology analysis in order to get a 3D image of the catalyst layer. The second step is finding a means to quantitatively describe the morphology of such a geometry. Finally we intend to calculate an optimum morphology eliminating or at least reducing some of the sources of performance loss. In this paper we present an analytical method for morphology analysis suited for the catalyst layer and the first 3D reconstruction of such a layer of a polymer electrolyte fuel cell. We further present first results on our way to quantitatively describe the morphology.

2009

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M. Karle, J. Miwa, G. Roth, R. Zengerle, F. von Stetten
A novel microfluidic platform for continuous DNA extraction and purification using laminar flow magnetophoresis
2009 Proc. IEEE-MEMS; 25 – 29 January 2009, Sorrento, Italy , Seiten: 276 - 279
KurzfassungFor the first time we present a novel microfluidic platform using laminar-flow magnetophoresis for combined continuous extraction and purification of DNA from cells. All essential unit operations (DNA binding, sample washing and DNA elution) are integrated on one single chip. The key function is the motion of magnetic beads given by the interplay of laminar flow and a time-varying magnetic field. The magnetic beads enable the transport of the DNA across the interfaces between co-flowing laminar streams in a circular channel arrangement around a central rotating permanent magnet inducing time-varying magnetic field, which prevents the beads from sticking to the channel walls and enables controlled transfer of beads between different extraction reagents. The system was fabricated by micromilling in polycarbonate. Pressure driven experiments were performed to analyze the magnetophoretic concept and the biotechnical functionality. Compared to a macroscopic reference system 25% of total DNA have been recovered. An inlet flow velocity of 12.5 mm∙s-1 lead to an average bead velocity of 1.6 mm∙s-1 The sample transition time is approximately 1 minute. The device is a central part of a complete biochemical sensing system for continuous monitoring of cell growth in bioreactors, but allows also continuous purification of DNA, RNA, proteins or cells, including their subsequent real-time analysis.
S. Lutz, P. Weber, M. Focke, B. Faltin, C. Mueller, G. Roth, D. Mark, N. Armes, O. Piepenburg, R. Zengerle, F. von Stetten
Automated analysis of genetic markers by isothermal recombinase polymerase amplification in a centrifugal microfluidic cartridge
2009 Proc. Eurosensors XXIII, Lausanne, Schweiz , Seite: 131
KurzfassungRecombinase polymerase amplification (RPA) is a new isothermal DNA amplification method that runs at 37 °C, amplifies single copies in less than 15 minutes, and allows real-time fluorescence detection. For the first time we automated this method by microfluidic integration into a centrifugal lab-on-a-chip system, comprising unit operations for reconstitution of reagents, mixing with the sample, and aliquoting to test cavities. As the cartridge contains all of the required liquid and dry reagents only the addition of sample DNA is required. The system was demonstrated by the qualitative detection of < 10 copies of the antibiotic resistance gene mecA in less than 15 minutes. The presented disk-shaped Lab-on-a-Chip cartridge consists of a COP-foil structured by blow-molding [1]. The surface is coated with BSA for blocking and hydrophilization. Glass ampoules with liquid reagents and lyophilized dry reagents are inserted into reservoirs and the disk is sealed by an adhesive foil (fig 1A). When operated the sample is added to the cartridge, the liquid reagent ampoule is manually disrupted through the foil to release the reaction buffer, and the cartridge is placed into a centrifugal analyzer with integrated fluorescence detection (modified RotorGene 2000, Corbett Research, Australia). At spinning frequency of 27 Hz 50 μl of reaction buffer is transferred from the disrupted ampoule to the lyophilized RPA reagents. After dissolving the lyophilisate the solution is divided into 5 x 10 μL aliquots and transferred into the test cavities via a centrifugopneumatic valve (fig 1B). Each of the test cavities may contain a different primer and probe system. The RPA reaction is based on a special recombinase-primer-complex that allows strand displacement and amplification at 37 °C [2].
Maximilian Focke, Bernd Faltin, Claas Müller, Roland Zengerle, Felix von Stetten
Blasformen von Mikrofluidikstrukturen für Lab-on-Foil Anwendungen
2009 Tagungsband Mikrosystemtechnik-Kongress 2009, Berlin, 12.-14. Oktober , Seite: P 22
KurzfassungPräsentiert wird ein neuartiger Prozeß zur schnellen Herstellung dünnwandiger Folienkartuschen aus thermoplastischen Kunststofffolien durch Blasformen. Der Prozeßdurchlauf benötigt vom CAD-Entwurf bis zur fertigen Folienkartusche 6-8 Stunden. Die Folienkartuschen eignen sich durch ihre dünnen Wände insbesondere für mikrofluidische Anwendungen die eine schnelle Temperierung erfordern. In der In-Vitro-Diagnostik ist zum Beispiel der Einsatz für Nukleinsäure-Analysen mit Hilfe der Polymerase Kettenreaktion (PCR) extrem vorteilhaft. Während in herkömmlichen Folienformprozessen Entformschrägen an den Formwerkzeugen von mindestens 3° erforderlich sind, sind bei der hier vorgestellte Technologie keine Entformschrägen erforderlich. Das vereinfacht sowohl den Konstruktions- als auch den Herstellungsprozess signifikant. Die hergestellten Kartuschen zeichnen sich durch eine sehr geringe Maßabweichung von lediglich 0,4% aus. Die Konturtreue einer typischen Kavität mit einem Durchmesser von 3 mm beträgt 18 µm (Halbwertsbreite). Ihre Eignung für diagnostische „Lab-on-a-Foil“-Anwendungen wurde erfolgreich mit einer komplexen mikrofluidischen Aliquotierstruktur sowie der Durchführung einer Real-Time PCR gezeigt.
N. Paust, S. Krumbholz, S. Munt, C. Müller, R. Zengerle, C. Ziegler, P. Koltay
Design of a passive and portable DMFC operating in all orientations
2009 Proc. IEEE-MEMS; 25 – 29 January 2009, Sorrento, Italy , Seiten: 1091 - 1094
KurzfassungA microfluidic layout concept for passive and portable Direct Methanol fuel Cells (DMFCs) is presented. We proofed this concept by developing a DMFC that continuously runs for 40 hours in all orientations without the need for any active components such as pumps or valves. In contrast to our previous work [1], the system now is truly portable. In any orientation of the DMFC, a bubble driven self regulating supply mechanism safely removes carbon dioxide and transports at least 3.5 times more methanol to the anode than critically needed to sustain DMFC operation. On the cathode, diffusive oxygen supply and the transport of the reaction product water along a capillary gradient out of the DMFC ensures a stable performance. Compared to our previous work [1], the power output was increased by a factor of 2.5 and reached p = 5.5 mW cm-2. A stable power output for 40 hours of p = 4 mW cm-2 was achieved for the preferred vertical position with bubbles moving against buoyancy forces. In the most challenging horizontal position with the anode facing downwards, a power output of at least p = 3.1 mW cm-2 was reached for the same period of time.
D. Mark, M. Focke, G. Roth, R. Zengerle, F. von Stetten
Detection of Biological Threats with Fully Automated Lab-on-a-chip Systems in the project SONDE
2009 Proc. Future Security - 4th Security Research Conference Karlsruhe, Germany, September 29th – October 1st , Seiten: 487 - 490
KurzfassungIncidents and terrorist attacks with biological agents bear the risk of causing widespread damage and panic. Rapid detection of such threats is not possible with state of the art technologies, since laboratory methods are time-consuming and often not available in the vicinity. However, to enable a fast assessment of patient symptoms and allow an appropriate quarantine and decontamination response, a robust point-of-care diagnostic system is required. To address this problem, novel lab-ona- chip platforms can be used. One solution is the centrifugal microfluidic platform. It allows automated liquid handling on a rotating structured polymer disk enabling the integration and automation of complex biochemical analysis, such as nucleic acid tests and immunoassays for B-detection.
Kloke A, Kerzenmacher S, Zengerle R, von Stetten F
Electrodeposited thin-layer electrodes for the use in potentially implantable glucose fuel cells
2009 Proc. Transducers, Denver, USA Transducers '09 - Digest of Technical Papers, Seiten: 537 - 540
KurzfassungWe present a novel concept for the fabrication ofelectrodes to be used in thin-layer implantable glucose fuelcells employing platinum based materials as long-termstable abiotic catalysts. A highly porous anode for glucoseoxidation is fabricated by a multiple alternation ofelectrodeposition of platinum-copper alloy and subsequentelectrochemical extraction of the non-noble copper. Toform a permeable oxygen reduction cathode, platinumblack is deposited onto a gold-coated polycarbonate tracketchmembrane (PC-TEM). Power densities of up to3.1 ìW cm-2 are obtained for consequently assembled fuelcells. The novel electrode structures exhibit comparableperformance to state of the art at significantly reducedthickness and facilitated fabrication.
Simon Herrlich, Stephan Messner, Roland Zengerle, Stefan Haeberle
Elektrisch schaltbarer Mikro-Schließmuskel zur Medikamentendosierung
2009 Tagungsband Mikrosystemtechnik-Kongress, Berlin, 12.-14. Oktober , Seite: P 70
KurzfassungWir präsentieren Mikroaktoren, die in ihrer Funktionsweise Schließmuskeln ähneln, indem sie eine oder mehrere Durchlassöffnungen einer Membran durch reversibles Quellen des elektroaktiven Polymers (EAP) Polypyrrol (PPy) verschließen und wieder öffnen können. Eine mögliche Anwendung des Aktors ist die gesteuerte Pharmakonfreisetzung aus miniaturisierten Medikamentendepots. Drei verschiedene Durchlassvarianten werden miteinander verglichen, wobei die Quellung bei Vermeidung in sich geschlossener EAP-Strukturen verdoppelt werden konnte. Die Aktoren haben keine mechanisch beweglichen Teile und werden bei kleinen Spannungen (1 V) und Strömen (ab 45 μA) betrieben.
S. Rubenwolf, J. Kestel, S. Kerzenmacher, R. Zengerle, F. von Stetten
Enhancing the lifetime of laccase-based biofuel cell cathodes by sequential renewal of enzyme
2009 60th Annual Meeting of the International Society of Electrochemistry, Bejing , Seiten: S-01 - P-011
KurzfassungWe present a novel bio-inspired approach to enhance the lifetime of enzymatic biofuel cell electrodes. Due to limited enzyme stability the lifetime of such fuel cells is at present only in the order of weeks or months [1]. While current research approaches to overcome this problem focus on enzyme stabilization by immobilization [2], living organisms separate enzyme lifetime from system lifetime by the continuous regeneration of fresh enzyme. We transfer this principle to biofuel cells by sequentially exchanging the electrolyte to re-supply active enzyme to the electrode. Since this concepts demands reversible adsorption of the enzyme, we chose a mediator-less graphite felt cathode with adsorbed laccase as biocatalyst, operating in oxygen saturated 100 mM citrate buffer (pH = 5) [3].
A. Kloke, S. Kerzenmacher, R. Zengerle, F. von Stetten
Facile Fabrication of Ultra Porous Platinum Electrodes and Their Application for Energy Harvesting Glucose Fuel Cells, Abstract number #205
2009 Proc. of 215th ECS Meeting, San Francisco, USA, May 24-29 , Seite: 572
KurzfassungWe present a new method for the generation of porous noble metal surfaces utilizing cyclic repetition of alloy deposition and removal of a non-noble alloy partner in cyclic voltammetry. This method was applied in acidic solution of H2PtCl6 and CuSO4 to fabricate ultra porous platinum electrodes with a roughness factor of above 5000, higher than elsewhere reported. Such platinum surfaces were characterized and tested as electrodes for the use in implantable glucose fuel cells, showing a competitive performance to state of the art with several general technological advantages.
Kiril Kalkandjiev, Roland Zengerle, Peter Koltay
Fertigung von Hybriddruckköpfen aus Silizium und Kunststoff
2009 Tagungsband Mikrosystemtechnik-Kongress, Berlin, 12.-14. Oktober , Seite: P7.1
KurzfassungWir präsentieren einen Ansatz für die hybride Fertigung von mikrofluidischen Produkten durch die Integration von Sili-zium und Kunststoff. Der Ansatz ist besonders für die kostengünstige Herstellung von Produkten geeignet, in welchen hochpräzise Siliziumstrukturen mit anderen, großflächigen Komponenten verbunden werden sollen. Wir zeigen das Po-tential dieser Technik durch die Fertigung eines 24-kanaligen Dispensers für die Herstellung von Microarrays mittels der TopSpot Technologie. Der Hybriddruckkopf ist dreilagig aufgebaut und besteht aus einer Reservoirplatte aus Cyclo-Olefin-Copolymer (COC), einem Siliziumchip mit mikrofluidischen Strukturen und einer Deckelschicht aus Epoxy-basiertem Trockenresist (TMMF). Diese Materialkombination führt zu einer Reduzierung der Herstellungskosten um mehr als 50 % bei gleichbleibender Performance im Vergleich zu den kommerziell verfügbaren Dispenser in Silizium-Glas-Technik [1]. Der hybride Fertigungsansatz kann somit als eine vorteilhafte Alternative und Ergänzung zu den klas-sischen Materialien und Prozessen der Mikrosystemtechnik angesehen werden.
N. Wangler, O. Brett, M. Laufer, M. Strasser, A. Dovzhenko, K. Voigt, K. Palme, M. Daub, R. Zengerle, J. Steigert
Gezielte chemische Stimulation einzelner Tabak Protoplasten mittels hochaufgelöster Wirkstoffabgabe
2009 Tagungsband Mikrosystemtechnik-Kongress, Berlin, 12.-14. Oktober , Seite: P 33
KurzfassungDiese Arbeit präsentiert die diskrete und gezielte Abgabe von zwei individuell adressierbaren Substanzen im unteren pl Bereich (10 pl) mit einer hohen räumlichen (< 50 µm) und zeitlichen (< 100 µs) Auflösung zur chemischen Stimulation einzelner Zellen. Die Zellen werden in einer dünnen Alginatschicht kultiviert und durch kleine Tropfen beschossen, die einen zu Tabak-Protoplasten vergleichbaren Durchmesser aufweisen. Das kleine Volumen erzeugt im unmittelbaren Umfeld der Zielzelle eine wohl definierte Wirkstoffkonzentration, während der Konzentrationsgradient aufgrund der dreidimensionalen Diffusion mit wachsender Distanz drastisch abfällt und somit zeitnah zu einem extrem niedrigen Hintergrundsignal führt. Demonstriert wird dies durch die hoch aufgelöste Färbung eines einzelnen Protoplasten der Tabakpflanze mit Carboxyfluorescein Diacetat.
Dennis Trebbels, Roland Zengerle, David Hradetzky
Hematocrit Measurement – A high precision on-line measurement system based on impedance spectroscopy for use in hemodialysis machines
2009 Proc. of World Congress on Medical Physics and Biomedical Engineering (WC), IFMBE Proceedings 25/VIII , Seiten: 247 - 250
KurzfassungThis paper presents a unique technical approach to measure the proportion of blood volume occupied by red blood cells, the hematocrit value (HCT) on-line and in-line. A practical method has been developed to measure without the need for extracting blood samples out of an existing extracorporeal blood circulation system. The new sensor is based on Impedance Spectroscopy and measures electrical properties of the blood at various frequencies. In order to achieve the required precision resolution the sensor geometry has been optimized by Finite Element Analysis. For sensor readout a digital measurement circuitry based on cheap standard components is developed and allows practical implementation of HCT-sensor devices for the first time. Special care has been taken in order to compensate for the temperature effects. Keywords— impedance spectroscopy, on-line measurement, hematocrit measurement, hemodialysis, extracorporal blood flow
S. Lutz, P. Weber, M. Focke, B. Faltin, G. Roth, O. Piepenburg, N. Armes, D. Mark, R. Zengerle, F. v. Stetten
Integration of Isothermal Polymerase Amplification into a Centrifugal Microfluidic Cartridge
2009 Proc. of the Thirteenth International Conference on Miniaturized Systems for Chemistry and Life Sciences (µTAS), Jeju, Korea, November 1-5 , Seiten: 433 - 435
KurzfassungRecombinase polymerase amplification (RPA) is a new isothermal DNA amplification method that runs at 37°C, amplifies single copies in less than 15 minutes, and allows real-time fluorescence detection. For the first time we automated this method by microfluidic integration into a centrifugal lab-on-a-chip system, comprising unit operations for reconstitution of reagents, mixing with the sample, and aliquoting to test cavities. As the cartridge contains all of the required liquid and dry reagents only the addition of sample DNA is required. The system was demonstrated by the qualitative detection of < 10 copies of the antibiotic resistance gene mecA in less than 15 minutes.
Marc Karle, Junichi Miwa, Günter Roth, Stefan Haeberle, Roland Zengerle, Felix von Stetten
Kontinuierlich arbeitende Mikrofluidik-Plattform zur Aufreinigung von Biomolekülen
2009 Tagungsband Mikrosystemtechnik-Kongress, Berlin, 12.-14. Oktober , Seite: P 31
KurzfassungWir präsentieren eine neue Mikrofluidik-Plattform, die eine kontinuierliche Extraktion und Aufreinigung von Biomolekülen z.B. aus einem Fermenter ermöglicht. Die Plattform beruht auf dem Einsatz der Magnetophorese in einer Laminarströmung. Alle erforderlichen Arbeitsschritte (Binden, Waschen und Eluieren der Biomoleküle) sind auf einem Chip integriert. Eine Schlüsselfunktion nehmen superparamagnetische Partikel in einer Laminarströmung in Verbindung mit einem zeitlich variierenden Magnetfeld ein. Die Partikel ermöglichen den Transport der Biomoleküle über die Phasengrenze der Laminarströmung in einer kreisförmig um einen zentralen, rotierenden Permanentmagneten angeordneten Kanalstruktur. Die Rotation des Permanentmagneten erzeugt ein periodisch variierendes Magnetfeld, das die kontrollierte Bewegung der magnetischen Partikel zwischen unterschiedlichen Extraktionsreagenzien ermöglicht, ohne die Partikel an der Kanalwand zu immobilisieren. Als erste Applikation wurde ein Chip zur DNA-Extraktion aus Polykarbonat mittels Mikrofräsen hergestellt. Um die biotechnische Funktionalität und das magnetophoretische Konzept zu untersuchen, wurde bakterielle DNA direkt aus dem Lysat extrahiert. Im Vergleich mit einem makroskopischen Referenzsystem wurden 80 % der DNA aufgereinigt. Eine Eingangsflussgeschwindigkeit von 12.5 mm∙s-1 führte zu einer durchschnittlichen Partikelgeschwindigkeit von 1.6 mm∙s-1 und zu einer DNA-Extraktion innerhalb ca. 1 Minute. Die Plattform ist ein zentrales Element eines Überwachungssystems zur kontinuierlichen Kontrolle des Zellwachstums in Bioreaktoren. Darüber hinaus kann sie, je nach Oberflächenmodifikation der magnetischen Partikel, auch für die Aufreinigung von RNA, Proteinen oder Zellen für nachfolgende Echtzeitanalysen verwendet werden.
S. Lutz, D. Mark, R. Zengerle, F. von Stetten
Lab-on-a-Chip Cartridge zur Durchführung von Immunoassays mit integrierter Probenaufbereitung
2009 Tagungsband Mikrosystemtechnik-Kongress 2009, Berlin, 12.-14. Oktober , Seite: P 7.3
KurzfassungWir stellen ein neuartiges Lab-on-a-Chip System vor, das unter Ausnutzung von Zentrifugalkräften eine integrierte Prozessierung von Immunoassays mit kompletter Probenaufbereitung ermöglicht. Unsere Lab-on-a-Chip Cartdige erlaubt die Separation von Blutzellen und Blutplasma, die Dosierung eines definierten Plasmavolumens, die Durchführung von Inkubations-, Misch- und Waschschritten sowie ein integriertes Abfallreservoir. Aus einem Blutvolumen von 10 µL extrahieren wir durch Sedimentation 4 µL Blutplasma mit einem cv von 6 %. Das Schalten der Fluide in der Cartridge wird mittels kapillarer und volumengesteuerter Siphonventile durchgeführt. Die Verlässlichkeit des fluidischen Systems wird erhöht durch eine Hydrophilisierung der Oberfläche mit BSA. Die Reaktionskammer ermöglicht effiziente Misch- und Waschprozesse und erlaubt die Vorlagerung von Trockenreagenzien. Um die Funktionalität unseres Lab-on-a-Chip Systems zu demonstrieren, zeigen wir eine quantitative Bestimmung des Hormons Estradiol in Konzentrationen von 25 pg/mL bis 1 ng/mL mittels eines Chemolumineszenz-basierten kompetitiven Immunoassays.
T Metz, D Mark, S Lutz, O Strohmeier, D Kosse, M Focke, B Faltin, J Burger, J Böning, J Miwa, M Karle, G Müller, C Müller, S Messner, H Reinecke, R Zengerle, F von Stetten
Lab-on-a-Chip Foundry Service – enabling the miniaturization of in vitro diagnostics
2009 Euromedlab, Innsbruck, Austria, 2009, 350-368 Clinical Chemistry and Laboratory Medicine, Seiten: 350 - 368
T. Metz, M. Karle, T. Preis, D. Mark, G. Roth, C. Müller, R. Zengerle, F. von Stetten
Lab-on-a-Chip Foundry Service: Schnelle kundenspezifische Implementierung miniaturisierter biochemischer Assays
2009 Tagungsband Mikrosystemtechnik-Kongress 2009, Berlin, 12.-14. Oktober , Seite: P 42
KurzfassungWir präsentieren eine konsistente Methodik zur effizienten Miniaturisierung, Integration und Automatisierung bio-chemischer Assays auf der Grundlage definierter mikrofluidischer Plattformen [1]. Eine mikrofluidische Plattform stellt einen Satz fluidischer Grundfunktionen (sogenannte Einheitsoperationen) zur Verfügung welche einfach kombiniert und durch eine günstige, wohl definierte Fertigungstechnologie hergestellt werden können. Anwendungsspezifische Assays lassen sich hierüber flexibel und mit geringem Entwicklungsrisiko durch die systematische Verknüpfung plattformspezifischer, validierter, Einheitsoperationen implementieren. Die mikrofluidischen Layouts der Einheitsoperationen werden in einem Design Handbuch, zusammen mit Validierungsergebnissen und den Fertigungsprozessen dokumentiert. Für die Validierung werden standardisierte Strukturen eingesetzt. Dies wird beispielhaft anhand einer Teststruktur für die kapillare Befüllung gezeigt.
Hoffmann J, Mark D, Zengerle R, von Stetten F
Liquid Reagent Storage and Release for Centrifugally Operated Lab-on-a-Chip Systems Based on a Burstable Seal
2009 Proc. Transducers, Denver, USA Proceedings of the 15th IEEE International Conference on Solid-State Sensors, Actuators and Microsystems, Band: 15, Seiten: 1991 - 1994
KurzfassungWe present a new approach for the pre-storage and release of liquid reagents in centrifugally operated Lab-ona- Chip (LoaC) cartridges. Liquids are stored in sealed cavities which are separated from the fluidic system by a weak-bonded interface. During centrifugal rotation, the liquid exerts an inertial force onto the predetermined area. This delaminates the sealing foil locally, resulting in a fluidic connection to the downstream channel. Time-torelease could be adjusted to a range between 31 s and 143 s by geometrical variations of the structure, enabling time controlled release. In sum, the burstable seal is a universal and robust valve: it is vapor tight, independent on wetting properties of liquids, and time controllable. Hence it excels siphon based valving concepts often used in centrifugal microfluidics and is most valuable for the design of LoaC cartridges for point of care applications.
C. Ziegler, N. Paust, R. Zengerle
Micro two-phase transport in polymer electrolyte fuel cells
2009 Book of abstracts; 6th Symposium on Fuel Cell Modelling and Experimental Validation, German Aerospace Center (DLR), Bad Herrenalb / Karlsruhe , Seite: 67
KurzfassungMicro two-phase flow plays an important role for the operation of polymer electrolyte fuel cells. Hydrogen fuel cells (PEMFC) and direct methanol fuel cells (DMFC) are the most important types of polymer membrane fuel cells. At the cathode water is generated as a result of the oxygen reduction reaction in the PEMFC and DMFC. This leads to two-phase flow of gas and liquid water in the porous components (gas diffusion layer, catalyst layer) and channels of the fuel cell. Moreover in the DMFC carbon dioxide is generated and forms gas bubbles at the anode side. Through the complex coupling of the two-phase flow with the electrochemical reaction the performance and stability of the fuel cell are influenced by the transport on the micro-scale. We present modelling approaches that allow for the analysis of two-phase flow on the micro scale and derive engineering approaches for fuel cell components. Finally experiments are presented that show how the negative impact of the two-phase flow can be mitigated and even be turned into better system efficiency.
T. Metz, D. Mark, S. Häberle, G. Roth, C. Müller, F. von Stetten, R. Zengerle
Microfluidic Platforms for Miniaturization, Integration and Automation of Biochemical Assays
2009 Proc. of International Conferences on Multi-Material Micro Manufacture (4M) / International Conferences on Micro Manufacturing (ICOMM), Karlsruhe , Seiten: 25 - 29
KurzfassungDuring the last decade many technological progresses were achieved in the field of Lab-on-a-Chip for the miniaturization, integration and automation of biochemical assays. Nowadays an unmanageable variety of alternative approaches exist that can perform these tasks. To cope with the complexity of those systems the paradigm of development changed from component oriented approaches towards the development of microfluidic platforms. A microfluidic platform provides a set of fluidic unit operations, which are designed for easy combination within a well defined (and low cost) fabrication technology. The platform allows implementation of different application specific systems (assays) in an easy and flexible way, based on the same fabrication technology. In this work we will discuss important issues for the successful implementation of a platform oriented development environment for Lab-on-a-Chip on the example of the newly set up Lab-on-a-Chip Foundry Service of the HSG-IMT. The systematic development of Lab-on-a-Chip will be shown on the example of a nucleidic acid assay on the centrifugal microfluidic platform. In the Lab-on-a-Chip Foundry Service, development is based on standardized microfluidics and standardized fabrication processes that are maintained in a knowledge management system, the Lab-on-a-Chip Design Handbook of the HSGIMIT. Facilities and experts are provided for microfabrication and microfluidics as well as for biochemistry and biology to enable fast development cylces in a one-stop shop approach. Prototyping is organized in rapid prototyping chains for polymer fabrication, sealing and assembly in a rapid prototyping workshop.
Daniel Mark, Markus Rombach, Sascha Lutz, Roland Zengerle, Felix von Stetten
Microfluidic unidirectional pneumatic switch for automated DNA-extraction on standard laboratory centrifuges
2009 Proc. of the Thirteenth International Conference on Miniaturized Systems for Chemistry and Life Sciences (µTAS), Jeju, Korea, November 1-5 , Seiten: 110 - 112
KurzfassungFor the first time, we present a new, unidirectional liquid switching concept for the centrifugal microfluidic platform. The concept relies on a controlled liquid-air interface instability. It enables automated DNA-extraction and potentially other microfluidic protocols on standard laboratory centrifuges, superseding the need for expensive base instruments, which are common to all state of the art Lab-on-a-Chip platforms. As a proof of concept we fabricated a Lab-on-a-Chip cartridge for automated DNA extraction from 32 μL whole blood on a standard laboratory centrifuge. The obtained DNA yield was 88 ± 44 ng (42 % of the optimized reference extraction [1]).
S. Haeberle, D. Hradetzky, A. Schumacher, M. Vosseler, S. Messner, R. Zengerle
Microfluidics for Drug Delivery
2009 Proc. of World Congress on Medical Physics and Biomedical Engineering (WC), IFMBE Proceedings 25/VIII , Seiten: 359 - 362
KurzfassungDrug delivery, i.e. the way a pharmacologically active substance is delivered to the body, has a significant impact on the therapeutic value of medication. The paper gives an overview on different drug delivery schemes and describes the limitations of the oral route, which is the current gold standard in the market. Following these limitations, plenty of alternative (parenteral) drug delivery technologies are currently under development. Many of them require the precise handling of small liquid volumes using small sized and low energy consuming devices. So microfluidics is a key enabling technology for these upcoming drug delivery devices. Ease of use and autonomous operation are the most important aspects for high acceptance and compliance of the patients. So for short term therapy (e.g. antibiotics), the devices should be small and portable. For long term therapy (e.g. cardiac), implantable devices are favorable since they can operate autonomously and deliver precise doses exactly to the target site (local therapy). The paper describes two examples for microfluidic drug delivery devices in more detail, namely the intra-oral transmucosal "IntelliDrug system" and the transdermal "ChronopaDD" device. Keywords— microfluidics, drug delivery, microsystems
Fabian Trenkle, Stefan Haeberle, Roland Zengerle
Normal-geschlossene Mikropumpe mit fluidischem Einwegchip und wiederverwendbarer Aktoreinheit
2009 Tagungsband Mikrosystemtechnik-Kongress, Berlin, 12.-14. Oktober , Seite: P 7.2
KurzfassungWir präsentieren eine normal-geschlossene Mikropumpe, basierend auf Piezostack-Aktoren. Das integrierte normal-geschlossene Verhalten der peristaltischen Pumpe verhindert eine Flüssigkeitsabgabe im energielosen Zustand, bis zu einem Überdruck von 100 kPa. Der modulare Aufbau beinhaltet eine wiederverwendbare Aktoreinheit sowie einen kostengünstigen, fluidischen Einwegchip. Dieser kann nach Gebrauch oder Kontamination leicht gewechselt werden. Bei einer Pumpfrequenz von 28,6 Hz wurden Förderraten bis 40 μl/min für Wasser erreicht. Die Flussraten sind gegendruckunabhängig bis 7 kPa und eine Flüssigkeitsförderung ist bis zu einem maximalen Gegendruck von 45 kPa möglich. Auch hochviskose Medien mit 46 mPas konnten erfolgreiche gepumpt werden.
F. Trenkle, S. Haeberle, R. Zengerle
Normally-Closed Peristaltic Micropump With Re-Usable Actuator And Disposable Fluidic Chip
2009 Proc. Eurosensors XXIII, Lausanne, Schweiz , Seite: 377
KurzfassungThis paper describes a piezostack actuated peristaltic micropump featuring a normally-closed function up to pressures of 100 kPa, when the electric power is off. The design is based on a modular setup with a re-usable actuator unit and a low-cost disposable fluidic chip that can easily be exchanged after contamination or use. Pump rates up to 40 μl/min at 28.6 Hz are demonstrated with water. The flow rates are backpressure independent up to 7 kPa, with a maximum backpressure of 45 kPa at 140 V. Also liquids with high viscosities up to 46 mPas are pumped successfully.
J. Burger, D. Mark, G. Roth, C. Müller, R. Zengerle, F. von Stetten, Y. Park
Physiologische Assays in einem DVD Player am Beispiel der Messung des Hämatokrit
2009 Tagungsband Mikrosystemtechnik-Kongress 2009, Berlin, 12.-14. Oktober , Seite: P 78
KurzfassungDie Bestimmung des Hämatokrits (Erythrozytengehalt im Blut) mit zentrifugal mikrofluidischen Bio-Disks [1] in einem low-cost DVD Player wurde bereits in früheren Arbeiten untersucht [2,3]. Nun strukturieren wir konventionelle DVD Halbscheiben aus Massenproduktionsprozessen und Bonden diese zu mikrofluidischen Bio-DVD’s. Somit kann der Standard DVD-Player sowohl als Zentrifuge zur mikrofluidischen Prozessierung als auch zur Detektion der Ergebnisse mit dessen integrierter Opto-Elektronik verwendet werden. Der Hämatokrit gibt unter anderem Aufschluss über den Wasserhaushalt des Patienten oder den Erythrozytenanteil im Blut. Er wird häufig im Rahmen von point-of-care Tests neben anderen Parametern in der Notfallmedizin, in Dopingtests oder vor Blutspenden ermittelt. Somit stellt diese Arbeit einen weiteren Schritt hin zu kompletten DVD-basierten point-of-care Tests dar und bietet eine Grundlage für die Implementierung weiterer Assays.
J. Rupp, M. Schmidt, M. Stumber, P. Rothacher, R. Zengerle, M. Daub
Platform for lab-on-a-chip systems based on integrated active valves made in polymers suitable for mass production
2009 Tagungsband Mikrosystemtechnik-Kongress, Berlin, 12.-14. Oktober , Seite: P 78
KurzfassungFor the first time we present integrated pneumatically controllable valves realized with three layers consisting of two injection compression molded parts separated by a 25 μm thin elastic TPE (thermoplastic elastomer) membrane welded together in one step. The device shows excellent response time and sealing quality at a very low sealing pressure. The production technologies injection compression molding and laser welding fulfill the requirements of a high throughput production and have the potential to manufacture cheap and reliable lab on a chip systems. The elastic TPE membrane works as a joining layer between the two outer layers, each made of cycloolefinpolymere (COP), cycloolefincopolymere (COC) or polycarbonate (PC). Valving is realized by applying pressure in a displacement chamber above a microfluidic channel and deforming the elastic membrane. The materials used show a high chemical resistance against a broad range of commonly used liquids [1]. This consistent technological approach represents a flexible platform for μTAS applications with the active valve as a basic element for more complex applications, such as pumping and mixing on chip.
Goetz M, Messner S, Ashauer M, Zengerle R
Precise dosage system for controlled liquid delivery based on fast MEMS based flow sensor
2009 Proc. Transducers, Denver, USA , Seiten: 1261 - 1264
KurzfassungWe present a system approach for precise liquid dosing at low costs. The highly integrated system operates at flow rates of 0-10mL/min and with a back pressure of 0- 75kPa. It enables a flow with significantly reduced pulsation and a maximum deviation of 1.5%. The realization of the system is based on a smart combination of commercially available low cost fluidic components with a MEMS based thermal mass flow sensor of 1ms response time. KEYWORDS: pump, valve, flow sensor, dosing system, metering
N. Wangler, M. Welsche, M. Laufer, A. Träger, N. Paust, M. Thielen, O. Sobolev, G. Roth, R. Zengerle, J. Steigert
Predictable and defined microgradients in liquid environment for chemical single cell stimulation
2009 Proc. of the Thirteenth International Conference on Miniaturized Systems for Chemistry and Life Sciences (µTAS), Jeju, Korea, November 1-5 , Seiten: 679 - 681
KurzfassungWe present a new method for the precise and predictable generation of defined concentration spots in space and time within liquid environments via a discrete substance release in the sub pL-range (V = 10 pL) with a high spatial (< 50 μm) resolution to stimulate individual cells within densely populated cell cultures. A modular diffusion barrier (phase-gap) placed on the tip of the pL-dispenser (Pico-Injector) prevents of any diffusion based leakage. This allows for the positioning of the dispensing system at any position in a target liquid (e.g. next to an individual cell) to realize sharp and controlled concentration profiles predicted by analytical diffusion model. Dispensing individual droplets enables concentration profiles locally (c < 1/5⋅cmax outside a radius of r = 50 μm) and temporally (c < 1/5⋅cmax after 8 s) well defined. This setup was proven by labeling a single L 929 cell [1].
Ernst A, Streule W, Zengerle R, Koltay P
Quantitative volume determination of dispensed nanoliter droplets on the fly
2009 Proc. Transducers, Denver, USA , Seiten: 1750 - 1753
KurzfassungIn this paper we present a sensor for non-contact monitoring of dispensed micro-droplets on the fly. In extension to our previous work [1], the sensor now allows for a direct, quantitative volume determination of single liquid droplets in the volume range from 20 to 100 nl. The improved electronic transducer enables to measure the droplet volume with an accuracy of ΔV ± 3 nl. The sensor signal provides a variety of information about the monitored droplet like for examples droplet velocity. This paper considers in particular the influence of the droplet velocity on the volume measurement. It turned out that the velocity effect can be fully compensated, if the signals are interpreted correctly.
M. Welsche, N. Wangler, M. Laufer, A. Träger, M. Thielen, M. Daub, R. Zengerle, J. Steigert
Rapid single cell transfection by localised and discreate release of DNA-lipid nanoemulsions
2009 Proc. of the Thirteenth International Conference on Miniaturized Systems for Chemistry and Life Sciences (µTAS), Jeju, Korea, November 1-5 , Seiten: 1802 - 1804
KurzfassungWe present a new tool for the gentle and fast transfection of single cells within a confluent cell culture by precisely localized release (< 50 μm) of discrete agent volume in the pl-range (V = 10 pl). The gentle cell transfection is realized by applying nanoemulsions of liposomes containing DNA (Lipofectamine™2000 [1]) in Opti-MEM® [2] medium directly on a mammalian cell where the released agent droplet is in the size of the target cell (Øcell ~ Ødroplet = 26 μm). By delivering DNA-lipid complexes directly onto the target cell the complexes are absorbed extremely fast within 2.5 min (typically 4-6 hours according to State-of-the-Art) and the transfected DNA-vector is expressed within 24 hours.
Henning Hoefemann, Hans-Martin Trotter, Roland Gronmaier, Felix von Stetten, Roland Zengerle, Stefan Haeberle
Rheoplug – Segmented flow based viscometer
2009 Proc. of the Thirteenth International Conference on Miniaturized Systems for Chemistry and Life Sciences (µTAS), Jeju, Korea, November 1-5 , Seiten: 76 - 78
KurzfassungWe present a novel method to measure the viscosity of liquid mixtures in μLvolume plugs based on a segmented flow platform [1]. Therefore, up to three different liquids of different viscosities are injected into a common plug which is afterwards transported through an air filled channel by a 15-20 mbar vacuum below ambient pressure at the chip outlet. Rapid mixing within the plugs is enabled by internal advection and the plug velocity directly depends on the viscosity of the plug. Following this approach, the viscosities of water/PEG mixtures in the range of 1-68 mPa s could be successfully measured on-chip.
M. Focke, R. Feuerstein, F. Stumpf, D. Mark, T. Metz, R. Zengerle, F. von Stetten
Self-blocking valve for a highly wetting fluids based on pinning of gas entrapments
2009 Proc. of the Thirteenth International Conference on Miniaturized Systems for Chemistry and Life Sciences (µTAS), Jeju, Korea, November 1-5 , Seiten: 1397 - 1399
KurzfassungWe present a novel valving principle for a highly wetting fluid in centrifugal microfluidics by self-blocking pinning structures. While usual geometrical stopping valves prove instable for highly wetting liquids, the novel valve reproducibly generates gas entrapments in a fishbone-like structure. Their pinning pressures add up to a total burst pressure pburst that efficiently avoids uncontrolled capillary priming of microfluidic systems. In centrifugal experiments, burst pressures of 14-18 hPa (12 ± 2 Hz) were reproducibly achieved for isopropyl, a completely wetting alcohol (θ ~ 0°; σ = 22 mNm-1). The same structure also acts as a geometrical stopping valve for less wetting liquids (θ = 31°; σ = 30 mNm-1) [1].
S. Spieth, A. Schumacher, S. van de Moosdijk, S. Haeberle, R. Zengerle
Silicon Microprobe Systems for Neural Drug Delivery: Experimental Characterization of Liquid Distribution
2009 Proc. of World Congress on Medical Physics and Biomedical Engineering (WC), IFMBE Proceedings 25/VIII , Seiten: 158 - 161
KurzfassungNeural drug delivery by microprobes is considered to be one of the most promising methods for treating brain related diseases since the drug liquid can be directly infused into a specific brain region. However, this requires in turn knowledge on the liquid distribution during infusion. This work evaluates the liquid distribution in agarose gel of microfabricated silicon probes with two different outlet styles in comparison to a conventional stainless steel capillary. The optical liquid distributions for infusion rates of 0.2, 0.5, and 1.2 μL/min are determined in a special experimental setup which allows in parallel the measurement of pressure and flow during infusion. Flexible fluidic interfacing to the silicon probes is achieved by small o-rings for easy interchangeability. Since the actual pressure and flow conditions at the outlets of the inserted microprobes cannot be directly measured, a system model of the experimental setup is derived which allows to determine these values. Information on the predominant liquid distributions for the different probe types and infusion rates is qualitatively provided. Finally, actual pressure and flow conditions as well as backflow heights are exemplary presented for an infusion rate of 0.2 μL/min. Keywords—drug delivery, silicon microprobes, microfluidics, liquid distribution.
Herrlich S, Zengerle R, Haeberle S
Sphincter-like micro actuators based on electroactive polymer
2009 Proc. Transducers, Denver, USA , Seiten: 1517 - 1520
KurzfassungWe present sphincter-like micro actuators enabling the reversible adjustment of the aperture area of one or several orifices using the swelling of the conjugated electroactive polymer (EAP) polypyrrole. One possible application is the controlled diffusion- or infusion-based transport of drugs out of miniaturized delivery devices. Three different orifice configurations are proposed and swelling could be doubled by avoiding closed EAP-structures. The actuators do not contain any complex moveable part and can be controlled using low voltages (1 V) and currents (peak down to 45 μA).
T. Metz, G. Birkle, R. Zengerle, P. Koltay
StarJet: Pneumatic dispensing of nano- to picoliter droplets of liquid metal
2009 Proc. IEEE-MEMS; 25 – 29 January 2009, Sorrento, Italy , Seiten: 43 - 46
KurzfassungIn this work we present a novel, simple and robust, pneumatically actuated dispenser for nano- to picoliter sized droplets of liquid metals. The so called StarJet dispenser utilizes a star-shaped nozzle geometry that stabilizes plugs of liquid in the centre of the nozzle by capillary force. This minimizes the wall contact of the liquid plug and reduces contact line friction. Individual droplets of liquid metal can be pneumatically generated by interplay of the sheathing gas flow in the outer grooves of the nozzle and the liquid metal. The working principle was first discovered and studied by Computational Fluid Dynamic (CFD) simulations. For experimental validation silicon chips with the star-shaped geometry were fabricated by Deep Reactive Ion Etching (DRIE) and assembled into a printhead. With different nozzle chips volumes between 120 pl and 3.6 nl could be generated at natural frequencies of 90 Hz and 400 Hz. The StarJet can either be operated as drop on demand or as continuous droplet dispenser. We printed columns of metal with 0,5 to 1,0 mm width and 40 mm height (aspect ratio >40) to demonstrate the directional stability of the ejection.
Tobias Metz, Gerhard Birkle, Christoph Ziegler, Roland Zengerle, Peter Koltay
StarJet: Pneumatische Erzeugung von Nano- bis Picoliter Tropfen flüssigen Lötzinns in einer sternförmigen Düse
2009 Tagungsband Mikrosystemtechnik-Kongress, Berlin, 12.-14. Oktober , Seite: P 81
KurzfassungIn dieser Arbeit zeigen wir einen einfachen und robusten, pneumatisch aktuierten drop-on-demand Dispensierer (StarJet) zur Generierung von Tropfen flüssigen Lötzinns im Nano- bis Pikoliterbereich. Das System basiert auf einer sternförmigen Düsengeometrie, die das flüssige Metall im Zentrum der Düse durch Kapillarkräfte stabilisiert. Dabei ist der Wandkontakt und damit die Wandreibung zwischen dem Flüssigkeitstropfen und der Düse minimiert. Die sternförmige Geometrie ermöglicht in einem selbstorganisierten Wechselspiel mit der Strömung des Schutzgases (N2) in den Fingern des Sternprofils einen pneumatisch erzeugten Tropfenabriss. Dabei stellt sich bei konstanter Aktuation eine natürliche Eigenfrequenz der Tropfengenerierung ein. In Experimenten wurden Tropfen flüssigen Lötzinns, die beispielsweise für das Flip-Chip Bonding genutzt werden können, mit Volumen von 450 pl und 7.2 nl bei natürlichen Frequenzen zwischen 30 und 400 Hz erzeugt. Einzeltropfen konnten durch Aktuationszeiten im Bereich der Eigenfrequenz generiert werden. Durch kontinuierliche Aktuation konnten Säulen flüssigen Lötzinns mit einer Höhe bis zu 30mm bei einer Breite von 500µm erzeugt werden.
J. Hoffmann, L. Riegger, D. Mark, F. von Stetten, R. Zengerle, J. Ducrée
TIR-based dynamic liquid-level and flow-rate sensing and ist application on centrifugal microfluidic platforms
2009 Proc. IEEE-MEMS; 25 – 29 January 2009, Sorrento, Italy , Seiten: 539 - 542
KurzfassungWe for the first time present a technique for the time-resolved localization of the liquid-gas interface on a centrifugal microfluidic platform based on total internal reflection (TIR) at the channel wall. The simple setup consists of a line laser and a linear image sensor array mounted in a stationary instrument. The linear detector allows a meniscus detection which can be realized at high speed rotation up to 30 Hz and features a spatial resolution of 50 µm. Apart from checking the presence of gas bubbles, the unique combination of centrifugation for compacting liquids, the dynamic meniscus detection allows to accurately measure liquid volumes with a high precision of 1.9 % as well as flow rates and viscosities (range: 1 – 12 mPas) with a precision of 4.7 % and 4.3 %, respectively.
Riegger L, Mielnik MM, Mark D, Streule W, Clad M, Zengerle R, Koltay P
Teflon-carbon black as new material for the hydrophobic patterning of polymer labs-on-a-chip
2009 Proc. Transducers '09, Denver, USA , Seiten: 2026 - 2029
KurzfassungWe provide a new method for the selective surfacepatterning of microfluidic chips with hydrophobicfluoropolymers which is demonstrated by the fabricationof hydrophobic valves. It enables efficient optical qualitycontrol for the surface patterning thus permitting the lowcostproduction of highly reproducible hydrophobicvalves. Specifically, a fluoropolymer-solvent-dye solutionbased on carbon black (CB) is presented which createssuperhydrophobic surfaces (contact angle = 157.9°) onchips made from cyclic olefin copolymer (COC). It furtherprovides good visibility for the quality control (QC) inpolymer labs-on-a-chip and increases the burst pressure ofhydrophobic valves. Finally, an application which aims forthe amplification of mRNA on-chip and relies on thedefined flow control by hydrophobic valves is presented.Here, the QC in combination with the Teflon-CB coatingimproves the average standard deviation of the burstpressures from 14.5% down to 6.1 % compared to solelyTeflon-coated valves
Daniel Mark, Stefan Haeberle, Junichi Miwa, Patrick Weber, Guenter Roth, Marc Karle, Max Focke, Sascha Lutz, Jochen Hoffmann, Claas Müller, Felix von Stetten, Roland Zengerle
Two Microfluidic Platforms for Miniaturization, Integration and Automation of Assays
2009 Proc. of COMS, Copenhagen , Seite: -
KurzfassungTwo different platform concepts for microfluidic miniaturization, integration and automation of biochemical assays are presented. First, unit operations for batch-wise nucleic acid analysis on the centrifugal microfluidic platform are demonstrated, including unit operations for DNA extraction, aliquoting and real-time PCR. Second, the newly developed continuous phase transfer magnetophoresis platform is introduced. It enables continuous online process monitoring, demonstrated by implementation of unit operations for DNA extraction.
Christian Köhler, Arne Kloke, Sven Kerzenmacher, Roland Zengerle, Felix von Stetten
Two reaction-specific electrodes fabricated with the same process for the use in tissue implantable glucose fuelcells
2009 Bunsen Colloquium, Dez. 2009 , Seiten: 60 - 61
KurzfassungAbiotically catalyzed glucose fuel cells (GFCs) represent a promising approach for a self-sufficient power supply of low power implants from electrochemical conversion of the in tissue fluids simultaneously present glucose and oxygen. uch systems require two reaction-specific electrodes to achieve a reasonably high cell voltage. This is because both electrodes are operated in the same media and therefore a mixed electrode potential results from the two competing electrode reactions. Hence state of the art GFCs use two electrocatalysts differing in fabrication and material. Here we demonstrate the applicability of a novel catalyst deposition process to fabrication of both electro-des using the same material. Here, Pt-catalysts are fabricated from alternation of Pt-Cu co-deposition and Cu-dissolution
Mark D, Haeberle S, Lutz S, Zengerle R, von Stetten F
Vacuum supported liquid waste handling for DNA extraction on centrifugally operated Lab-on-a-chip systems
2009 Denver, USA Proc Transducers, Seiten: 1230 - 1233
KurzfassungWe present a reliable liquid waste containment for centrifugally operated Lab-on-a-Chip systems that works even for highly wetting reagents. It is based on the passive generation and enclosure of vacuum in a closed storage chamber that prevents all liquids from capillary reflux into the microfluidic channel network.The new waste handling presented here enabled the implementation of an integrated deoxyribonucleic acid (DNA) extraction chemistry without contamination risks based on purely passive structures. Using a 32 µL whole blood sample we achieved an extraction of 290 ng ± 80 ng DNA in 100 µL of eluate.

2008

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J. Böning, D. Mark, S. Lutz, B. Faltin, M. Focke, M. Karle, J. Ducrée, S. Messner, R. Zengerle, F. von Stetten
"Lab-on-a-Chip Foundry Service": A Systematic Approach to the Development of Centrifugal Microfluidic Technologies
2008 Actuator 2008 / Bremen Messe Bremen, Seiten: 814 - 817
KurzfassungThis contribution provides a novel approach to a time and cost-efficient development of polymeric lab-on-a-chip applications. Rather than starting from scratch, new designs are derived from a library of validated laboratory unit operations (LUOs) and prototyped by standard operating procedures (SOPs). LUOs as well as SOPs are systematically documented and retrieved from a "BlueBook". The essential ingredients for the development of lab-on-a-chip applications are liquid handling technologies and fabrication technologies as well as test and development tools. This paper outlines a streamlined approach based on a microfluidic platform concept to reduce the cost, time and risks for the development of lab-on-a-chip technologies. As an example illustrating the platform concept, we describe our centrifugal microfluidic “Lab-ona- Disk” platform. The paradigm of the platform concept is to establish a library of LUOs such as metering, mixing and routing which are validated by experiments and accompanying simulations for a certain parameter range. The concatenation of these LUOs allows to realize complex applications. The layout is then transferred into hardware according to SOPs and afterwards measured at a designated test and development stand. Design rules for the LUOs, procedures (SOPs) and other relevant information such as materials or device components are documented and retrieved from a wiki-based software-based knowledge management portal called “BlueBook”. Keywords: Lab-on-a-Chip Foundry Service, centrifugal microfluidic platform, standard operating procedures, laboratory unit operations, knowledge management system
S. Kerzenmacher, U. Kräling, J. Ducrée, R. Zengerle, F. von Stetten
A Binder-less Glucose Fuel Cell with Improved Chemical Stability Intended as Power Supply for Medical Implants
2008 Proceedings of the 4th European Conference of the International Federation for Medical and Biological Engineering (eMBEC), Antwerpen, 23–27 November , Seiten: 2379 - 2384
KurzfassungWe present an improved abiotically catalyzed glucose fuel cell, intended as tissue implantable power supply for medical implants. A novelty is the application of binderless platinum electrodes for both, anode and cathode. This overcomes the limited chemical stability of glucose fuel cells fabricated from activated carbon particles dispersed in a hydrogel matrix. For the first time the diffusion resistance to be expected from tissue capsule formation has been taken into account during performance characterization under physiological concentrations of glucose and oxygen. Despite the resulting limited oxygen supply, the binder-less fuel cells exhibit a power density of (2.3 ± 0.2) μW cm-2, which is comparable to our previous prototypes. We show that this is due to the increased performance of the novel electrodes. Keywords — glucose, fuel cell, implantable, energy harvesting, platinum
Kloke A, Kerzenmacher S, Kräling U, Zengerle R, von Stetten F
A Permeable Foil-Based Thin Layer Oxygen Cathode for Biofuel Cell and Sensor Applications
2008 Tenth World Congress on Biosensors, Shanghai, China 2008 , Seite: P2.24
KurzfassungIn fuel cell and sensor research foil-based electrodes offering high surface area are of special interest. Here we demonstrate the development of an oxygen cathode established on a polyimide track etch membrane. Furthermore this cathode is permeable and therefore especially interesting for applications desiring mass transport through the cathode. We developed this electrode for abiotically catalyzed glucose fuel cells which require a permeable oxygen cathode on top of a glucose anode to enable separate electrode reactions [1], but this approach is also interesting for enzymatic fuel cells and sensor technology. Following a protocol similar to van der Wal et al. [2], we formed platinum alloys with aluminum (figure 1). Layers of 500 nm platinum and 500 nm aluminum were vapor-deposited on silicon. Samples were annealed at 300 °C for 120 minutes and subsequently activated in NaOH. We observed roughness factors comparable to van der Wal (about 150) using cyclic voltammetry (figure 2). Operated in aerated phosphate buffered solution these electrodes showed their applicability as oxygen reduction cathodes even after adding glucose to the solution and lowering the oxygen concentration (figures 3, 4). Using this process with 250 nm thick layers of platinum and aluminum on polyimide track etch membranes having straight pores of 2 μm in diameter we succeeded in developing thin (25 μm), permeable and flexible electrodes (figure 5). Their roughness factor is higher than 30. As cathode the foil-based electrode polarizes less under load than the ones fabricated on silicon but show a slightly lower open circuit voltage (figure 4). We showed the applicability of platinum-aluminum alloy formation for production of an oxygen cathode working under physiological concentrations of oxygen and glucose and succeeded in transferring this process onto a thin permeable foil substrate. Their electrochemical performance is comparable to carbon based oxygen cathodes which are state of the art in abiotically catalyzed glucose fuel cells (figure 3) [3].
J. Steigert, M. Strasser, O. Brett, N. Wangler, W. Streule, P. Koltay, M. Daub, R. Zengerle
A modular dispensing system for leakage-free picoliter droplet release in liquid environments
2008 Proceedings of The 12th International Conference on Miniaturized Systems for Chemistry and Life Sciences (µTAS 2008) , Seiten: 360 - 362
KurzfassungWe present a new tool that can be positioned accurately next to any individual cell for the precisely controlled transfer of individual picoliter (pL) droplets in the range of 150-950 pL (CV < 3.5%) in liquid environment while avoiding any leakage. This is achieved by a low-cost, disposable and biocompatible cap that is placed on top of any pL-dispenser and generates a phase-gap between dispensing agent and target liquid when the dispenser is dipped into the latter thus avoiding diffusive transport. We developed two different working modes: (i) the standard mode enables an instant injection (<< 1 ms) of the droplet into the liquid environment and (ii) the focus mode further increases the spatial resolution from 100 μm to 50 μm. For the phase-gap we have proven an excellent long-term stability of more than 30 hours against capillary priming and a maximum volume ejection rate of up to 137 nL/s without flooding.
A. Kloke, B. Biller, S. Kerzenmacher, U. Kräling, R. Zengerle, F. von Stetten
A single layer biofuel cell as potential coating for implantable low power devices
2008 Proc. Eurosensors XXII, Dresden, Germany, September 7-10 , Seiten: 1416 - 1419
KurzfassungAbiotically catalyzed glucose fuel cells were considered to only work with specific assemblies for electrode reaction separation. Using a highly porous oxygen tolerant catalyst for glucose oxidation we were able to realize a fuel cell with anode and cathode placed side by side. These results open the opportunity of having a sustainable power source implemented as single layer coating of medical implants. Further potential for power enhancement and cost reduction is identified within the variation of anode to cathode proportions.
Mark, Daniel, Häberle, Stefan, Metz, Tobias, Lutz, Sascha, Ducree, Jens, Zengerle, Roland, von Stetten, Felix
Aliquoting structure for centrifugal microfluidics based on a new pneumatic valve
2008 Proc. IEEE-MEMS 2008, Tucson, USA , Seiten: 611 - 614
KurzfassungWe present a new microvalve that can be monolithically integrated in centrifugally driven lab-on-achip systems. In contrast to existing operation principles that use hydrophobic patches [1], geometrically defined capillary stops [2] or siphons [3], here we present a pneumatic principle. It needs neither additional local coatings [1] nor expensive micro sized geometries [2]. The valve is controlled by the spinning frequency and can be switched to be open when the centrifugal pressure overcomes the pneumatic pressure inside an unvented reaction cavity. We designed and characterized valves ranging in centrifugal burst pressure from 6700 Pa to 2100 Pa. Based on this valving principle we present a new structure for aliquoting of liquids. We experimentally demonstrated this by splitting 105 μL volumes into 16 aliquots with a volume CV of 3 %.
S. Kerzenmacher, S. Zehnle, T. Volk, D. Jansen, F. von Stetten, R. Zengerle
Autarke Energieversorgung eines Herzschrittmachers mittels Glukosebrennstoffzelle und effizientem DC-DC-Wandler
2008 Tagungsband 14. Heiligenstädter Kolloquium - Technische Systeme für die Lebenswissenschaften; Heiligenstadt 22.-24.09.2008 , Seiten: 397 - 404
KurzfassungImplantierbare Glukosebrennstoffzellen auf Basis abiotischer Katalys-atoren sind ein vielversprechender Ansatz zur batterieunabhängigen Energieversorgung von aktiven Implantaten. Während sich unter physiologischen Bedingungen Leistungsdichten von 3 µW/cm² erreichen lassen, ist es in der praktischen Umsetzung des Konzepts erforderlich die mit 0,2 V recht geringe Zellspannung auf die für elektronische Schaltkreise typische Betriebsspannung von 3 V zu transformieren. Bei Ausgangs-leistungen im µW-Bereich zeigen kommerziell erhältliche DC-DC-Wandler jedoch nur sehr geringe Wirkungsgrade von etwa 4 %. Folglich wäre zum Betrieb eines 15 µW Herzschrittmachers eine Brennstoffzelle von mindestens 125 cm² erforderlich – zu groß um direkt auf dem Schrittmachergehäuse platziert werden zu können. Um die Wandlungsverluste zu minimieren, wurde daher eine optimierte Aufwärtswandler-Schaltung mit einem Wirkungsgrad von über 40 % aufgebaut, die den kontinuierlichen Betrieb eines 15 µW Herzschrittmachers mit einer nur 18 cm² großen Glukosebrennstoffzelle erlaubt. Der verringerte Flächenbedarf würde die zukünftige Ausführung der Brennstoffzelle als direkt auf der Oberfläche des Implantats integrierte Stromversorgung erlauben.
A. Kloke, S. Rubenwolf, C. Bücking, J. Gescher, S. Kerzenmacher, R. Zengerle, F. von Stetten
Bausatz für einen modularen Miniatur-Bioreaktor und seine Anwendung als elektrochemische Testzelle für Bio-Brennstoffzellen
2008 Tagungsband 14. Heiligenstädter Kolloquium - Technische Systeme für die Lebenswissenschaften; Heiligenstadt 22.-24.09.2008 , Seiten: 303 - 310
KurzfassungReproduzierbare Untersuchungen an Biomikrosystemen erfordern einen sehr flexiblen und vollständig charakterisierten experimentellen Aufbau, der in seinen Eigenschaften einem Bioreaktor entspricht. Wir stellen einen zu diesem Zweck neu entwickelten Miniatur-Bioreaktor vor, der aus Baukastenelementen zusammengesetzt wird. Der modulare Aufbau ermöglicht eine Anpassung in Volumen und verfügbaren Schnittstellen für Begasung, Medienwechsel, Sensorik und Probenahme. Ferner können mehrere einzelne Bioreaktoren zusammengeschlossen betrieben oder für elektrochemische Messungen über Membranen gekoppelt werden. Die Charakterisierung des Reaktors ergibt kLa-Werte und Mischzeiten, die im üblichen Bereich für nicht-modulare Blasensäulenreaktoren liegen. Die vielseitige Anwendbarkeit des neuen Systems wurde anhand der Wachstumskurve einer Escherichia coli Kultur sowie durch elektrochemi-sche Untersuchungen an einer enzymatischen Kathode und einer mikrobiellen Anode für Bio-Brennstoffzellen demonstriert.
M. Focke, B. Faltin, T. Hösel, C. Müller, J. Ducrée, R. Zengerle, F. von Stetten
Blow molding of polymer foils for rapid prototyping of microfluidic cartridges
2008 Proceedings of The 12th International Conference on Miniaturized Systems for Chemistry and Life Sciences (µTAS 2008) , Seiten: 988 - 990
KurzfassungWe present a novel process for small-lot manufacturing of microfluidic lab-on-achip cartridges made of thin polymer foils within 8 hours starting from a CAD layout. A master tool is micromilled and then casted with polydimethysiloxane (PDMS) to obtain an elastic replication mold. This is used for blow molding of thermoplastic foils in order to manufacture lab-on-a-chip cartridges with very thin sidewalls of 100 to 180 μm. These are suited for microfluidic applications requiring fast heat transfers, most prominently thermocycling for polymerase chain reactions (PCR) as demonstrated with our technology.
Peter Koltay, Roland Zengerle, Christoph Ziegler
Coarse grid modelling of capillary driven two-phase flow in direct methanol fuel cells
2008 Proceedings of the 1st European Conference on Microfluidics (Microfluidics), Bologna, December 10-12
S. Lutz, P. Lang, L. Riegger, W. Streule, M. Daub, P. Koltay, F. von Stetten, R. Zengerle, J. Ducrée
Contact-Free Dispensing of Living Cells in Nanoliter Droplets
2008 Actuator 2008 / Bremen Messe Bremen
KurzfassungWe present a novel method for automated dispensing of living cells in nanoliter range droplets using a disposable pipette tip combined with an elastic polymer tube. After introduction of an unmetered suspension of cells into a reservoir connected to the pipette tip, a tuneable volume of 10 - 80 nL of cells suspension is issued in a non-contact procedure. Droplet ejection is enabled by a piezostack driven piston squeezing the tube at a defined position. We achieve a reproducibility of the printed cell culture medium volumes better than 5% and survival rate of the cells of 97% directly after dispensing. In addition we demonstrated good culturability and cell differentiation in order to consider potential long term effects of the dispensing process that could harness the cells. Keywords: nanoliter dispensing, cells, piezo actuation
Rubenwolf S, Kloke A, Kerzenmacher S, Zengerle R, von Stetten F
Direct Electron Transfer from Adsorption-Bound Laccase to Different Carbon Based Electrodes
2008 Tenth World Congress on Biosensors, Shanghai, China 2008 , Seite: P2.23
N. Wangler, O. Brett, M. Laufer, M. Straßer, A. Dovzhenko, K. Voigt, K. Palme, M. Daub, R. Zengerle, J. Steigert
Discrete stimulation of single protoplast cells by highly resolved drug release
2008 Proceedings of The 12th International Conference on Miniaturized Systems for Chemistry and Life Sciences (µTAS 2008), Seiten: 1172 - 1174
KurzfassungFor the first time we present the discrete release of two individually addressable substances in the sub pl-range (10 pl) with a high spatial (< 50 μm) and temporal (< 100 μs) resolution for the stimulation of single cells, embedded in a thin-alginatelayer. This is ensured by dispensing a small droplet (Ø < 25 μm) with a diameter smaller or comparable to a single tobacco protoplast (Ø ≈ 30 μm). Furthermore, the pl-volume generates defined drug concentration at the target cell while the concentration gradient in the vicinity decreases drastically in time due to the 3- dimensional diffusion and leads to extremely low background signals. The two channels of the presented dispenser allow for the discrete stimulation of single cells with one channel and the simultaneous labeling with the other one. This was proven by highly resolved labeling of a single tobacco protoplast with carboxyfluorescein diacetate.
Paust, Nils, Litterst, Christian, Metz, Tobias, Zengerle, Roland, Koltay, Peter
Fully passive degassing and fuel supply in direct methanol fuel cells
2008 Proc. IEEE-MEMS 2008, Tucson, USA , Seiten: 34 - 37
KurzfassungIn this paper a micro direct methanol fuel cell (μDMFC) is presented, which is operated in a completely passive way, i.e. the cell does not require an external pump for fuel supply. The surface energy of deformed CO2 bubbles, generated as a reaction product during DMFC operation, is employed to supply methanol to the anode. In contrast to a digital valve based approach presented earlier by Meng et. al. [1], a tapered channel is applied to achieve a pumping mechanism. This way the pump rates can be adapted to the requirements of a specific cell. The presented study reveals that this concept is able to maintain the supply for all typical DMFC operation conditions. Experimental results are presented that demonstrate the continuous operation of a passive μDMFC for more than 15 hours.
S. Rubenwolf, O. Strohmeier, R. Zengerle, F. von Stetten
Influence of Carbon Fiber Morphology on Direct Electron Transfer
2008 213th ECS Meeting, Phoenix, USA, 2008 , Seite: Abstr. 205
E. Fiedler, M. Schuettler, C. Henle, R. Zengerle, T. Stieglitz
Integration of Microfluidic Channels into Laser-Fabricated Neural Electrode Arrays
2008 4th European Conference of the International Federation for Medical and Biological Engineering 23 - 27 November 2008, Antwerp, Belgium; IFMBE Proceedings Volume 22, 2009, pp 2431-2434
KurzfassungNeural interfaces are most commonly of electrical/electrochemical nature, employing metal electrodes that allow sensing of neural activity or stimulation of nerve cells by introduction of electrical currents. Some interfaces require additional ports for localized release of chemical agents, such as drugs that alter the behavior of the neural system, or dies that allow labeling of regions in the observed tissue for subsequent histological studies. In this paper we present a fabrication procedure for neural electrode arrays based on laser-ablation of medical grade silicone rubber and platinum foil, to which an additional laser-process is added in order to integrate fluidic channels into the silicone substrate. A variety of channels were produced having cross sectional areas ranging from approx. 40 · 80 µm2 to 130 · 170 µm2. In order to characterize the main fluidic properties of such channels, the pressure/flow rate ratio was measured and the burst pressure for two different channel geometries was determined. As a proof of concept, a prototype of a microfluidic nerve electrode was fabricated, having 4 metal electrodes and one fluidic channel that branches to each of the metal electrodes, ending in nozzles located at the rim of each electrode surface. The fluid dynamics were visualized by injecting died solvent into the channel inlet; a simultaneous escape of the fluid on each electrode site was observed.
M. Vosseler, M. Jugl, M. Blaesing, D. Hradetzky, S. Messner, R. Zengerle
Integration of microneedle-arrays and micro pumps in disposable and cheap drug delivery devices
2008 Proceedings of the 4th European Conference of the International Federation for Medical and Biological Engineering (eMBEC), Antwerpen, 23–27 November , Seiten: 2364 - 2367
KurzfassungMicroneedle-arrays offer the chance to establish a fluidic interface between a drug delivery device and the human body. By bypassing the rate limiting diffusion barrier (skin) one is able to deliver a wide range of molecules. Novel physicochemical pumping concepts offer the possibility of controlling the time of delivery without any electronic control and thus enable the realization of cheap and disposable night time dosing devices. Infusion studies and experimental data of drug delivery components presented in this paper demonstrate the feasibility of delivering a drug to the patient hours after starting the drug delivery device. Keywords — drug delivery device, transdermal, microneedle-array, chronopharmaceutical, night time dosing
Andreas Ernst, Wolfgang Streule, Roland Zengerle, Peter Koltay
Kontaktfreie Detektion von frei fliegenden Nanoliter-Tropfen
2008 Tagungsband Sensoren und Messsysteme 2008, 14. Fachtagung Ludwigsburg, 11.-12. März, ISBN 978-3-18-092011-5 VDI Wissensforum GmbH, Seiten: 881 - 889
KurzfassungIm Folgenden wird ein Sensor zur kontaktfreien Detektion von frei fliegenden Tropfen mit Durchmessern im Bereich von 200 – 500 µm vorgestellt. Der Signalgeber basiert auf einem kapazitiven Prinzip und kann problemlos in die Flugbahn des dispensierten Mediums eingebracht werden. Durch die kleine Bauform kann dies auch bei kleinen Abständen (~ 3 mm) der Dispenserdüse zum Substrat umgesetzt werden. Ein Hauptaugenmerk dieses Sensors ist seine kontaktfreie Arbeitsweise, durch welche die Kontamination der dispensierten Flüssigkeit und somit der Verlust einzelner Tropfen vermieden wird. Der Sensor ist in konventioneller Lieterplattentechnologie (engl. PCB-Technologie ) hergestellt und kann in seiner momentanen Form zur direkten Prozesskontrolle eingesetzt werden. Durch Vergleichen der aktuellen Sensorsignale mit spezifischen „Fingerprint“ Signalen der dosierten Flüssigkeiten können Volumenänderungen und Geschwindigkeitsabweichungen im Dosierprozess festgestellt werden.
T Metz, D Mark, S Lutz, R Simon, M Focke, B Faltin, J Burger, J Böning, J Miwa, M Karle, G Müller, C Blattert, C Müller, S Messner, H Reinecke, R Zengerle, F von Stetten
Lab-on-a-Chip Foundry Service – speeding up the miniaturization of in vitro diagnostics
2008 Proc. 3rd Technology Forum Diagnostics & Bioanalytical Devices, Frankfurt, 2008, 3 , Band: 3
KurzfassungWe present the Lab-on-a-Chip Foundry Service of the HSG-IMIT that was founded to speed up the realization of in vitro diagnostic assays (IVD) as miniaturized microfluidic systems (Lab-on-a-Chip). The Lab-on-a-Chip Foundry Service opens the advantages of Lab-on-a-Chip - smaller consumption of reagents and faster turnaround times in compact, automated diagnostics - to a broad community. We offer everything from one hand: Layout, prototyping, fluidic and biochemical testing.
S. Lutz, P. Lang, I. Malki, D. Mark, J. Ducree, R. Zengerle, F. von Stetten
Lab-on-a-chip cartridge for processing of immunoassays with integrated sample preparation
2008 Proceedings of The 12th International Conference on Miniaturized Systems for Chemistry and Life Sciences (µTAS 2008) , Seiten: 1759 - 1761
KurzfassungWe present a novel centrifugal microfluidic lab-on-a-chip cartridge for the fully integrated processing of immunoassays including sample preparation and metering, incubation, washing and waste handling. From a sample of 10 μL human whole blood we extract 4 μL of blood plasma by sedimentation of blood cells driven by centrifugal forces with a CV of 6%. Routing of fluids is realized by capillary and volume triggered siphon valves. The reliability of the capillary-driven fluid channels is increased by surface coating with BSA for hydrophilization and blocking. The reaction chamber allows efficient mixing of fluids and dissolution of prestored reagents [1]. For demonstration purposes we quantified estradiol with a range of 25 pg/mL to 1 ng/mL using a chemiluminescent competitive immunoassay within 30 minutes [2].
S. Häberle, A. Schumacher, R. Gronmaier, T. Göttsche, M. Vosseler, A. Kain, M. Reiterer, D. Hradetzky, S. Messner, C. Müller, R. Zengerle
Mobile Drug-Delivery for Ambient Assisted Living: Implantable and Extracorporeal Devices
2008 Ambient Assisted Living. 1. Deutscher Kongress mit Ausstellung / Technologien - Anwendungen - Management VDE, AAL, BMBF, Seiten: 33 - 36
KurzfassungMiniaturized smart drug delivery devices pave the way for a personalized treatment of many diseases by un-skilled persons outside the hospital. Many therapies require a repetitive delivery of a defined amount of drug in well defined time slots. Innovative drug delivery systems constitute an important prerequisite for ambient assisted living: The reliable delivery of drugs, in time and dosage, to the patient in his familiar surrounding. As different therapies and drugs require different pathways, we develop mobile drug delivery systems for a variety of possible pathways. In this paper we analyse different pathways for delivery of drugs and show results of our work on in-traoral, extracorporeal and transdermal drug delivery devices.
Hau, Winky L.W., Liu, Zhenyu, Korvink, Jan, Zengerle, Roland, Ducree, Jens
Near-wall velocity of suspended particles in microchannel flow
2008 Proc. IEEE-MEMS 2008, Tucson, USA , Seiten: 633 - 636
D. Mark, M. Focke, B. Faltin, J. Ducrée, R. Zengerle, F. von Stetten
Nukleinsäurediagnostik auf der Bio-Disk Plattform
2008 Tagungsband 14. Heiligenstädter Kolloquium - Technische Systeme für die Lebenswissenschaften; Heiligenstadt 22.-24.09.2008 , Seiten: 321 - 328
KurzfassungDie zentrifugale Mikrofluidik gehört zu den vielversprechenden, mikrofluidischen Entwicklungsplattformen zur Miniaturisierung, Integration und Automatisierung biochemischer Analyseprotokolle [1]. Sie beruht auf der kontrollierten Prozessierung kleinster Flüssigkeitsmengen in einem zentrifugalen Beschleunigungsfeld und ermöglicht die Portierung von Analyse- und Diagnoseaufgaben von Großlabors in den Point-of-Care (POC) Bereich [2]. Auf Grundlage der zentrifugal-mikrofluidischen Bio-Disk Plattform [3] zeigen wir die Integration grundlegender Laborprotokolle für die Nukleinsäureanalytik: Nukleinsäure-Extraktion und Real-Time-PCR. Die Entwicklungen sollen eine vollständig integrierte und automatisierte Point-of-Care Plattform für die molekulare Diagnostik ermöglichen. Die Isolierung und Aufreinigung von DNA aus Probenmaterial wird durch einen Lyseschritt und eine Festphasenextraktion mit einer Silikamembran erreicht. Die Membran ist im Gegensatz zu Silika-Beads einfach zu handhaben und kann durch PCR-kompatible Klebstoffe oder mechanische Halterungen gut in mikrofluidische Strukturen integriert werden. Aus einer 20 µl Vollblutprobe konnten durchschnittlich 0,21 µg ± 0,09 µg DNA extrahiert werden. Die PCR Tauglichkeit der extrahierten DNA wurde in einem Real-Time PCR Thermocycler nachgewiesen und war nahezu identisch zu einer Referenzextraktion (QIAamp DNA Blood Mini Kit). Der Schwellwertzyklus (CT = Threshold Cycle) lag bei 2300 extrahierten Kopien eines vollständigen Genoms bei beiden Extraktionen bei 30. Um die extrahierte DNA zur parallelen Bestimmung mehrerer genetischer Parameter in kreuzkontaminationsfreie Kammern zu verteilen, wurde eine Aliquotierstruktur entwickelt, die auf einem passiven zentrifugo-pneumatischen Ventil basiert. Dieses robuste Ventil weist Schaltfrequenzen auf, die um mindestens das vierfache über denen von gleich dimensionierten kapillaren Ventilen liegen, und die Fertigung erfordert keine lokale Oberflächenmodifikation [4]. Die Aliquotierstruktur ermöglicht eine Aufteilung eines ca. 100 µl großen Probenvolumens in z. B. 16 Aliquote mit einem Volumen-Variationskoeffizenten von 3 %. Wir demonstrierten ferner die Durchführung einer Real-Time PCR in einer thermogeformten folienbasierten Bio-Disk mit Mikrofluidikstruktur. Die Foliendisk eignet sich aufgrund ihrer geringen thermischen Masse besonders für ein rasches Thermocycling. Standardkurven für die Amplifikation verschiedener Kopienzahlen des Exfoliatin-A-Gens (Staphylococcus aureus) wurden auf der Foliendisk sowie in standard Polypropylen (PP) PCR-Tubes durchgeführt. Die Schwellenwertzyklen für 100, 1000, und 10.000 Kopien waren 35,6, 31,5 und 27,5 für die die PP-Tubes und 33,6, 29,7 und 25,7 für die Foliendisk. Die Integration der vorgestellten Module für DNA-Extraktion und Real-Time PCR auf der Bio-Disk Plattform zeigt gutes Potential für die automatisierte und vollintegrierte Durchführung von kompletten Nukleinsäureanalysen.
J. Steigert, N. Wangler, O. Brett, M. Straßer, M. Laufer, M. Daub, R. Zengerle
Pico-Injector for the Discrete Chemical Stimulation of Individual Cells with a High Temporal and Spatial Resolution
2008 Proceedings of the 4th European Conference of the International Federation for Medical and Biological Engineering (eMBEC), Antwerpen, 23–27 November , Seiten: 1434 - 1437
KurzfassungWe present a new tool (Pico-Injector) for the discrete chemical stimulation of individual cells in their physiological environment. Key features are the precisely controlled release of two individually addressable substances in the lower picoliter (pL) range (V = 9 pL) with a high spatial (< 50 μm) and temporal (< 100 μs) resolution while avoiding any diffusion-based leakage of the drugs. This is achieved by a disposable and biocompatible cap that is placed on top of a dispenser generating a phase-gap between dispensing agent and target liquid when the dispenser is dipped into the latter. For the phase-gap we have proven a long term stability of more than 30 hours against capillary priming and a maximum volume ejection rate of up to 220 nL/s. Keywords — single cell, chemical stimulation, discrete chemical release, drug delivery, pL-droplets
T. Metz, L. Riegger, C. Ziegler, R. Zengerle, P. Koltay
Pressure characteristics modelling for rapid design of capillary microfluidic systems
2008 Proceedings of The 12th International Conference on Miniaturized Systems for Chemistry and Life Sciences (µTAS 2008) , Seiten: 1354 - 1356
KurzfassungThis work presents a novel compact modelling approach for microfluidic systems which rely on the control of plugs or gas bubbles by capillary forces. A generic network model is derived to calculate the capillary pressure of such systems. By applying the model the behaviour of liquid plugs or gas bubbles can be analyzed. This is simply performed by shifting “virtual” volumes along the volume scale at the xaxis of the graph and deducing pressure drops. Pressure characteristics are calculated for two systems and the predicted behaviour is compared to experiments. The approach is simple but efficient and enables a rapid design of capillary micro fluidics for μTAS.
Clemens Bücking, Stefanie Rubenwolf, Felix von Stetten, Johannes Gescher
Reductase activity of outer membrane c-type cytochromes in Shewanella oneidensis
2008 Jahrestagung der Vereinigung für Allgemeine und Angewandte Mikrobiologie und der Gesellschaft für Biochemie und Molekularbiologie, Frankfurt/Main, Germany , Seite: 91
KurzfassungDissimilatory iron reduction (DIR) is a respiratory process in which microorganism couple the reduction of metals to energy production. This process widely shaped the bio- and geosphere on our planet (Nealson, et al 2002). A better understanding of DIR is crucial for applications in biotechnology like remediation of contaminated soils or current production in microbial fuel cells. An important model organism to investigate DIR is the γ-proteobacterium Shewanella oneidensis which has to use an extended respiratory pathway to transport electrons through the periplasmic space to insoluble crystalline Fe(III)-oxides. C-type cytochromes are thought to mediate the electron transfer to the transition metal. Genome analysis revealed five genes for outer membrane c-type cytochromes, three of those have an unknown function so far. We wanted to investigate the specificity of all five putative outer membrane cytochromes towards metallic electron acceptors. Therefore we constructed a mutant with an in-frame-deletion of genes mtrD-omcB and inserted an inducible promotor in front of the known key players mtrA and mtrB. Genes for membrane cytochromes were cloned into pBad202-vector and transformed into the mutant. After characterizing protein expression, we measured reduction rates of cell suspensions with different metal-oxides. To further investigate the functionality of the proteins, we measured the ability to generate electricity in a microbial fuel cell. The results so far point towards different reduction abilities of the cytochromes for reducing soluble and insoluble iron forms.
S. Spieth, A. Schumacher, K. Seidl, K. Hiltmann, S. Haeberle, R. McNamara, J.W. Dalley, S.A. Edgley, P. Ruther, R. Zengerle
Robust microprobe systems for simultaneous neural recording and drug delivery
2008 Proceedings of the 4th European Conference of the International Federation for Medical and Biological Engineering (eMBEC), Antwerpen, 23–27 November , Seiten: 2426 - 2430
KurzfassungThis paper reports on novel robust microprobe systems for simultaneous neural recording and drug delivery. The systems comprise needle-shaped silicon probes with microfluidic channels and recording electrodes integrated into a robust polyetheretherketone (PEEK) packaging. The microprobes are fabricated using deep reactive ion etching (DRIE) of silicon combined with silicon wafer bonding, wafer grinding, and thin film processing. An integrated system assembly with mechanical, fluidic and electrical interfaces is developed for easy handling and robustness during operation. This enables the microprobe systems to be used in acute as well as chronic applications. The assembly process includes a dead volume free fluidic interconnection technology which attaches polytetrafluoroethylene (PTFE) tubing to the probes by using heat shrinkable tubing. Furthermore, the novel approach of system integration is characterized with respect to its mechanical, fluidic, and electrical properties. Finally, the operation of the microprobe systems is verified in acute in-vivo experiments in which liquid delivery and recording of neural signals is successfully demonstrated. Keywords — drug delivery, silicon microprobes, neural recording, microfluidics.
Patrick Ruther, Arno Aarts, Olivier Frey, Stanislav Herwik, Sebastian Kisban, Karsten Seidl, Sven Spieth, Axel Schumacher, Milena Koudelka-Hep, Oliver Paul, Thomas Stieglitz, Roland Zengerle, Herc Neves
The NeuroProbes Project – Multifunctional Probe Arrays for Neural Recording and Stimulation
2008 Proc. of the 13th Annual Conf. of the IFESS, Sept. 21-25, 2008, Freiburg, Germany
KurzfassungThis paper summarizes recent advances of the NeuroProbes project, a 4-year Integrated Project funded by the European Commission under the Information Society Technologies (IST) topic of the 6th Framework Program. NeuroProbes aims at the development of multifunctional probe arrays comprising a 3-dimensional (3D) arrangement of recording and stimulation electrodes in conjunction with microfluidic functionality and integrated biosensors. The silicon based probes with planar electrodes are available as single shafts, in a comb-like arrangement and as 3D arrays for both, acute and chronic applications. The modular system concept and respective fabrication technology allows for a slim design of the 3D array conducive to its floating application. Initial recording and stimulation experiments demonstrated the feasibility of the concept and showed stable recordings of single and multiple unit activity as well as local field potential measurements over a time frame of one week.
H. Höfemann, T. Borchardt, C. Cupelli, R. Gronmaier, C. Müller, S. Haeberle, R. Zengerle
Towards a Microfluidic Platform for Cell Handling
2008 4M Cell Handling and Actuation Workshop, June 19-20, Vienna, Austria, 2008
KurzfassungThis paper describes our capabilities in design, fabrication and testing of microfluidic chips for cell-handling and separation. A rapid prototyping process, based on soft embossing in thermoplastic substrates enables the fast and cost-efficient fabrication of up to several tens of identical chips as pre-stage to later micro injection molding. As an application example, we present a passive microfluidic chip for the separation of leukocytes (white blood cells, WBC) from erythrocytes (red blood cells, RBC) out of a suspension, based on the hydrodynamics within the laminar flow regime. The achieved separation efficiency is about 87 %.
S. Lutz, V. Reitenbach, D. Mark, J. Ducree, R. Zengerle, F. von Stetten
Unidirectional shake-mode for mixing highly wetting fluids on centrifugal platforms
2008 Proceedings of The 12th International Conference on Miniaturized Systems for Chemistry and Life Sciences (µTAS 2008) , Seiten: 748 - 750
KurzfassungWe present a novel approach for washing and mixing on centrifugal microfluidic platforms. Mixing and washing are essential unit operations for lab-on-a-chip platforms but often cause valving problems if they are performed with “real life fluids” like washing buffers containing high detergent or salt concentrations which are often used in diagnostic or biological assays. We therefore improved the shakemode mixing technique to find a method that combines reliable siphon-based valving with high mixing and washing efficiency. Therefore the so called unidirectional shakemode, is introduced and correlated to the already established technologies.

2007

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Fleischhauer,B., Kloke,A., Rubenwolf,S., Schuh,K., Schlipf,C., Krüger,M., Müller,C., Prucker,O., Reinecke,H., Rühe,J, von Stetten,F., Zengerle,R., Woias,P.
"Micro Engery Harvesting" durch Mikro-Brennstoffzellen
2007 MikroSystemTechnik Kongress, Dresden, Germany, 15.-12. Oktober 2007 Proceedings, VDE, Seiten: 349 - 352
S. Kerzenmacher, R. Sumbharaju, J. Ducrée, R. Zengerle, F. von Stetten
A Surface Mountable Glucose Fuel Cell for Medical Implants
2007 14th Intern. Conf. on Solid-State Sensors, ..., Lyon/France, Jun 2007 Transducers '07 - Digest of Technical Papers, Band: 1+2, Seiten: U66 - U67
Kerzenmacher,S., Ducree,J., Zengerle,R., von Stetten,F.
A novel fabrication route yielding self-supporting porous platinum anodes for implantable glucose micro fuel cells
2007 Proceedings of PowerMEMS 2007, Freiburg, Germany, 2007 , Seiten: 31 - 34
Bundgaard,F., Geschke,O., Zengerle,R., Ducree,J.
A simple opto-fluidic switch detecting liquid filling in polymer-based microfluidic systems
2007 11th International Conference on Solid State Sensors, Actuators and Microsystems, Lyon, France, June 10-14, 2007 , Seiten: 759 - 762
Haeberle,S., Naegele,L., Burger,R., Zengerle,R., Ducrée,J.
Alginate Micro-Bead Fabrication on a Centrifugal Microfluidics Platform
2007 MEMS 2007, Kobe, Japan, 21-25 January 2007 , Seiten: 497 - 500
Riegger,L., Steigert,J., Lutz,S., Streule,W., Zengerle,R., Ducree,J.
Automated hematocrit measurement and patient data labelling by a commercial DvD-writer with a low-cost optical add-on
2007 Eleventh International Conference on Miniaturized Systems for Chemistry and Life Sciences 7 – 11 October 2007, Paris, FRANCE , Seiten: 1249 - 1251
Haeberle,S., Pausch,S., Burger,R., Lutz,S., von Stetten,F., Zengerle,R., Ducree,J.
Automation of nucleid acid extraction by a coriolis-force actuated droplet router
2007 MicroTAS 2007, Paris, France, 07.10. - 11.10.2007 , Seiten: 1231 - 1233
Paust,N., Litterst,C., Metz,T., Eck,M., Zengerle,R., Koltay,P.
Capillary driven fuel supply in direct methanol fuel cells with double tapered t-shaped channel flow fields
2007 Proceedings of PowerMEMS, Freiburg, Germany, 28-29 November 2007 , Seiten: 185 - 188
Schuhmacher,D., Scheithauer,H., Alavi,M., Niekrawietz,R., de Heij,B., Zengerle,R., Koltay,P.
Erzeugung von Mikrotropfen aus flüssigem Lötzinn mittels einer hochparallelen und kontaktlosen Drucktechnik
2007 MikroSystemTechnik Kongress, Dresden, Germany, 15.-12. Oktober 2007 Proceedings, VDE, Seiten: 655 - 658
Hradetzky,D., Kliche,K., Ehrbrecht,B., Anka,L., Wölfle,M., Zengerle,R.
Eye-Cam: Sprachgesteuerte Miniaturkamera integriert in einer Brille
2007 MikroSystemTechnik Kongress, Dresden, Germany, 15.-12. Oktober 2007 Proceedings, VDE, Seiten: 715 - 718
Paust,N., Litterst,C., Metz,T., Zengerle,R., Koltay,P.
Gasblasengetriebene Pumpe für Mikroreaktoren
2007 MikroSystemTechnik Kongress, Dresden, Germany, 15.-12. Oktober 2007 Proceedings, VDE, Seiten: 481 - 484
Goetz,M., Storz,M., Ashauer,M., Zengerle,R.
Geregeltes Flüssigkeiten-Dosiersystem für portable Anwendungen
2007 MikroSystemTechnik Kongress, Dresden, Germany, 15.-12. Oktober 2007 Proceedings, VDE, Seiten: 917 - 920
Vosseler,M., Dobmeier,M., Blaesing,M., Stehr,M., Aslanidis,G., Zengerle,R.
Gesteuerte Verdampfung als fluidischer Transportmechanismus in geregelten Medikamentendosiersystemen
2007 MikroSystemTechnik Kongress, Dresden, Germany, 15.-12. Oktober 2007 Proceedings, VDE, Seiten: 473 - 476
Kerzenmacher,S., von Stetten,F., Ducree,J., Zengerle,R.
Glukose-Brennstoffzellen als autarke Engergieversorgung für medizinische Mikro-Implantate: Stand der Technik und aktuelle Entwicklungen
2007 MikroSystemTechnik Kongress, Dresden, Germany, 15.-12. Oktober 2007 Proceedings, VDE, Seiten: 341 - 344
Pirk,T., Pinter,S., Fuertsch,M., Finkbeiner,S., Ducree,J., Wilde,J., Zengerle,R.
Implementing Microfluidic Applications with the Twin Epipoly Process
2007 Proceedings of Smart Systems Integration (SSI) - 1st European Conference & Exhibition on integration issues of miniaturized systems - MEMS, MOEMS, ICs and electronic components, March 27-28, Paris, Fr , Seiten: 199 - 207
Haeberle,S., Pausch,S., Burger,R., Lutz,S., von Stetten,F., Zengerle,R., Ducree,J.
Integration, Automatisierung und Parallelisierung von Silika-basierten Nukleinsäure-Extraktionen mit dem virtuellen Coriolis-Schalter
2007 MikroSystemTechnik Kongress, Dresden, Germany, 15.-12. Oktober 2007 Proceedings, VDE, Seiten: 465 - 468
Billat,S., Kliche,K., Gronmaier,R, Nommensen,P., Auber,J., Hedrich,F., Ashauer,M., Zengerle,R.
Low-cost Strömungssensoren mit Chip-integrierter Fluidführung für Anwendungen in der Medizintechnik
2007 MikroSystemTechnik Kongress, Dresden, Germany, 15.-12. Oktober 2007 Proceedings, VDE, Seiten: 909 - 912
Metz,T., Paust,N., Müller,C., Zengerle,R., Koltay,P.
Micro structured flow field for passive water management in miniaturized PEM fuel cells
2007 MEMS 2007, Kobe, Japan, 21-25 January 2007 Proceedings of the 20th IEEE International Conference on Micro Electro Mechanical Systems, MEMS
Haeberle,S., Ducree,J., von Stetten,F., Zengerle,R.
Microfluidic Platforms for Miniaturization, Integration, and Automation of Biochemical Assays
2007 MikroSystemTechnik-Kongress 2007, Dresden, Germany, 15.10. - 17.10.2007 Proceedings, Seiten: 449 - 455
Metz,T., Paust,N., Müller,C., Zengerle,R., Koltay,P.
Mikrostrukturierte Gasverteilerstrukturen für den passiven Wasseraustrag aus PEM Brennstoffzellen
2007 MikroSystemTechnik Kongress, Dresden, Germany, 15.-12. Oktober 2007 Proceedings, VDE, Seiten: 913 - 916
Steinert,C.P., Mueller-Dieckmann,J., Weiss,M., Roessle,M., Zengerle,R., Koltay,P.
Miniaturized and Highly Parallel Protein Crystallization on a Microfluidic Disc
2007 MEMS 2007, Kobe, Japan, 21-25 January 2007 , Seiten: 561 - 564
Ruther,P., Herwik,S., Kisban,S., Seidl,S., Spieth,S., Rubehn,B., Haj-Hosseini,N., Steigert,J., Daub,M., Paul,O., Stieglitz,T., Zengerle,R., Neves,H.
NeuroProbes - Development of Modular Multifunctional Probe Arrays for Neuroscience
2007 MikroSystemTechnik Kongress, Dresden, Germany, 15.-12. Oktober 2007 Proceedings, VDE, Seiten: 739 - 742
Ernst,A., Streule,W., Koltay,P., Zengerle,R.
Non-contact detection of free flying nanoliter droplets
2007 11th International Conference on Solid State Sensors, Actuators and Microsystems, Lyon, France, June 10-14, 2007 , Seiten: 751 - 754
Koltay,P., Zengerle,R.
Non-contact nanoliter & picoliter liquid dispensing
2007 11th International Conference on Solid State Sensors, Actuators and Microsystems, Lyon, France, June 10-14, 2007 , Seiten: 125 - 129
Wangler,N., Zengerle,R., Koltay,P.
Optische Qualitätskontrolle für hoch parallelen TopSpot® Microarray Printer
2007 MikroSystemTechnik Kongress, Dresden, Germany, 15.-12. Oktober 2007 Proceedings, VDE, Seiten: 869 - 872
Metz,T., Kerzenmacher,S., Paust,N., Mueller,C., Zengerle,R., Koltay,P.
Passive water management system for pem fuelcells using microstructures
2007 Proceedings of PowerMEMS 2007, Freiburg, Germany , Seiten: 177 - 180
Riegger,L., Streule,W., Henze,C., Zengerle,R., Koltay,P.
PipeJet P4.5 - Kostengünstiger Kompakt-Nanoliter-Dosierer im Mikrotiterplattenformat
2007 MikroSystemTechnik Kongress, Dresden, Germany, 15.-12. Oktober 2007 Proceedings, VDE, Seiten: 925 - 926
Streule,W., Hiltmann,K., Arnold,M., Kück,H, Zengerle,R., Koltay,P.
PipeJet-Tip - Nanoliter-Dispenser mit kostengünstigen Dosierelementen und eingebautem Reservoir
2007 MikroSystemTechnik Kongress, Dresden, Germany, 15.-12. Oktober 2007 Proceedings, VDE, Seiten: 943 - 946
Schuhmacher,D., Niekrawietz,R., Scheithauer,H., de Heij,B., Alavi,M., Zengerle,R., Koltay,P.
Production of solder microdroplets using a highly parallel and contact-free printing method
2007 MEMS 2007, Kobe, Japan, 21-25 January 2007 , Seiten: 357 - 360
Metz,T., Streule,W., Zengerle,R., Koltay,P.
Startube: A novel tube design for bubble tolerant interconnection in fluidic systems
2007 MicroTAS 2007, Paris, France, 07.10. - 11.10.2007 , Seiten: 1149 - 1151
Lutz,S., Lang,P., Faltin,B., Haeberle,S., von Stetten,F., Zengerle,R., Ducree,J.
Towards a comprehensive centrifugal process integration by rotationally induced lyophilisate dissolution and cell lysis
2007 Eleventh International Conference on Miniaturized Systems for Chemistry and Life Sciences 7 – 11 October 2007, Paris, FRANCE , Seiten: 1516 - 1518

2006

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Glatzel T, Cupelli C, Kuester U, Zengerle R, Santer M
3D-Simulations Of Aggregating Beads In Microfluidic Chambers On High Performance Computers Compared To Experiments
2006 Proc. of the 10th International Conference on Miniaturized Systems for Chemistry and Life Sciences (Microtas 2006); Tokyo, Japan, Seiten: 53 - 55
Haeberle S, Zengerle R, Ducrée J
A Centrifugal Platform for Micro Process Engineering
2006 ACHEMA 2006, Frankfurt, Germany, May 15-19, 2006
Haeberle S, Schmitt N, Zengerle R, Ducrée J
A Centrifugo-Magnetically Actuated Gas Micropump
2006 Proceedings of 19th International Conference on Micro Electro Mechanical Systems (MEMS 2006), Istanbul, Turkey, Seiten: 166 - 169
Haeberle S, Naegele L, Zengerle R, Ducrée J
A Digital Centrifugal Droplet Switch For Routing of Liquids
2006 MicroTAS 2006, Tokyo, Japan Proc. of the 10th International Conference on Miniaturized Systems for Chemistry and Life Sciences (Microtas 2006); Tokyo, Japan, Seiten: 570 - 572
F. von Stetten, S. Kerzenmacher, A. Lorenz, V. Chokkalingam, N. Miyakawa, R. Zengerle, J. Ducree
A one compartment, direct Glucose fuel cell for powering long-term medical implants
2006 Proc of IEEE MEMS 2006, Istanbul, Turkey, Seiten: 934 - 937
Ducrée J, Grumann M, Brenner T, Haeberle S, Riegger L, Steigert J, Zengerle R
Bio-Disk: A Centrifugal Microfluidic Platform for Process Integration and Automation of Bioanalytic Assays
2006 13. ITG-/GMA-Fachtagung Sensoren und Messsysteme, 2006, Freiburg, Germany, March 13-14, 2006 Proceedings of 13. ITG-/GMA-Fachtagung Sensoren und Messsysteme
F. von Stetten, J. Ducrée
Biofuel cells as power generators for implantable devices (invited key-note presentation)
2006 Proc. Eurosensors XX, Göteborg, Sweden, 2006, 1, 222-225
Lutz S, Grumann M, Gutmann O, Dube M, Riegger L, Steigert J, Daub M, Zengerle R, Ducrée J
Centrifugal Processor For Standard Microarray Slides
2006 Proc. of the 10th International Conference on Miniaturized Systems for Chemistry and Life Sciences (Microtas 2006); Tokyo, Japan, Seiten: 329 - 331
Steigert J, Brenner T, Grumann M, Riegger L, Zengerle R, Ducrée J
Design and Fabrication of a Centrifugally Driven Microfluidic Disk for Fully Integrated Metabolic Assays on Whole Blood
2006 Proc. IEEE-MEMS 2006; Istanbul, Turkey, Seiten: 418 - 421
Hu M, Lindemann T, Goettsche T, Kohnle J, Zengerle R, Koltay P
Discrete chemical release from a microfluidic chip
2006 Proc. IEEE-MEMS 2006; Istanbul, Turkey, Seiten: 28 - 31
Riegger L, Steigert J, Grumann M, Lutz S, Olofsson G, Khayyami M, Bessler W, Mittenbühler K, Zengerle R, Ducrée J
Disk-based Parallel Chemiluminescent Detection of Diagnostic Markers for Acute Myocardial Infarction
2006 MicroTAS 2006, Tokyo, Japan Proc. of the 10th International Conference on Miniaturized Systems for Chemistry and Life Sciences (Microtas 2006), Tokyo, Japan, Seiten: 819 - 821
Steger R, Mehne C, Wangler N, Heckele M, Zengerle R, Koltay P
Drop In Drop Nanoliter Kinase Assay Made With Hot Embossed Disposable Multi Channel Dispenser
2006 Proc. of the 10th International Conference on Miniaturized Systems for Chemistry and Life Sciences (Microtas 2006), Tokyo, Japan, Seiten: 999 - 1001
Hu M, Zengerle R
Microfabricated devices for controlled biochemical release
2006 Proc. ACTUATOR 2006; Bremen; Germany, Seiten: 263 - 271
Riegger L, Grumann M, Steigert J, Zengerle R, Ducrèe J
Microfluidics On A Conventional 10-$ CD-ROM Drive: All-In-One Determination Of The Hematocrit
2006 Proceedings of the 10th International Conference on Miniaturized Systems for Chemistry and Life Sciences (µTAS), Tokyo, Japan, Seiten: 1555 - 1557
Litterst C, Eccarius S, Hebling C, Zengerle R, Koltay P
Novel Structure for Passive CO2 Degassing in µDMFC
2006 Proc. IEEE-MEMS 2006; Istanbul, Turkey, Seiten: 102 - 105

2005

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Haeberle S, Schlosser H, Zengerle R, Ducrée J
A Centrifuge-Based Microreactor
2005 8th International Conference on Microreaction Technology, April 10-14, Atlanta, USA Proceedings of IMRET 8, Seiten: TK - 129f
Steinert CP, Schmitt N, Deier E, Daub M, de Heij B, Zengerle R
A Novel Fabrication Method for Hybrid, Microfluidic Devices
2005 Miami, USA, Jan. 30 - Feb. 3 Proceedings of IEEE International Conference on Micro Electro Mechanical Systems, Seiten: 552 - 555
Brenner T, Grumann M, Haeberle S, Riegger L, Steigert J, Zengerle R, Ducrée J
An Extended Tooblox for Fully Integrated Sample Processing and Detection on a High-Frequency Centrifugal Microfluidic Platform
2005 Karlsruhe, Germany Proceedings of Multi-Material-Micro-Manufacture (4M), Seiten: 413 - 417
Zibek S, Goettsche T, Hu M, Kentsch J, Kohnle J, Koltay P, Martin D, Zengerle R, Stett A, Stelzle M
Artificial Synapse – Nanofluidiksystem zur lokalen Substanzapplikation mittels nanoporöser Membran mit schaltbarer Permeabilität
2005 Freiburg, Germany Proceedings Mikrosystemtechnik-Kongress 2005, VDI/VDE/IT
Ducrée J, Grumann M, Brenner T, Steigert J, Riegger L, Haeberle S, Zengerle R
Bio-Disk: Eine vielseitige, zentrifugale mikrofluidische Plattform für die Point-of-Care Diagnostik
2005 Freiburg, Germany, October 10-12, VID/VDE/IT Proceedings Mikrosystemtechnik-Kongress 2005
Lindemann T, Ashauer H, Goettsche T, Sandmaier H, Yu Y, Peters R, Sassano D, Bellone A, Zengerle R, Koltay P
Bubble Jet Printhead with Integrated Polyimide Nozzle Plate
2005 Miami Beach, Florida, USA Proceedings of 18th IEEE International Conference on Micro Electro Mechanical Systems, MEMS, Band: 1, Nummer: 1, Seiten: 560 - 563
Riegger L, Grumann M, Brefka T, Steigert J, Steinert CP, Brenner T, Zengerle R, Ducrée J
Bubble-free Priming Of Blind Capillaries For High-accuracy Centrifugal Hematocrit Measurements
2005 Boston, USA Proceedings 9th International Conference on Miniaturized Systems for Chemistry and Life Science (µTAS 2005), Seiten: 796 - 798
Brenner T, Gottschlich N, Knebel G, Mueller C, Reinecke H, Zengerle R, Ducrée J
Charakterisierung der mechanischen Zuverlässigkeit von wafergebondeten Mikrosstemen
2005 Freiburg/Germany Proc. Mikrosystemtechnik Kongress 2005, VDI-VDE-IT
Cupelli C, Koltay P, Santer M, Zengerle R
Compact Model of a Laminar Micro Mixer
2005 Technical Proceedings of the 2005 Nanotechnology Conference and Trade Show, Seiten: 724 - 727
Goettsche T, Ruddy C, Heller U, Stehr M, Ashauer H, Lindemann T, Koltay P, Yu Y, Peters R, Soriani P, Bellone A
Development of highly precise bonding procedures for structured polyimide films on silicon substrates
2005 Karlsruhe, Germany Proc. 4M Conference
Grumann M, Dube M, Brefka T, Steigert J, Riegger L, Brenner T, Mittmann K, Zengerle R, Ducrée J
Direct Hemoglobin Measurement by Monolithically Integrated Optical Beam Guidance
2005 Seoul, Korea, June 05-09 Proceedings of the 13th internationals Conference on Solid-State Sensors, Actuators and Microsystems (Transducers 05 ), Seiten: 1106 - 1109
Gutmann O, Wintermantel MK, Niekrawietz R, de Heij B, Zengerle R, Daub M
Dispensing of Cells for Highly Parallel Production of Living Cell Microarrays
2005 Soeul, Korea, June 5 - 9 Proceedings of IEEE International Conference on Solid-State Sensors, Actuators and Microsystems (Transducers), Seiten: 449 - 452
Santer M, Moseler M, Cupelli C, Henrich B, Wonisch A, Glatzel T, Zengerle R
Dissipative Particle Dynamics as a practical Simulation Tool for Nanofluidic Applications
2005 Freiburg, Germany Proc. Mikrosystemtechnik-Kongress 2005, VDI-VDE-IT
Gutmann O, Steinert CP, Dernick G, de Heij B, Fattinger C, Certa U, Zengerle R, Daub M
Fast Selective Surface Modification of Microfluidic Printheads for Improvement of Droplet Ejection
2005 Boston, USA Proceedings of the International Conference on Miniaturized Systems for Chemistry and Life Sciences (µTAS), Seiten: 1267 - 1269
Brenner T, Gottschlich N, Knebel G, Mueller C, Reinecke H, Zengerle R, Ducrée J
Injection Molding of Microfluidic Chips by Epoxy-Based Master Tools
2005 Boston, USA Proceedings 9th International Conference on Miniaturized Systems for Chemistry and Life Sciences (µTAS 2005), Seiten: 193 - 195
Niekrawietz R, Honstein W, Gutmann O, de Heij B, Daub M, Zengerle R
Integrated Process Control for Highly Parallel and Contact-Free Microarray Printing
2005 Miami, USA, Jan. 30 - Feb. 3 Proceedings of IEEE International Conference on Micro Electro Mechanical Systems, Seiten: 738 - 741
Streule W, Storz M, Gracki S, Ashauer H, Zengerle R, Koltay P
Kontaktfreie und medienunabhängige Volumenbestimmung in Nanoliter Dispensern
2005 Freiburg, Germany Proc. Mikrosystemtechnik-Kongress 2005, VDI-VDE-IT
Gottschlich N, Brenner T, Knebel G, Zengerle R, Ducrée J
Low-Cost Injection Molding of Microfluidic Chips using Molding Tools made from Elastomers
2005 January 30 – February 3, 2005, San Jose, CA, USA Proc. Lab Automation
Koltay P, Steger R, Streule W, Zengerle R
Mikrodosiertechnik für die Biotechnologie und industrielle Anwendungen
2005 Freiburg, Germany Proc. Mikrosystemtechnik-Kongress 2005, VDI-VDE-IT
Gronmaier R, Gehring KF, Claußen J, Scheufele B, Grumann M, Cupelli C, Viertel J, Kohnle J, Rühe J, Ziegler C, Northoff H, Zengerle R
Mikrofluidische Plattform für die massensensitive Blutanalytik
2005 Freiburg, Germany Mikrosystemtechnik-Kongress 2005, VDI/VDE/IT
Brenner T, Gottschlich N, Knebel G, Mueller C, Reinecke H, Zengerle R, Ducrée J
Mikrostrukturierte Formeinsätze aus Epoxidharz für den Spritzguss und das Heißprägen von Kunststoffen
2005 Freiburg, Germany Proc. Mikrosystemtechnik-Kongress 2005, VDI-VDE-IT
Haeberle S, Zengerle R, Ducrée J
Monodisperse Droplet Trains and Segmented Flow for Centrifugal Microfluidics
2005 Boston, USA Proceedings 9th International Conference on Miniaturized Systems for Chemistry and Life Sciences (µTAS 2005), Seiten: 635 - 637
Koltay P, Steger R, Streule W, Zengerle R
Nanoliter Liquid Handling enabled by Microsystem Technology
2005 Lab Automation 2005; San Jose, CA, USA
KurzfassungIn this paper we report on micro dispensing devices for precise and highly parallel liquid handling of nanoliter quantities. Two different microfluidic systems are presented: The so called Dispensing Well Plate (DWP) is a device similar to a standard micro well plate which is able to fill aliquots of about 50 nL contact-free into 384 and 1536 well plates. To do so the DWP-device comprises of 384 micromachined dispensing units, each consisting of a reservoir, a supply channel and a nozzle. The whole DWP can be actuated pneumatically by a simple external driving unit to provide 384 different liquids simultaneously to a well plate or any other substrate within a tenth of a second. Characterization experiments performed with water and DMSO prove a homogeneity and reproducibility of better 5%. The so called PipeJet dispenser is a novel single channel dispenser which consists merely of a simple polymer tube with a few hundred microns diameter. In contrast to syringe solenoid dispensers or similar the PipeJet does not require any valve which makes it extremely robust and insensitive to clogging. Single droplets can be ejected from the tube’s orifice by squeezing a certain section of the fluidic line with an external actuator with high dynamics. In this way droplets with volumes between 1.5 nL and 100 nL can be delivered contact-free. In particular the systems is able to cope with difficult liquids like protein solutions of high concentration, DMSO, methanol, ethanol and bead solutions with excellent CVs between 1% and 5%.
Steger R, Streule W, Zengerle R, Koltay P
Novel Disposable Devices for precise Nanoliter Liquid Handling
2005 SBS 11th Annual Conference & ExhibitionDrug Discovery: From Targets to Candidates, September 11-15,
Litterst C, Eccarius S, Hebling C, Zengerle R, Koltay P
Novel Structure for Passive CO2 Degassing in µDMFC
2005 Tokyo Proc. of PowerMEMS 2005, Seiten: 194 - 197
Haeberle S, Zengerle R, Ducrée J
Online Process Control for Centrifugal Microfluidics
2005 June 5-9, Seoul, Korea Proceedings of Transducers 05, The 13th International Conference on Solid-State Sensors, Actuators and Microsystems, June 5-9, Seoul, Korea, Seiten: 1525 - 1528
Grumann M, Moser I, Steigert J, Riegger L, Geipel A, Kohn C, Urban G, Zengerle R, Ducrée J
Optical Beam Guidance in Monolithic Polymer Chips for Miniaturized Colorimetric Assays
2005 Miami, Florida, USA, January 30 - February 3 Proc. IEEE-MEMS 2005, Seiten: 108 - 111
Grumann M, Riegger L, Nann T, Riegler J, Ehlert O, Mittenbühler K, Urban G, Pastewka L, Brenner T, Zengerle R, Ducrée J
Parallelization of Chip-based Fluorescence Immuno-Assays with Quantum-Dot Labelled Beads
2005 June 05-09, 2005 Proceedings of the 13th internationals Conference on Solid-State Sensors, Actuators and Microsystems (Transducers 05 ), Seiten: 1114 - 1117
Gutmann O, Dernick G, Mangold C, Tessier M, Daub M, de Heij B, Fattinger C, Zengerle R, Certa U
Production of custom oligonucleotides microarrays for pharma research using a 96 nozzles printhead
2005 Frankfurt, Germany, Feb. 3 - Feb. 4 Proceedings of Statusseminar Chiptechnologien, Seiten: 68 - 69
Steigert J, Riegger L, Grumann M, Brenner T, Harter J, Zengerle R, Ducrée J
Rapid Alcohol Testing In Whole Blood By Disk-based Real-time Absorption Measurement
2005 Boston, USA, October 9-13 Proceedings of µTAS 2005 conference, Seiten: 1 - 3
Grumann M, Gutmann O, Dube M, Lutz S, Steigert J, Riegger L, Mittmann K, Daub M, Zengerle R, Ducrée J
Rapid Centrifugal Processing Of Microarray Experiments
2005 Boston, USA; October 9-13 Proceedings of µTAS 2005 conference, Seiten: 328 - 330
Ducrée J, Haeberle S, Brenner T, Grumann M, Riegger L, Steigert J, Zengerle R
Scaling Laws and Prospects of Centrifugal Nanofluidics
2005 April 18-20, Boekelo, the Netherlands Proceedings of First International Nanofluidics Workshop
Litterst C, Streule W, Koltay P, Zengerle R
Simulation Toolkit for Micro-Fluidic Pumps using Lumped Models
2005 Anaheim Technical Proceedings of the 2005 Nanotechnology Conference and Trade Show, Seiten: 736 - 739
Eccarius S, Litterst C, Wolff A, Tranitz M, Koltay P, Agert C
Systemaspekte in planaren Mikrobrennstoffzellensystemen
2005 Freiburg, Germany Proc. of Mikrosystemtechnik-Kongress 2005
Cupelli C, Koltay P, Zengerle R, Santer M
Systembeschreibung und Modellierung von Mischprozessen
2005 Freiburg, Germany Proc. Mikrosystemtechnik-Kongress 2005, VDI-VDE-IT
Koltay P, Zengerle R
The TopSpot - Microarrayer: An example for high priced micromachined components creating added value"; "
2005 10th International Conference on the Commercialization of Micro and Nano Systems (COMS-05); Baden-Baden; Germany , Seiten: 364 - 367
Steinert C, de Heij B, Koltay P, Sandmaier H, Zengerle R
TopSpot Vario: New Method for Parallel Nanoliter Dosing by Direct Liquid Displacement
2005 Freiburg, Germany Proc. Mikrosystemtechnik-Kongress 2005, VDI-VDE-IT
Cupelli C, Koltay P, Ducrée J, Zengerle R, Santer M
Towards a Modular Split & Recombine Micro Mixer
2005 IMRET, Atlanta, USA Proc. 8th international Conference on Microreaction Technology (IMRET)
Grumann M, Steigert J, Riegger L, Dube M, Lutz S, Brenner T, Harter J, Zengerle R, Ducrée J
Vollintegrierte Alkoholbestimmung in Vollblut über CD-basierte, zeitaufgelöste Absorptionsmessung
2005 Freiburg, Germany Proceedings Mikrosystemtechnik-Kongress 2005, VDI/VDE/IT

2004

nach oben zur Jahresübersicht

Steger R, Bohl B, Neurath A, Messner S, Sandmaier H, Zengerle R, Koltay P
A Highly Parallel Nanoliter Dispensing SystemFabricated by High-Speed Micromilling of Polymers
2004 Actuator, Bremen, Germany, 14-16 June Proc. ACTUATOR 2004, Seiten: 545 - 548
Ducrée J, Grumann M, Brenner T, Haeberle S, Zengerle R
An extended toolbox for fully integrated sample processing and detection on rotating disks
2004 The 8th Annual European Conference On Micro & Nanoscale Technologies for the Biosciences, Montreux, Switzerland, November 16 - 18 NanoTec 2004, Seiten: 554 - 556
Steinert CP, Sandmaier H, Daub M, de Heij B, Zengerle R
Bubble-Free Priming of Blind Channels
2004 January 25-29, Maastricht, The Netherlands Proc. of IEEE-MEMS 2004, Seiten: 224 - 228
Ducrée J, Schlosser H, Haeberle S, Glatzel T, Brenner T, Zengerle R
Centrifugal Platform for High-Throughput Reactive Micromixing
2004 Malmö, Sweden, September 26-30 Proc. MicroTAS 2004, Seiten: 554 - 556
Brenner T, Haeberle S, Zengerle R, Ducrée J
Continuous Centrifugal Separation of Whole Blood an a Disk
2004 Malmö, Sweden, September 26-30 Proc. MicroTAS 2004, Seiten: 566 - 568
Dernick G, Gutmann O, Mangold C, Daub M, de Heij B, Fattinger C, Zengerle R
Custom Microarrays for Pharma Research Printed with TopSpot® Technology
2004 7th MIPTEC conference; 3-6 May, Basel, Switzerland
Steger R, Bohl B, Zengerle R, Koltay P
Dispensing Well Plate: A Highly Parallel Nanoliter Liquid Handling Device for HTS
2004 3. – 6. May, Basel, Switzerland Proc 7th MIPTEC conference
Gutmann O, Kuehlewein R, Reinbold S, Niekrawietz R, Steinert C P, de Heij B, Zengerle R, Daub M
Fast and reliable protein microarray production by a new drop-in-drop technique
2004 Malmö, Sweden, September 26-30 Proc. MicroTAS 2004, Seiten: 381 - 383
Steger R, Bohl B, Steinert C, Zengerle R, Koltay P
Fixed Volume 384 channel NANOLITER DISPENSER for highly parallel and simultaneous liquid transfer into well plates
2004 MicroTAS 2004, Malmö, Sweden, September 26-30 Proceedings of MicroTAS 2004, Seiten: 518 - 520
Litterst C, Kohnle J, Ernst H, Messner S, Sandmaier H, Zengerle R, Koltay P
Improved Gas Bubble Mobility in CHIC-Type Flow Channels
2004 Actuator 2004, Bremen; Germany; 14-16 June Proc. ACTUATOR 2004, Seiten: 541 - 544
Kaack RM, Reinbold S, Zengerle R, Daub M
Integrating assay steps on a miniaturized platform: from PCR to hybridization
2004 Malmö, Sweden, September 26-30 Proc. MicroTAS 2004, Seiten: 436 - 438
Grumann M, Geipel A, Riegger L, Zengerle R, Ducrée J
Magneto-Hydrodynamic Micromixing for Centrifugal Lab-on-a-disk Platforms
2004 Malmö, Sweden, September 26-30 Proc. MicroTAS 2004, Seiten: 593 - 595
Grumann M, Geipel A, Klaunick C, Brenner T, Zengerle R, Ducrée J
Microfluidic Mixing by Actuation of Magnetic Beads on Rotating Lab-on-a-Disk platforms
2004 Bremen; Germany; 14-16 June Proc. ACTUATOR 2004, Seiten: 553 - 556
Zengerle R, Ducrée J, Koltay P
Microfluidics - An Enabling Technology for the Life Sciences
2004 International Symposium on Micro-Nanomechatronics and Human Science (MHS 2004), Nagoya University, Japan, Seiten: 1 - 6
Zengerle, R
Microfluidics - An Enabling Technology for the Life Sciences";
2004 Proc. Micro- and Nano-Technologies in the Life Sciences; Technopark Zurich, Switzerland
Daub M, Kaack RM, Gutmann O, Steinert C, Niekrawietz R, Koltay P, de Heij B, Zengerle R
Microfluidics and Beyond - Devices for Applications in Biotechnology
2004 San Francisco, USA Proc. MRS Symposium R 2004
Zengerle R, Ducrée J
Microfluidics roadmap: The trend to use low-cost technologies and microfluidics platforms
2004 Bremen; Germany; 14-16 June Proc. ACTUATOR 2004, Seiten: 200 - 203
Litterst C, Kohnle J, Ernst H, Messner S, Sandmaier H, Zengerle R, Koltay P
Mobility of Gas Bubbles in CHIC-type Flow Channels
2004 Proc. ACTUATOR 2004; Bremen; Germany , Seiten: 541 - 544
Kaack RM, Jung A, Wenz MH, Zengerle R, Daub M
PCR-slide: A modular and cascadable platform for DNA sample processing with integrated nanolitre dosage
2004 Maastricht, The Netherlands Proc. of IEEE-MEMS 2004, Seiten: 338 - 342
Lindemann T, Streule W, Birkle G, Zengerle R, Koltay P
PipeJet™ – A Simple Disposable Dispenser for the Nanoliter Range
2004 Bremen; Germany; 14-16 June Proceedings of Actuator 2004, Band: 1, Nummer: 1, Seiten: 224 - 227
Pirk T, Pintér S, Fuertsch M, Kaschner A, Weiss S, Finkbeiner S, Wilde J, Ducrée J, Zengerle R
TWEAK - The Twin Epipoly Layer Process for a Microfluidic Application Kit in Silicon/Glass
2004 Actuator 2004, Bremen, Germany, 14-16 June 2004 , Seiten: 200 - 203
Grumann M, Dobmeier M, Schippers P, Brenner T, Zengerle R, Ducrée J
The Model of Porous Media - Complete Description for aggregation of bead-monolayers in flat microfluidic chambers
2004 March 7-11, Boston, Massachusetts, U.S.A., NSTI-Nanotech Proc. MSM 2004, Nummer: 2, Seiten: 383 - 386
Lindemann T, Ashauer H, Goettsche T, Sandmaier H, Yu Y, Peters R, Sassano D, Bellone A, Scardovi A, Zengerle R, Koltay P
Thermal Bubble Jet Printhead with Integrated Nozzle Plate
2004 International Conference on Digital Printing Technologies, Salt Lake City, Utah, United States Proceedings of NIP20, Band: 1, Nummer: 1, Seiten: 834 - 839
Lindemann T, Sassano D, Bellone A, Zengerle R, Koltay P
Three-Dimensional CFD-Simulation of a Thermal Bubble Jet Printhead
2004 March 7-11, Boston, Massachusetts, U.S.A. Proc. MSM 2004, Band: 2, Seiten: 227 - 230
Ducrée J, Brenner T, Glatzel T, Zengerle R
Ultrafast Micromixing by Coriolis-Induced Multi-Lamination of Centrifugal Flow
2004 Bremen; Germany; 14-16 June Proc. ACTUATOR 2004, Seiten: 533 - 536

2003

nach oben zur Jahresübersicht

Ducrée J, Brenner T, Glatzel T, Zengerle R
A Coriolis-Based Split-and-Recombine Laminator for Ultrafast Mixing on Rotating Disks
2003 October 5-9, Squaw Valley, California, USA Proc. µTAS 2003, Seiten: 603 - 606
Brenner T, Glatzel T, Zengerle R, Ducrée J
A flow switch based on Coriolis force
2003 October 5-9, Squaw Valley, California, USA Proc. µTAS, Band: 1, Seiten: 903 - 906
Steger R, Bohl B, Moosmann C, Birkle G, Zengerle R, Koltay P
A highly integrated nanoliter dispensing systemfor fast liquid handling
2003 October 14-15, Munich, Germany Proc Micro.tec 2003, Seiten: 563 - 566
Steinert CP, Goutier I, Gutmann O, Sandmaier H, Messner S, Daub M, de Heij B, Zengerle R
An Improved 24 Channel Picoliter Dispenser Based on Direct Liquid Displacement
2003 8.-12.06.2003, Boston, USA Proc. of IEEE-Transducers 2003, Seiten: 376 - 379
Ducrée J, Glatzel T, Brenner T, Zengerle R
Coriolis-Induced Flow Control for Micro- and Nanofluidic Lab-on-a-Disk Technologies
2003 3-4. December, Potsdam, Germany nternational Forum on Micro nano Integration (MINIT), Seiten: 147 - 153
Ducrée J, Glatzel T, Brenner T, Zengerle R
Coriolis-Induced Flow Control in Centrifugal Microfluidics
2003 November 25-27, Montreux, Switzerland Proc NanoTech 2003
Ducrée J, Brenner T, Glatzel T, Zengerle R
Coriolis-Induced Switching and Mixing of Laminar Flows in Rotating Microchannels
2003 October 14-15, Munich, Germany Proc Micro tec 2003, Seiten: 397 - 404
Koltay P, Steger R, Bohl B, Taoufik S, Messner S, Sandmaier H, Zengerle R
DISPENSING WELL PLATE (DWP): A Highly Integrated Nanoliter Dispensing System
2003 Boston, USA Transducers '03 Digest of Technical Papers, Band: 1, Seiten: 16 - 19
Gutmann O, Niekrawietz R, Steinert C, Sandmaier H, Messner S, de Heij B, Daub M, Zengerle R
Droplet release in a highly parallel pressure driven nanoliter dispenser
2003 8.-12.06., Boston, USA Proc. of IEEE-Transducers 2003, Seiten: 364 - 367
Messner S, Schaible J, Vollmer J, Sandmaier H, Zengerle R
Electrostatic Driven 3-Way Silicon Microvalve for Pneumatic Applications
2003 Kyoto, Japan Proc of IEEE-MEMS, Seiten: 88 - 91
Kuhn C, Fritsche M, Brenner T, Grumann M, Dobmeier M, Schippers P, Zengerle R, Ducrèe J, Stähler C F, Stähler F
Fluidic Microchip for Bead-Based Assay Systems
2003 Proc. MipTec 2003; Basel, Switzerland
Grumann M, Schippers P, Dobmeier M, Haeberle S, Geipel A, Brenner T, Kuhn C, Fritsche M, Zengerle R, Ducrée J
Formation of hexagonal monolayers by flow of bead suspensions into flat microchambers
2003 November 16-21, Washington, DC, USA ASME International Mechanical Engineering Congress and RD&D Expo 2003
Gutmann O, Kuehlewein R, Niekrawietz R, Steinert C, de Heij B, Zengerle R, Daub M
Highly Parallel Droplet Release in a Nanoliter Dispenser
2003 October 14-15, Munich, Germany Proc. Micro.tec 2003, Seiten: 73 - 76
Steinert CP, Goutier I, Gutmann O, Sandmaier H, Daub M, de Heij B, Zengerle R
Highly Parallel Picoliter Dispensing Based on Direct Liquid Displacement
2003 October 14-15, Munich, Germany Proc. Micro.tec 2003, Seiten: 555 - 558
Eberhardt W, Kück H, Koltay P, Sandmaier H, Spritzendorfer M, Steger R, Willmann M, Zengerle R
Low Cost Fabrication Technology for Microfluidic Devices Basedon Micro Injection Moulding
2003 October 14-15, Munich, Germany Proc. Micro.tec 2003, Seiten: 129 - 134
Brenner T, Grumann M, Beer C, Zengerle R, Ducrée J
Microscopic Characterisation of Flow Patterns in Rotating Microchannels
2003 October 14-15, Munich, Germany Proc. Micro.tec 2003, Seiten: 171 - 174
Goettsche T, Kohnle J, Willmann M, Ernst H, Messner S, Steger R, Storz M, Lang W, Zengerle R, Sandmaier H
NOVEL APPROACHES TO MICROFLUIDIC COMPONENTSIN HIGH-END MEDICAL APPLICATIONS
2003 8.-12.06., Boston, USA Proc. of IEEE-Transducers 2003, Band: 2, Seiten: 623 - 626
Grumann M, Dobmeier M, Schippers P, Brenner T, Zengerle R, Ducrée J, Fritsche M
Optimized Creation of Monolayers for Parallel Readout of Bead-Based Assays
2003 3-4. December , Potsdam, Germany International Forum on Micro nano Integration (MINIT), Seiten: 117 - 124
Grumann M, Schippers P, Dobmeier M, Haeberle S, Geipel A
Stacking of beads into monolayers by flow through flat microfluidic chambers
2003 October 14-15, Munich, Germany Proc. Micro.tec 2003, Seiten: 545 - 550
Grumann M, Schippers P, Dobmeier M, Haeberle S, Geipel A, Brenner T, Zengerle R, Ducrée J, Kuhn C, Fritsche M
Stacking of beads into monolayers by flow through flat microfluidic chambers
2003 Proc. Micro.tec 2003; Munich, Germany, , Seiten: 545 - 550
Daub M
TopSpot technology: high-throughput production of microarrays
2003 Potsdam, Germany Proc. Biosensor Symposium 2003
de Heij B, Daub M, Niekrawietz R, Steinert C, Gutmann O, Löhr M, Sandmaier H, Zengerle R
TopSpot technology; high-throughput production of microarrays
2003 BioSensor Symposium Potsdam

2002

nach oben zur Jahresübersicht

Bas de Heij, Chris Steinert, Hermann Sandmaier, Roland Zengerle
A Tunable and Highly Parallel Picoliter Dispenser Based on Direct Liquid Displacement
2002 Las Vegas, USA; January 20-24 Proc of IEEE-MEMS 2002, Seiten: 706 - 709
Steger R, Koltay P, Birkle G, Strobelt T, Sandmaier H, Zengerle R
A Two-Dimensional Array of Piezostack Actuated Nanoliter Dispensers
2002 8th International Conference on New Actuators, Bremen, Germany Proc. Actuator 2002, Seiten: 537 - 541
Jörg Kohnle, Günter Waibel, Robert Cernosa, Matthias Storz, Herbert Ernst, Hermann Sandmaier, Tilo Strobelt, Roland Zengerle
A Unique Solution for Preventing Clogging of Flow Channels by Gas Bubbles
2002 Las Vegas, USA; January 20-24 Proc. of IEEE-MEMS 2002, Seiten: 77 - 80
Comley J, Koltay P, Steger R, Zengerle R, Sandmaier H, Knebel G, Gerlach A, Gottschlich N
DWPTM - A new Nanoliter Liquid Handling Tool For uHTS
2002 8th Annual Conference and Exhibition of the Society for Biomolecular Screening; The Hague, The Netherlands
Günter Waibel, Jörg Kohnle, Robert Cernosa, Matthias Storz, Manfred Schmitt, Herbert Ernst, Hermann Sandmaier, Roland Zengerle, Tilo Strobelt
Electronic Fountain Pen – A Highly Integrated Stand Alone Microdosage System
2002 Las Vegas, USA; January 20-24 Proc. of IEEE-MEMS 2002, Seiten: 6 - 10
Steinert C, de Heij B, Daub M, Zengerle R
Highly Parallel Nanoliter and Picoliter Liquid Handling for Biotech and Pharmaceutical Industry
2002 China - EU forum on Nanosized Technology; Beijing, China , Seiten: 251 - 258
Ernst H, de Heij B, Koltay P, Storz M, Sandmaier H, Zengerle R
Liquid Handling für Life Science Anwendungen
2002 GMM-Workshop: „Mikrosystemtechnik auf dem Gebiet Life Science”, Jena, Germany
Koltay P, Birkenmaier B, Steger R, Sandmaier H, Zengerle R
Massive Parallel Liquid Dispensing in the Nanoliter Range by Pneumatic Actuation
2002 8th International Conference on New Actuators, Bremen, Germany Proc. ACTUATOR 2002, Seiten: 235 - 239
Willmann M, Goettsche T, Kohnle J, Ernst H, Sandmaier H, Zengerle R
Microvalves for Implantable Microdosage Systems
2002 IEEE Meeting in Engineering in Medicine and Biology Society, Huston, Texas, USA Proc EMBS 2002
Sandmaier S, Steger R, Zengerle R, Eberhardt W, Kück H, Münch M, Spritzendorfer M
Mikrofluidikelemente in Low Cost Spritzgießtechnik für Life Sciences
2002 75. Tagung des Wissenschaftlichen Rates der AIF; Magdeburg
Koltay P, Daub M, Steger R, Birkle G, Birkenmaier B, Zengerle R
Miniaturized screening using a Dispensing Well Plate
2002 San Diego, USA Proc High-Throughput Screening & Miniaturization Technologies (screentech)
Koltay P, Moosmann C, Litterst C, Streule W, Birkenmaier B, Zengerle R
Modelling free jet ejection on a system level – an approach for microfluidics
2002 April 22-25, San Juan, Puerto Rico, USA Fifth International Conference on Modeling and Simulation of Microsystems (MSM), Seiten: 170 - 173
Koltay P, Moosmann C, Litterst C, Streule W, Zengerle R
Simulation of a micro dispenser using lumped models
2002 April 22-25, San Juan, Puerto Rico, USA Fifth International Conference on Modeling and Simulation of Microsystems (MSM), Seiten: 112 - 115
Koltay P, Taoufik S, Litterst C, Hansen-Schmidt J, Zengerle R
Simulation of micro dispensing devices
2002 Friedrichshafen, Germany Proc. of 20th CAD-FEM Users´ Meeting, International Congress on FEM-Technology

2001

nach oben zur Jahresübersicht

Bas de Heij, Stefan Bekesi, Markus Löhr, Gerhard Kattinger, Hermann Sandmaier, Roland Zengerle
A 96-channel printhead for production of microarrays
2001 Proc. International MEMS Workshop (I-MEMS) 2001 (Singapore; July 4-6, 2001); pp 125-131
Jochen Schaible, J. Vollmer, Roland Zengerle, Hermann Sandmaier, Tilo Strobelt
Electrostatic Microvalves in Silicon with 2-way-Function for industrial applications
2001 Proc. Transducers 2001 (Munich), Seiten: 928 - 931
Peter Koltay, Gerhard Birkle, Reinhard Steger, H. Kuhn, M. Mayer, Hermann Sandmaier, Roland, Zengerle
Highly parallel and accurate nanoliter dispenser for High Throughput Synthesis of chemical compounds.
2001 Proc International MEMS Workshop (I-MEMS) 2001 (Singapore, July 4-6, 2001); pp 115-124
Peter Koltay, Reinhard Steger, Gerhard Birkle, Hsi-Che Huang, Hermann Sandmaier, Roland Zengerle
Microdispenser array for highly parallel and aqccurate liquid handling.
2001 SPIE’s International Symposium on Microelectronics and Micro-Electro-Mechanical Systems; (Adelaide, Australia; December 17-19, 2001)

2000

nach oben zur Jahresübersicht

Tilo Strobelt, M. Willmann, Jörg Kohnle, Günter Waibel, Hermann Sandmaier, Roland Zengerle
Energy optimized valve with low leakage rates
2000 Proc IMECE 2000 (Orlando, Florida; November 5-10, 2000)
Roland Zengerle
Mass Production of Microarrays: TopSpot Dispensing Technology.
2000 Proc. EuroLab Automation (London; October 27, 2000)
Jens Ducrée
Mass production of Biochips; MICRO tec 2000; Expo
2000 MICRO.tec 2000 (Expo Hannover; September 25-27, 2000)
Roland Zengerle
Nanoliter Liquid Handling.
2000 IBC-conference on Drug Discovery Technologies 2000 (Basel; April 10-12, 2000)
Nicolaus Hey, Stefan Bekesi, Holger Gruhler, Gerhard Kattinger, M. Müller, Hermann Sandmaier, Roland Zengerle; TopSpot, – the second generation of the new microarray method;1st International Symposium, Synthesis, Screening, Sequencing; 22.-27.5.2000; Frankfurt
TopSpot – the second generation of the new microarray method.
2000 1st International Symposium Synthesis, Screening, Sequencing (Frankfurt May 22-27,.2000)
Roland Zengerle; TopSpot – A Fast Method for Spotting Microarrays; Analytica 2000, München, 14.4.2000
TopSpot – A Fast Method for Spotting Microarrays.
2000 Analytica 2000 (München, April 4, 2000)
Jens Ducrée, Holger Gruhler, Nicolas Hey, M. Müller, Stefan Bekesi, M. Freygang, Hermann Sandmaier, Roland, Zengerle
TopSpot – A new method for the fabrication of Microarrays.
2000 Proc. MEMS 2000, Miyazaki, Japan, Seiten: 317 - 322
Jens Ducrée
TopSpot – Kostengünstige Technik für die Produktion von Microarrays.
2000 Biotechnologie Symposium Luckenwalde (September 21, 2000)
Roland Zengerle
TopSpot: Mass Production of Microarrays.
2000 IBC-conference Eurobiochips 2000 (Hamburg, June 5-7, 2000)

1999

nach oben zur Jahresübersicht

Schaible J, Messner S, Müller M, Fuchs N, Sandmaier H, Zengerle R
A modular integrated pressure control unit for gases
1999 Proc. of IEEE-conference on Micro Electro Mechanical Systems MEMS´99, Orlando, USA
Mellmann J, Sesterhenn M, Löhr M, Stierle B, Strobelt T, Zengerle R, Sandmaier H
Simulation of Microfluidic Systems - A New Approach Considering Capillarity
1999 Proceedings of International Mechanical Engineering Congress and Exposition (IMECE) 1999, Nashville Tennessee , Seite: 371ff
Gruhler H, Hey N, Müller M, Bekesi S, Freygang M, Sandmaier H, Zengerle R
TopSpot - A New Method for the Fabrication of BioChips
1999 Proceedings of International Mechanical Engineering Congress and Exposition (IMECE) 1999, Nashville Tennessee , Seite: 413ff

1998

nach oben zur Jahresübersicht

Messner S, Müller M, Burger V, Schaible J, Sandmaier H, Zengerle R
3-way microvalve for pneumatic applications fabricated by silicon micromachining
1998 Proc. International Mechanical Engineering Congress and Exposition (IMECE); Anaheim, USA , Seiten: 159 - 164
Messner S, Mueller M, Burger V, Schaible J, Zengerle R
A 3-way silicon microvalve for pneumatic applications
1998 Proc. Actuator 98; Bremen, Germany , Seiten: 107 - 110
Hey N, Freygang M, Gruhler H, Sandmaier H, Zengerle R
A new device for multifunctional dosage of liquids by a free jet
1998 Proc. of IEEE-conference on Micro Electro Mechanical Systems MEMS´98; Heidelberg, Germany, Seiten: 429 - 431
Messner S, Müller M, Burger V, Schaible J, Sandmaier H, Zengerle R
A normally- closed, bimetalically actuated 3-way microvalve for pneumatic applications
1998 Proc. of IEEE-conference on Micro Electro Mechanical Systems MEMS´98; Heidelberg, Germany, Seiten: 40 - 44
Veser G, Friedrich G, Freygang M, Zengerle R
A simple and flexible micro reactor for investigations on heterogeneous catalytic gas phase reactions
1998 International Symposium on Reaction Kinetics and the Development of Catalytic Processes
Veser G, Friedrich G, Freygang M, Zengerle R
A simple and flexible micro reactor for studies of heterogeneously catalysed High-temperature reactions
1998 International Symposium on Reaction Kinetics and the Development of Catalytic Processes and Exposition (IMECE) '98, Anaheim, USA , Seiten: 199 - 205
Hey N, Freygang M, Gruhler H, Sandmaier H, Zengerle R
Microdosage of Liquids by a free jet comprising extraordinary operating range
1998 Proc. Actuator ´98; Bremen, Germany; , Seiten: 111 - 113
Zengerle R
Microfluidics
1998 Proc. Micromechanics Europe (MME), Ulvik, Norway, Seiten: 111 - 122

1997

nach oben zur Jahresübersicht

Messner S, Mueller M, Hey N, Gruhler H, Freygang M, Stehr M, Roßberg R, Sandmaier H, Zengerle R
Microfabricated Devices and Systems for Handling Liquids and Gases
1997 3. Chemnitzer Fachtagung Mikrosystemtechnik , Seiten: 150 - 157
Zengerle R, Stehr M, Freygang M, Haffner H, Messner S, Sandmaier H
Microfabricated devices for handling liquids and gases
1997 International Conference on Microreaction Technology; Frankfurt, Germany , Seite: P.2.01
Zengerle R, Sandmaier H
Microfluidics in Europe
1997 28th AIAA Fluid Dynamics Conference; Snowmass, Colorado, USA
Stehr M, Gruhler H, Straatmann H, Messner S, Sandmaier H, Zengerle R
The Selfpriming VAMP
1997 Proc. Transducers´97; Chicago, USA, Seiten: 351 - 352

1996

nach oben zur Jahresübersicht

Stehr M, Messner S, Ulrich J, Sandmaier H, Zengerle R
A microvalve with bidirectional pump effect
1996 Proc. EUROSENSORS X; Leuven, Belgium , Seiten: 845 - 848
Stehr M, Messner S, Zengerle R
A new bidirectional micropump for liquids and gases
1996 , Seiten: 61 - 64
Stehr M, Messner S, Sandmaier H, Zengerle R
A new micropump with bidirectional fluid transport and selfblocking effect
1996 Proc. of IEEE-conference on Micro Electro Mechanical Systems MEMS ´96; San Diego, USA, Seiten: 485 - 490
Zengerle R, Stehr M, Freygang M, Haffner H, Messner S, Roßberg R, Sandmaier H
Microfabricated devices and systems for handling liquids and gases
1996 Proc. Microtas 96; Basel, Switzerland , Seiten: 91 - 93
Zengerle R, Sandmaier H
Microfluidics
1996 Seventh International Symposium on Micro Machine and Human Science; Nagoya, Japan , Seiten: 13 - 20
Ulrich J, Stehr M, Zengerle R
Simulation of a bidirectional pumping microvalve using FEM
1996 Proc. EUROSENSORS X; Leuven, Belgium , Seiten: 1241 - 1244

1995

nach oben zur Jahresübersicht

Zengerle R, Kluge S, Richter M, Richter A
A bidirectional silicon micropump
1995 Proc. of IEEE-conference on Micro Electro Mechanical Systems MEMS ´95; Amsterdam; The Netherlands, Seiten: 19 - 24
Zengerle R, Leitner M, Kluge S, Richter A
Carbon dioxide priming of micro liquid systems
1995 Proc. of IEEE-conference on Micro Electro Mechanical Systems MEMS ´95; Amsterdam; The Netherlands, Seiten: 340 - 343
Ulrich J, Füller H, Zengerle R
Static and dynamic flow simulation of a KOH-Etched micro valve
1995 Proc. Transducers 95; Stockholm, Sweden, Seiten: 17 - 20

1994

nach oben zur Jahresübersicht

Zengerle R, Geiger W, Richter M, Ulrich J, Kluge S, Richter A
Application of micro diaphragm pumps in microfluid systems
1994 4rd International Conference of New Actuators (ACTUATOR ´94), Bremen, Germany , Seiten: 25 - 29
Sandmaier H, Zengerle R, Richter A
Microfabricated liquid handling elements
1994 Workshop on Micro Total Analysis Systems A. Van den Berg and P. Bergfeld, Seiten: 71 - 72

1993

nach oben zur Jahresübersicht

Zengerle R, Richter M, Brosinger F, Richter A, Sandmaier H
Performance simulation of microminiaturized membrane pumps"; pp. 106-109
1993 Proc. 7 th International Conference of Solid-State Sensors and Actuators (TRANSDUCERS ), Yokohama, Japan, Seiten: 106 - 109

1992

nach oben zur Jahresübersicht

Zengerle R, Richter A, Sandmaier H
A Micro Membrane Pump With Electrostatic Actuation
1992 Proc of Micro Electro Mechanical Systems '92 (MEMS 92), Seiten: 19 - 24
Zengerle R
Eine Mikropumpe mit elektrostatischem oder pneumatischen Antrieb
1992 Zweites Symposium Mikrosystemtechnik, Regensburg , Seiten: 206 - 214
Zengerle R, Richter A
Properties and applications of a micro membrane pump with electrostatic drive
1992 3 rd International Conference of New Actuators (ACTUATOR ´92), Bremen, Germany , Seiten: 28 - 33

Sonstige Publikationen

Jahre: 2007 | 2006 | 1997 | 1993

zurück zur Übersicht aller Publikationen

2007

nach oben zur Jahresübersicht

P. Koltay
Frei fliegende Mikrotröpfchen
labor & more, Band: 02/07, Seite: 60, 2007

2006

nach oben zur Jahresübersicht

T. Göttsche, A. Wolff
IntelliDrug - An Integrated Intelligent Drug Delivery System
mst news, Band: 1/06, Seiten: 36 - 37, 2006
R. Gronmaier, B. Scheufele, S. Haeberle, J. Kohnle, R. Zengerle, H. Northoff, F. K. Gehring
Mikrofluidische Plattform für die Blutanalytik
BIOforum, Band: 6, Seiten: 38 - 40, 2006

1997

nach oben zur Jahresübersicht

Büstgens B, Schneck M, Woias P, Zengerle R
Leitlinien für die entwicklungsbegleitende Normung bei Mikropumpen"
DIN-Fachbericht "Mikrosystemtechnik", 1997

1993

nach oben zur Jahresübersicht

Woias P, Zengerle R, Richter A, Drost S, Sandmaier H
Mikrofluidsysteme
Studie im Auftrag des VDI|VDE-Technologiezentrum Informationstechnik GmbH, Berlin, 1993

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