Publikationsliste Dr. Susanna Früh

• Originalarbeiten in wissenschaftlichen Fachzeitschriften
• Reviews/Übersichtsartikel in wissenschaftlichen Fachzeitschriften
• Buchbeiträge
• Konferenzbeiträge

Originalarbeiten in wissenschaftlichen Fachzeitschriften

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2025

• 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

2024

• 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

2023

• 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

2022

• 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
• 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

2021

• 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
• 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
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  Kurzfassung

  We 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.
• 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
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  Kurzfassung

  The 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.
• 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
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  Kurzfassung

  The 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.

2019

• 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
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  Kurzfassung

  Saliva 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.
• 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
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  Kurzfassung

  Lateral 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.

Reviews/Übersichtsartikel in wissenschaftlichen Fachzeitschriften

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2021

• 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
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  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.

Buchbeiträge

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2020

• A. Brunauer, H. Ceren Ates, C. Dincer, S. M. Früh
  Integrated paper-based sensing devices for diagnostic applications
  In: Comprehensive Analytical Chemistry
  2020, Elsevier,
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  Kurzfassung

  Paper-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.

Konferenzbeiträge

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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

• 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
• 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
• 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
• 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

2020

• 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

2019

• 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
• 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
• 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
• 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
• 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

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