List of Publications Dr.-Ing. Jochen Kieninger

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Journal Articles

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2020

• Urban S, Tamilselvi Sundaram V, Weltin A, Kieninger J, Urban G, Weltin A
  Microsensor Electrodes for 3D Inline Process Monitoring in Multiphase Microreactors
  2020 Sensors-basel, volume: 20, issue: 17, page: 4876
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  Abstract

  We present an electrochemical microsensor for the monitoring of hydrogen peroxide direct synthesis in a membrane microreactor environment by measuring the hydrogen peroxide and oxygen concentrations. In prior work, for the first time, we performed in situ measurements with electrochemical microsensors in a microreactor setup. However, the sensors used were only able to measure at the bottom of the microchannel. Therefore, only a limited assessment of the gas distribution and concentration change over the reaction channel dimensions was possible because the dissolved gases entered the reactor through a membrane at the top of the channel. In this work, we developed a new fabrication process to allow the sensor wires, with electrodes at the tip, to protrude from the sensor housing into the reactor channel. This enables measurements not only at the channel bottom, but also along the vertical axis within the channel, between the channel wall and membrane. The new sensor design was integrated into a multiphase microreactor and calibrated for oxygen and hydrogen peroxide measurements. The importance of measurements in three dimensions was demonstrated by the detection of strongly increased gas concentrations towards the membrane, in contrast to measurements at the channel bottom. These findings allow a better understanding of the analyte distribution and diffusion processes in the microreactor channel as the basis for process control of the synthesis reaction.
• Weltin A, Ganatra D, König K, Joseph K, Hofmann UG, Urban G, Kieninger J
  New life for old wires: Electrochemical sensor method for neural implants
  2020 J Neural Eng, volume: 17, issue: 1, page: 016007
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  Abstract

  Objective. Electrochemical microsensors based on noble metals can give essential information on their microenvironment with high spatio‐temporal resolution. However, most advanced chemo‐ and biosensors lack the long‐term stability for physiological monitoring of brain tissue beyond an acute application. Noble metal electrodes are widely used as neural interfaces, particularly for stimulating in the central nervous system. Our goal was to recruit already deployed, unmodified noble metal electrodes (Pt, Pt/Ir) as in situ chemical sensors. Approach. With advanced electrochemical sensor methods, we investigated electrode surface processes, oxidizable species and oxygen as an indicator for tissue mass transport. We developed a unique, multi‐step, amperometric/potentiometric sensing procedure derived from the investigation of Pt surface processes by chronocoulometry providing fundamental characterization of the electrode itself. Main results. The resulting electrochemical protocol preconditions the electrode, measures oxidizable and reducible species, and the open circuit potential. A linear, stable sensor performance was demonstrated, also in the presence of proteins, validating signal stability of our cyclic protocol in complex environments. We investigated our sensor protocol with microelectrodes on custom Pt/Ir‐wire tetrodes by in vivo measurements in the rat brain for up to four weeks. Results showed that catalytic activity of the electrode is lost over time, but our protocol is repeatedly able to both quantify and restore electrode sensitivity in vivo. Significance. Our approach is highly relevant because it can be applied to any existing Pt electrode. Current methods to assess the brain/electrode microenvironment mainly rely on imaging techniques, histology and analysis of explanted devices, which are often end‐point methods. Our procedure delivers online and time‐transient information on the chemical microenvironment directly at the electrode/tissue interface of neural implants, gives new insight into the charge transfer processes, and delivers information on the state of the electrode itself addressing long‐term electrode degradation.
  
  
   
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• Liebisch F, Weltin A, Marzioch J, Urban G, Kieninger J
  Zero-Consumption Clark-Type Microsensor for Oxygen Monitoring in Cell Culture and Organ-on-Chip Systems
  2020 Sensor Actuat B-chem, page: 128652
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  Abstract

  Clark-type oxygen microsensors promise zero analyte consumption if the feedback mode (Ross principle) is successfully implemented. Our approach was a microsensor with platinum as working and counter electrode material, a pHEMA hydrogel layer containing buffer solution as electrolyte and PDMS as gas-permeable membrane. We were able to demonstrate successful implementation of the Ross principle by measurement of the counter electrode potential. The microsensors could be stored dry and activated by immersion into aqueous analyte. Chronoamperometric protocols were applied to enable long-term stability for more than one week without recalibration. The microsensors were integrated in conventional tissue culture flasks for cell measurements. Respiration monitoring was done in T-47D breast cancer monolayer culture. The unique feature combination of zero analyte consumption, 1-point calibration and sufficient long-term stability make these sensors an ideal candidate to monitor oxygenation and respiration in different cell culture and organ-on-chip systems.

2019

• Dornhof J, Urban G, Kieninger J
  Deposition of Copper Nanofilms by Surface-Limited Redox Replacement of Underpotentially Deposited Lead on Polycrystalline Gold
  2019 J Electrochem Soc, volume: 166, issue: 1, pages: D3001 - D3005
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  Abstract

  Electrochemical atomic layer deposition (E-ALD) of copper on polycrystalline gold is a promising method to achieve highly reproducible nanofilms. Cu films of more than 30 nm were deposited by the repetitive execution of underpotential deposition (UPD) of lead and a subsequent surface limited redox replacement by Cu. Both steps were carried out in the same solution. The method enables, in contrast to conventional gas phase ALD, the deposition of layers with different height on the same substrate. Deposit growth in this one-pot system was monitored in-situ with an electrochemical quartz crystal microbalance. Film thickness, measured by optical profilometry, was compared to the number of deposition cycles and indicated a highly linear dependency. Obtained layers were characterized by means of atomic force and scanning electron microscopy and showed a slight roughening with almost no increase in the effective surface area. Energy dispersive X-ray measurements confirmed the purity of deposited Cu nanofilms. It was shown, that even with a simple setup, the described method allows the reproducible deposition of Cu on polycrystalline Au.
  
  
   
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2018

• Zimmermann P, Weltin A, Urban G, Kieninger J
  Active Potentiometry for Dissolved Oxygen Monitoring with Platinum Electrodes
  2018 Sensors, volume: 18, issue: 8, page: 2404
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  Abstract

  Potentiometric oxygen monitoring using platinum as the electrode material was enabled by the combination of conventional potentiometry with active prepolarization protocols, what we call active potentiometry. The obtained logarithmic transfer function is well-suited for the measurement of dissolved oxygen in biomedical applications, as the physiological oxygen concentration typically varies over several decades. We describe the application of active potentiometry in phosphate buffered salt solution at different pH and ion strength. Sensitivity was in the range of 60 mV/dec oxygen concentration; the transfer function deviated from logarithmic behavior for smaller oxygen concentration and higher ion strength of the electrolyte. Long-term stability was demonstrated for 60 h. Based on these measurement results and additional cyclic voltammetry investigations a model is discussed to explain the potential forming mechanism. The described method of active potentiometry is applicable to many different potentiometric sensors possibly enhancing sensitivity or selectivity for a specific parameter.
  
  
   
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• Urban S, Weltin A, Flamm H, Kieninger J, Deschner BJ, Kraut M, Dittmeyer R, Urban G
  Electrochemical multisensor system for monitoring hydrogen peroxide, hydrogen and oxygen in direct synthesis microreactors
  2018 Sensor Actuat B-chem, volume: 273, pages: 973 - 982
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  Abstract

  We present an electrochemical microsensor system for the monitoring of hydrogen peroxide, dissolved hydrogen and dissolved oxygen inside a direct synthesis microreactor. The setup allows the online, in situ measurement of high reactant concentrations by amperometric detection of all three reactants in aqueous solution using chronoamperometric protocols. Hydrogen peroxide is a key chemical for industrial oxidation applications, and its catalyzed direct synthesis is an attractive process route. For the first time, we integrated an electrochemical cell into a high pressure stainless steel microreactor environment (pressures up to 100  bar, pH of 3-4 and presence of bromide) by fabricating sensor plugs with 300  µm platinum microelectrodes encapsulated into a robust epoxy housing. The first microfabricated silver/silver bromide pseudo-reference electrode, integrated by electrodeposition, allowed to obtain a stable measurement potential directly from the electrolyte containing bromide. The investigation of platinum electrochemistry in the presence of bromide by cyclic voltammetry led to the development of chronoamperometric protocols for the stable, precise and reproducible measurement in this environment. Hydrogen peroxide was detected under reaction conditions showing linear behaviour up to 20  mM with high sensitivity of 55  μA  cm⁻²  mM⁻¹ and excellent stability by application of a diffusion limiting hydrogel layer to the electrode surface. This linear range surpasses most micro- and nanostructured platinum approaches. Oxygen and hydrogen were both measured at elevated pressures up to 70  bar and high dissolved concentrations up to 52  mM and 40  mM with measured sensitivities of 26  μA  cm⁻²  mM⁻¹ and 356  μA  cm⁻²  mM⁻¹, respectively. We have successfully shown the application of electrochemical sensors for online, in situ monitoring of analyte concentrations under conditions found in direct synthesis microreactors.
• Kieninger J, Weltin A, Flamm H, Urban G
  Microsensor systems for cell metabolism – from 2D culture to organ-on-chip
  2018 Lab Chip, volume: 18, pages: 1274 - 1291
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  Abstract

  Microsensor systems for cell metabolism are essential tools for investigation and standardization in cell cul- ture. Electrochemical and optical read-out schemes dominate, which enable the marker-free, continuous, online recording of transient effects and deliver information beyond microscopy and end-point tests. There has been much progress in microfluidics and microsensors, but the translation of both into standard cell culture procedures is still limited. Within this critical review, we discuss different cell culture formats ranging from standard culture vessels to dedicated microfluidic platforms. Key aspects are the appropriate supply of cells, mass transport of metabolites to the sensors and generation of stimuli. Microfluidics enable the transition from static to dynamic conditions in culture and measurement. We illustrate the parameters oxy- gen (respiration), pH (acidification), glucose and lactate (energy metabolism) as well as short-lived reactive species (ROS/RNS) from the perspective of microsensor integration in 2D and 3D cell culture. We discuss different sensor principles and types, along with their limitations, microfabrication technologies and mate- rials. The state-of-the-art of microsensor platforms for cell culture is discussed with respect to sensor per- formance, the number of parameters and timescale of application. That includes the advances from 2D culture to the increasingly important 3D approaches, with specific requirements for organotypic micro- tissues, spheroids and solid matrix cultures. We conclude on the current progress, potential, benefits and limitations of cell culture monitoring systems from monolayer culture to organ-on-chip systems.
  
  
   
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• Unmüssig T, Daubinger P, Weltin A, Urban S, Urban G, Kieninger J
  Non-enzymatic glucose sensing based on hierarchical platinum micro-/nanostructures
  2018 J Electroanal Chem, volume: 816, pages: 215 - 222
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  Abstract

  Non-enzymatic glucose monitoring for biomedical applications asks for long-term stable and selective sensors at neutral pH. A hierarchical platinum micro-/nanostructured electrode along with a novel measurement scheme leads to increased sensitivity, selectivity and stability compared to state-of-the-art. The hierarchical electrode coating was applied by a scalable two-step process, which combined electrochemical deposition and colloidal synthesis to obtain a hierarchical structure with high surface roughness. This three-dimensional structure consists of a cauliflower-like platinum deposition, which is coated by a platinum nanowire network. Amperometric glucose measurements showed a 10,000-fold increase in sensitivity (473  μA  cm⁻²  mM⁻¹) compared to unmodified electrodes and linear behavior in the physiological range. The obtained sensitivities are among the highest values reported for non-enzymatic glucose sensors in neutral pH media. The hierarchical morphology provides a selectivity mechanism depending on the reaction kinetics, improving the selectivity for glucose in the presence of the interferent ascorbic acid 2,000-fold. Selectivity was further enhanced by low-frequency electrochemical impedance spectroscopy (EIS). Chronoamperometric protocols were developed to achieve long-term stability and overcome the loss of sensitivity due to electrode poisoning. Using chronoamperometric protocols for both the amperometry and the EIS measurements improved stability significantly. The presented results make hierarchical platinum micro-/nanostructured electrodes a promising candidate for continuous glucose monitoring.
• Marzioch J, Kieninger J, Weltin A, Flamm H, Aravindalochanan K, Sandvik J A, Pettersen E O, Peng Q, Urban G
  On-Chip Photodynamic Therapy – Monitoring Cell Metabolism by Electrochemical Microsensors
  2018 Lab Chip, volume: 18, pages: 3353 - 3360
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  Abstract

  We introduce a new system which combines metabolic monitoring by electrochemical microsensors with photodynamic therapy on-chip for the first time. Oxygen consumption of T-47D breast cancer cells was measured during therapy with protoporphyrin IX. We determined the efficacy of therapy and revealed recovery effects, which underlines the high relevance of continuous monitoring.
• Kieninger J, Tamari Y, Enderle B, Jobst G, Sandvik JA, Pettersen EO, Urban G
  Sensor Access to the Cellular Microenvironment Using the Sensing Cell Culture Flask
  2018 Biosensors, volume: 8, issue: 2, page: 44
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  Abstract

  The Sensing Cell Culture Flask (SCCF) is a cell culture monitoring system accessing the cellular microenvironment in 2D cell culture using electrochemical microsensors. The system is based on microfabricated sensor chips embedded in standard cell culture flasks. Ideally, the sensor chips could be equipped with any electrochemical sensor. Its transparency allows optical inspection of the cells during measurement. The surface of the sensor chip is in-plane with the flask surface allowing undisturbed cell growth on the sensor chip. A custom developed rack system allows easy usage of multiple flasks in parallel within an incubator. The presented data demonstrates the application of the SCCF with brain tumor (T98G) and breast cancer (T-47D) cells. Amperometric oxygen sensors were used to monitor cellular respiration with different incubation conditions. Cellular acidification was accessed with potentiometric pH sensors using electrodeposited iridium oxide films. The system itself provides the foundation for electrochemical monitoring systems in 3D cell culture.
  
  
   
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2017

• Weltin A, Hammer S, Noor F, Kaminski Y, Kieninger J, Urban G
  Accessing 3D Microtissue Metabolism: Lactate and Oxygen Monitoring in Hepatocyte Spheroids
  2017 Biosens Bioelectron, volume: 87, pages: 941 - 948
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  Abstract

  3D hepatic microtissues, unlike 2D cell cultures, retain many of the in-vivo-like functionalities even after long-term cultivation. Such 3D cultures are increasingly applied to investigate liver damage due to drug exposure in toxicology. However, there is a need for thorough metabolic characterization of these microtissues for mechanistic understanding of effects on culture behaviour. We measured metabolic parameters from single human HepaRG hepatocyte spheroids online and continuously with electrochemical microsensors. A microsensor platform for lactate and oxygen was integrated in a standard 96-well plate. Electrochemical microsensors for lactate and oxygen allow fast, precise and continuous long-term measurement of metabolic parameters directly in the microwell. The demonstrated capability to precisely detect small concentration changes by single spheroids is the key to access their metabolism. Lactate levels in the culture medium starting from 50 μM with production rates of 5 μM h⁻¹ were monitored and precisely quantified over three days. Parallel long- term oxygen measurements showed no oxygen depletion or hypoxic conditions in the microwell. Increased lactate production by spheroids upon suppression of the aerobic metabolism was observed. The dose-dependent decrease in lactate production caused by the addition of the hepatotoxic drug Bosentan was determined. We showed that in a toxicological application, metabolic monitoring yields quantitative, online information on cell viability, which complements and supports other methods such as microscopy. The demonstrated continuous access to 3D cell culture metabolism within a standard setup improves in vitro toxicology models in replacement strategies of animal experiments. Controlling the microenvironment of such organotypic cultures has impact in tissue engineering, cancer therapy and personalized medicine.
• Ring A, Sorg H, Weltin A, Tilkorn D J, Kieninger J, Urban G, Hauser J
  In-vivo monitoring of infection via implantable microsensors: a pilot study
  2017 Biomed Eng-biomed Te
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  Abstract

  The most common complication after implantation of foreign material is infection, leading to implant failure and severe patient discomfort. Smoldering-infections proceed inapparently and might not get verified by radiological diagnostics. Early identification of this type of infection might significantly reduce the rate of complications. Therefore, we manufactured a microsensor strip in a hybrid of thin-film and laminate technology in a wafer-level process. It comprises electrochemical, amperometric microsensors for glucose, oxygen and lactate as well as an integrated reference electrode. Microsensors have been implanted in the mouse dorsal skin fold chamber, which got inoculated with a human-pathogen bacterial strain. A selective signal could be measured for all parameters and time points. The infection led to measurable changes of the wound environment as given by a decrease of the oxygen- as well as the glucose-concentration while the lactate concentration increased markedly over time. The given results in this study are the first hints on a promising new tool and should therefore be interpreted as a proof of the principle to show the functionality of the microsensors in an in vivo setting. These microsensors could be used to monitor smoldering infections of implantable foreign materials reducing foreign implant associated complications.
• Qazzazie D, Yurchenko O, Urban S, Kieninger J, Urban G
  Platinum nanowires anchored on graphene-supported platinum nanoparticles as highly active electrocatalyst towards glucose oxidation for fuel cell applications
  2017 Nanoscale, volume: 9, pages: 6436 - 6447
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  Abstract

  The limited performance of platinum-based electrocatalysts for glucose electrooxidation is a major concern for glucose fuel cells, since glucose electrooxidation is characterized by slow reaction kinetics and low diffusion coefficient. Here, the presented graphene-supported platinum-based hierarchical nanostructures attain highly enhanced electrocatalytic activity towards glucose oxidation. Platinum nanoparticles electrodeposited on graphene support retain mechanical stability and act as junctions allowing a reliable, smooth and dense growth of platinum nanowires with extremely small diameters (>10 nm) on graphene. The electrode’s surface roughness was increased by factors up to 4000 to the geometrical surface area enabling maximized exploitation of the electrocatalytic activity of platinum and efficient electron transfer between nanowires and substrate. The unique three-dimensional geometry of these hierarchical nanostructures has a significant impact on their catalytic performance offering short diffusional paths for slow glucose species, thus, mass transport limitations are optimized leading to lower polarization losses. This was examined by galvanostatic measurements of the operation as anodes in glucose half-cells at conditions corresponding to implantable glucose fuel cells. The presented hierarchical nanostructures show remarkably enhanced catalytic performance for glucose electrooxidation, i.e. negatively shifted open circuit potential of -580 mV vs. Ag/AgCl, hence, representing appropriate electrocatalysts for uses as anodes in glucose fuel cells. In combination with a non-metal N-doped graphene cathode, a cell potential of 0.65 V was achieved at a galvanostatic load of 17.5 µA cm⁻² which noticeably surpasses the performance of state of the art catalysts for aforementioned operation conditions.
• Al-Halhouli M, Kieninger J, Yurchenko O, Urban G
  Rational design of morphological characteristics to determine the optimal hierarchical nanostructures in heterogeneous catalysis
  2017 Chemcatchem, volume: 9, pages: 354 - 364
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  Abstract

  This work draws attention to the optimal hierarchical nanostructures morphology and the morphological characteristics that lead to a rational design of heterogeneous nanocatalysts, especially for reactions exhibiting sluggish kinetics. A simplified methanol oxidation on two types of hierarchical nanostructures, external and internal, is reported. A complex system of asymmetric geometries was simplified by mapping 3D geometries into 2D using mass transport approach. Macropore-size turned out to be the most comprehensive characteristic for evaluating specific activity and current density of hierarchical nanostructures. The optimal current densities for both types of nanostructures were achieved in macropore-size ranges of 3.2 - 4.5 µm and 1.9 - 3.2 µm, respectively. The optimal mass activity of internal nanostructures was achieved at the porosity range of 40 - 50% whereas the optimal mass activity of external hierarchical nanostructures was achieved at high porosity values. External hierarchical nanostructures in comparison to internal hierarchical nanostructures tend to be the cost-effective catalysts that have high catalytic activity.

2016

• Dincer C, Kling A, Chatelle C, Armbrecht L, Kieninger J, Weber W, Urban G
  Designed miniaturization of microfluidic biosensor platforms using the stop-flow technique
  2016 Analyst, volume: 141, pages: 6073 - 6079
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  Abstract

  Here, we present a novel approach to increase the degree of miniaturization as well as the sensitivity of biosensor platforms by optimization of microfluidic stop-flow techniques independent of the applied detection technique (e.g. electrochemical or optical). The readout of labeled bioassays, immobilized in a microfluidic channel, under stop-flow conditions leads to a rectangular shaped peak signal. Data evaluation using the peak height allows for a high level miniaturization of the channel geometries. To study the main advantages and limitations of this method by numerical simulations, a universally applicable model system is introduced for the first time. Consequently, proof-of-principle experiments were successfully performed with standard and miniaturized versions of an electrochemical biosensor platform utilizing a repressor protein-based assay for tetracycline antibiotics. Herein, the measured current peak heights are the same despite the sextuple reduction of the channel dimensions. Thus, it results in a 22-fold signal amplification compared to the constant flow measurements in the case of the miniaturized version.
  
  
   
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• Partel S, Dincer C, Kasemann S, Kieninger J, Edlinger J, Urban G
  Lift-Off Free Fabrication Approach for Periodic Structures with Tunable Nano Gaps for Interdigitated Electrode Arrays
  2016 Acs Nano, volume: 10, issue: 1, pages: 1086 - 1092
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  Abstract

  We report a simple, low-cost and lift-off free fabrication approach for periodic structures with adjustable nanometer gaps for interdigitated electrode arrays (IDAs). It combines an initial structure and two deposition process steps; first a dielectric layer is deposited, followed by a metal evaporation. The initial structure can be realised by lithography or any other structuring technique (e.g. nano imprint, hot embossing or injection moulding). This method allows the fabrication of nanometer sized gaps and completely eliminates the need for a lift-off process. Different substrate materials like silicon, Pyrex® or polymers can be used. The electrode gap is controlled primarily by sputter deposition of the initial structure, and thus, adjustable gaps in the nanometer range can be realized independent of the mask or stamp pattern. Electrochemical characterizations using redox cycling in ferrocenemethanol (FcMeOH) demonstrate signal amplification factors of more than 110 together with collection factors higher than 99 %. Furthermore, the correlation between the gap width and the amplification factor was studied to obtain an electrochemical performance assessment of the nano gap electrodes. The results demonstrate an exponential relationship between amplification factor and gap width.
• Al-Halhouli M, Kieninger J, Yurchenko O, Urban G
  Mass transport and catalytic activity in hierarchical/non-hierarchical and internal/external nanostructures: A novel comparison using 3D simulation
  2016 Appl Catal A-gen, volume: 517, pages: 12 - 20
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  Abstract

  The distinct organization of nanostructured materials influences several catalytic characteristics, like selectivity, sensitivity or catalytic efficiency. This paper studies the effect of geometrical configuration of nanostructured catalyst on mass transport and catalytic activity based on 3D simulations of hierarchical external, hierarchical internal, non-hierarchical external and non-hierarchical internal nanostructures. Generally, external nanostructures revealed higher utilization of catalytic surface than the internal nanostructures. Among the four investigated nanostructures, the mass transport in hierarchical external nanostructures was found to be the best; they even showed kinetic controlled regime for the species with low diffusion coefficient. In contrast, hierarchical internal nanostructures showed slightly less specific activity than non-hierarchical internal nanostructures because of higher total diffusional resistance and longer diffusional path. As a result, although hierarchical nanostructures possess large surface area, only the hierarchical external nanostructures provided an outstanding accessibility of active sites. The obtained results provide the tool for understanding the catalytic efficiency in complex nanostructure and phenomena that are technically difficult to measure.
• Weltin A, Kieninger J, Urban G
  Microfabricated, amperometric, enzyme-based biosensors for in vivo applications
  2016 Anal Bioanal Chem, volume: 408, pages: 4503 - 4521
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  Abstract

  Miniaturized electrochemical in vivo biosensors allow the measurement of fast extracellular dynamics of neurotransmitter and energy metabolism directly in the tissue. Enzyme-based amperometric biosensing is characterized by high specificity and precision as well as high spatial and temporal resolution. Aside from glucose monitoring, many systems have been introduced mainly for application in the central nervous system in animal models. We compare the microsensor principle with other methods applied in biomedical research to show advantages and drawbacks. Electrochemical sensor systems are easily miniaturized and fabricated by microtechnology processes. We review different microfabrication approaches for in vivo sensor platforms, ranging from simple modified wires and fibres to fully microfabricated systems on silicon, ceramic or polymer substrates. The various immobilization methods for the enzyme such as chemical cross-linking and entrapment in polymer membranes are discussed. The resulting sensor performance is compared in detail. We also examine different concepts to reject interfering substances by additional membranes, aspects of instrumentation and biocompatibility. Practical considerations are elaborated, and conclusions for future developments are presented.
  
  
   
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• Kling A, Chatelle C, Armbrecht L, Qelibari E, Kieninger J, Dincer C, Weber W, Urban G
  Multianalyte antibiotic detection on an electrochemical microfluidic platform
  2016 Anal Chem, volume: 88, issue: 20, pages: 10036 - 10043
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  Abstract

  Fast and easy-to-handle multi-analyte single-use sensors are of increasing interest for many fields such as medical analysis or environmental and food control. This report presents an electrochemical and universally applicable microfluidic platform enabling the simultaneous readout of up to eight enzyme-linked assays. For this purpose, microfluidic channel networks are designed each comprising distinct numbers of immobilization sections with a very low volume of 680 nl each. These immobilization sections can be actuated separately for an individual functionalization and assay procedure. To demonstrate the applicability of this platform in the context of surveillance and monitoring of different antibiotics, the simultaneous detection of the two commonly employed antibiotics tetracycline and pristinamycin is investigated. The limits of detection (LOD) are determined to 6.33 and 9.42 ng ml⁻¹ for tetracycline and pristinamycin, respectively, with inter-assay coefficients of variation (CV) below 10 %. The device provides a shelf-life of at least three months. The ability for multi-analyte measurements in a complex medium is demonstrated by the simultaneous detection of both antibiotics in spiked human plasma within a sample-to-result time of 15 minutes.
  
  
   
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• Al-Halhouli M, Kieninger J, Daubinger P, Yurchenko O, Urban G
  Sensitivity and selectivity of porous electrodes in heterogeneous liquid-based catalytic reactions: 3D simulation study
  2016 J Electrochem Soc, volume: 163, issue: 10, pages: E273 - E281
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  Abstract

  Efficiency, selectivity and sensitivity are important issues in catalytic applications, such as fuel cells and electrochemical sensors. This paper discusses the catalytic activity of porous layers in heterogeneous reactions based on the impact of pore morphology on pore accessibility in liquids. We present three-dimensional simulations to discuss some critical geometrical characteristics that influence the overall catalytic activity of porous catalyst. Sensitivity is proportional to the overall catalytic activity of the surface area. However, selectivity depends on pore accessibility. Simulation results demonstrate that at constant k⁰, porous layers with small pores and large numbers of pores are selective to the species with high diffusion coefficient because of high pore accessibility. In contrast, porous electrodes with low number of large pores and a large top surface area are selective to the species with low diffusion coefficient because of low pore accessibility. Additionally, pore accessibility influences the diffusional resistance, which has an impact on the local pH-value. High diffusional resistance in the porous layer leads to an accumulation of reaction products and a modification in the concentration of buffer molecules, which change local pH-value and therefore the catalytic behavior.

2015

• Dincer C, Ktaich R, Laubender E, Hees J J, Kieninger J, Nebel C E, Heinze J, Urban G
  Nanocrystalline boron-doped diamond nanoelectrode arrays for ultrasensitive dopamine detection
  2015 Electrochim Acta, volume: 185, pages: 101 - 106
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  Abstract

  In this paper we present nanocrystalline boron-doped diamond nanoelectrode arrays (BDD-NEAs) for the low-level detection of biogenic substances such as dopamine (DA) without the need for a selective membrane. We achieved a sensitive and reproducible detection of dopamine in the presence of ascorbic acid (AA) with oxygen (O-) terminated BDD-NEAs. To improve the peak separation between dopamine and ascorbic acid, differential pulse voltammetry (DPV) was employed. Therewith, it was possible to measure dopamine with a sensitivity of 57.9 nA μM⁻¹ cm⁻². The detection limit was less than 100 nM with a linear behavior up to a concentration of 20 μM. The choice of the appropriate termination, the combination of the advantages of nanoelectrode arrays together with the outstanding electrochemical properties of boron-doped diamond and the right measurement method allowed successful measurement of dopamine in physiological concentrations in the presence of ascorbic acid.
• Armbrecht L, Dincer C, Kling A, Horak J, Kieninger J, Urban G
  Self-assembled magnetic bead chains for sensitivity enhancement of microfluidic electrochemical biosensor platforms
  2015 Lab Chip, volume: 15, pages: 4314 - 4321
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  Abstract

  In this paper, we present a novel approach to enhance the sensitivity of microfluidic biosensor platforms with self-assembled magnetic bead chains. An adjustable, more than 5-fold sensitivity enhancement is achieved by introducing a magnetic field gradient along a microfluidic channel by means of a soft- magnetic lattice with a 350 μm spacing. The alternating magnetic field induces the self-assembly of the magnetic beads in chains or clusters and thus improves the perfusion and active contact between the analyte and the beads. The soft-magnetic lattices can be applied independent of the channel geometry or chip material to any microfluidic biosensing platform. At the same time, the bead-based approach achieves chip reusability and shortened measurement times. The bead chain properties and the maximum flow velocity for bead retention were validated by optical microscopy in a glass capillary. The magnetic actuation system was successfully validated with a biotin–streptavidin model assay on a low-cost electrochemical microfluidic chip, fabricated by dry-film photoresist technology (DFR). Labelling with glucose oxidase (GOx) per- mits rapid electrochemical detection of enzymatically produced hydrogen peroxide.
  
  
   
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• Flamm H, Kieninger J, Weltin A, Urban G
  Superoxide Microsensor Integrated into a Sensing Cell Culture Flask Microsystem Using Direct Oxidation for Cell Culture Application
  2015 Biosens Bioelectron, volume: 65, pages: 354 - 359
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  Abstract

  A new electrochemical sensor system for reliable and continuous detection of superoxide radical release from cell culture was developed utilizing direct oxidation of superoxide on polymer covered gold microelectrodes. Direct superoxide oxidation was demonstrated to provide robust measurement principle for sensitive and selective reactive oxygen species (ROS) quantification without the need for biocomponent supported conversion. Sensor performance was investigated by using artificial enzymatic superoxide production revealing a sensitivity of 2235 A M⁻¹ m⁻². An electrode protection layer with molecular weight cut-off property from adsorbed linear branched polyethylenimine was successfully introduced for long term and selectivity improvement. Thin-film based sensor chip fabrication with implemented three-electrode setup and full integration into the technological platform Sensing Cell Culture Flask was described. Cell culturing directly on-chip and free radical release by phorbol-12-myristate-13-acetate (PMA) stimulation was demonstrated using T-47D human breast cancer carcinoma cell model. Transient extracellular superoxide production upon stimulation was successfully observed from amperometric monitoring. Signal inhibition from scavenging of extracellular superoxide by specific superoxide dismutase (SOD) showed the applicability for selective in vitro ROS determination. The results confirm the possibility of direct superoxide oxidation, with exclusion of the main interfering substances uric acid and hydrogen peroxide. This offers new insights into the development of reliable and robust ROS sensors.

2014

• Weltin A, Slotwinski K, Kieninger J, Moser I, Jobst G, Wego M, Ehret R, Urban G
  Cell Culture Monitoring for Drug Screening and Cancer Research: a Chip-Based, Transparent, Microfluidic, Multi-Sensor Microsystem
  2014 Lab Chip, volume: 14, issue: 1, pages: 138 - 146
• Daubinger P, Kieninger J, Unmüssig T, Urban G
  Electrochemical Characteristics of Nanostructured Platinum Electrodes – A Cyclic Voltammetry Study
  2014 Phys Chem Chem Phys, volume: 16, issue: 18, pages: 8392 - 8399
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  Abstract

  Platinum surfaces play a decisive role in catalysis in sensors, fuel cells, solar cells and other applications like neuronal stimulation and recording. Technical advances in nanotechnology contributed tremendously to the progress in these fields. A fundamental understanding of the chemical and physical interactions between the nanostructured surfaces and electrolytes is essential, but was barely investigated up to now. In this article, we present a wet-chemical process for the deposition of nanostructures on polycrystalline platinum surfaces. The electrochemically active surface area was increased by a factor of over 1000 times with respect to the geometrical surface. The influence of the nanostructures was examined in different acidic, alkaline, and neutral electrolytes. Comparing cyclic voltammograms of nanostructured and planar polycrystalline platinum revealed new insights into the microenvironment at the electrode-electrolyte interface. The characteristic features of the cyclic voltammograms were altered in their shape and strongly shifted with respect to the applied potential. In neutral buffered and unbuffered electrolytes the water window was expanded from 1.4 V to more than 2 V. The shifts were interpreted as local pH-changes and exhausted buffer capacity in direct proximity of the electrode surface due to the strong release and binding of protons, respectively. These polarized electrodes induce significant changes in the electrochemical potential of the electrolyte due to the high roughness of their surface. The electrochemical phenomena and the observed voltage shifts are crucial for the understanding of the basic mechanism at nanostructured electrodes and mandatory for designing fuel cells, sensors and many other devices
• Weltin A, Enderle B, Kieninger J, Urban G
  Multiparametric, Flexible Microsensor Platform for Metabolic Monitoring In Vivo
  2014 Ieee Sens J, volume: 14, issue: 10, pages: 3345 - 3351
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  Abstract

  In this paper, we present a multiparametric microsensor platform for metabolic monitoring in vivo. In contrast to silicon or ceramic-based systems, the flexible, implantable polymer-based sensor strip is manufactured in a cost-effective hybrid of thin-film and laminate technology in a wafer-level process. Flexibility allows easy handling and placement in soft tissue. It comprises a microelectrode array for up to four electrochemical, amperometric micro-(bio)sensors, and an integrated reference electrode. The energy metabolism parameters glucose, lactate, and oxygen as well as the neurotransmitter glutamate were measured. The sensors allow dynamic, highly sensitive, localized, long-term, online measurement of up to four metabolic parameters with a single device. The reliable analytical performance of the sensors, stability of the reference electrode, and the multiparametric measurement are shown. The sensor can be inserted directly into the tissue for in vivo applications.
• Partel S, Kasemann S, Choleva P, Dincer C, Kieninger J, Urban G
  Novel fabrication process for sub-μm interdigitated electrode arrays for highly sensitive electrochemical detection
  2014 Sensor Actuat B-chem, volume: 205, pages: 193 - 198
  » show abstract« hide abstract
  Abstract

  Interdigitated electrode arrays (IDAs) are often used for electrochemical detection using redox-cycling for signal amplification. Its geometry, especially the gap width, is an important factor defining its electrochemical performance (sensitivity and collection efficiency). Minimal defect density on a wafer is a must as a single shortcut prevents the function of the sensor chip. Therefore, the fabrication of interdigitated electrode arrays is a fundamental step in the integration of electrochemical sensors. This paper presents a novel fabrication approach that allows electrode spacing in the sub-micrometer region by using standard equipment such as UV Mask Aligner, physical vapor deposition and diffusion furnace. The fabrication procedure is a combination of dry etching, thermal oxidation and wet etching. This approach has potential to realize electrode distances down to 140 nm or even less. The proposed method enables the fabrication of sub-micron IDAs with the use of a conventional Mask Aligner and standard silicon technology. Moreover, it allows the electrode spacing adjustment without changing the mask design. The presented results demonstrate high sensitivity electrochemical sensors with amplification factors more than 12 without the need of e-beam lithography. Hence, this fabrication method offers a low-cost alternative to sub-micron e-beam written IDAs.
• Kieninger J, Aravindalochanan K, Sandvik J, Pettersen E, Urban G
  Pericellular oxygen monitoring with integrated sensor chips for reproducible cell culture experiments
  2014 Cell Proliferat, volume: 47, issue: 2, pages: 180 - 188
• Weltin A, Kieninger J, Enderle B, Gellner AK, Fritsch B, Urban G
  Polymer-Based, Flexible Glutamate and Lactate Microsensors for in vivo Applications
  2014 Biosens Bioelectron, volume: 61, pages: 192 - 199
• Pettersen E, Ebbesen P, Gieling R, Williams K, Dubois L, Lambin P, Ward C, Meehan J, Kunkler I, Langdon S, Ree A, Flatmark K, Lyng H, Calzada M, del Peso L, Landazuri M, Görlach A, Flamm H, Kieninger J, Urban G, Weltin A, Singleton D, Haider S, Buffa F, Harris A, Scozzafava A, Supuran C, Moser I, Jobst G, Busk M, Toustrup K, Overgaard J, Alsner J, Pouyssegur J, Chiche J, Mazure N, Marchiq I, Parks S, Ahmed A, Ashcroft M, Pastorekova S, Cao Y, Rouschop K, Wouters B, Koritzinsky M, Mujcic H, Cojocari D
  Targeting Tumour Hypoxia to Prevent Cancer Metastasis. From Biology, Biosensing And Technology to Drug Development: the METOXIA Consortium
  2014 J Enzym Inhib Med Ch, volume: 29, issue: 5, pages: 1 - 33

2012

• Partel S, Mayer M, Hudek P, Dincer C, Kieninger J, Urban G, Motzek K, Matay L
  Fabrication Process Development for a High Sensitive Electrochemical IDA Sensor
  2012 Microelectron Eng, volume: 97, pages: 235 - 240
  » show abstract« hide abstract
  Abstract

  We present recent results on a development and fabrication process of the electrochemical sensor with high sensitivity. The electrochemical sensor is based on an enzyme-linked immunosorbent assay (ELISA). The used ELISA provides a redox active species as intermediate product for the electrochemical detection. The increase in sensitivity due to the redox cycling process was evaluated with an interdigitated electrode array (IDA) consisting of 300 fingers with 2 μm width and 1 μm gap each. The lithography process was simulated to estimate the impact of the sensor stack and the illumination source during the lithography step on the sensor’s critical features. Development characteristics of the photoresist were precisely determined using a multi-wavelength dissolution rate monitor (DRM). The final sensor was tested with the ferri/ferro cyanide couple as well as with para-aminophenol (PAP). Both results prove amplification factors of more than 10 measured in a flow cell. The results presented demonstrate that high sensitivity electrochemical immunosensors based on redox cycling at IDAs on Pyrex substrate can be fabricated with conventional but highly optimized UV lithography.

2011

• Aravindalochanan K, Kieninger J, Flamm H, Urban G
  P7. An Approach to Distinguish and Monitor NO from NO2-/NO3- Levels in Pericellular Region
  2011 Nitric Oxide-biol Ch, volume: 24, supplement: May, pages: 18 - 19

2009

• Ebbesen P, Pettersen E, Gorr T, Jobst G, Williams, Kieninger J, Wenger R, Pastorekova S, Dubois L, Lambin P, Wouters B, Van Den Beucken T, Supuran C, Poellinger L, Ratcliffe P, Kanopka A, Goerlach A, Gasmann M, Harris A, Maxwell P, Scozzafava A
  Taking Advantage of Tumor Cell Adaptations to Hypoxia for Developing New Tumor Markers and Treatment Strategies
  2009 J Enzym Inhib Med Ch, volume: 24, issue: s1, pages: 1 - 39

Book chapters

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2011

• Pruszak J, Döbrössy M, Kieninger J, Aravindalochanan K, Urban G, Nikkhah G
  Neural Stem Cells: From Cell Fate and Metabolic Monitoring Towards Clinical Applications
  In: Stem Cell Engineering
  2011, Springer Verlag, G. Artmann, pages: 435 - 455, G. Artmann,

2009

• Urban G, Guttmann J, Kieninger J, Weltin A, Wöllenstein J, Zosel J
  CO₂ Sensing in Medicine
  In: Carbon Dioxide Sensing: Fundamentals, Principles, and Applications
  2009, Wiley‐VCH Verlag GmbH & Co. KGaA, pages: 391 - 413, ISBN: 9783527688302
  » show abstract« hide abstract
  Abstract

  The measurement of biochemical parameters is primarily done in centralized laboratories, in intensive care units, and in the operating theatre with near‐patient point‐of‐care testing (POCT). The measurement of carbon dioxide (CO₂) in blood as a part of the so‐called blood gas panel. POCT is a patient‐centred diagnostic test that is not performed in a centralized laboratory, but in the hospital immediately near the operating room or intensive care or in the ambulance. CO₂ is a gaseous waste product of metabolism and physiologically very tightly controlled. The CO₂ balance is maintained by a carbonate buffer system in blood. Clinical blood gas analysis systems can be grouped into devices for single analysis of a discrete blood sample and continuous monitoring devices. The measurement of CO₂ in human breath – called capnometry – is common practice in respiratory gas monitoring in intensive caremedicine, emergency medicine, and anaesthesiology.

Talks

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2015

• Kling A, Dincer C, Armbrecht L, Horak J, Kieninger J, Urban G
  Microfluidic multiplexed electrochemical biosensor platform
  2015 BMT 2015, Lübeck, Germany

2011

• Aravindalochanan K, Kieninger J, Flamm H, Urban G
  An Integrated Bio-MEMS Measurement Platform for Nitric Oxide Research
  2011 Gordon Research Conference on Nitric Oxide, Ventura, CA

2008

• Kieninger J
  Global and local oxygen control in in vitro systems
  2008 EUROXY course, Tuscany, Italy

2007

• Kieninger J
  Tools for oxygen measurement
  2007 EUROXY course, Maastricht, Netherlands

Conference papers

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2019

• Urban S, Kieninger J, Deschner BJ, Kraut M, Dittmeyer R, Urban G, Weltin A
  Multiparametric, Spatially Resolved Detection of H2O2 and O2 with Electrochemical Microsensor Array in Synthesis Membrane Microreactors
  2019 20th International Conference on Solid-State Sensors, Actuators and Microsystems & Eurosensors XXXIII (TRANSDUCERS & EUROSENSORS XXXIII), Berlin, Germany
  » show abstract« hide abstract
  Abstract

  We present an electrochemical microsensor system for the multiparametric detection of dissolved concentrations of hydrogen peroxide (H₂O₂) and oxygen (O₂) inside a direct synthesis membrane microreactor. Both reactants are detected with high sensitivity on the same Pt-based electrode by changing the applied measurement potential in a chronoamperometric protocol. The robust integration of the electrochemical cell in the microreactor was demonstrated and allowed for in situ detection of the spatial gradient of the changing oxygen concentration diffusing through a membrane into the microreactor, emphasizing the capabilities of our monitoring system.
• Dornhof J, Kieninger J, Maurer J, Urban G, Weltin A
  Next Generation Organ-on-Chip System for Directional Control of Culture Conditions and Metabolic Monitoring of Tumor Organoids
  2019 20th International Conference on Solid-State Sensors, Actuators and Microsystems & Eurosensors XXXIII (TRANSDUCERS & EUROSENSORS XXXIII), Berlin, Germany
  » show abstract« hide abstract
  Abstract

  In vitro replica of 3D heterogeneous tumor systems are essential models on the path towards personalized chemotherapy in cancer research. Here, we present an organ-on-chip platform with integrated microelectrodes enabling online-monitoring of culture conditions and metabolic parameters of patient-derived, triple-negative breast cancer stem cells. Tumor organoids grow in compartments separated by microfluidic channels, permitting the generation of oxygen and drug gradients as seen in real tumors. Besides the electrochemical analysis, e.g. for oxygen or lactate, the transparent chip also allows characterization with optical methods. Such in situ monitoring systems bear a high potential for replacing animal models in drug research.
• Marzioch J, Kieninger J, Weltin A, Urban G
  Oxygen Microsensor Array to Study Spatial Efficacy of Photodynamic Therapy in Vitro
  2019 20th International Conference on Solid-State Sensors, Actuators and Microsystems & Eurosensors XXXIII (TRANSDUCERS & EUROSENSORS XXXIII), Berlin, Germany
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  Abstract

  We present a cell culture monitoring platform to study effects of photodynamic therapy (PDT) on cancer cells. For the first time, it was possible to observe differences in cellular respiration at the transition between treated and untreated tumor cells in the same culture. Therewith more realistic in vitro studies of treatment efficiency and edge effects during PDT are possible. This resembles the spatially limited exposure in the in vivo situation. The sensor platform comprises an optically transparent microsensor chip with an integrated array of electrochemical oxygen microsensors and a LED light source for the photodynamic treatment.
• Weltin A, Ganatra D, Durisin M, Urban G, Kieninger J
  Electrochemical Protocols Upgrade Conventional Noble Metal Electrodes to Long-term Stable Sensors at the Tissue/Electrode Interface
  2019 IEEE EMBC, Berlin, Germany Proc. 41th Int. Conf. of the IEEE Eng. in Medicine and Biology Soc. (EMBC), volume: 1, pages: 1 - 1
• Pfau J, Ganatra D, Weltin A, Urban G, Kieninger J, Stieglitz T
  Electrochemical Stability of Thin-Film Platinum as Suitable Material for Neural Stimulation Electrodes
  2019 IEEE EMBC, Berlin, Germany

2018

• Pfau J, Ganatra D, Weltin A, Urban G, Kieninger J, Stieglitz T
  Electrochemical Stability of Thin-Film Platinum as Suitable Material for Neural Stimulation Electrodes
  2018 BMT 2018, Aachen, Germany Biomed Eng-biomed Te, volume: 63, supplement: 1, page: S121

2017

• Urban S, Weltin A, Flamm H, Kieninger J, Deschner B J, Kraut M, Dittmeyer R, Urban G
  Electrochemical Multisensor System for Monitoring the Hydrogen Peroxide Direct Synthesis in Microreactors
  2017 Eurosensors 2017 Conference, Paris, France Proceedings, volume: 1, issue: 4, page: 630
  » show abstract« hide abstract
  Abstract

  We present an electrochemical sensor system for the detection of hydrogen peroxide inside a direct synthesis microreactor. The setup allows the online, in situ measurement of high reactant concentrations by amperometric detection across the micro channel width and length. The robust integration of the electrochemical cell in the microreactor was demonstrated. Hydrogen peroxide was detected under reaction conditions (pH 3–4, presence of bromide) showing linear behaviour up to 2 mM with high sensitivity and excellent stability. The linear range was increased up to 10 mM by applying a diffusion limiting pHEMA layer to the electrode surface.
  
  
   
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• Weltin A, Kieninger J, Urban G
  Highly Sensitive Electrochemical Glutamate Microsensors for Food Analysis
  2017 Eurosensors 2017 Conference, Paris, France Proceedings, volume: 1, issue: 4, page: 521
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  Abstract

  Electrochemical microsensors are ideal to measure substances with low concentration in complex environments. The primary excitatory neurotransmitter l-glutamate is present in many foods as a distinctive flavour (enhancer) with a wide concentration range. In comparison to other methods, electrochemical sensors allow the rapid, precise, cost-effective, online measurement without any sample treatment. We developed a disposable electrochemical microsensor platform with multiple integrated, highly sensitive (detection limit <150 nM) and selective enzyme-based glutamate biosensors. We showed both the precise determination of glutamate levels in processed foods with high glutamate content (15–40 mM), e.g., broth, and in foods with low natural concentrations such as different types of cow’s milk (~250 μM). Hereby, we successfully demonstrated the capabilities of electrochemical biosensors in food monitoring, analysis and quality control.
  
  
   
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• Weltin A, Joseph K, Kieninger J, Hofmann UG, Urban G
  Investigation of electrical stimulation by glutamate sensing from brain slices with microsensors
  2017 MicroTAS 2017, Savannah, USA 21st International Conference on Miniaturized Systems for Chemistry and Life Sciences, pages: 1563 - 1564
• Marzioch J, Kramer F, Dungel P, Kieninger J, Urban G
  Pericellular Oxygen Monitoring during Low-Level Light Therapy in Cell Culture Using a Microsensor System
  2017 Eurosensors 2017 Conference, Paris, France Proceedings, volume: 1, issue: 4, page: 499
  » show abstract« hide abstract
  Abstract

  An electrochemical microsensor system to monitor the pericellular oxygen concentration of fibroblasts during low-level light therapy in vitro was developed. The system provides in-sight into the metabolism of the cells during and in consequence of illumination with visible red light. This approach is a unique method for real-time investigations of cellular respiration during light therapy. The presented sensor system features direct amperometric measurements by using chronoamperometric protocols for long-term stability. The oxygen measurements do not show a disturbance by light.
  
  
   
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• Kieninger J, Liebisch F, Weltin A, Marzioch J, Urban G
  Zero consumption Clark-type oxygen microsensor for cell culture monitoring
  2017 Transducers 2017, Kaohsiung, Taiwan

2016

• Marzioch J, Kieninger J, Sandvik J A, Pettersen E A, Peng Q, Urban G
  Electrochemical microsensor system for cancer research on photodynamic therapy in vitro
  2016 27th Micromechanics and Microsystems Europe (MME) workshop, Cork, Irland Journal of Physics: Conference Series, volume: 757
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  Abstract

  An electrochemical microsensor system to investigate photodynamic therapy of cancer cells in vitro was developed and applied to monitor the cellular respiration during and after photodynamic therapy. The redox activity and therefore influence of the photodynamic drug on the sensor performance was investigated by electrochemical characterization. It was shown, that appropriate operation conditions avoid cross-sensitivity of the sensors to the drug itself. The presented system features a cell culture chamber equipped with microsensors and a laser source to photodynamically treat the cells while simultaneous monitoring of metabolic parameter in situ. Additionally, the optical setup allows to read back fluorescence signals from the photosensitizer itself or other marker molecules parallel to the microsensor readings.

2015

• Flamm H, Kieninger J, Weltin A, Urban G
  Advanced Electrochemical in Vitro Detection of Superoxide Radicals with Fully Integrated Microsensor System
  2015 Eurosensors 2015, Freiburg, Germany Procedia Engineering, volume: 120, pages: 26 - 30
• Kling A, Dincer C, Armbrecht L, Horak J, Kieninger J, Urban G
  Electrochemical Microfluidic Platform for Simultaneous Multi-Analyte Detection
  2015 Eurosensors 2015, Freiburg, Germany Procedia Engineering, volume: 120, pages: 916 - 919
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  Abstract

  We present an electrochemical lab-on-a-chip (LOC) platform for the simultaneous detection of up to four different analytes. The possibility to separately immobilize different assays in a channel network, without active valves, was successfully demonstrated using a model assay linked to glucose oxidase. This enables the detection of various analytes even with different assay formats. For the assay immobilization, the channel surface, made out of dry film photoresist (DFR), could be activated by means of EDC/NHS-linker chemistry and used for the covalent binding of primary amines. Cross-sensitivity due to diffusion within the channel network could be experimentally excluded.
• Hammer S, Weltin A, Kaminski Y, Noor F, Kieninger J, Urban G
  Lactate Monitoring in Organotypic 3D Cell Cultures
  2015 Eurosensors 2015, Freiburg, Germany Procedia Engineering, volume: 120, pages: 961 - 964
• Marzioch J, Kieninger J, Sandvik J, Pettersen E, Peng Q, Urban G
  Photodynamic Therapy – In Vitro Investigation Using an Electrochemical Microsensor System
  2015 Eurosensors 2015, Freiburg, Germany Procedia Engineering, volume: 120, pages: 468 - 471
• Urban S, Unmüssig T, Daubinger P, Kieninger J, Urban G
  Stability of Non-enzymatic Glucose Sensor Based on Platinum Micro-/Nanostructures
  2015 Eurosensors 2015, Freiburg, Germany Procedia Engineering, volume: 120, pages: 1145 - 1148
• Unmuessig T, Daubinger P, Kieninger J, Urban G
  Hierarchical Platinum Nanostructure for the Non-Enzymatic Detection of Glucose by Amperometry and Impedance Analysis
  2015 18th International Conference on Solid-State Sensors, Actuators and Microsystems; Anchorage, Alaska, USA Solid-State Sensors, Actuators and Microsystems, volume: M
• Flamm H, Weltin A, Kieninger J, Urban G
  Measurement of reactive oxygen species release from stimulated cell culture with fully integrated microsensor system by advanced electrochemical detection principle
  2015 18th International Conference on Solid-State Sensors, Actuators and Microsystems; Anchorage, Alaska, USA Solid-State Sensors, Actuators and Microsystems, volume: M, pages: 1561 - 1564
• Kling A, Dincer C, Armbrecht L, Horak J, Kieninger J, Urban G
  Microfluidic multiplexed multi-analyte immunosensing platform
  2015 MicroTAS 2015, Gyeongju, Korea
• Armbrecht L, Dincer C, Kling A, Horak J, Kieninger J, Urban G
  Signal amplification using magnetic bead chains in microfluidic electrochemical biosensors
  2015 Transducers 2015, Alaska, USA

2014

• Marzioch J, Kieninger J, Aravindalochanan K, Sandvik J, Pettersen E, Urban G
  Microsensor System for Cancer Research on Photodynamic Therapy
  2014 Biosensors, Melbourne, Australia
• Partel S, Kasemann S, Choleva P, Dincer C, Kieninger J, Urban G
  Novel fabrication process for sub-µm interdigitated electrode arrays for highly sensitive electrochemical detection
  2014 Biosensors, Melbourne, Australia

2013

• Erhardt J, Nock V, Kieninger J, Urban G
  Non-invasive characterization of dissolved oxygen dynamics in water-in-oil droplet microfluidics - Towards 3d micro tumor spheroids for high throughput cancer drug screening.
  2013 17th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS 2013), Freiburg, Germany , pages: 1376 - 1378
• Osterberg N, Aravindalochanan K, Kieninger J, Urban G, Weyerbrock A
  Development and Evaluation of an Electrochemical Nitric Oxide Sensing On-Chip Cell Culture System for Measurement of Pericellular NO in Glioma Cell Cultures
  2013 64. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Düsseldorf, Deutschland

2012

• Weltin A, Enderle B, Slotwinski K, Kieninger J, Urban G
  A Flexible Multiparametric Microsensor for in-vivo Application
  2012 Biosensor (Elsevier), Cancun, Mexico
• Kieninger J, Tamari Y, Enderle B, Sandvik J, Pettersen E, Urban G
  Cell Culture Monitoring with Integrated Biosensors for Novel Insights into Metabolic Pathways in Tumor Cells
  2012 Biosensor (Elsevier), Cancun, Mexico
• Flamm H, Aravindalochanan K, Kieninger J, Urban G
  Enzyme-less Superoxide Sensor for Longtime Monitoring in Tumor Cell Culture
  2012 Biosensor (Elsevier), Cancun, Mexico

2010

• Kieninger J, Aravindalochanan K, Urban G, Sandvik J, Pettersen E, Jobst G
  Monitoring of Peri-cellular Oxygen Levels in Tumor Cell Cultures by Amperometric Oxygen Sensor Array
  2010 IEEE Sensors, Hawai, USA Ieee Sens J, pages: 1234 - 1237

2009

• Kieninger J
  Microbiosensor-Systems for Cellular Monitoring
  2009 SENSOR+Test Conference 2009, 26.-28.05.2009
• Aravindalochanan K, Kieninger J, Sandvik A, Pettersen E O, Urban G A
  Optimizing a Nitric Oxide Sensing Technique for Hypoxic Tumor Cell Cultures
  2009 IEEE Transducers, Denver (USA)
• Aravindalochanan K, Kieninger J, Urban G, Jobst G
  Simulation and Design of A Nitric Oxide Sensor Array for Cell Cultures
  2009 IEEE Sensors, Christchurch (New Zealand)
• Kieninger J, Marx A, Spies F, Weltin A, Urban G A, Jobst G
  pH Micro Sensor with Micro-fluidic Liquid-junction Reference Electrode On-chip for Cell Culture Applications
  2009 IEEE SENSORS 2009 Conference

2008

• Kahlert U, Kieninger J, Papazoglou A, Urban G, Nikkah G
  Characterisation of menchymal stem cells (MSC)
  2008

2007

• Kieninger J, Dannenberg A, Aravindalochanan K, Jobst G, Pettersen E O, Urban G A
  Amperometric oxygen sensor array with novel chronoamperometric protocols
  2007 Transducers 2007/Eurosensors XXI/ Lyon, France Proc. of Transducers `07/Eurosensors XXI; Vol. 2, volume: 2, pages: 1907 - 1910
• Aravindalochanan K, Kieninger J, Jobst G, Igel G, Urban G A
  Micro Electrode Array for Sensing Nitric Oxide in Hypoxic Cell Culture Environment
  2007 IEEE Sensors, Atlanta (USA) , volume: 1, pages: 111 - 116

2005

• Kieninger J, Aravindalochanan K, Jobst G, Igel G, Urban G
  Electro Chemical Oxygen Sensor Array for Hypoxic Environment
  2005 Sensors, Nürnberg, Germany Sensors Proceedings, volume: II, pages: 259 - 262