title: A novel 384-multiwell microelectrode array for the impedimetric monitoring of Tau protein induced neurodegenerative processes.
abstract: Over the last decades, countless bioelectronic monitoring systems were developed for the analysis of cells as well as complex tissues. Most studies addressed the sensitivity and specificity of the bioelectronic detection method in comparison to classical molecular biological assays. In contrast, the up scaling as a prerequisite for the practical application of these novel bioelectronic monitoring systems is mostly only discussed theoretically. In this context, we developed a novel 384-multiwell microelectrode array (MMEA) based measurement system for the sensitive label-free real-time monitoring of neurodegenerative processes by impedance spectroscopy. With respect to the needs of productive screening systems for robust and reproducible measurements on high numbers of plates, we focused on reducing the critical contacting of more than 400 electrodes for a 384-MMEA. Therefore, we introduced an on top array of immersive counter electrodes that are individually addressed by a multiplexer and connected all measurement electrodes on the 384-MMEA to a single contact point. More strikingly, our novel approach provided a comparable signal stability and sensitivity similar to an array with integrated counter electrodes. Next, we optimized a SH-SY5Y cell based tauopathy model by introducing a novel 5-fold Tau mutation eliminating the need of artificial tauopathy induction. In combination with our novel 384-MMEA based measurement system, the concentration and time dependent neuroregenerative effect of the kinase inhibitor SRN-003-556 could be quantitatively monitored. Thus, our novel screening system could be a useful tool to identify and develop potential novel therapeutics in the field of Tau-related neurodegenerative diseases.
authors: Centre for Biotechnology and Biomedicine, Molecular biological-biochemical Processing Technology, Leipzig University, Deutscher Platz 5, Leipzig, D-04103 Germany.
authors: Heinz-Georg
authors: HG
authors: Jahnke
authors: Centre for Biotechnology and Biomedicine, Molecular biological-biochemical Processing Technology, Leipzig University, Deutscher Platz 5, Leipzig, D-04103 Germany.
authors: Dana
authors: D
authors: Krinke
authors: Centre for Biotechnology and Biomedicine, Molecular biological-biochemical Processing Technology, Leipzig University, Deutscher Platz 5, Leipzig, D-04103 Germany.
authors: Diana
authors: D
authors: Seidel
authors: Institute of Micro, and Nanotechnologies MacroNano®, Nano-biosystem Technology (Microfluidics and Biosensors group), Technische Universität Ilmenau, Gustav-Kirchhoff-Straße 7, Ilmenau, 98693 Germany.
authors: Katharina
authors: K
authors: Lilienthal
authors: Centre for Biotechnology and Biomedicine, Molecular biological-biochemical Processing Technology, Leipzig University, Deutscher Platz 5, Leipzig, D-04103 Germany.
authors: Sabine
authors: S
authors: Schmidt
authors: Centre for Biotechnology and Biomedicine, Molecular biological-biochemical Processing Technology, Leipzig University, Deutscher Platz 5, Leipzig, D-04103 Germany.
authors: Ronny
authors: R
authors: Azendorf
authors: Institute of Micro, and Nanotechnologies MacroNano®, Nano-biosystem Technology (Microfluidics and Biosensors group), Technische Universität Ilmenau, Gustav-Kirchhoff-Straße 7, Ilmenau, 98693 Germany.
authors: Michael
authors: M
authors: Fischer
authors: KeyNeurotek Pharmaceuticals AG, Zenit Technologiepark, Leipziger Str. 44, Magdeburg, 39120 Germany; Department of Neurodegeneration and Intervention Strategies, German Center for Neurodegenerative Diseases (DZNE), Leipziger Str. 44, Magdeburg, D-39120 Germany.
authors: Till
authors: T
authors: Mack
authors: KeyNeurotek Pharmaceuticals AG, Zenit Technologiepark, Leipziger Str. 44, Magdeburg, 39120 Germany; Department of Neurodegeneration and Intervention Strategies, German Center for Neurodegenerative Diseases (DZNE), Leipziger Str. 44, Magdeburg, D-39120 Germany.
authors: Frank
authors: F
authors: Striggow
authors: Fraunhofer Institute for Factory Operation and Automation IFF, Magdeburg, Germany.
authors: Holger
authors: H
authors: Althaus
authors: Institute of Micro, and Nanotechnologies MacroNano®, Nano-biosystem Technology (Microfluidics and Biosensors group), Technische Universität Ilmenau, Gustav-Kirchhoff-Straße 7, Ilmenau, 98693 Germany.
authors: Andreas
authors: A
authors: Schober
authors: Centre for Biotechnology and Biomedicine, Molecular biological-biochemical Processing Technology, Leipzig University, Deutscher Platz 5, Leipzig, D-04103 Germany. Electronic address: andrea.robitzki@bbz.uni-leipzig.de.
authors: Andrea A
authors: AA
authors: Robitzki
mesh_terms: D002227:Carbazoles / Q000494:pharmacology; D002460:Cell Line; D058266:Dielectric Spectroscopy / Q000295:instrumentation* / Q000379:methods; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation / Q000379:methods; D004867:Equipment Design; D006801:Humans; D008839:Microelectrodes; D024801:Tauopathies / Q000175:diagnosis* / Q000188:drug therapy; D016875:tau Proteins / Q000032:analysis*
chemical_list: D002227:Carbazoles; C512359:SRN 003-556; D016875:tau Proteins
keywords: 384-multiwell microelectrode array; Cell-based tauopathy model; Impedance spectroscopy; Kinase inhibitor SRN-003-556; Phenotypic screening; SH-SY5Y cells