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Electrophysiological Phenotype Characterization of Human iPSC-Derived Neuronal Cell Lines by Means of High-Density Microelectrode Arrays

Silvia Ronchi, Alessio Paolo Buccino, Gustavo Prack, Sreedhar Saseendran Kumar, Manuel Schröter, Michele Fiscella, Andreas Hierlemann
doi: https://doi.org/10.1101/2020.09.02.271403
Silvia Ronchi
1Department of Biosystems Science and Engineering, ETH Zürich, Mattenstrasse 26, 4058 Basel, Switzerland
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  • For correspondence: silvia.ronchi@bsse.ethz.ch michele.fiscella@bsse.ethz.ch
Alessio Paolo Buccino
1Department of Biosystems Science and Engineering, ETH Zürich, Mattenstrasse 26, 4058 Basel, Switzerland
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Gustavo Prack
1Department of Biosystems Science and Engineering, ETH Zürich, Mattenstrasse 26, 4058 Basel, Switzerland
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Sreedhar Saseendran Kumar
1Department of Biosystems Science and Engineering, ETH Zürich, Mattenstrasse 26, 4058 Basel, Switzerland
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Manuel Schröter
1Department of Biosystems Science and Engineering, ETH Zürich, Mattenstrasse 26, 4058 Basel, Switzerland
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Michele Fiscella
1Department of Biosystems Science and Engineering, ETH Zürich, Mattenstrasse 26, 4058 Basel, Switzerland
2MaxWell Biosystems AG, Albisriederstrasse 253, 8047 Zürich, Switzerland
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  • For correspondence: silvia.ronchi@bsse.ethz.ch michele.fiscella@bsse.ethz.ch
Andreas Hierlemann
1Department of Biosystems Science and Engineering, ETH Zürich, Mattenstrasse 26, 4058 Basel, Switzerland
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Abstract

Recent advances in the field of cellular reprogramming have opened a route to study the fundamental mechanisms underlying common neurological disorders. High-density microelectrode-arrays (HD-MEAs) provide unprecedented means to study neuronal physiology at different scales, ranging from network through single-neuron to subcellular features. In this work, we used HD-MEAs in vitro to characterize and compare human induced-pluripotent-stem-cell (iPSC)-derived dopaminergic and motor neurons, including isogenic neuronal lines modeling Parkinson’s disease and amyotrophic lateral sclerosis. We established reproducible electrophysiological network, single-cell and subcellular metrics, which were used for phenotype characterization and drug testing. Metrics such as burst shapes and axonal velocity enabled the distinction of healthy and diseased neurons. The HD-MEA metrics could also be used to detect the effects of dosing the drug retigabine to human motor neurons. Finally, we showed that the ability to detect drug effects and the observed culture-to-culture variability critically depend on the number of available recording electrodes.

Competing Interest Statement

M.F. is co-founder of MaxWell Biosystems AG, which commercializes HD-MEA technology.

Footnotes

  • ↵† Authors share senior authorship

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted September 02, 2020.
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Electrophysiological Phenotype Characterization of Human iPSC-Derived Neuronal Cell Lines by Means of High-Density Microelectrode Arrays
Silvia Ronchi, Alessio Paolo Buccino, Gustavo Prack, Sreedhar Saseendran Kumar, Manuel Schröter, Michele Fiscella, Andreas Hierlemann
bioRxiv 2020.09.02.271403; doi: https://doi.org/10.1101/2020.09.02.271403
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Electrophysiological Phenotype Characterization of Human iPSC-Derived Neuronal Cell Lines by Means of High-Density Microelectrode Arrays
Silvia Ronchi, Alessio Paolo Buccino, Gustavo Prack, Sreedhar Saseendran Kumar, Manuel Schröter, Michele Fiscella, Andreas Hierlemann
bioRxiv 2020.09.02.271403; doi: https://doi.org/10.1101/2020.09.02.271403

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