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Nanocrown electrodes for parallel and robust intracellular recording of cardiomyocytes.

ABSTRACT: Drug-induced cardiotoxicity arises primarily when a compound alters the electrophysiological properties of cardiomyocytes. Features of intracellular action potentials (iAPs) are powerful biomarkers that predict proarrhythmic risks. In the last decade, a number of vertical nanoelectrodes have been demonstrated to achieve parallel and minimally-invasive iAP recordings. However, the large variability in success rate and signal strength have hindered nanoelectrodes from being broadly adopted for proarrhythmia drug assessment. In this work, we develop vertically-aligned nanocrown electrodes that are mechanically robust and achieve > 99% success rates in obtaining intracellular access through electroporation. We validate the accuracy of nanocrown electrode recordings by simultaneous patch clamp recording from the same cell. Finally, we demonstrate that nanocrown electrodes enable prolonged iAP recording for continual monitoring of the same cells upon the sequential addition of four incremental drug doses. Our technology development provides an advancement towards establishing an iAP screening assay for preclinical evaluation of drug-induced arrhythmogenicity.

SUBMITTER: Jahed Z

PROVIDER: S-EPMC9042818 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Nanocrown electrodes for parallel and robust intracellular recording of cardiomyocytes.

Jahed Zeinab Z Yang Yang Y Tsai Ching-Ting CT Foster Ethan P EP McGuire Allister F AF Yang Huaxiao H Liu Aofei A Forro Csaba C Yan Zen Z Jiang Xin X Zhao Ming-Tao MT Zhang Wei W Li Xiao X Li Thomas T Pawlosky Annalisa A Wu Joseph C JC Cui Bianxiao B

Nature communications 20220426 1

Drug-induced cardiotoxicity arises primarily when a compound alters the electrophysiological properties of cardiomyocytes. Features of intracellular action potentials (iAPs) are powerful biomarkers that predict proarrhythmic risks. In the last decade, a number of vertical nanoelectrodes have been demonstrated to achieve parallel and minimally-invasive iAP recordings. However, the large variability in success rate and signal strength have hindered nanoelectrodes from being broadly adopted for pro ...[more]

PMID: 35474069

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Nanocrown electrodes for parallel and robust intracellular recording of cardiomyocytes.

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Nanocrown electrodes for parallel and robust intracellular recording of cardiomyocytes.

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