Nanocrown electrodes for parallel and robust intracellular recording of cardiomyocytes

Zeinab Jahed, Yang Yang, Ching-Ting Tsai, Ethan P. Foster, Allister F. McGuire, Huaxiao Yang, Aofei Liu, Csaba Forro, Zen Yan, Xin Jiang, Ming-Tao Zhao, Wei Zhang, Xiao Li, Thomas Li, Annalisa Pawlosky, Joseph C. Wu and Bianxiao Cui ()
Additional contact information
Zeinab Jahed: Stanford University
Yang Yang: Stanford University
Ching-Ting Tsai: Stanford University
Ethan P. Foster: Stanford University
Allister F. McGuire: Stanford University
Huaxiao Yang: Stanford University
Aofei Liu: Stanford University
Csaba Forro: Stanford University
Zen Yan: LLC
Xin Jiang: LLC
Ming-Tao Zhao: Stanford University
Wei Zhang: Stanford University
Xiao Li: Stanford University
Thomas Li: Stanford University
Annalisa Pawlosky: Google LLC
Joseph C. Wu: Stanford University
Bianxiao Cui: Stanford University

Nature Communications, 2022, vol. 13, issue 1, 1-14

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-29726-2

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