Integrated Electrophysiological and Optical Analysis of Human iPSC-Derived Cardiomyocytes Using Transparent ITO Microelectrode Chip

Cardiotoxicity assessment is a crucial step in the drug development process. With growing interest in alternatives to animal testing, preclinical cardiotoxicity evaluation has become increasingly important. Human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) offer a physiologically relevant <i>in vitro</i> model for this purpose. As a result, electrophysiological analysis platforms using iPSC-CMs have gained attention. However, conventional microelectrode array (MEA) chips rely on metal electrodes, which are costly and optically opaque. This lack of transparency limits detailed morphological observation of the cells. In this study, we employed an MEA chip incorporating transparent and conductive indium tin oxide (ITO) electrodes to simultaneously monitor both morphological changes and field potential (FP) of iPSC-CMs. iPSC-CMs cultured on ITO chips exhibited stable electrophysiological signals reflecting coupled depolarization and repolarization, along with self-organization. Short-term exposure to ion channel blockers did not induce noticeable morphological alterations; however, dose-dependent changes in FPs were observed. In contrast, treatment with cardiotoxic drugs resulted in morphological damage and reduced cell viability, accompanied by progressive alterations in key FP parameters over the treatment period. These findings demonstrate the potential of ITO-based MEA as next-generation cardiotoxicity evaluation platforms capable of real-time monitoring of both drug-induced electrophysiological responses and optical cellular changes.