Long-term in vitro recording of cardiac action potentials on microelectrode arrays for chronic cardiotoxicity assessment

Abstract

The reliable identification of chronic cardiotoxic effects in in vitro screenings is fundamental for filtering out toxic molecular entities before in vivo animal experimentation and clinical trials. Present techniques such as patch-clamp, voltage indicators, and standard microelectrode arrays do not offer at the same time high sensitivity for measuring transmembrane ion currents and low-invasiveness for monitoring cells over long time. Here, we show that optoporation applied to microelectrode arrays enables measuring action potentials from human-derived cardiac syncytia for more than 1 continuous month and provides reliable data on chronic cardiotoxic effects caused by known compounds such as pentamidine. The technique has high potential for detecting chronic cardiotoxicity in the early phases of drug development.

CardioMEA: Comprehensive Data Analysis Platform for Studying Cardiac Diseases and Drug Responses

“…A combination of human induced pluripotent stem cell (iPSC) and microelectrode array (MEA) technologies has been effectively employed to characterize disease phenotypes and evaluate drug responses in vitro. Measurements of either extracellular field potentials [4][5][6][7] or intracellular-like signals [8][9][10] emanating from iPSC-derived cardiomyocytes (CMs) have been conducted. The use of high-density MEAs (HD-MEAs) offers notable advantages in characterizing the electrophysiology of electrogenic cells and conducting drug tests.…”