We present an integrated microelectrode array (MEA) platform for high-precision electrophysiological characterization of patient-derived 3D cardiac organoids (COs), enabling dynamic recordings from both healthy and Duchenne muscular dystrophy (DMD) "mini-hearts." A deformable MEA, fabricated by photolithographic patterning of support layers and microelectrodes, is conformally assembled onto a customized scoop-slide well. The concave geometry enables passive self-alignment of millimeter-scale COs within a multichannel electrode array, allowing simultaneous extracellular field potential (EFP) recording and video-based motion analysis. Using COs derived from human induced pluripotent stem cells of healthy donors and a DMD patient, we resolved region-specific EFP waveforms, which were validated by calcium imaging. DMD COs exhibited severe arrhythmic firing and aberrant waveform morphologies, in contrast to the stable, isochronal rhythms of healthy controls. Single-cell transcriptomic analysis revealed a pathological DMD signature marked by excessive extracellular matrix accumulation and disorganized cardiac architecture, contributing to conduction heterogeneity. Pharmacological challenge with the hERG blocker E-4031 prolonged field potential duration in normal COs but triggered disorganized arrhythmogenic storms in DMD COs. By overcoming the limitations of rigid interfaces and ensuring structural preservation with stable impedance coupling, the presented platform provides a robust biointerface for disease phenotyping, drug screening, and mechanistic interrogation of 3D cardiac tissues.
Kim et al. (2026) studied this question.