3D Spatiotemporal Electrophysiology of Cardiac Organoids Using Shell Microelectrode Arrays

Abstract Cardiac organoids have emerged as powerful platforms for modeling human heart development and disease. However, traditional 2D microelectrode arrays (MEAs) are limited to planar recordings and fail to capture the 3D propagation of electrical signals. Here, programmable, shape‐adaptive, organoid‐encapsulating shell MEAs are presented as a technology that enables comprehensive 3D electrophysiological mapping. These on‐chip‐fabricated devices feature customizable geometries and electrode layouts tailored to an organoid's unique morphology. Shell MEAs generate high‐resolution 3D isochrone and conduction velocity maps, unveiling long‐term spatiotemporal field potential dynamics in spontaneously beating organoids. Furthermore, they integrate multiple modalities, such as calcium imaging to corroborate electrophysiological findings and pharmacological screening to assess organoid responses to isoproterenol, E‐4031, and serotonin. This platform represents a significant advance in bioelectronic interfaces, enabling high‐content 3D spatiotemporal functional analysis for cardiac disease modeling and pharmacological testing.