3D Spatiotemporal Activation Mapping of Cardiac Organoids Using Conformal Shell Microelectrode Arrays (MEAs).

Cardiac organoids have emerged as transformative models for investigating cardiogenesis and cardiac diseases. While traditional 2D microelectrode arrays (MEAs) have been used to assess the functionality of cardiac organoids, they are limited to electrophysiological measurements from a single plane and do not capture the 3D propagation of electrical signals. Here, we present a programmable, shape-adaptive shell MEA designed to map the electrical activity across the entire surface of cardiac organoids. These shell MEAs are fabricated on-chip, with tunable dimensions and electrode layout, enabling precise encapsulation of spherical organoids. Using shell MEAs, we generated 3D isochrone maps with conduction velocity vectors, revealing the speed and trajectory of electrical signal propagation in spontaneously beating cardiac organoids. The optical transparency of the shell MEAs allowed for simultaneous calcium imaging, validating the electrophysiological propagation pattern. To demonstrate their utility in cardiotoxicity screening, we monitored the electrophysiological changes of organoids treated with isoproterenol and E-4031 over nine days. We anticipate that shell MEAs, combined with spatiotemporal mapping, can significantly advance the development of spatially organized cardiac organoids, structural disease models, and high-throughput drug screening platforms.