A scalable mesh microelectrode array platform for longitudinal electrophysiology in neural spheroids

Electrophysiological interfacing remains difficult in three-dimensional in vitro models, when using planar microelectrode arrays or optical methods. This challenge limits experimental progress using such models, despite their promise of better physiological relevance than monolayer cell culture. Mesh MEAs which can integrate conformally on or even within tissue offer a possible solution but are not yet widely accessible. Here, we present a mesh MEA device, designed as a simple, manufacturable platform for spheroid electrophysiology. In neural spheroids, the device enabled longitudinal electrophysiological recordings and pharmacological modulation of spontaneous electrical activity. On native polyimide meshes, spheroids maintained their shape while cells enveloped the mesh, embedding electrodes to a depth of 100 {micro}m after 2 weeks. In contrast, laminin biofunctionalization of the mesh promoted outgrowth and migration of cells. This device and associated methods should be adaptable to organoids, ex vivo tissue, or bioengineered in vitro models.