Erlandsdotter, L.-M. | Search bioRxiv

bioRxiv2026

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.

neuroscience↗

bioRxiv2026

Electrophysiological profiling of hiPSC-derived neurospheres using a novel NeuroMPS with integrated electrodes

Despite advances in microphysiological systems, in vitro platforms for neuronal models remain limited by insufficient electrophysiological resolution, poor structural compatibility with 3D tissue architecture, and an inability to capture functional network dynamics alongside morphological and metabolic readouts. Here, we develop a neuromicrophysiological system (NeuroMPS) that pairs human iPSC-derived neurospheres, comprising neurons and glial cells, with tailored microelectrode arrays (MEAs) for non-invasive, high-resolution monitoring of neuronal network dynamics and functional maturation in vitro. The NeuroMPS combines a custom MEA with capped electrodes optimized for neurite-level signal detection and a glass microwell module that provides structural confinement and optical compatibility for imaging. Importantly, this configuration enables stable, longitudinal electrophysiological recordings from 3D neural constructs while supporting multimodal analyses. Following exposure to pharmacological modulators (PTX, TTX, bicuculline, CNQX, and 4-AP) and the neurotoxin rotenone, NeuroMPS detects alterations in network activity within minutes, even at the lowest concentrations tested, whereas morphological and metabolic changes emerge only at higher doses and later time points. This work provides a physiologically relevant, scalable, non-invasive platform that integrates high-sensitivity electrophysiological readouts with morphological and metabolic profiling to enable early prediction of compound-induced effects in human iPSC-derived 3D neural networks, with applications in neuropharmacology, neurotoxicology, and disease modeling.

bioengineering↗