Bridging the Gap: Integrated High-Density Microelectrode Arrays for Cellular, Organoid, and Clinical Electrophysiology

High-density microelectrode arrays (HDMEAs) have become increasingly important tools in neuroscience and biomedical engineering because of their high spatial and temporal resolution for recording and modulating electrical activity across diverse biological systems. Initially developed for in vitro studies of cultured cells, HDMEAs are now being applied to increasingly complex models, including organoids, animal systems, and even human neural systems. These advancements enable a deeper investigation of cellular interactions, network dynamics, and disease mechanisms, as well as providing novel therapeutic and diagnostic tools for neurological disorders. This review explores the evolution of HDMEAs, emphasizing recent innovations in their design, fabrication, and functionalization. We discuss their applications across cellular models, organoid systems, animal studies, and human electrophysiology, and highlight current challenges such as biocompatibility, long-term stability, scalability, and translational deployment. Finally, we outline future directions for advancing HDMEA technologies in both research and clinical settings.