Beyond Structure: Next-Generation Electrophysiological Platforms for Functional Brain Organoids

Brain organoids have emerged as transformative models for studying human neurodevelopment, neurological disorders, and personalized therapeutics. Central to their utility is the ability to monitor neural activity with high spatial and temporal resolution. Traditional electrophysiological tools-such as planar microelectrode arrays and patch-clamp techniques-offer limited access to the three-dimensional and dynamic nature of organoid neural networks. Recent technological advancements have led to the development of next-generation platforms including surface-embedded, flexible, and fully implantable electrodes. Moreover, multifunctional probes incorporating optical, chemical, and mechanical sensing open new avenues for multimodal interrogation of organoid physiology. This review summarizes the current state of electrophysiological technologies applied to brain organoids, highlighting innovations in recording fidelity, spatiotemporal resolution, and device-tissue integration. We also discuss key challenges such as maintaining organoid viability, achieving sufficient electrode density, and enabling non-disruptive, chronic interfacing throughout organoid development. Looking forward, future systems are expected to evolve toward ultra-dense, multimodal, and closed-loop interfaces capable of investigating organoid function throughout extended growth periods. These advances will not only deepen our understanding of brain-like activity in organoids but also support the design of more functionally accurate and translationally relevant neural models.