As brain organoids become increasingly important for studying neurological diseases and evaluating potential therapeutics, researchers are looking for ways to capture the most accurate picture of neural function. One challenge remains: many traditional recording techniques only measure activity at the surface of an organoid.
Three-dimensional brain organoids contain thousands of interconnected neurons that form complex networks throughout the entire tissue. While surface recordings can detect activity from cells closest to the exterior, they may miss important signaling occurring deeper within the organoid. This can result in an incomplete understanding of neural circuit development, network synchronization, and disease-related phenotypes.
Surface-based microelectrode arrays (MEAs) have become a common tool for measuring electrophysiological activity in organoids. These systems provide valuable information about spontaneous firing and network behavior at the tissue interface. However, because electrodes remain on the surface, recordings are largely limited to neurons in direct contact with the array. As organoids mature and increase in size, deeper neuronal populations become even less accessible.
This limitation is particularly important when studying diseases that affect neural circuits rather than individual cells. Disorders such as epilepsy, autism spectrum disorder, Tourette syndrome, schizophrenia, and Parkinson's disease involve changes in communication across neuronal networks. Understanding these changes requires measuring activity throughout the three-dimensional structure—not just at its outer layer.
Capturing electrophysiological signals from inside intact organoids provides a more comprehensive view of neural activity. Recording from multiple depths allows researchers to investigate how signals propagate through tissue, identify region-specific activity, and evaluate functional connectivity between neuronal populations. These insights can improve disease modeling, therapeutic screening, and confidence in experimental results.
The SomaFocus™ platform was developed to enable electrophysiological recordings from within intact brain organoids. Using automated probe insertion, the platform measures neuronal spiking and local field potentials from deep inside the tissue without requiring slicing, dissociation, or extensive sample preparation. By preserving the organoid's native three-dimensional architecture, researchers can obtain functional data that more accurately reflects physiological network behavior.
As brain organoids continue to advance as models for neuroscience research and drug discovery, obtaining meaningful functional readouts is becoming just as important as measuring gene expression or cellular composition. Looking beyond the surface allows researchers to better understand how neural circuits develop, communicate, and respond to disease or treatment.
Whether validating a disease model or evaluating a potential therapeutic, measuring neural activity throughout the entire organoid can provide a more complete picture of brain function. As the field moves toward increasingly sophisticated in vitro models, technologies capable of recording deep within intact organoids will play an essential role in unlocking their full potential.