Human brain organoids have become indispensable tools for studying neurological disease, neural development, and drug responses. As these models grow increasingly sophisticated, so does the need for technologies that can accurately measure their functional activity. Electrophysiology remains the gold standard for capturing neuronal communication, but researchers are often faced with an important question: Should I use a surface microelectrode array (MEA) or a penetrating electrode array?
The answer depends on the biological question being asked.
Microelectrode arrays (MEAs) have long been the gold standard for electrophysiological recordings in 2D neuronal cultures. Because neurons grow directly on the electrode surface, MEAs provide reliable measurements of spontaneous activity, network formation, and drug responses. Their success in two-dimensional systems has made them a valuable tool across neuroscience research.
Applying this same technology to 3D brain organoids, however, presents new challenges.
Conventional MEAs record only from neurons that are in direct contact with the electrode surface. Since most neurons within an organoid are embedded deep inside the tissue, researchers often need to modify their experimental workflow to obtain meaningful signals. Common approaches include waiting weeks for neurons to migrate out of the organoid and adhere to the MEA, co-culturing dissociated neurons on the recording surface, or slicing the organoid before placing it on the array.
While these strategies can improve recordings, they also alter the biological model. Neurons that migrate onto the MEA no longer exist within their native three-dimensional environment, and sliced organoids lose the structural organization and long-range connections that make them valuable models of human brain physiology. For researchers interested in understanding intact neural circuitry, these compromises may limit the biological relevance of the data.
Penetrating electrode arrays were developed with a different goal in mind: recording directly from within intact tissue. Rather than relying on neurons to reach the recording surface, fine silicon-based probes are inserted into the organoid, allowing electrical activity to be measured throughout its depth while preserving its three-dimensional architecture.
This approach enables researchers to record both single-neuron spiking and local field potentials from multiple depths, providing a more complete picture of neural network function. Accessing neurons throughout the tissue allows researchers to investigate circuit organization, depth-dependent activity, and functional connectivity in ways that surface recordings alone cannot.
The SomaFocus™ platform was designed specifically for this purpose. By automating electrophysiological recordings from inside intact brain organoids, SomaFocus eliminates the need for slicing, dissociation, or prolonged outgrowth cultures, enabling researchers to study neural function within the organoid's native 3D environment.
As brain organoids continue to play a larger role in disease modeling and drug discovery, the choice of electrophysiology technology should match the biology being studied. While MEAs remain an excellent solution for two-dimensional cultures, penetrating electrode arrays provide the direct access needed to fully understand neural activity inside intact three-dimensional organoids.