Monitoring of Electrophysiological Functions in Brain-on-a-Chip and Brain Organoids

Though animal models are still the gold standard for fundamental biological studies and drug evaluation for brain diseases, concerns arise from an apparent lack of reflecting the human genetics and pathophysiology. Recently, human avatars such as brain-on-a-chip and brain organoids which are generated in a 3D manner using multiple types of human-originated cells have risen as alternative testing models. Particularly in monitoring the functional neuronal cells that express action potentials in brain-on-a-chip or brain organoids, various methods of measuring their electrophysiological function have been suggested for the study of brain-related disease. Recent methodologies for analyzing the electrophysiology of different types of cells in brain-on-a-chip and brain organoids are summarized in this review. We first emphasize the inherent features of brain-on-a-chip and brain organoids from the perspective of the cell culture environment and accessibility to cells in the deep layer. The applicable monitoring techniques are then overviewed based on these features. Finally, we discuss the unmet needs for electrophysiology monitoring in advanced human brain avatar models.