A method for three-dimensional single-cell chronic electrophysiology from developing brain organoids

Human induced pluripotent stem cell-derived brain organoids have shown great potential for studies of human brain development and neurological disorders. However, quantifying the evolution and development of electrical functions in brain organoids is currently limited by measurement techniques that cannot provide long-term stable three-dimensional (3D) bioelectrical interfaces with brain organoids during development. Here, we report a cyborg brain organoid platform, in which 2D progenitor or stem cell sheets can fold “tissue-like” stretchable mesh nanoelectronics through organogenesis, distributing stretchable electrode arrays across 3D organoids. The tissue-wide integrated stretchable electrode arrays show no interruption to neuronal differentiation, adapt to the volume and morphological changes during organogenesis, and provide long-term stable electrical contacts with neurons within brain organoids during development. The seamless and non-invasive coupling of electrodes to neurons enables a 6-month continuous recording of the same brain organoids and captures the emergence of single-cell action potentials from early-stage brain organoid development.