Stretchable Mesh Nanoelectronics for 3D 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 of the electrical properties of brain organoids during development is currently limited by the measurement techniques, which cannot provide long-term stable 3D bioelectrical interfaces with developing brain organoids. Here, a cyborg brain organoid platform is reported, in which "tissue-like" stretchable mesh nanoelectronics are designed to match the mechanical properties of brain organoids and to be folded by the organogenetic process of progenitor or stem cells, distributing stretchable electrode arrays across the 3D organoids. The tissue-wide integrated stretchable electrode arrays show no interruption to brain organoid development, adapt to the volume and morphological changes during brain organoid organogenesis, and provide long-term stable electrical contacts with neurons within brain organoids during development. The seamless and noninvasive coupling of electrodes to neurons enables long-term stable, continuous recording and captures the emergence of single-cell action potentials from early-stage brain organoid development.