Transparent neural interface for in vivo interrogation of human organoids

Recent advances in pluripotent stem cell technology have enabled generation of neuronal cell lines and cerebral organoids from human induced pluripotent stem cells (hiPSCs). These organoids are self-assembled, 3D cellular structures that resemble early developmental stages of the human brain. However, the lack of the natural brain microenvironment in cultured organoids can influence the phenotype and maturation of the reprogrammed neurons. To mitigate this limitation, cerebral organoids are transplanted into the mouse brain where their activity can be monitored using 2-photon imaging through cranial “windows.” Here, we will replace these windows with optically transparent graphene electrode microgrids to enable multimodal longitudinal monitoring and interrogation of neuronal activity in the graft and the surrounding host neuronal circuits. We envision that this technology can helpful for modeling of disease, examination of candidate treatments, and replacement therapy.