Kirigami Electronics for Long-Term Electrophysiological Recording of Human Neural Organoids and Assembloids

Human stem cell-based organoids and assembloids have emerged as a promising platform to model aspects of nervous system development. Long-term, minimally invasive recordings in these three-dimensional (3D) multi-cellular systems are essential for developing disease models. Current technologies, such as patch clamp, penetrating microelectrodes, planar electrode arrays and substrate-attached flexible electrodes, do not, however, allow chronic recording of neural organoids in suspension, which is necessary to preserve their 3D architecture. Here, inspired by the art of kirigami, we develop flexible electronics that transition from a flat 2D pattern to a 3D basket-like configuration to accommodate the long-term culture of human neural organoids in suspension. We show that this novel platform named kirigami electronics (KiriE) integrates with and enables chronic recording of intact cortical organoids for 170 days while preserving their morphology, cytoarchitecture and cell composition. KiriE can be integrated with optogenetic and pharmacological stimulation and detect a disease-related hyperactive phenotype. Moreover, KiriE is compatible with simultaneous recordings from organoids in assembloid and can capture activity in emerging cortico-striatal circuits. Moving forward, this flexible electronics system could reveal disease phenotypes and the patterns of activity underlying the assembly of the nervous system.