Kirigami Electronics for Chronic Electrophysiological Recording of Human Neural Organoids

Neurons transmit information via electrical signals. Recent advancement in neural organoids and assembloid technologies, derived from human stem cells, have offered a promising avenue for modeling aspects of nervous system development. To understand brain development and develop effective disease models, it is crucial to enable long-term, minimally invasive recordings from these three-dimensional systems. 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. 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. This 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 detects disease-related hyperactive phenotype. Furthermore, KiriE is compatible with simultaneous recordings from individual organoids in an assembloid and can capture activity in emerging cortico-striatal circuits. Moving forward, this flexible electronics system holds the potential to unveil disease phenotypes and reveal the activity patterns underlying the assembly of the nervous system.