Human Nervous System‐Based Biohybrid Robot‐On‐A‐Chip with Sensing Function for Toxicity Screening

Abstract Biohybrid robots and biohybrid robot‐on‐a‐chip have been developed for drug screening and toxicity screening the complementing animal experiments. A sensing system is needed to evaluate the response to external stimulation, but until now, only the human motor system‐based biohybrid robot‐on‐a‐chip with neuromuscular system has been developed without a sensing system. A human nervous system‐based biohybrid robot‐on‐a‐chip with eye function as a sensing system in addition to brain/motor neuron/muscle functions is proposed for the first time. Eye assembloid is fabricated by a combination of thalamic organoid covered with Au nanomesh and four retinal organoids. By a combination of eye assembloid, cerebral organoid, motor neuron spheroid, and muscle bundle on polymer substrate, a human nervous system‐based biohybrid robot‐on‐a‐chip is made. When blue light is used to cause retinal damage or a hydroxychloroquine (HCQ), a retinal toxic chemical, is applied to the eye assembloid, they caused a decrease in muscle bundle contraction. These results indicated that electrophysiological signals generated by the eye assembloid are transmitted to the muscle bundle through cerebral organoid and motor neuron spheroids, and thus the proposed system can perform the toxicity screening. Human nervous system‐based biohybrid robot‐on‐a‐chip can be applied to drug screening of neurodegenerative diseases and toxicity screening for the complement of animal experiments in the future.