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

Area of Science:

• Bioengineering
• Neuroscience
• Toxicology

Background:

• Biohybrid robots and robot-on-a-chip systems are used for drug and toxicity screening.
• Existing systems lack integrated sensing capabilities for evaluating responses to external stimuli.
• Previous biohybrid robots were primarily based on the human motor system without sensory feedback.

Purpose of the Study:

• To propose the first human nervous system-based biohybrid robot-on-a-chip incorporating eye function as a sensing system.
• To create a functional model integrating brain, motor neuron, muscle, and eye components.
• To establish a platform for toxicity screening that mimics human nervous system responses.

Main Methods:

• Fabrication of an eye assembloid using a thalamic organoid and retinal organoids.
• Assembly of the biohybrid robot-on-a-chip using the eye assembloid, cerebral organoid, motor neuron spheroid, and muscle bundle on a polymer substrate.
• Evaluation of the system's response to blue light-induced retinal damage and hydroxychloroquine (HCQ) exposure.

Main Results:

• The fabricated eye assembloid successfully integrated with cerebral organoids, motor neurons, and muscle bundles.
• Exposure to blue light or HCQ resulted in a measurable decrease in muscle bundle contraction.
• Electrophysiological signals from the eye assembloid were transmitted through the neural network to affect muscle activity.

Conclusions:

• The developed human nervous system-based biohybrid robot-on-a-chip demonstrates the feasibility of using eye function for toxicity screening.
• The system effectively transmits sensory information through a complex neural network to elicit a physiological response.
• This platform holds potential for drug screening in neurodegenerative diseases and complementing animal-based toxicity assessments.