# Nervous System-on-Chip: Innovative Microfluidic Platform to Compartmentalize hiPSC-Derived Neural Networks

## TL;DR

This paper introduces a microfluidic platform called Nervous System-on-Chip to grow and study human neural networks in a controlled environment.

## Contribution

The study introduces a novel microfluidic platform using microtunnel devices to compartmentalize and culture human iPSC-derived neural networks.

## Key findings

- Microtunnel devices enable axonal growth while restricting soma and dendrite migration between compartments.
- The platform supports the formation of viable, organized cortical and enteric neural networks.
- The system shows potential for modeling human nervous system biology and studying neurodegenerative diseases.

## Abstract

This study presents the development of a Nervous System-on-Chip (NoC) using microfabrication techniques, focusing on the integration of human induced pluripotent stem cell (hiPSC)-derived neurons. We designed and fabricated NoCs based on microtunnel devices (MDs) with radial and linear configurations to facilitate the compartmentalized culture of cortical and enteric neural networks. Our findings demonstrate that these MDs allow axonal growth while restricting migration of somas and dendrites between compartments, thereby promoting the formation of organized neural networks. This creates a microfluidic platform capable of supporting the growth of different culture systems, which could potentially be combined to study interactions between the central and enteric nervous systems. The resulting neuronal networks exhibited viability, expression of key lineage markers, and synapse formation, highlighting the platform’s potential for advanced nervous system modeling. MD-based NoC models provide an innovative microfluidic platform for studying the biology of human neural networks, with implications for the investigation of neurodegenerative diseases such as Parkinson’s Disease and applications in pre-clinical research.