Elastic Thermoplastic Polyurethane/Graphene Microneedle-Mesh Interfaces via Microfluidic Patterning for Electrophysiology in Neural Organoids.

Abstract

Connecting electronics to the brain and neural organoids is critical for establishing machine-human interfaces, exploring complex mechanisms of the nervous system, and developing theranostic approaches. However, electrophysiological monitoring of these three-dimensional (3D) nervous tissues remains challenging due to their highly irregular surfaces, which severely limit electrode-tissue contact. Here, we present a stretchable mesh electrode array integrated with elastic graphene microneedles for interfacing with human neural organoids and their assemblies. The device is fabricated via microfluidic patterning technology, enabling low-cost and reproducible production. Graphene microneedles (50-100 μm in height) seamlessly interconnected with liquid metal-polymer conductor (MPC) interconnects within the stretchable mesh architecture. Graphene microneedles and MPC interconnects retain structural integrity under 200% strain. This configuration enhances multisite electrode-tissue contact, enabling recordings of spontaneous and stimulus-evoked electrophysiological activity. Over 60% of channels were activated, surpassing the performance of commercial planar electrodes. This biocompatible interface overcomes the mechanical mismatch between flexible electronics and the surface irregularities of neural organoids, providing an avenue for investigating emergent neural network behaviors in 3D models.