A laser-induced graphene neural probe for multiplexed multimodal readout via site-selective functionalization

Abstract

Simultaneous monitoring of multiple neurochemicals in the brain is critical for elucidating complex neuronal processes, yet it remains technically challenging because of limited spatial selectivity, device complexity, and signal cross-interference. Existing multiplexed neurochemical probes often depend on physically separated sensors or intricate microfluidic architectures, which constrain spatial resolution, scalability, and practical integration for in vivo applications. Here, we present a flexible neural probe based on laser-induced graphene (LIG) that enables multiplexed, multimodal readout within a compact, scalable platform. Using a site-selective, sequential enzyme functionalization strategy, we created independent sensing interfaces for glucose, lactate, and dopamine on closely spaced electrodes while minimizing cross-contamination and interference between adjacent channels. The fabricated probe exhibited selective, concentration-dependent electrochemical responses in vitro and successfully detected stimulus-dependent dopamine release in neuronal cell models. In vivo experiments further demonstrated stable sensing performance after implantation, enabling real-time, multiplexed monitoring of neurochemical dynamics in the mouse medial prefrontal cortex. In addition, the probe supported simultaneous recording of neurochemical signals and electrophysiological activity, highlighting its potential for multimodal neural interfacing in vivo. Collectively, this work establishes a practical and scalable approach to high-density multiplexed neurochemical sensing and provides a versatile platform for investigating dynamic neurochemical signaling and its relationship to brain function.