PROJECT SUMMARY Boron-doped diamond (BDD) is considered to be an ideal candidate for sensing dynamic changes in neurotransmitters and neurophysiological signals, because of its unique combination of electrical conductivity, a broad potential window, a low background baseline, resistance to molecular adsorption, biocompatibility, and chemical inertness. While BDD based electrodes have demonstrated potential for rapid detection of neurotransmitters with high sensitivity, one major challenge of implantable diamond sensors is mechanical property mismatch between rigid diamond (with a Young's modulus of ~1012 Pa) and soft tissues (with a Young's modulus of ~103-105 Pa), which can increase risks of negative neural response, glial scar formation, inflammation, and mechanically induced trauma. To address this critical issue, previously, our team had developed flexible BDD microelectrodes by transferring patterned BDD structures from a solid silicon substrate onto soft polymer substrates. We demonstrated that the hybrid BDD/polymer films have a Young's modulus of over ten times lower than solid BDD, and are capable of sensing dopamine concentrations using fast-scan cyclic voltammetry. Building on our preliminary studies, the goal of this research is to design and develop a fully implantable, mechanically flexible, hybrid diamond-polymer microsensor platform for electrophysiology recording and electrochemical sensing of brain activity with high sensitivity, selectivity, and spatiotemporal resolution. For proof of concept studies, this R21 application will focus on: 1) synthesizing, characterizing, and optimizing thin BDD films with desired electrical properties; 2) revising and optimizing wafer-level microfabrication, pattern transferring, and integration/packaging processes for building the proposed sensors; and 3) evaluating the feasibility of a 16-channel sensor prototype for rapid, real-time recording of neurotransmitters and neurophysiology signals in living animal brains. The proposed project will be carried out by a multidisciplinary team combining investigators from different areas of diamond material synthesis and processing, microelectromechanical system (MEMS) fabrication and packaging, and neurophysiology. The successful completion of this pilot study will pave the way for future development and optimization of a large-scale, high-density, flexible sensor platform for in-situ monitoring electrophysiological and electrochemical signals in various biological models (from rodents to non-human primates) and disease conditions.