Abstract In both neuroscience research and clinical practice, measurements predominantly focus either on neurochemical or electrophysiological function within the nervous system. This bifurcated approach limits our comprehensive understanding of the nervous system. Ideally, simultaneously recording both multichannel electrophysiological and neurochemical biomarkers would provide a more complete view of neurological function, paving the way for dynamic, multi-biomarker, closed-loop solutions. Such advancements would address a significant clinical need, for the treatment and of study neurological disorders such as Parkinson’s Disease, depression, and drug abuse. Over the last decade, Dr. Alexander Zestos has developed carbon-based microelectrodes to simultaneously detect multiple neurotransmitters using Fast-Scan Cyclic Voltammetry (FSCV). Additionally, he has integrated this neurochemical sensing technology with electrophysiology techniques, offering a dual-function, multi-channel probe. This represents a critical proof-of-concept, foundational for both advanced research tools and prospective medical device development. Dr. Zestos' preliminary endeavors have yielded innovative carbon coating processes for metal electrodes and carbon fiber multielectrode arrays, both utilized with multichannel potentiostats for enhanced FSCV neurochemical measurements. His techniques have notably showcased the simultaneous measurement of neurotransmitters like dopamine, serotonin, and adenosine in both in vitro and ex vivo settings. Moreover, these carbon-based approaches have demonstrated superior sensitivity compared to traditional methods, presenting a promising direction for future applications. In this two-year STTR, Dr. Zestos is partnering with Spike Neuro to combine his carbon coating techniques with Spike Neuro’s electrophysiology Silicon microelectrodes (SiME) to create a dual-function neurochemistry and electrophysiology microelectrode. This work will also explore recent promising developments with the use of Silicon-Carbide microelectrodes (4H-SiCME) for both neurochemistry and electrophysiology function. 4H- SiCMEs promise to offer a more robust and biocompatible material option compared to existing neurochemistry and electrophysiology electrode materials. The project is structured around two primary aims. Aim 1 will concentrate on refining the carbon deposition process for SiMEs, optimizing contact size, and evaluating longevity and function. Aim 2 efforts will pivot to the development of 4H-SiCMEs, addressing inherent production limitations, evaluating the use of pyrolyzed photoresist glassy carbon contacts, and assessing the utility of the wider water window provided by Silicon-Carbide for enhanced neurochemical detection. Spike Neuro will commercialize one or more designs from this work as a research tool as part of their existing product line while continuing to work with Dr. Zestos toward clinical applications for the development of a multi- biom...