Functionalized Multi-Modal Tetrode Arrays for Real-Time, Site-Specific Neurochemical Monitoring

ABSTRACT The goal of this Phase II proposal is to develop and commercialize a multimodal, multianalyte sensor system, including new specialized electronics and software. This suite of tools will enable simultaneous recording of multiple biochemical and electrophysiological signals, specifically targeting analytes such as glutamate, glucose, lactate, choline, and oxygen, alongside fast-scan cyclic voltammetry (FSCV) for biogenic amines and local field potential (LFP) measurements in conscious, freely moving rodents. The proposed functionalized tetrode array and integrated measurement system will facilitate the synchronous monitoring of both chemical and electrical conditions within the rodent brain, providing unprecedented insight into the complex interactions governing brain function. In Phase I, Pinnacle successfully achieved both specific aims: (1) the development and commercialization of single analyte micro-biosensors for lactate and glucose, designed for use in whole brain or brain slices, and (2) the demonstration of targeted deposition of multiple enzymes to specific sites on a tetrode array. Building on these accomplishments, Phase II will expand the catalog with new micro-biosensors for glutamate, D-serine, choline, and oxygen. The novel functionalized tetrode array will allow for the recording of various modalities and analytes at a single brain location, enhancing the spatial and temporal resolution of neurochemical and electrophysiological measurements. An ideal multimodal sensor system should support a diverse range of measurements within a minimal volume, avoid chemical or electrical crosstalk, and maintain the integrity of the local environment, all while enabling long-term, quantifiable measurements of targeted analytes or phenomena. While individual measurement modalities each have inherent limitations, combining them into a single, configurable probe allows researchers to leverage the strengths of each technique, tailoring the system to meet specific experimental needs. The NIH Brain Initiative has emphasized the need for integrated tools that can map circuits and measure fluctuating patterns of electrical and chemical activity within those circuits, ultimately leading to a deeper understanding of mental experiences and behavior. The proposed functionalized tetrode array, along with its associated instrumentation and software, will provide the experimental flexibility necessary to achieve these goals while ensuring consistency in mechanical design, data quality, and overall reproducibility. Moreover, this technology aims to maximize research efficiency and minimize the use of rodents by enabling more comprehensive and robust experiments.