Commercialization of Enzyme Modified Carbon-Fiber Electrodes Paired with Voltammetry for Simultaneous Real-Time Monitoring of Electroactive and Non-Electroactive Species at Discrete Brain Locations

ABSTRACT Commercially available biosensors are designed to measure only one molecule at a time at a given recording site. This is a problem because chemical signals in the brain do not work in isolation; rather, neurotransmission involves many chemical species simultaneously released and little is known about how specific neurochemicals fluctuate relative to one another. Understanding these relationships is critical to the development of drugs and treatments for a wide range of neurological disorders. The Sombers Lab has established the feasibility of using fast-scan cyclic voltammetry (FSCV) and carbon-fiber microelectrodes for the simultaneous detection of rapid dopamine fluctuations and those of non-electroactive species, such as glucose, at the same recording site. This is done with higher spatial and temporal resolution than currently available methods. The goal of this Lab to Marketplace: Tools for Brain and Behavioral Research SBIR is to translate and commercialize the technology developed by the Sombers team at North Carolina State University. The first goal is to transfer the core technology for the co-detection of dopamine and glucose from the Sombers laboratory to Pinnacle Technology, a company that has developed, manufactured and sold biosensors and electrochemical measurement systems worldwide. Pinnacle-produced sensors will be fully characterized and detailed specifications for the technology (sensitivity, linear range, shelf-life and benchmarks for in vivo performance) will be outlined. The second goal is to develop training tools and software to minimize the learning curve associated with the proper implementation, characterization and analysis of FSCV in research or pre-clinical applications. This will be accomplished by modifying existing Pinnacle software to create an intuitive platform for acquisition and analysis of voltammetry data using the commercial probes. Finally, high production value training videos will be created and made freely available on the Pinnacle website. These will detail experimental procedures for all aspects of in vivo voltammetry including probe calibration, surgical procedures, and data acquisition and analysis protocols. Overall, this project is innovative, because it departs from the status quo by utilizing the redox activity inherent to enzymatically generated H2O2 to identify targeted non-electroactive species, even in the presence of electroactive molecules that are typically excluded as interferents. It is significant, because it combines two state-of-the-art and well-characterized technologies for neurochemical monitoring in a clever, straightforward, and unprecedented manner to provide the community with an established tool that can be used to study the role of glucose in complex physiological processes ranging from basic endocrine function to motivation. It promises to have a transformative effect on neuroscience by allowing researchers interested in diverse aspects of brain function to better understand how these specific neurochemicals rapidly co-fluctuate in discrete brain locations.NARRATIVE This effort will enable researchers to simultaneously measure multiple chemicals at a precise point in the brain. In any given year, 1 in 4 adults in the United States report some type of mental illness resulting in an economic cost of approximately $318 billion annually to the US economy. While symptoms of mental health disorders are well known, the underlying causes are not, and the probes resulting from this effort will greatly aid the search for understanding and the development of cures.