Collaborative Research: A multiplexed microbiosensing platform for understanding real time neurotransmitter dynamics in the brain

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Neurotransmitters (NTs) are responsible for biological and physiological functions controlling mood, memory, behavior and coordination in the brain. Understanding NT dynamics is essential to understanding brain function but the means by which specific neurotransmitters achieve their behavioral effects is still largely unknown and requires accurate, real-time quantification in brain structures. To meet this challenge, in this project funded by the CBET, Biosensing program of the CMMI division, a collaborative team of biosensing experts, computer engineers and neurophysiologists at Clarkson University and the White River Junction VA Medical center are developing novel electrochemical enzyme biosensors that can measure multiple NTs with increased accuracy with little or no false detection. The biosensors will be integrated with statistical and machine learning methods and will be used to study the neurochemical environment in a rat model of Parkinson’s Disease. The research will enhance education and training of life sciences and engineering students at Clarkson University who will work synergistically with the team of investigators to develop next generation biosensing technologies for monitoring neurotransmission in the brain. The project will develop biosensing devices that incorporate NT-specific materials and electrode surfaces for in vivo monitoring of neuronal activity. The research team will engineer an oxygen-rich nanoarchitecture containing an enzyme-like biomimetic catalyst and NT-specific enzymes, stabilized within a conductive network and develop automatic fabrication procedures to ensure scalable and reproducible manufacturing of these biosensors. These materials will be designed to ensure long-term bioactivity and operability for recognition of specific NTs and are expected to improve our ability to study the complex neural mechanisms involved in signaling in the brain. Research will involve the following tasks: 1) develop selective NT-specific nanostructures with high durability and sensitivity for enzyme-based microbiosensors that can measure dopamine, glutamate and acetylcholine, 2) computational work to produce predictive fingerprint models of NT dynamics using electrochemical data, and 3) in vivo work to determine the temporal profile of changes in NT concentrations during high frequency stimulation in normal and ‘hemi-parkinsonian’ animals. Educational activities will involve 1) student participation in research and dissemination through presentations and publications, 2) hands on education though implementation of a biosensing module in the new interdisciplinary Biomedical Engineering and Biomedical Science and Technology degree programs at Clarkson, 3) sites and virtual visits and demonstrations of neuromonitoring and neurostimulation experiments in live animals at Dartmouth College. The broader impacts of this work include potential societal benefit from the discovery of new NT-specific materials and the development of novel biosensing tolls that could be used broadly by the biomedical community for studying neurochemical changes in the brain, as well as the education and training of students who will be uniquely trained to tackle grand challenges in neuroscience and device engineering.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.