CAREER: Engineering Light Addressable Electrochemical Sensors for Imaging Chemical Neurotransmission

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Chemical signaling between cells is a fundamental component of life. Decades of work have made tremendous gains in understanding how the movement of small molecules called neurotransmitters in the brain influence behavior and disease. However, there are still gaps in our understanding of neurotransmission processes because the analytical tools for studying these processes do not have sufficient resolution. This project will develop tools that will produce chemical images of neurotransmitters around living neurons with high resolution in order to better understand neurotransmission at the sub-cellular level. Semiconductor/metal junctions will serve as sensors for measuring neurotransmitters with high spatial and temporal resolution. The educational plan of this research seeks to address retention of community college transfer students in upper-level chemistry courses. In addition to the scientific developments, this project seeks to provide research opportunities to underrepresented groups, provide community engagement through demonstrations and outreach activities, and provide training to undergraduate and graduate students in technologically relevant areas. Chemical neurotransmission occurs when one neuron releases signaling molecules, called neurotransmitters, into the small gap between itself and an adjacent neuron, called a synapse. Once outside the synapse, neurotransmitters are either taken up by the post-synaptic neuron or diffuse away. Measuring the flux of neurotransmitters around living neurons is critical to increasing our understanding of chemical neurotransmission. Unfortunately, analytical tools to measure these fluxes with both high spatial and temporal resolution are lacking. The objective of this CAREER proposal is to develop light-addressable electrochemical sensors for high spatial and temporal resolution detection of neurotransmitter fluxes excreted from individual living cells in vitro. The two specific aims of this research are to: (1) Improve the detection limits of light-addressable electrochemical sensors by maximizing sensitivity and decreasing background signal, (2) Develop a quantitative imaging platform using light-addressable electrochemical sensors for in vitro imaging of chemical neurotransmission. The research aims will be accomplished by performing careful studies of semiconductor metal junctions using physical and electrochemical methods, finite element modeling of the semiconductor/metal/solution interface, and performing localized electrochemical measurements on semiconductor/metal interfaces. This research makes significant contributions to biosensing, semiconductor photoelectrochemistry, and light-addressable electrochemical sensing. The educational plan will integrate research and teaching by providing a pathway to increase retention of community college transfer students in upper-level coursework. This approach will enable community college transfer students to have access to research experience. Students trained on this project will learn state-of-the-art fabrication, analysis, measurement, and characterization skills that will assist them when they enter the workforce or graduate school.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.