Jordan Holmes

Date of Award

Fall 2019

Document Type

Open Access Dissertation

Department

Chemistry and Biochemistry

First Advisor

Parastoo Hashemi

Abstract

Electrochemical sensors are beneficial towards the development and advancement of monitoring devices. As this type of technology progresses, so does our ability to create state-of-the-art sensing strategies to probe environmental and biological systems at the source. In the environment, it is essential to monitor particularly harmful contaminants like trace metals in order to better mitigate risk. Additionally, biological molecules are often times challenging to measure because matrices are complex and difficult to probe; Recent advancements in chemical ex vivo and in vivo sensing platforms have offered insight into physiological processes. The brain in particular requires a sophisticated, implantable sensor as biomarkers from the periphery do not reflect brain concentrations. The overarching goal of this dissertation is to develop electrochemical sensing strategies to measure molecules that are chemically elusive in the environment and in the brain using a powerful electrochemical technique called fast-scan cyclic voltammetry (FSCV). FSCV offers selective and sensitive measurements in real-time on an electrode small enough to probe systems without perturbation or eliciting an immune response. While traditionally employed to measure dopamine neurotransmission in vivo, here we expand the scope of FSCV to explore novel analytes and model systems, including those beyond the brain. First, we discuss the significance of on-site, in situ and real-time analysis for trace metal monitoring in dynamic environmental systems. We introduce our approach using ionophore-grafted carbon fiber microelectrodes (CFM) to selectively detect Cu(II) metal ions and characterize the Cu(II)-ionophore grafted CFM interface.

Second, we explore the functionality of human induced pluripotent stem cells derived into serotonin neurons (5-HTNs) in a multifaceted voltammetric and biophysical study, finding that 5-HTNs possess in vivo chemical characteristics. We then investigate the electroactivity of glutamate, a neurotransmitter that is difficult to measure electrochemically, finding that glutamate electropolymerizes forming poly-glutamic acid (PGA) at high potentials and fast scan rates. We characterize the PGA coating and our results suggests that glutamate polymerizes in brain tissue, improving the sensitivity of sensors during in vivo analysis. Finally, we present a sensing strategy for direct, enzyme- free glutamate detection while avoiding polymerization and characterize the analytical performance of the glutamate voltammetric signature. Together, our data showcases the power of FSCV for rapid trace metal monitoring, serotonin detection in 5-HTNs, electropolymerization, and sensing of new and challenging analytes.

Rights

© 2019, Jordan Holmes

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