Novel engineering and characterization of sensing materials and fluidic devices for neuroscience
File(s)
Author(s)
Hexter, Melissa
Type
Thesis
Abstract
Many aspects of neurophysiology such as the pathophysiology of neuropsychiatric illness remain unclear due to challenges in non-invasively probing the brain while considering its chemical and physical heterogeneity. Further investigation of the neurochemicals responsible for neuropsychiatric illness, as indicated by the monoamine hypothesis of depression, is therefore limited without addressing these obstacles. The Hashemi lab studies these neurotransmitters and develops translational tools to minimize challenges associated with in vivo analysis while maximizing the predicative power of in vitro models of the brain. The work in this thesis furthers our understanding of the behaviour of carbon fiber micro-electrodes for serotonin measurement and the fluid dynamics of FSCV measurements. This information is critical for the acquisition of physiologically relevant measurements from translational models of neuropsychiatric illness. In this thesis, I begin by reviewing techniques that have been developed to monitor neurotransmitters in Chapter 1. Next, in Chapter 2, I outline the specific methods used to collect measurements with FSCV/FSCAV and to construct the electrodes and fluidic devices characterized in this work. In Chapter 3, I establish a design criterion for the development of fluidic devices for FSCV measurements. I then use this criterion to design a flow cell for FSCV measurements and challenge its reproducibility and stability. This work enabled the validation of the analyte specific decay and variability of CFMEs. Chapter 4 introduced a simple and inexpensive fabrication protocol for a versatile carbon-based electrode with excellent electrochemical kinetics and sensitivity for serotonin measurements with FSCV. After characterizing the performance of this electrode, it was integrated into a simple polydimethylsiloxane (PDMS) based device to provide a preliminary platform for the optimization of measurements from cells using FSCV (Chapter 5). This work identified adhesion, dead space, electrode geometry, and material rigidity as key parameters in the design of a microfluidic device with an incorporated capacity for FSCV measurements. Chapter 6 concludes the thesis and highlights the future implications of the work.
In sum, this work offers novel tools for characterizing sensors for FSCV measurement and a concept for a microfluidic device capable of sensor calibration and measurement from patient-specific in vitro models of the brain. This type of analytical platform would permit the characterization of neurotransmission for preclinical pharmacological screening and/or elucidation of personalized therapies for neuropsychiatric illness.
In sum, this work offers novel tools for characterizing sensors for FSCV measurement and a concept for a microfluidic device capable of sensor calibration and measurement from patient-specific in vitro models of the brain. This type of analytical platform would permit the characterization of neurotransmission for preclinical pharmacological screening and/or elucidation of personalized therapies for neuropsychiatric illness.
Version
Open Access
Date Issued
2023-04
Date Awarded
2023-09
Copyright Statement
Creative Commons Attribution NonCommercial Licence
License URL
Advisor
Hashemi, Parastoo
Publisher Department
Bioengineering
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)