Rerick, Michael T
(2021)
Development and Optimization of Analytical Methods to Study Neurochemistry Using Capillary Liquid Chromatography.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
In recent decades, advances in probing the neurochemical environment of the brain have led to a deeper understanding of how behavioral and clinically relevant information is encoded. Regulation of neuronal release and reuptake mechanisms and hydrolysis breakdown influences a broad range of biological processes, and the dysregulation of these mechanisms has been linked to neurological disorders of clinical importance. It is therefore imperative that technology to sample the fragile tissue of the brain and to detect signaling molecules be improved. Efforts to develop minimally invasive approaches with high spatial resolution, temporal resolution, and selectivity lie at the forefront of this research to further our knowledge of the central nervous system. In this work, we investigate methods to improve the temporal resolution and density of information for online measurements of microdialysis coupled high-performance liquid chromatography. Through the incorporation of temperature-assisted solute focusing (TASF), we were able to develop a method for 1-minute simultaneous monitoring of two clinically relevant neurotransmitters, dopamine (DA) and serotonin (5-HT). Microdialysis methods were further investigated using capillary LC-MS/MS methods to validate long-term microdialysis membrane integrity in traumatic brain injury animal models. Lastly, a 3D printable device was developed combining electroosmotic perfusion and microdialysis sampling for a novel approach to neurochemical monitoring. This device is less invasive than traditional microdialysis implantation, and provides more control over tissue residence time than passive diffusion approaches. Finite element models to study fluid flow were also concurrently developed and compared to experimental data to determine the validity of results relative to theory.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
8 October 2021 |
| Date Type: |
Publication |
| Defense Date: |
2 August 2021 |
| Approval Date: |
8 October 2021 |
| Submission Date: |
5 August 2021 |
| Access Restriction: |
1 year -- Restrict access to University of Pittsburgh for a period of 1 year. |
| Number of Pages: |
184 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
Dietrich School of Arts and Sciences > Chemistry |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
High-Performance Liquid Chromatography, Analytical Chemistry, Capillary Chromatography, Bioanalytical, Neuropeptides, Neurotransmitters Electroosmotic Perfusion-Microdialysis, Microdialysis, in vivo, Temperature-Assisted Solute Focusing, TASF, EOP-MD, EOP-EMD |
| Date Deposited: |
08 Oct 2022 05:00 |
| Last Modified: |
08 Oct 2022 05:15 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/41596 |
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