| dc.description.abstract | Neurological disorders affect millions of people worldwide every day. These disorders range from issues affecting mental health, like depression to degenerative diseases such as Alzheimer's and Parkinson's disease. The neurotransmitters dopamine and nitric oxide are of particular interest. Incorrect regulation of dopamine has been implicated in disorders such as depression, obsessive compulsive disorder, and attention deficit disorder as well as neurological degenerative diseases such as Parkinson's and Alzheimer's. Nitric oxide (NO) has been shown to affect sexual behavior and aggression in rats. NO has been identified as not just a neurotransmitter but also a neuromodulator and is associated with oxidative stress resulting in neurodegeneration. This small gaseous molecule has a short physiological half-life, so nitrite is commonly used for the indirect detection of nitric oxide. In order to study neurological disorders methods often reduce or eliminate the in vivo concentrations of a compound of interest in order to determine its behavioral effect. However, dopamine and NO have complex metabolic pathways and functions, so the resulting behavior may be due to a series of chemical changes in the brain. In order to fully understand how these two neurotransmitters affect behavior both the in vivo concentration of multiple analytes and behavior need to be monitored simultaneously. In this thesis, the development of a small and simple microchip electrophoresis device that can be used as a component of a portable analysis system, which is capable of functioning on an awake and freely moving animal, is described. The development of low cost polymer microchip electrophoresis (ME) devices capable of interfacing with microdialysis (MD) sampling with electrochemical (EC) detection for the determination of dopamine and nitrite is described. Different fabrication processes were evaluated and optimized to create low cost polymer microchips. A polydimethylsiloxane (PDMS)/glass hybrid microchip capable of interfacing with the hydrodynamic flow from an on-line microdialysis probe was developed with an integrated carbon electrode for EC detection and used for the detection of nitrite. This microchip failed to inject sample into the separation channel when the conductivities of the sample and the BGE were significantly different. In order to understand the injection failure a finite element modeling program, COMSOL, was employed to simulate the sample injection method used for the PDMS/glass hybrid microchip. Also, a new microchip electrophoresis device, called a bow microchip, capable of injecting high conductivity samples while using a low conductivity BGE for electrophoretic separation was modeled. That bow microchip was then evaluated experimentally and made possible the injection of a plug of artificial cerebral spinal fluid into a separation channel containing low conductivity BGE. In addition to the microchip fabrication and optimization, a graphite/polymethylmethacrylate (PMMA) composite electrode was developed and optimized. This electrode was integrated into a polymer substrate for EC detection and evaluated by both flowinjection analysis and microchip electrophoresis. Future directions include the further optimization of the bow microchip design to simplify the operation and increase the functionality of the microchip. Also, the addition of ionic liquids, which may increase the electron transfer rate, to the graphite/PMMA composite electrode (GPCE) and the use of electrode arrays, which should increase the signal without significantly increasing the background noise, may lower the limits of detection. | |
