Microfabricated Liquid Chromatography System for Analysis of Neurotransmitters

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 DESCRIPTION (provided by applicant): The proposed research is designed to help understand the underlying neurotransmission that occurs during deep brain stimulation (DBS), a common therapeutic technique used to relieve tremor symptoms in patients suffering from Parkinson's Disease. While the benefits of DBS are well known, the mechanisms of how it occurs are still in debate. It is anticipated that improved techniques for the analysis of neurotransmitters will be able to help uncover changes in brain chemistry that occur during DBS that could then be used to support advances to this therapeutic method that helps reduce the debilitating nature of Parkinson's Disease. This will be achieved through the development of a miniaturized liquid chromatography (LC) analysis system. Current microdialysis techniques used for measuring neurotransmitter uptake and release require probes that limit both the spatial and temporal resolution for such sampling. Miniaturized sample probes are now available that improve spatial resolution, so advances must be made to current analytical techniques (based on separations utilizing LC) in order to also improve temporal resolution. By miniaturizing a LC system through common microfabrication techniques, an entire integrated microfluidic device can be developed to help enhance both the speed and sensitivity of the method. By utilizing recently available superficially porous particles in the separation column, segmented flow techniques for sample droplet manipulation, and integrated electrospray for mass spectrometric detection, a faster and more efficient LC system will be available for biological analyses. Once developed, the miniaturized LC will be used to monitor concentrations of several neurotransmitters (including GABA and glutamate) during DBS stimulation of the subthalamic nucleus in parkinsonian rat models in order to test which neural pathways are most relevant to the therapeutic benefits.