Microfabricated Liquid Chromatography System for Analysis of Neurotransmitters

用于分析神经递质的微型液相色谱系统

• 批准号: 8982717
• 负责人: James P Grinias
• 金额: $ 5.24万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-15 至 2017-09-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8982717
• 关键词: Affect; Animal Model; Biological; Biological Assay; Brain; Brain Chemistry; Chemicals; Coupled; Deep Brain Stimulation; Detection; Development; Devices; Electrospray Ionization; Frequencies; Glass; Glutamates; Goals; Injection of therapeutic agent; Liquid Chromatography; Measurement; Measures; Methods; Microdialysis; Microfabrication; Microfluidic Microchips; Modeling; Monitor; Movement Disorders; Nature; Neural Pathways; Neurotransmitters; Parkinson Disease; Parkinsonian Disorders; Patients; Performance; Perfusion; Preparation; Pump; Rattus; Research; Resistance; Resolution; Rodent Model; STN stimulation; Sampling; Signal Transduction; Solvents; Speed; Structure of subthalamic nucleus; Symptoms; System; Systems Analysis; Systems Integration; Techniques; Testing; Therapeutic; Time; Tremor; Work; base; design; gamma-Aminobutyric Acid; improved; in vivo; liquid chromatography mass spectrometry; miniaturize; nanolitre; neurochemistry; neurotransmission; neurotransmitter release; neurotransmitter uptake; particle; platinum electrode; pressure; presynaptic; public health relevance; research study; success; temporal measurement; tool; wasting

 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.