Collaborative Research: IDBR: Development of a Biofluid Transport, Separation and Molecular Analysis System using Microfluidics and a Miniature Mass Spectrometer

合作研究：IDBR：使用微流体和微型质谱仪开发生物流体传输、分离和分子分析系统

• 批准号: 0852740
• 负责人: Robert Cooks
• 金额: $ 72.5万
• 依托单位: Purdue University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2013-11-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0852740&HistoricalAwards=false
• 关键词: Collaborative; Research; IDBR; Development; Biofluid

Biological systems respond to environmental stresses and chemical agents by producing unique biochemical signatures, i.e. biomarkers, that - when detected and interpreted correctly - yield enormous insight into the state of the organism. Thus, the central objective of this work is to develop an integrated instrument that detects and identifies biomarkers by acquiring small- volume fluid samples, separating and pre-concentrating the biologically important components in a nanofluidic-microfluidic chip, and then characterizing them using on-line mass spectrometry in a miniature mass spectrometer. In the process, the applicability of molecular identification tools in biological research will be enhanced by significantly decreasing the concentration levels at which specific organic molecules can be detected in complex mixtures. Novel protocols for transferring and ionizing compounds of interest based on high-frequency ac electrospray ionization and desorption electrospray ionization methods will be developed and compared with respect to figures of merit, such as mass transfer efficiency, sensitivity and background interferences. One specific aim is to improve the efficiency of the ionization step, by far the least efficient process in mass spectrometry. Critical performance tests of the analysis system will target biomarkers for oxidative stress using biofluids which mimic cerebrospinal fluid (CSF). The coupling of micro/nano fluidic sample preparation to miniature atmospheric pressure mass spectrometers offers much value to the biological sciences, for example making it possible to realize real-time functional assays of changes in fundamental metabolic, regulatory and signaling processes in response to environmental factors. Fundamental improvements in the performance of mass spectrometers and in microfluidic devices will result from the synergy of this project, making possible future generations of biological instruments of great power and utility. In addition to the direct relevance to biological research, successful instrumentation development will impact medical diagnostics: The same markers relevant to biological oxidation processes are germane to the early detection and prognosis in a host of diseases, including multiple sclerosis, Alzheimer's disease, Niemann-Pick C, amyotrophic lateral sclerosis, heart disease, Parkinson's disease and ischemic stroke, making the results readily translatable to human health studies. Furthermore, the training of highly skilled instrumentation scientists is an emerging national need, and this need will be addressed by formalizing collaboration through (1) research student exchange between Notre Dame and Purdue and (2) larger scale exchanges between Purdue's Center for Analytical Instrumentation Development (CAID) and Notre Dame's Advanced Diagnostics and Therapeutics Initiative. Both institutions aim to (i) train graduate students in instrumentation science (ii) engage in instrumentation development, (iii) facilitate its commercialization, (iv) benefit the regional economy through instrument commercialization. The public can follow these activities at the relevant websites: http://sri.nd.edu/advanced-diagnostics- and-therapeutics/ and www.purdue.edu/dp/caid/.

生物系统通过产生独特的生化特征（即生物标志物）来应对环境压力和化学剂，当正确检测和解释时，可以对生物体的状态产生巨大的见解。因此，这项工作的核心目的是开发一种集成的仪器，该仪器通过获取小体液样品来检测和识别生物标志物，从而在纳米富集 - 微氟芯片中分离和预估算生物学上重要的成分，然后在线质量图中使用它们来表征它们。在此过程中，通过显着降低在复杂混合物中可以检测到的特定有机分子的浓度水平，可以增强分子鉴定工具在生物学研究中的适用性。基于高频AC电喷雾电离和解吸电喷雾电离方法的转移和电离化合物的新颖方案将得到开发，并将其与功绩数字（例如传质效率，灵敏度和背景干扰）相比进行比较。一个具体的目的是提高电离步骤的效率，这是迄今为止质谱中效率最低的过程。分析系统的关键性能测试将使用模仿脑脊液（CSF）的生物流体靶向生物标志物来氧化应激。微/纳米流体样品制备与微型大气压质谱仪的耦合为生物学科学带来了很大的价值，例如，可以实现实时功能性测定，以实现对环境因素响应的基本代谢，调控和信号传导过程的变化。质谱仪和微流体设备的性能的基本改进将是由于该项目的协同作用而产生的，这使得可能的后代具有强大和效用的生物学工具。 In addition to the direct relevance to biological research, successful instrumentation development will impact medical diagnostics: The same markers relevant to biological oxidation processes are germane to the early detection and prognosis in a host of diseases, including multiple sclerosis, Alzheimer's disease, Niemann-Pick C, amyotrophic lateral sclerosis, heart disease, Parkinson's disease and ischemic stroke, making the results readily translatable to human health研究。 此外，对高科技仪器科学家的培训是一种新兴的民族需求，通过（1）通过（1）研​​究学生在巴黎圣母院和普渡大学之间进行正式的协作来解决这一需求，以及（2）Purdue的分析仪器开发中心（CAID）和Notre Dame的高级诊断和治疗方法之间的较大规模交流。这两个机构旨在（i）培训仪器科学培训研究生（II）从事仪器开发，（iii）促进其商业化，（iv）通过仪器商业化使区域经济受益。公众可以在相关网站上遵循这些活动：http：//sri.nd.edu/advanced-diarostics-- and-therapeutics/以及www.purdue.edu/dp/caid/。