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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

基本信息

批准号：
0852741
负责人：
Paul Bohn
金额：
$ 72.5万
依托单位：
University of Notre Dame
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 2013-05-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=0852741&HistoricalAwards=false
关键词：
Collaborative Research IDBR Development Biofluid

项目摘要

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）来响应环境压力和化学试剂，如果检测和正确解释这些特征，则可以对生物体的状态产生巨大的了解。因此，本工作的中心目标是开发一种集成仪器，通过获取小体积流体样品，在纳米流体-微流体芯片中分离和预浓缩生物重要成分，然后在微型质谱仪中使用在线质谱法对其进行表征，从而检测和识别生物标志物。在此过程中，通过显著降低复杂混合物中特定有机分子的检测浓度水平，分子鉴定工具在生物学研究中的适用性将得到增强。将开发基于高频交流电喷雾电离和解吸电喷雾电离方法的转移和电离感兴趣的化合物的新方案，并在传质效率、灵敏度和本底干扰等优点方面进行比较。一个具体的目标是提高电离步骤的效率，到目前为止，电离步骤是质谱法中效率最低的过程。该分析系统的关键性能测试将使用模拟脑脊液（CSF）的生物流体针对氧化应激的生物标志物。微/纳米流体样品制备与微型大气压质谱的耦合为生物科学提供了很大的价值，例如可以实现对基础代谢，调节和信号过程响应环境因素变化的实时功能分析。质谱仪和微流体装置的性能将从这个项目的协同作用中得到根本性的改进，使未来几代大功率和实用的生物仪器成为可能。除了与生物学研究直接相关外，成功的仪器开发将影响医学诊断：与生物氧化过程相关的相同标记与许多疾病的早期检测和预后密切相关，包括多发性硬化症、阿尔茨海默病、尼曼-匹克C、肌萎缩侧索硬化症、心脏病、帕金森病和缺血性中风，使结果很容易转化为人类健康研究。此外，培养高技能的仪器科学家是一项新兴的国家需求，这一需求将通过正式的合作来解决(1)圣母大学和普渡大学之间的研究学生交换，(2)普渡大学分析仪器开发中心（CAID）和圣母大学高级诊断和治疗计划之间的更大规模交流。这两个机构的目标是：(1)培养仪器科学的研究生；(2)从事仪器开发；(3)促进其商业化；(4)通过仪器商业化使地区经济受益。公众可以在相关网站上关注这些活动：http://sri.nd.edu/advanced-diagnostics- and-therapeutics/和www.purdue.edu/dp/caid/。