INTEGRATING LCEC/LCM IN A SINGLE METABOLOMICS PLATFORM

描述（由申请人提供）：我们的广泛目标是扩展和整合电化学（EC）和MS技术，以促进一系列代谢组学研究。我们的假设是，联用EC-MS将允许更大程度地阐明代谢物组，这得到了我们的初步研究的支持，这些研究表明，平行的EC-Array和MS大大扩展了LC分析的范围、定性和定量能力。此外，串联EC可以辅助和控制MS电离并模拟生物氧化还原反应。EC从合成到高通量和纳米级格式的缩放以及电极和电子控制的变体允许针对特定应用进行优化。具体目标是：1.集成现有的EC和MS技术，以模块化方式用于串联和并联配置，适用于多个LC-MS系统。代谢组学的这种联用方法将用表征良好的多变量方法进行评估，以作为性能基准。2.开发创新的EC传感器和反应器，软件和检测模式，以大大扩展EC和MS的范围，吞吐量，定量和定性能力。3.表征已开发的EC和MS技术，并实施代谢物结构解析的新策略，并开发供我们的合作者使用的定性信息的共享知识库。4.使用大鼠异生物质毒性模型和广泛使用的生物模型C，表征技术与多变量分析、生物解析和生物标志物发现的相关性。优雅。5.将技术转移到具有活性代谢组学项目的实验室，以帮助建立正式开发的规范。6.实施生产的技术，广泛传播到代谢组学研究界。

DESCRIPTION (provided by applicant): Our broad objective is to extend and integrate electrochemical (EC) and MS technologies to facilitate a range of metabolomics studies. Our hypothesis is that hyphenated EC-MS will allow for greater elucidation of the metabolome is supported by our preliminary studies, which show that parallel EC-Array and MS substantially extends the scope, qualitative and quantitative capabilities of LC analysis. Additionally, serial EC can assist and control MS ionization and mimic biological redox reactions. Scaling of EC from synthetic to high through put and nanoscale formats and variants of electrode and electronic control allow optimization for specific applications. The specific aims are to: 1. Integrate existing EC and MS technologies for modular use in serial and parallel configurations adaptable to several LC-MS systems. This hyphenated approach for metabolomics will be evaluated with well-characterized multivariate methods to serve as a performance benchmark. 2. Develop innovative EC sensors and reactors, software and detection modalities to substantially extend the range, throughput, quantitative, and qualitative capabilities of both EC and MS as compared to the benchmark. 3. Characterize the developed EC and MS technologies and implement novel strategies for structural elucidation of metabolites and develop a shared knowledge base of qualitative information for use by our collaborators. 4. Characterize technology relevance to multivariate analysis, biological resolution and biomarker discovery using models of xenobiotic toxicity in rats and the widely used biological model C. Elegans. 5. Transfer technology to laboratories with active metabolomics programs to help establish specifications for formal development. 6. Implement production of the technology for wide dissemination to the metabolomics research community.