INTEGRATING LCEC/LCM IN A SINGLE METABOLOMICS PLATFORM

描述（由申请人提供）：我们的主要目标是扩展和整合电化学（EC）和质谱技术，以促进一系列代谢组学研究。我们的假设是，我们的初步研究支持联用EC-MS将允许更好地阐明代谢组，这表明并行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电离和模拟生物氧化还原反应。缩放EC从合成到高通量放和纳米尺度格式和变体的电极和电子控制允许优化特定的应用。具体目标是：1。集成现有的EC和MS技术，用于模块化使用串行和并行配置，适用于多个LC-MS系统。这种代谢组学的连字符方法将用具有良好特征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，与基准相比，大大扩展EC和MS的范围、吞吐量、定量和定性能力。3. 描述已开发的EC和MS技术，并实施新的代谢物结构解析策略，并开发一个共享的定性信息知识库，供我们的合作者使用。4. 利用大鼠外源毒性模型和广泛使用的秀丽隐杆线虫生物模型，描述与多变量分析、生物分辨率和生物标志物发现相关的技术。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. 实施该技术的生产，以便在代谢组学研究界广泛传播。

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.