INTEGRATING LCEC/LCM:SINGLE METABOLOMICS PLATFORM (RMI)

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，连接的EC-MS将允许更好地解释代谢组，这得到了我们的初步研究的支持，这些研究表明，并行EC-阵列和MS大大扩展了LC分析的范围、定性和定量能力。此外，系列EC可以帮助和控制MS电离和模拟生物氧化还原反应。EC的规模从合成到高通量，电极和电子控制的纳米和纳米格式和变体允许针对特定应用进行优化。其具体目标是：1.集成现有的EC和MS技术，以适合于几个LC-MS系统的串联和并行配置的模块化使用。这种联用的代谢组学方法将用特征良好的多变量方法进行评估，作为性能基准。2.开发创新的EC传感器和反应堆、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.确定已开发的EC和MS技术的特征，并实施代谢物结构分析的新策略，并开发供我们的合作者使用的共享定性信息知识库。4.利用大鼠异种生物毒性模型和广泛使用的线虫生物模型，表征与多变量分析、生物分辨和生物标志物发现相关的技术。5.将技术转让给拥有主动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，以便向代谢组学研究社区广泛传播。

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.