LC/electrochemistry/mass spectrometry in (bio)analytical chemistry, drug metabolism and proteomics

（生物）分析化学、药物代谢和蛋白质组学中的 LC/电化学/质谱

• 批准号: 28402393
• 负责人: Professor Dr. Uwe Karst
• 金额: --
• 依托单位: Institut für Anorganische und Analytische Chemie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2006
• 资助国家: 德国
• 起止时间: 2005-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/28402393?language=en
• 关键词: LC; electrochemistry; mass; spectrometry; bio

This proposal comprises four major aspects, which contain the combination of electrochemistry and mass spectrometry as common denominator: Modification of sample molecules with the goal to achieve improved limits of detection and selectivity in mass spectrometry. Electrochemical protein cleavage with respect to the development of an electrochemical alternative to enzymatic digests. Electrochemical oxidation of Pharmaceuticals with the goal to imitate the metabolic pathways occurring in the body and to accelerate in vitro tests for new drug candidates. Miniaturization of electrochemical cells to allow small-scale conversions in a lab-on-a-chip format. For all four aspects, the proofs of principle have already been performed. The research will be focused on the development of new applications in various fields, including proteomics and pharmaceutical analysis based on the combination of liquid chromatography, electrochemistry and mass spectrometry. The applicant and his collaborators at the University of Groningen (The Netherlands), Prof. Rainer Bischoff and Dr. Andries Bruins, and at the Univeristy of Twente (Enschede, The Netherlands), Dr. Wouter Olthuis/Prof. Dr. Albert van den Berg will work on general chemical aspects of this coupling technique: How do the electrochemical processes occur, how can reactions be enabled, which are not possible under the current conditions and how can the methods be implemented for example for pharmaceutical analysis? To enlarge the range of applications, the working electrode of the electrochemical cell shall be optimized with respect to geometry and material. Materials properties, construction details and fabrication technology are the key aspects in the miniaturization part. In general, the combination of chemical research, materials properties and microfabrication shall lead to strong synergistic effects, which are required to apply the methodology in so diverse fields as (bio)analytical chemistry, proteomics, pharmaceutical analysis, and chromatography. As several industries are interested in rapidly applying the technology to be developed in their enterprises, the project is supported by the industrial partners Organon (Pharmaceuticals Oss, The Netherlands), AstraZeneca (Pharmaceuticals, Mölndal, Sweden), ESA (electrochemistry, Chelmsford, MA, U.S.A), LC Packings (nano-scale chromatography, Amsterdam, The Netherlands), Bruker Daltonics (mass spectrometry, Bremen, Germany), Ionics (mass spectrometry, Concord, ON, Canada), and Micronit (microsystem technology, Enschede, The Netherlands).

这一建议包括四个主要方面，其中包括电化学和质谱学的结合作为公分母：对样品分子进行修饰，以达到提高检测限和质谱学选择性的目的。与发展一种电化学替代酶消化的蛋白质有关的电化学蛋白质切割。药物的电化学氧化，目的是模拟体内发生的代谢途径，并加速新药候选的体外试验。电化学电池的小型化，允许以芯片实验室的形式进行小规模转换。对于这四个方面，都已经进行了原则性的论证。这项研究将集中在不同领域的新应用的开发，包括蛋白质组学和基于液相色谱、电化学和质谱学相结合的药物分析。申请人及其在格罗宁根大学(荷兰)的合作者Rainer Bischoff教授和Andries Bruins博士，以及在特温特大学(荷兰恩斯赫德)的Wter Oltheis博士/Albert van den Berg教授将致力于这种耦合技术的一般化学方面的工作：如何发生电化学过程，如何实现在当前条件下不可能发生的反应，以及如何实施这些方法，例如用于药物分析？为了扩大应用范围，电化学电池的工作电极应从几何和材料方面进行优化。材料性能、构造细节和制造工艺是小型化部分的关键环节。一般来说，化学研究、材料性能和微制造的结合将产生强大的协同效应，这是将该方法应用于(生物)分析化学、蛋白质组学、药物分析和层析等不同领域所必需的。由于有几个行业对在其企业中快速应用将开发的技术感兴趣，该项目得到了以下工业合作伙伴的支持：Organon(PharmPharmticals Oss，荷兰)、AstraZeneca(PharmPharmticals，Mölndal，瑞典)、ESA(电化学，切姆斯福德，马萨诸塞州，美国)、LC填充(纳米级层析，荷兰阿姆斯特丹)、Bruker Daltonics(质谱学，不来梅，德国)、Ionics(质谱学，康科德，加拿大)和Micronit(微系统技术，恩斯赫德，荷兰)。