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

本方案包括四个主要方面，其中以电化学和质谱法的结合为共同点：对样品分子进行修饰，以提高质谱法的检测极限和选择性。电化学蛋白质切割与电化学替代酶解的发展。药物的电化学氧化，目的是模仿体内发生的代谢途径，并加速新的候选药物的体外试验。微型化的电化学电池，允许在芯片上的实验室格式的小规模转换。对于这四个方面，已经进行了原理证明。研究将集中在各个领域的新应用开发，包括蛋白质组学和基于液相色谱，电化学和质谱相结合的药物分析。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schede）的合作者Wouter Olthuis博士/教授。Albert van den Berg博士将研究这种耦合技术的一般化学方面：电化学过程是如何发生的，反应是如何实现的，在当前条件下是不可能的，这些方法是如何实施的，例如药物分析？为了扩大应用范围，电化学电池的工作电极应在几何形状和材料方面进行优化。材料性能、结构细节和制造技术是微型化部分的关键。一般来说，化学研究、材料特性和微加工的结合将产生强大的协同效应，这需要将该方法应用于（生物）分析化学、蛋白质组学、药物分析和色谱等多个领域。由于一些行业有兴趣在其企业中快速应用该技术，因此该项目得到了工业合作伙伴Organon（荷兰奥斯制药公司），阿斯利康（制药公司，Mölndal，瑞典），ESA（电化学，切姆斯福德，马萨诸塞州，美国），LC Packings（纳米级色谱，荷兰阿姆斯特丹），Bruker Daltonics（质谱，不莱梅，德国），Ionics（质谱，康科德，加拿大），Micronit（微系统技术，恩斯赫德，荷兰）。

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).