IDBR: Development of an Electrostatic Ion Trap Tandem Mass Spectrometer

该奖项支持一种基于静电离子陷阱和使用电子捕获(EC)和真空紫外线(VUV)辐射进行解离的新兴技术的串联质谱学的新方法。与现有的串联质谱仪相比，这有望在许多重要的生物应用中提供关键的优势。电子捕获解离已被证明可以保存许多不稳定的翻译后蛋白质修饰，最近作为常用的碰撞碎裂方法的替代方法而出现。然而，由于与传统的射频离子陷阱不兼容，它的使用目前仅限于昂贵的傅立叶变换离子回旋共振质谱仪。随着最近报道的简单静电离子陷阱的出现，有了一个新的机会，可以使用不那么苛刻的碎裂，如EC或VUV提供的碎裂，作为串联质谱分析的基础。其结果将是一种构造简单且相对便宜的设备，同时可以同时结合电子捕获和激光产生的紫外线辐射来裂解大的生物分子。这项工作本质上是跨学科的，这将促进培训具备应对未来几十年化学和生物科学所面临挑战的理想装备的科学家。对于直接参与的博士后和研究生来说，它将同时为他们提供最先进的质谱学硬件开发方面的深厚专业知识，使他们深入了解离子化学和裂解机制的实际问题，并使他们接触到蛋白质纯化、测序和样品制备的要点。对于本科生来说，它将在设计、建造和演示串联质谱学的新方法方面提供宝贵的实践经验。在所有非历史黑人大学中，韦恩州立大学拥有最多的非裔美国人人口，它有许多外展项目，旨在招募未被充分代表的少数族裔参加科学教育和培训。目前的提案提供了一个极好的机会，可以在本科生和研究生一级利用这些方案，以及在接触底特律社区方面利用这些方案。

This award supports a new approach to tandem mass spectrometry based upon the emerging technology of electrostatic ion traps and use of electron capture (EC) and vacuum ultraviolet (VUV) radiation for dissociation. This is expected to afford key advantages in many important biological applications over existing tandem mass spectrometers. Electron capture dissociation, which has been shown to preserve many labile post-translational protein modifications, has recently emerged as an alternative to commonly used collisional fragmentation methods. However, its use is currently restricted to costly Fourier transform ion cyclotron resonance mass spectrometers owing to incompatibility with conventional RF ion traps. With the advent of simple electrostatic ion traps recently reported, there is a new opportunity for using less harsh fragmentation such as that provided by EC or VUV, as a basis for tandem mass spectrometry. The result will be a device that is simple and relatively inexpensive to construct and at the same time amenable to incorporation of both electron capture and laser generated ultraviolet radiation to fragment large biomolecules. The inherently interdisciplinary nature of this work will promote training of scientists ideally equipped to address the challenges facing the chemical and biological sciences in the coming decades. For the post-doc and graduate students directly involved, it will simultaneously give them deep expertise in the development of state-of-the art mass spectrometry hardware, steep them in the practical issues in ion chemistry and fragmentation mechanisms, and expose them to the essentials of protein purification, sequencing and sample preparation. For the undergraduates, it will provide invaluable hands-on experience in design, construction, and demonstration of a new approach to tandem mass spectrometry. Wayne State University, with the largest African-American population of any nonhistorically Black university, has a number of outreach programs to enlist underrepresented minorities in science education and training. The present proposal provides an excellent opportunity to take advantage of these programs at the undergraduate and graduate levels as well as in outreach to the Detroit community.