IDBR: Development of an Advanced Quadrupole Ion Trap Mass Spectrometer for Proteomics

这个奖项是为了开发一个改进的四极杆离子阱质谱仪的蛋白质组学的开始研究。 一种新的电动力学方法将被用于在四极离子阱（QIT）中碎裂生物离子。 与传统方法相比，这种新方法具有四个潜在优势：1）每秒获得比商业仪器更多串联质谱的能力，因此当与自下而上分离系统结合时，能够实现更完整的蛋白质组覆盖; 2）探测更高能量片段化途径的能力，这将提供与传统方法互补的序列覆盖; 3）重新捕获和质量分析低质量产物离子的能力，这对于测序肽和进行定量蛋白质组学非常有益; 4）增加可以在QIT中片段化的前体离子的大小的能力，从而将能力扩展到自上而下的蛋白质组学。新仪器将利用一种称为动态碰撞诱导解离（DCID）的碰撞激活方法，从而可以在质量采集扫描期间选择性地将前体离子碎片化。这项工作的大部分将涉及软件开发，以便在完成DCID所需的非传统方法中运行离子阱。还将编写程序来执行能够以自动化方式检查或优化不同实验参数的影响的序列循环实验。为了帮助简化这一发展到未来的仪器的实施，相当大的努力将放在确定一套或几套最佳的实验参数，将普遍适用于广泛的前体离子。由于这种新的碎裂方法的应用不需要任何硬件修改，通过这项工作所取得的进展将很容易实现到现有的或新的四极或线性离子阱，因此可以立即在各种生物应用中使用。质谱是蛋白质组学的核心技术。 蛋白质组学是对蛋白质的大规模研究，对了解生物体至关重要。 除了这项科学效益外，该奖项还将具有宝贵的教育效益。 本科生和研究生将学习第一手的仪器开发和生物研究中使用的各种质谱法。该奖学金将在暑期资助两名女研究生和两名本科生。学生将学习与仪器仪表开发相关的技术和工程技能，这些技能在仪器仪表行业中并不常见且备受追捧。

This award is to a beginning investigator for developing an improved quadrupole ion trap mass spectrometer for proteomics. A new electrodynamic approach will be used for fragmenting biological ions in quadrupole ion traps (QIT). This new approach has four potential advantages over conventional methods: 1) the ability to acquire more tandem mass spectra per second than commercial instruments, thus enabling more complete proteome coverage when combined with bottom-up separation systems; 2) the ability to probe higher energy fragmentation pathways, which will offer complementary sequence coverage to conventional methods; 3) the ability to recapture and mass-analyze low mass product ions, which is highly beneficial for sequencing peptides and performing quantitative proteomics; 4) the ability to increase the size of precursor ions that can be fragmented in QITs, thereby expanding capabilities to top-down proteomics. The new instrument will utilize a method of collisional activation, called dynamic collision-induced dissociation (DCID), whereby precursor ions can be selectively fragmented during the mass acquisition scan. The majority of this work will involve software development in order to run an ion trap in the non-conventional method required to accomplish DCID. Programs will also be written to perform sequence-looped experiments that are capable of examining or optimizing the influence of different experimental parameters in an automated manner. To help streamline the implementation of this development into future instruments, considerable effort will be placed on determining a set or sets of optimal experimental parameters that will be universally applicable to a wide range of precursor ions. Because the application of this novel fragmentation method does not require any hardware modifications, developments made through this work will be readily available for implementation into existing or new quadrupole or linear ion traps, and could therefore find immediate use in diverse biological applications. Mass spectrometry is a central technology for proteomics. Proteomics, the large-scale study of proteins, is vital to understanding organisms. In addition to this scientific benefit, the award will have valuable educational benefits. Undergraduate and graduate students will learn first-hand about instrumentation development and the various methods of mass spectrometry that are used in biological research. The award will support two female graduate students and also undergraduate students during the summer quarters. Students will learn technical and engineering skills related to instrumentation development that are uncommon and highly sought-after in the instrumentation industry.