A Universal Electromagnetostatic Tandem-Mass-Spectrometric Dissociation-Cell for

通用电磁静态串联质谱解离池

• 批准号: 8502711
• 负责人: DOUGLAS F BAROFSKY
• 金额: $ 34万
• 依托单位: OREGON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-10 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8502711
• 关键词: Biomedical Research; Cells; Charge; Clinical Research; Complex; Computer Simulation; Computer software; Data Set; Development; Devices; Dissociation; Electron Transport; Electrons; Exclusion; Frequencies; Gases; High Pressure Liquid Chromatography; Individual; Ions; Magnetism; Maintenance; Mass Spectrum Analysis; Methodology; Optics; Outcome; Output; Peptides; Performance; Phase; Process; Property; Proteins; Proteomics; Radio; Reliance; Research; Scientist; Series; Staging; Structure; System; Technology; Testing; base; computer generated; design; design and construction; electric field; instrument; instrumentation; mass spectrometer; meetings; model design; new technology; novel; operation; particle; protein structure; prototype; public health relevance; research study; two-dimensional

DESCRIPTION (provided by applicant): The broad objective of the proposed project is to pivotally advance the analytical power of tandem mass spectrometers used in biomedical research generally and in proteomics particularly. Performing multiple stages of mass spectrometric analysis in tandem has become indispensable both for unraveling the complex structures of proteins and identifying large numbers of proteins. A tandem mass spectrometer probes incisively into the complexities of a molecule's structure by partially breaking it into fragments. In proteomic applications, this is done by exploiting one of a number of physicochemical processes among which are collision-induced dissociation (CID), infrared multiphoton dissociation (IRMPD), electron capture dissociation (ECD), electron detachment dissociation (EDD), electron transfer dissociation (ETD), and electron impact excitation of ions from organics (EIEIO). These processes take place inside the instrument in a cell whose operation relies strictly on electric forces that rapidly change direction. This reliance on devices that depend solely on electric forces (to the exclusion of magnetic forces) needlessly restricts the design, fabrication, and application of tandem mass spectrometers. The applicants have taken advantage of modern magnetic materials to create an electromagnetostatic (EMS) cell that can be installed in any type of tandem mass spectrometer and used to perform all of the aforementioned dissociation processes. Specifically, the applicants submit that a universal EMS tandem- mass-spectrometric dissociation-cell can be built in which it is possible to conduct CID, IRMPD, ECD, EDD, ETD, and EIEIO individually or in various combinations at analytically practical levels. This hypothesis would be tested by 1) elucidating the action of EMS optics on low-energy electrons and ions of both polarities, and 2) quantifying the analytical utility of EMS charged-particle optics in tandem mass spectrometric analyses of peptides and proteins. To meet these two aims, the applicants would design a series of EMS cells using computer modeling, fabricate prototypes based on those designs, mount the prototypes in a high-performance tandem mass spectrometer, and conduct performance-trials on authentic peptides, authentic proteins, and protein-systems with biomedical import. Meeting this project's aims would usher in a transformative mass spectrometric technology. EMS dissociation cells would be simpler to implement, require less maintenance, be simpler to operate, and perform more robustly and productively than dissociation cells based on rapidly oscillating electric forces. From a manufacturing point of view, EMS technology would stimulate development of new instrumentation, software, and methodology; from a research point of view, it would inspire the design of new experiments in biomedical and clinical research, facilitate their execution, and increase their informational output. PUBLIC HEALTH RELEVANCE: Achieving the objectives of this project would usher in a transformative mass spectrometric technology. From a manufacturing point of view, this new technology would stimulate development of new instrumentation, software, and methodology for analyzing proteins and other molecules of biomedical import; from a research point of view, it would inspire the design of new experiments, facilitate their execution, and increase their informational output. Simply put, scientists would be able to exploit more fully the analytical power of mass spectrometry in biomedical and clinical research.

描述（由申请人提供）：拟议项目的总体目标是全面提高生物医学研究，特别是蛋白质组学中使用的串联质谱仪的分析能力。 串联进行多个阶段的质谱分析对于解开蛋白质的复杂结构和识别大量蛋白质来说已变得不可或缺。串联质谱仪通过将分子部分分解成碎片来深入探究分子结构的复杂性。在蛋白质组学应用中，这是通过利用多种物理化学过程之一来完成的，其中包括碰撞诱导解离（CID）、红外多光子解离（IRMPD）、电子捕获解离（ECD）、电子脱离解离（EDD）、电子转移解离 (ETD) 和有机物离子的电子碰撞激发 (EIEIO)。这些过程发生在仪器内部的一个单元中，其运行严格依赖于快速改变方向的电力。这种对仅依赖电力（排除磁力）的设备的依赖不必要地限制了串联质谱仪的设计、制造和应用。 申请人已经利用现代磁性材料来创建静电磁（EMS）单元，其可以安装在任何类型的串联质谱仪中并用于执行所有上述解离过程。具体而言，申请人提出，可以构建通用EMS串联质谱解离池，其中可以在分析实用水平上单独或以各种组合进行CID、IRMPD、ECD、EDD、ETD和EIEIO。这一假设将通过以下方式进行检验：1) 阐明 EMS 光学对低能电子和两种极性离子的作用，2) 量化 EMS 带电粒子光学在肽和蛋白质串联质谱分析中的分析效用。为了实现这两个目标，申请人将使用计算机建模设计一系列EMS单元，根据这些设计制造原型，将原型安装在高性能串联质谱仪中，并对真实的肽、真实的蛋白质、以及具有生物医学进口的蛋白质系统。 实现该项目的目标将迎来变革性的质谱技术。与基于快速振荡电力的解离单元相比，EMS 解离单元实施更简单，需要的维护更少，操作更简单，并且性能更稳健、更高效。从制造的角度来看，EMS 技术将刺激新仪器、软件和方法的开发；从研究的角度来看，它将激发生物医学和临床研究新实验的设计，促进其执行，并增加其信息输出。 公共卫生相关性：实现该项目的目标将迎来变革性的质谱技术。从制造的角度来看，这项新技术将刺激用于分析蛋白质和其他生物医学进口分子的新仪器、软件和方法的开发；从研究的角度来看，它将激发新实验的设计，促进其执行，并增加其信息输出。简而言之，科学家将能够在生物医学和临床研究中更充分地利用质谱分析能力。