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

描述(由申请人提供)：拟议项目的广泛目标是关键地提高串联质谱仪在生物医学研究中的分析能力，特别是在蛋白质组学中。同时进行多个阶段的质谱分析对于解开蛋白质的复杂结构和鉴定大量蛋白质都是不可或缺的。串联质谱仪通过将分子结构部分分解成碎片来深入探测分子结构的复杂性。在蛋白质组学应用中，这是通过利用碰撞诱导解离(CID)、红外多光子解离(IRMPD)、电子俘获解离(ECD)、电子脱离解离(EDD)、电子转移解离(ETD)和电子碰撞激发有机物离子(EIEIO)等物理化学过程之一来实现的。这些过程发生在仪器内部的电池中，电池的运行严格依赖于快速改变方向的电动力。这种对完全依赖于电动力(不包括磁力)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。申请人利用现代磁性材料制造了一种电磁(EMS)单元，该单元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。具体地说，申请人提出，可以建立一个通用的EMS串联-质谱解离池，在该池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1)阐明EMS光学对两种极性的低能电子和离子的作用，以及2)量化EMS带电粒子光学在多肽和蛋白质的串联质谱分析中的分析效用来检验。为了实现这两个目标，申请者将使用计算机建模设计一系列EMS细胞，基于这些设计制造原型，将原型安装在高性能串联质谱仪中，并对正品多肽、正品蛋白质和具有生物医学进口的蛋白质系统进行性能试验。实现该项目的目标将带来一种变革性的质谱学技术。与基于快速振荡电场力的解离单元相比，EMS解离单元将更容易实现，需要更少的维护，更简单的操作，并且表现得更健壮和高效。从制造的角度来看，EMS技术将促进新的仪器、软件和方法的发展；从研究的角度来看，它将激励生物医学和临床研究中新实验的设计，促进它们的执行，并增加它们的信息输出。 与公共卫生相关：实现该项目的目标将带来一种变革性的质谱学技术。从制造的角度来看，这项新技术将促进用于分析蛋白质和其他生物医学进口分子的新仪器、软件和方法的发展；从研究的角度来看，它将启发新实验的设计，促进实验的实施，并增加信息输出。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仪的分析能力。

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.