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: 8310944
• 负责人: DOUGLAS F BAROFSKY
• 金额: $ 35.23万
• 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/8310944
• 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）：拟议项目的广泛目的是偶尔提高生物医学研究中使用的串联质谱仪的分析能力，尤其是蛋白质组学。 在串联中进行多个质谱分析的多个阶段已经成为揭示蛋白质的复杂结构和鉴定大量蛋白质的复杂结构所必不可少的。串联质谱仪通过将其部分分解成片段来敏锐地探究分子结构的复杂性。 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).这些过程发生在仪器内部的单元格中，其操作严格依赖于迅速改变方向的电力。这种依赖不必要的电力（排除磁力）的设备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来创建一个可以安装在任何类型的串联质谱仪中，并用于执行上述所有上述解离过程。具体而言，申请人认为可以建立通用的EMS串联量子光谱分离细胞，在该分析中可以在分析实用级别上单独或以各种组合进行CID，IRMPD，ECD，EDD，ETD和EIEIO进行CID，IRMPD，ECD，EDD，ETD和EIEIO。该假设将通过1）阐明EMS光学元件对两极分化的低能电子和离子的作用，以及2）量化EMS带电粒子光学元件在肽和蛋白质的串联质谱分析中的分析效用。为了满足这两个目的，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的串联质谱仪中，并对具有生物医学进口的蛋白质蛋白和蛋白质系统进行真实的肽，正宗肽，正atrion的性能进行性能。 实现该项目的目标将引入一种变革性的质谱技术。 EMS解离细胞将更简单地实施，需要更少的维护，更简单地操作，并且比基于快速振荡电力的解离细胞更强大，更有效。从制造的角度来看，EMS技术将刺激新仪器，软件和方法的发展；从研究的角度来看，它将激发生物医学和临床研究中新实验的设计，促进其执行并增加其信息产出。 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，这项新技术将刺激新仪器，软件和方法的开发，用于分析生物医学进口的蛋白质和其他分子；从研究的角度来看，它将激发新实验的设计，促进其执行并增加信息产出。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的分析能力。