High Resolution Ion Mobility Mass Spectrometry (RMI)

高分辨率离子淌度质谱 (RMI)

• 批准号: 7234929
• 负责人: HERBERT H HILL
• 金额: $ 63.17万
• 依托单位: WASHINGTON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7234929
• 关键词: NIH Roadmap Initiative tag; biotechnology; clinical research; electrospray ionization mass spectrometry; gas chromatography; liquid chromatography; mass spectrometry; matrix assisted laser desorption ionization; metabolomics; technology /technique development

DESCRIPTION (provided by applicant): Ion Mobility Mass Spectrometry (IMMS) is an emerging analytical technique with the potential capability of detecting, quantifying and identifying thousands of compounds in a complex mixture in fractions of a second. While IMMS has been applied primarily to the proteome, this grant application proposes to develop and evaluate its potential to measure and monitor the metabolome. Using both electro spray ionization and matrix assisted laser desorption ionization to create peptide and protein ions in the gas phase, IMS separates isomeric peptides and protein conformations before mass spectral analysis. This separation mechanism is based on ion-molecule collisions as an ion migrates through a neutral buffer gas in an electric field. The time an ion takes to transverse the buffer gas region is related to its size and shape. In IMS instruments currently used for peptide and protein separations, ion migration through the buffer gas occurs at a reduced pressures (typically 10 torr) with a typical separation efficiency of about 2000 theoretical plates. For application to metabolomics, we propose to use ion mobility separations at atmospheric pressures or greater, increasing the separation efficiency to more than 300,000 theoretical plates and improving significantly the two-dimensional resolving power of IMMS. In addition to separation efficiency, separation range and selectivity will be enhanced. Using IMS parameters of temperature, pressure, buffer gas, and voltage, the separation range will be extended to achieve maximal peak capacity and the separation selectivity will be optimized for maximal resolution of a metabolome. IMMS will also be interfaced to both gas chromatography and liquid chromatography to provide maximal metabolite quantification and provide three dimensional separations. With IMMS, both pattern recognition algorithms to identify modification in an entire metabolome as well as identification and quantification of individual metabolites is possible.

描述（由申请人提供）：离子迁移质谱（IMMS）是一种新兴的分析技术，具有在几分之一秒内检测、定量和鉴定复杂混合物中数千种化合物的潜在能力。 虽然IMMS主要应用于蛋白质组，但该拨款申请提出开发和评估其测量和监测代谢组的潜力。使用电喷雾电离和基质辅助激光解吸电离在气相中产生肽和蛋白质离子，IMS在质谱分析之前分离异构肽和蛋白质构象。这种分离机制是基于离子在电场中迁移通过中性缓冲气体时的离子-分子碰撞。离子横穿缓冲气体区所需的时间与其大小和形状有关。在目前用于肽和蛋白质分离的IMS仪器中，通过缓冲气体的离子迁移发生在减压（通常为10 ℃）下，典型的分离效率为约2000个理论塔板。 对于代谢组学的应用，我们建议在大气压或更高的压力下使用离子迁移率分离，将分离效率提高到超过300，000个理论塔板，并显着提高IMMS的二维分辨能力。除了分离效率外，分离范围和选择性也将得到增强。使用温度、压力、缓冲气体和电压等IMS参数，分离范围将被扩展以实现最大峰容量，并且分离选择性将被优化以实现代谢组的最大分辨率。IMMS还将与气相色谱和液相色谱连接，以提供最大代谢物定量和三维分离。使用IMMS，可以使用模式识别算法来识别整个代谢物组中的修饰以及单个代谢物的识别和定量。