Rapid separation and quantitative analysis of peptides using a new nanoelectrospray-differential mobility spectrometer-mass spectrometer system
Rapid separation and quantitative analysis of peptides using a new nanoelectrospray-differential mobility spectrometer-mass spectrometer system
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DOI：
10.1021/ac060003f
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发表时间：
2006-08-01
影响因子：
7.4
通讯作者：
Vouros, Paul
中科院分区：
文献类型：
--
作者：
Levin, Daren S.;Miller, Raanan A.;Vouros, Paul
差示迁移率光谱法（DMS）（参见Buryakov，I.一、克雷洛夫，E.五、Nazarov，E. G.地;拉苏列夫Kh.国际质谱学杂志Ion Processes 1993，128，143148），通常也称为高场不对称波形离子迁移谱（FAIMS）（参见Purves，R. W.的; Guevremont，R.; Day，S.;皮皮奇角W的; Matyjaszcyk，M. S. Rev. Sci.仪器。1998，69，4094-4105）是一种快速发展的气相离子分离技术。DMS与质谱（MS）的接口提供了优于单独使用质谱的潜在优势。这些优点包括改进质谱信噪比、质谱的正交/互补离子分离、增强的离子和络合结构分析以及快速分析物定量的潜力。在这份报告中，我们研究了我们的nanoESI-DMS-MS系统的使用，以证明差异迁移率分离肽。通过电喷雾离子化形成更高级的肽聚集体离子（离子复合物），这对DMS肽分离的负面影响进行了检查。成功使用微分迁移率漂移气体改性剂（掺杂剂），以减少聚集离子的大小和改善DMS肽离子分离。在优化DMS肽分离条件后，我们接下来研究了一种新的分析平台的可行性，该平台使用nanoESI-DMS-MS直接样品输注进行超快速分析物定量。提供了从半复合物肽混合物中选择的肽的定量。这种新方法的初步可行性结果证明了良好的准确性和再现性，以及绝对质量灵敏度为6.8阿莫尔，最小动态范围为2500的肽的利益。本报告首次介绍了利用nanoESI-DMS-MS创建超快速（5 s以下）定量分析平台及其在高通量竞技场中的潜力。每种离子分离技术，DMS和MS，提供了相互正交的离子分离，增强了这种定量方法的整体特异性。
Differential mobility spectrometry (DMS) ( see Buryakov, I. A.; Krylov, E. V.; Nazarov, E. G.; Rasulev, U. Kh. Int. J. Mass Spectrom. Ion Processes 1993, 128, 143148), also commonly referred to as high-field asymmetric waveform ion mobility spectrometry (FAIMS) ( see Purves, R. W.; Guevremont, R.; Day, S.; Pipich, C. W.; Matyjaszcyk, M. S. Rev. Sci. Instrum. 1998, 69, 4094-4105), is a rapidly advancing technology for gas-phase ion separation. The interfacing of DMS with mass spectrometry ( MS) offers potential advantages over the use of mass spectrometry alone. Such advantages include improvements to mass spectral signal-to-noise, orthogonal/ complementary ion separation to mass spectrometry, enhanced ion and complexation structural analysis, and the potential for rapid analyte quantitation. In this report, we investigate the use of our nanoESI-DMS-MS system to demonstrate differential mobility separation of peptides. The formation of higher order peptide aggregate ions ( ion complexes) via electrospray ionization and the negative impact this has on DMS peptide separation are examined. The successful use of differential mobility drift gas modifiers (dopants) to reduce aggregate ion size and improve DMS peptide ion separation is presented. Following optimization of DMS peptide separation conditions, we examined next the feasibility of a new analytical platform which uses direct sample infusion with nanoESI-DMS-MS for ultrarapid analyte quantitation. Quantitation of a selected peptide from a semicomplex peptide mixture is presented. Initial feasibility results with this new approach demonstrate good accuracy and reproducibility, as well as an absolute mass sensitivity of 6.8 amol and a minimum dynamic range of 2500 for the peptide of interest. This report offers a first look at utilizing nanoESI-DMS-MS to create an ultrarapid ( under 5 s) quantitative analysis platform and its potential in the high-throughput arena. Each ion separation technique, DMS and MS, offers orthogonal ion separation to one another, enhancing the overall specificity for this quantitative approach.