Rapid Separation and Quantitative Analysis of Peptides Using a New Nanoelectrospray- Differential Mobility Spectrometer-Mass Spectrometer System

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• 作者：Daren S. Levin ; Raanan A. Miller ; Erkinjon G. Nazarov ; Paul Vouros
• 刊名：Analytical Chemistry
• 出版年：2006
• 出版时间：August 1, 2006
• 年：2006
• 卷：78
• 期：15
• 页码：5443 - 5452
• 全文大小：436K
• 年卷期：v.78,no.15(August 1, 2006)
• ISSN：1520-6882

文摘

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, 143-148), also commonly referred to as high-field asymmetricwaveform 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 ionseparation. The interfacing of DMS with mass spectrometry (MS) offers potential advantages over the use of massspectrometry alone. Such advantages include improvements to mass spectral signal-to-noise, orthogonal/complementary ion separation to mass spectrometry,enhanced ion and complexation structural analysis, andthe potential for rapid analyte quantitation. In this report,we investigate the use of our nanoESI-DMS-MS systemto demonstrate differential mobility separation of peptides.The formation of higher order peptide aggregate ions (ioncomplexes) via electrospray ionization and the negativeimpact this has on DMS peptide separation are examined.The successful use of differential mobility drift gas modifiers (dopants) to reduce aggregate ion size and improveDMS peptide ion separation is presented. Followingoptimization of DMS peptide separation conditions, weexamined next the feasibility of a new analytical platformwhich uses direct sample infusion with nanoESI-DMS-MS for ultrarapid analyte quantitation. Quantitation of aselected peptide from a semicomplex peptide mixture ispresented. Initial feasibility results with this new approachdemonstrate good accuracy and reproducibility, as wellas 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) quantitativeanalysis platform and its potential in the high-throughputarena. Each ion separation technique, DMS and MS,offers orthogonal ion separation to one another, enhancingthe overall specificity for this quantitative approach.