An Analytical Perspective on Protein Analysis and Discovery Proteomics by Ion Mobility-Mass Spectrometry

Ion mobility combined with mass spectrometry (IM-MS) is a powerful technique for the analysis of biomolecules and complex mixtures. This chapter reviews the current state-of-the-art in ion mobility technology and its application to biology, protein analysis, and quantitative discovery proteomics in particular, from an analytical perspective. IM-MS can be used as a technique to separate mixtures, to determine structural information (rotationally averaged cross-sectional area) and to enhance MS duty cycle and sensitivity. Moreover, IM-MS is ideally suited for hyphenating with liquid chromatography, or other front-end separation techniques such as, GC, microcolumn LC, capillary electrophoresis, and direct analysis, including MALDI and DESI, providing an semiorthogonal layer of separation, which affords the more unambiguous and confident detection of a wide range of analytes. To illustrate these enhancements, as well as recent developments, the principle of in-line IM separation and hyphenation to orthogonal acceleration time-of-flight mass spectrometers are discussed, in addition to the enhancement of biophysical MS-based analysis using typical proteomics and related application examples.