Capillary zone electrophoresis-mass spectrometry for bottom-up proteomics

Bottom-up proteomics characterizes proteins by analysis of peptides generated through proteolysis. Bottom-up analysis of a complex proteome inevitably generates tens of thousands of peptides, and the analysis of these peptides is a serious challenge. Capillary zone electrophoresis (CZE) generates separations that are orthogonal to reversed phase liquid chromatography, which has led to consideration of CZE as an alternative separation technology in proteomic analysis. The steady improvement in mass spectrometer (MS) technology coupled with improvements in capillary coatings and the development of robust CZE-MS interfaces have contributed to the rapid advancement of CZE's identification performance in bottom-up proteomics analysis. In this review, we focus on recent advances of CZE-MS based bottom-up proteomics, including optimization of CZE and MS conditions, and the application of CZE-MS in phosphoproteomics, glycoproteomics, clinical diagnosis, host cell protein analysis, ultrasensitive proteomics, and quantitative proteomics. Finally, we outline future opportunities and challenges in this field.