Technological development of multidimensional liquid chromatography-mass spectrometry in proteome research.

Liquid chromatography-mass spectrometry (LC-MS) is the method of choice for high-throughput proteomic research. Limited by the peak capacity, the separation performance of conventional single-dimensional LC hampers the development of proteomics. Combining different separation modes orthogonally, multidimensional liquid chromatography (MDLC) with high peak capacity was developed to address this challenge. MDLC has evolved rapidly since its establishment, and the progress of proteomics has been greatly facilitated by the advent of novel MDLC-MS-based methods. In this paper, we will review the advances of MDLC-MS-based methodologies and technologies in proteomics studies, from different perspectives including novel application scenarios and proteomic targets, automation, miniaturization, and the improvement of the classic methods in recent years. In addition, attempts regarding new MDLC-MS models are also mentioned together with the outlook of MDLC-MS-based proteomics methods.