Recent trends in two-dimensional liquid chromatography

Multi-dimensional liquid chromatography (MD-LC) continues to gain in popularity for applications where conventional one-dimensional liquid chromatography is insufficient to solve the analytical problem at hand. In this review we have focused on articles published in the years 2019 to early 2023 and look for trends using our previous review published in 2018 as a baseline. We have also explored usage patterns related to involvement of industrial laboratories in the published research. The two major areas of technical development have been continued work on modulation strategies that help mitigate problems associated with mobile phase mismatch when coupling complementary separation mechanisms, and development of computer-aided method development strategies. Progress in these areas is making 2D-LC easier to use, and it appears that this is translating to a shift toward more involvement by industrial laboratories. Indeed, over 34% of the more than 200 publications on 2D-LC in the last four years have had at least one-industry affiliated author. A recent inter-laboratory comparison study focused on the performance of a sophisticated multi-stage, multi-dimensional separation for therapeutic protein characterization is an exemplary indication of the increasing investment of industrial laboratories to MD-LC, and we expect this trend to continue for the foreseeable future.