Recent advances in on-line upfront devices for sensitive bioanalytical nano LC methods

Nano liquid chromatography-mass spectrometry (nLC-MS), is often a tool of choice for the analysis of very limited samples, especially in proteomics. Although highly powerful in itself, nLC-MS may often rely upon upfront procedures for sample preparation. On-line upfront devices are directly connected to the nLC-MS analysis system, allowing for efficient handling of precious samples. Focusing on nLC-MS based systems, this review discusses upfront on-line interactions, particularly based on the use of solid phase extraction columns, for obtaining high sensitivity, high selectivity and high robustness. Also discussed are approaches based on on-line reactions, e.g. on-line enzymatic digestion systems, for obtaining rapid sample preparation and minimal sample loss. Focus is placed on papers published from 2016 to medio 2020.