From high- to super-resolution mass spectrometry

High-resolution mass spectrometry (MS) is indispensable for the molecular-level analysis of biological and environmental samples with great intra- and inter-molecular complexity. Here, we summarize developments in Fourier transform mass spectrometry (FTMS), the flagship of high-resolution MS techniques, accomplished in our laboratory. Particularly, we describe the recent and envisioned progress in structural analysis of: i) isolated large proteins and their simple mixtures, with a focus on monoclonal antibodies, via top-down, middle-down, and extended bottom-up mass spectrometry; ii) complex protein mixtures and proteomes via extended bottom-up proteomics; and iii) crude oil fractions and similar complex molecular mixtures. Despite the unequivocal success in molecular structural analysis, the demonstrated results clearly indicate that the compromise between MS acquisition speed (throughput) and achievable resolution level inhibits further advances of MS applications in the areas related to life, environmental, and material sciences. To further advance beyond state-of-the-art FTMS capabilities in these areas, we present the technique of super-resolution mass spectrometry that has been pioneered by our laboratory.