Instrumentation at the leading edge of proteomics

The proteome, or collection of proteoforms expressed in a biological system, is dynamic and heterogeneous. As our appreciation for the complexity of the proteome has evolved, so have the technologies we use to interrogate its composition. More than three decades ago, a rapid expansion in the field of proteomics was driven by the advent of soft ionization techniques focusing on capturing protein sequence information using mass spectrometry (MS). As tools to automate peptide and protein sequencing with tandem MS (MS/MS) matured, our field recognized the limits of qualitatively cataloguing gene products. This realization drove a multi-pronged expansion of MS-centric technologies that seek to capture various aspects of proteins, including their abundance, modification states, conformation and structure, and spatiotemporal relationships. Here we review innovations in MS-based instrumentation that continue to expand our ability to survey the proteome with ever increasing sensitivity, speed, and flexibility. The march of progress in MS instrumentation has been steady over the better half of the past century, but our discussion here focuses on developments within the past five years that have ushered in an exciting era in proteomics, where MS is poised to be the dominant platform for exploring biological phenotypes in basic and translational sciences for the foreseeable future.