Ultrahigh-Mass Mass Spectrometry of Single Biomolecules and Bioparticles

Since the advent of soft ionization methods, mass spectrometry (MS) has found widespread application in the life sciences. Mass is now known to be a critical parameter for characterization of biomolecules and their complexes; it is also a useful parameter to characterize bioparticles such as viruses and cells. However, because of the genetic diversity of these entities, it is necessary to measure their masses individually and to obtain the corresponding mean masses and mass distributions. Here, I review recent technological developments that enable mass measurement of ultrahigh-mass biomolecules and bioparticles at the single-ion level. Some representative examples include cryodetection time-of-flight MS of single-megadalton protein ions, Millikan-type mass measurements of single viruses in a cylindrical ion trap, and charge-detection quadrupole ion trap MS of single whole cells. I also discuss the promises and challenges of these new technologies in real-world applications.