Individual Ion Mass Spectrometry Enhances the Sensitivity and Sequence Coverage of Top-Down Mass Spectrometry

Jared O. Kafader, Kenneth R. Durbin, Rafael D. Melani, Benjamin J. Des Soye, Luis F. Schachner, Michael W. Senko, Philip D. Compton, Neil L. Kelleher*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


Charge detection mass spectrometry (CDMS) is mainly utilized to determine the mass of intact molecules. Previous applications of CDMS have determined the mass-to-charge ratio and the charge of large polymers, DNA molecules, and native protein complexes, from which corresponding mass values could be assigned. Recent advances have demonstrated that CDMS using an Orbitrap mass analyzer yields the reliable assignment of integer charge states that enables individual ion mass spectrometry (I2MS) and spectral output directly into the mass domain. Here I2MS analysis was extended to isotopically resolved fragment ions from intact proteoforms for the first time. With a radically different bias for ion readout, I2MS identified low-abundance fragment ions containing many hundreds of residues that were undetectable by standard Orbitrap measurements, leading to a doubling in the sequence coverage of triosephosphate isomerase. Thus MS/MS with the detection of individual ions (MS/I2MS) provides a far greater ability to detect high mass fragment ions and exhibits strong complementarity to traditional spectral readout in this, its first application to top-down mass spectrometry.

Original languageEnglish (US)
Pages (from-to)1346-1350
Number of pages5
JournalJournal of Proteome Research
Issue number3
StatePublished - Mar 6 2020

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry


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