Keynote Session IV: Multiplexing the Orbitrap to Readout Individual Ion Mass Spectra of Virus-Like Particles

A new readout for individual ions in orbitraps has recently been reported in the April 2020 cover article in Nature Methods. Called I2MS, it uses principles of charge detection mass spectrometry (CDMS) to directly assignment each ion’s charge state and therefore allow production of spectra directly in the mass domain. This talk will describe the recent expansion of individual ion analysis to commercially deployable Orbitrap-based instruments. Additional major advancements demonstrated in our recent articles include some “firsts”:
1) Routine assignment of the charge state on single ions from 8 kDa to 3.5 MDa
2) 100x multiplexing of ion collection over the traditional CDMS technique
3) High resolution proteoform identification of samples containing ~1000 species
4) Operates on 100 fold more dilute solutions than typical ESI-MS (low nM versus low μM range)

Deriving from the major improvements above, we believe this new approach will gain major traction for analysis of Biopharmaceuticals and advanced therapeutics within just a few short years. We show that the use of ion-by-ion counting allows data to be generated where basically none could be generated using the standard approach to MS because of their extreme complexity. Offered in this brief seminar will be two prime examples of this– one on the successful deconvolution of a complex mixture with hundreds of proteoforms and the second on a set of engineered virus-like particles with a heterogeneous cargo held within their 27 vs. 17 nm diameter capsids.