Frequency chasing of individual megadalton ions in an Orbitrap analyzer improves precision of analysis in single molecule mass spectrometry

To enhance the performance of charge detection mass spectrometry, we investigated the behavior of macromolecular single ions on their paths towards and within the Orbitrap analyzer. We discovered that ions in mass beyond one megadalton reach a plateau of stability and can be successfully trapped for seconds, travelling a path length of multiple kilometers, thereby enabling precise mass analysis with an effective resolution of greater than 100,000 at m/z 35,000. Through monitoring the frequency of individual ions, we show that these high mass ions, rather than being lost from the trap, can gradually lose residual solvent molecules and, in rare cases, a single elementary charge. Our observations highlight the importance of efficient desolvation for optimal charge detection mass spectrometry and inspired us to implement multiple improved data acquisition strategies. We demonstrate that the frequency drift of single ions due to desolvation and charge stripping can be corrected, which improves the effective ion sampling 23-fold and gives a two-fold improvement in mass precision and resolution, as demonstrated in the analysis of various viral particles.

Multiplexed Mass Spectrometry of Individual Ions Improves Measurement of Proteoforms and Their Complexes

Protocol for sample preparation, instrumental settings, and processing for the individual ion mass spectrometry method (I2MS) utilizing an Orbitrap analyzer.

Isotope ratio characteristics and sensitivity for uranium determinations using a liquid sampling-atmospheric pressure glow discharge ion source coupled to an Orbitrap mass analyzer

The coupling of an LS-APGD microplasma with an Orbitrap analyzer is applied to the isotope ratio analysis of uranium.