Expanding the Frontiers of Charge Detection Mass Spectrometry: Ion Mobility Spectrometry of Megadalton Sized Ions

Charge Detection Mass Spectrometry (CDMS) is a single particle technique, capable of measuring the mass to charge ratio and charge of ions simultaneously. This allows for the accurate mass measurement of heterogeneous ions in the megadalton to gigadalton regime, beyond the range of conventional mass spectrometry. However, CDMS is unable to directly measure collisional cross section (CCS); large biological macromolecules such as virus capsids experience conformational change due to factors such as changing solution conditions and the inactivation process for vaccine production. Ion mobility spectrometry (IMS) coupled to mass spectrometers (MS) provides structural information for smaller biological molecules, in the kilodalton range, by adding a CCS measurement. In this work, simulations modeling a U-shaped mobility analyzer were used to characterize its performance in the megadalton range. The U-shaped mobility analyzer uses two channels, consisting of electric fields opposing a high velocity gas flow, as high pass, and low pass electrical mobility filters for high resolution selection of specific mobilities. These simulations focused upon optimization of the analyzer’s electric fields and electrode geometry, achieving a resolving power of 182. Furthermore, the simulated conditions mimicked the infrastructure of an existing CDMS instrument to facilitate the goal of coupling this analyzer to create the first IMS-CDMS instrument. The proposed IMS-CDMS instrument leverages CDMS’s ability to independently measure charge to allow for the measurement of CCS and mass of macromolecules beyond the means of conventional IMS-MS.