Charge Detection Mass Spectrometry (CDMS) is an advanced technique that measures the charge and mass-to-charge ratio (m/z) of each ion as it passes through a charge-sensitive amplifier after electrospray ionization [1]. Unlike traditional MS, CDMS can characterize highly charged molecular complexes and is therefore of growing interest to study biological macromolecules such as viruses, DNA or nanoparticles [2].
The main challenge is the electrical noise affecting measurement accuracy. Our group has developed a CDMS instrument with an eight-tube linear array inside an electrostatic ion trap with conical electrodes (cone trap), enabling multiple measurements per ion, either through the eight tubes or through the trap. This results in a signal gain over a conventional trap with a single detection tube and therefore offers a more reliable charge measurement than the single-pass CDMS, while maintaining a high throughput so that a spectrum can be measured in less than a minute.
European projects such as ARIADNE [3] and ViruSong [4] are currently underway to develop new analytical platforms with CDMS instrumentation for simple and radical identification of viral particles. We have used this instrument to characterize viruses such as adenoviruses and noroviruses. This allows us to evaluate the performance (mass accuracy, sensitivity) of this new CDMS instrument with viral particles in the mass range of 10 MDa to sub-GDa.
[1] S.H. Lai et al., Advances in Single Particle Mass Analysis, Mass Spectrom. Rev. Under revisions (2024).
[2] M.F. Jarrold, Single-Ion Mass Spectrometry for Heterogeneous and High Molecular Weight Samples, J. Am. Chem. Soc. 146 (2024) 5749–5758.
[3] European Commission, ARIADNE project, 2021. https://cordis.europa.eu/project/id/964553/reporting.
[4] European Union, VIRUSONG project, 2023. https://www.virusong.eu/project/.