Researchers modified a standard Q Exactive UHMR mass spectrometer with a pulsed valve to regulate gas flow, improving sensitivity and mass resolution during charge detection measurements, according to a study published in Nature Communications on August 13, 2026.
Native mass spectrometry relies on gas in collision cells to cool and desolvate electrospray-generated bioparticles before mass analysis. In Orbitrap-based systems, gas leaking into the mass analyzer destabilizes ion trajectories, particularly during the extended acquisition times required for high-resolution measurements of large biological assemblies. Installing a pulsed valve allows operators to restrict gas leakage into the Orbitrap, preserving the ultrahigh vacuum during acquisition while maintaining ion desolvation and transmission.
The modified setup improved ion detection, mass accuracy, and resolving power across macromolecular assemblies including adeno-associated viruses, IgM, and plasmid DNA. Partner institutions supplied test materials for the study: Roche provided an rAAV9 sample, Genmab provided an IgG1-RGY sample, and University Medical Center Utrecht provided recombinant anti-Strep IgM, IgG-I, and SpA-B samples.
Co-authors from Utrecht University, the Netherlands Proteomics Center, the University of Copenhagen, and Thermo Fisher Scientific contributed to the project. Thermo Fisher Scientific and Utrecht University filed UK patent application No. 2509750.2 for gas regulation in charge detection and native mass spectrometry. The research received financial support from ChemistryNL grant CHEMIE.PGT.2024.021 and Netherlands Organization for Scientific Research Spinoza Award SPI.2017.028.
