Expanding Differential Ion Mobility Separations into the MegaDalton Range
Wörner, Tobias P. Thurman, Hayden A. Makarov, Alexander A. Shvartsburg, Alexandre A.
Wörner, Tobias P.
Thurman, Hayden A.
Makarov, Alexander A.
Shvartsburg, Alexandre A.
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2023
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Article
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Keywords
Electrospray ionization,Ion mobility spectrometers,Mass spectrometry,Monoclonal antibodies,Viruses,Analytical method,Electron capture dissociation,Electron transfer dissociation,Electrospray ionization mass spectrometry,High definition,Ion Mobility,Large biomolecules,Mass spectrometry analysis,Native mass spectrometries,Protein complexes,Ions
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Citation
Wörner, T.P., Thurman, H.A., Makarov, A.A., Shvartsburg, A.A. Expanding Differential Ion Mobility Separations into the MegaDalton Range. (2023). Analytical Chemistry. DOI: 10.1021/acs.analchem.3c05012
Abstract
Along with mass spectrometry (MS), ion mobility separations (IMS) are advancing to ever larger biomolecules. The emergence of electrospray ionization (ESI) and native MS enabled the IMS/MS analyses of proteins up to ∼100 kDa in the 1990s and whole protein complexes and viruses up to ∼10 MDa since the 2000s. Differential IMS (FAIMS) is substantially orthogonal to linear IMS based on absolute mobility K and offers exceptional resolution, unique selectivity, and steady filtering readily compatible with slower analytical methods such as electron capture or transfer dissociation (ECD/ETD). However, the associated MS stages had limited FAIMS to ions with m/z < 8000 and masses under ∼300 kDa. Here, we integrate high-definition FAIMS with the Q-Exactive Orbitrap UHMR mass spectrometer that can handle m/z up to 80,000 and MDa-size ions in the native ESI regime. In the initial evaluation, the oligomers of monoclonal antibody adalimumab (148 kDa) are size-selected up to at least the nonamers (1.34 MDa) with m/z values up to ∼17,000. This demonstrates the survival and efficient separation of noncovalent MDa assemblies in the FAIMS process, opening the door to novel analyses of the heaviest macromolecules. © 2024 American Chemical Society.
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American Chemical Society
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Analytical Chemistry
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0003-2700