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Anal Chem. 2019 May 21;91(10):6918-6925. doi: 10.1021/acs.analchem.9b01309. Epub 2019 May 9.

High-Resolution Differential Ion Mobility Separations/Orbitrap Mass Spectrometry without Buffer Gas Limitations.

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Department of Chemistry , Wichita State University , 1845 Fairmount , Wichita , Kansas 67260 , United States.
Department of Biochemistry and Molecular Biology, VILLUM Center for Bioanalytical Sciences , University of Southern Denmark , DK-5230 Odense M , Denmark.
GAACE , 101904 Wiser Parkway Suite 105 , Kennewick , Washington 99338 , United States.
MassTech Inc. , 6992 Columbia Gateway Drive , Columbia , Maryland 21046 , United States.
Thermo Fisher Scientific , Hanna-Kunath Strasse 11 , Bremen 28199 , Germany.
Department of Chemistry , University of Utrecht , 3508 TC Utrecht , Netherlands.


Strong orthogonality between differential ion mobility spectrometry (FAIMS) and mass spectrometry (MS) makes their hybrid a powerful approach to separate isomers and isobars. Harnessing that power depends on high resolution in both dimensions. The ultimate mass resolution and accuracy are delivered by Fourier Transform MS increasingly realized in Orbitrap MS, whereas FAIMS resolution is generally maximized by buffers rich in He or H2 that elevate ion mobility and lead to prominent non-Blanc effects. However, turbomolecular pumps have lower efficiency for light gas molecules and their flow from the FAIMS stage complicates maintaining the ultrahigh vacuum (UHV) needed for Orbitrap operation. Here we address this challenge via two hardware modifications: (i) a differential pumping step between FAIMS and MS stages and (ii) reconfiguration of vacuum lines to isolate pumping of the high vacuum (HV) region. Either greatly ameliorates the pressure increases upon He or H2 aspiration. This development enables free optimization of FAIMS carrier gas without concerns about MS performance, maximizing the utility and flexibility of FAIMS/MS platforms.

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