High-Definition Ion Mobility/Mass Spectrometry with Structural Isotopic Shifts for Nominally Isobaric Isotopologues

We had reported the isotopic envelopes in differential IMS (FAIMS) separations depending on the ion structure. However, this new approach to distinguish isomers was constrained by the unit-mass resolution commingling all nominally isobaric isotopologues. Here, we directly couple high-definition FAIMS to ultrahigh-resolution (Orbitrap) MS and employ the resulting platform to explore the FAIMS spectra for isotopic fine structure. The peak shifts therein for isotopologues of halogenated anilines with ¹⁵N and ¹³C (split by 6 mDa) in N₂/CO₂ buffers dramatically differ, more than for the ¹³C, ³⁷Cl, or ⁸¹Br species apart by 1 or 2 Da. The shifts in FAIMS space upon different elemental isotopic substitutions are orthogonal mutually and to the underlying separations, forming fingerprint multidimensional matrices and 3-D trajectories across gas compositions that redundantly delineate all isomers considered. The interlocking instrumental and methodological upgrades in this work take the structural isotopic shift approach to the next level.