Ion mobility-mass spectrometry measurements which describe the gas-phase scaling of molecular size and mass are of both fundamental and pragmatic utility. Fundamentally, such measurements expand our understanding of intrinsic intramolecular folding forces in the absence of solvent. Practically, reproducible transport properties, such as gas-phase collision cross-section (CCS), are analytically useful metrics for identification and characterization purposes. Here, we report 594 CCS values obtained in nitrogen drift gas on an electrostatic drift tube ion mobility-mass spectrometry (IM-MS) instrument. The instrument platform is a newly developed prototype incorporating a uniform-field drift tube bracketed by electrodynamic ion funnels and coupled to a high resolution quadrupole time-of-flight mass spectrometer. The CCS values reported here are of high experimental precision (±0.5% or better) and represent four chemically distinct classes of molecules (quaternary ammonium salts, lipids, peptides, and carbohydrates), which enables structural comparisons to be made between molecules of different chemical compositions for the rapid “omni-omic” characterization of complex biological samples. Comparisons made between helium and nitrogen-derived CCS measurements demonstrate that nitrogen CCS values are systematically larger than helium values; however, general separation trends between chemical classes are retained regardless of the drift gas. These results underscore that, for the highest CCS accuracy, care must be exercised when utilizing helium-derived CCS values to calibrate measurements obtained in nitrogen, as is the common practice in the field.

In this review, we focus on an important aspect of ion mobility (IM) research, namely the reporting of quantitative ion mobility measurements in the form of the gas-phase collision cross section (CCS), which has provided a common basis for comparison across different instrument platforms and offers a unique form of structural information, namely size and shape preferences of analytes in the absence of bulk solvent. This review surveys the over 24,000 CCS values reported from IM methods spanning the era between 1975 to 2015, which provides both a historical and analytical context for the contributions made thus far, as well as insight into the future directions that quantitative ion mobility measurements will have in the analytical sciences. The analysis was conducted in 2016, so CCS values reported in that year are purposely omitted. In another few years, a review of this scope will be intractable, as the number of CCS values which will be reported in the next three to five years is expected to exceed the total amount currently published in the literature.

In this work we have established a collision cross section (CCS) library of primary metabolites based on analytical standards in the Mass Spectrometry Metabolite Library of Standards (MSMLS) using a commercially available ion mobility-mass spectrometer (IM-MS). From the 554 unique compounds in the MSMLS plate library, we obtained a total of 1246 CCS measurements over a wide range of biochemical classes and adduct types. Resulting data analysis demonstrated that the curated CCS library provides broad molecular coverage of metabolic pathways and highlights intrinsic mass/mobility relationships for specific metabolite super classes. The separation and characterization of isomeric metabolites were assessed, and all molecular species contained within the plate library, including isomers, were critically evaluated in order to determine the analytical separation efficiency in both the mass (m/z) and mobility (CCS/ΔCCS) dimension required for untargeted metabolomic analyses. To further demonstrate the analytical utility of CCS as an additional molecular descriptor, a well-characterized biological sample of human plasma serum (NIST SRM 1950) was examined by LC-IM-MS and used to provide a detailed isomeric analysis of carbohydrate constituents by ion mobility.