Ion Mobility Spectrometry: Fundamental Concepts, Instrumentation, Applications, and the Road Ahead

Abstract

Ion mobility spectrometry (IMS) is a rapid separation technique that has experienced exponential growth as a field of study. Interfacing IMS with mass spectrometry (IMS-MS) provides additional analytical power as complementary separations from each technique enable multidimensional characterization of detected analytes. IMS separations occur on a millisecond timescale, and therefore can be readily nested into traditional GC and LC/MS workflows. However, the continual development of novel IMS methods has generated some level of confusion regarding the advantages and disadvantages of each. In this critical insight, we aim to clarify some common misconceptions for new users in the community pertaining to the fundamental concepts of the various IMS instrumental platforms (i.e., DTIMS, TWIMS, TIMS, FAIMS, and DMA), while addressing the strengths and shortcomings associated with each. Common IMS-MS applications are also discussed in this review, such as separating isomeric species, performing signal filtering for MS, and incorporating collision cross-section (CCS) values into both targeted and untargeted omics-based workflows as additional ion descriptors for chemical annotation. Although many challenges must be addressed by the IMS community before mobility information is collected in a routine fashion, the future is bright with possibilities.

Keywords: IMS; Ion mobility spectrometry; Mass spectrometry; Untargeted metabolomics.

Figure 1.

Variations of IMS technology with representative descriptions of applied field and gas dynamics. Bullet points describe the relative parameters of each IMS platform with key attributes reflecting the ability to measure CCS information, ion packet distribution, instrument footprint, and modularity among other relevant descriptors. Also included are the main instrument manufacturers which currently market each IMS method. Instrument diagrams have been adapted/reprinted from Ref. 7 “Lipid analysis and lipidomics by structurally selective ion mobility-mass spectrometry” 1811, Kliman, M. et. al. 935–945. 2011, with permission from Elsevier.

Figure 2.

Illustrations of common applications of IMS-MS from recent publications. (A) Separation of lipid isomers with variations in cis/trans double bonds and variations in chain length adapted/reprinted from reference 80 with permission from Springer, Journal of the American Society for Mass Spectrometry. Bowman, A. P. et. al. Copyright, 2017. (B) Illustration of signal filtering by IMS for simplification of MS signals in targeted workflows. Adapted/reprinted from reference 85 with permission from Springer, Journal of the American Society for Mass Spectrometry. Levin, D. S. et. al. Copyright, 2007.

Figure 3.

Illustrative workflow of untargeted identifications by IMS-MS with incorporation of additional confidence gained with subsequent chemical information acquired from each analytical technique.

Figure 4.

Workflows for generation and interpretation of CCS values in IMS-MS experiments.