Leveraging High-Resolution Ion Mobility-Mass Spectrometry Approaches for Improved Biomolecular Identification

Ion mobility-mass spectrometry (IM-MS) has emerged as a powerful analytical technique in the biological -omics over the last two decades, due to advantages in speed and separation capabilities. Despite its now widespread utility, the resolving power of many commercial IM platforms (~40-60) is often insufficient for resolution of structurally similar compounds such as stereoisomers. As bioanalytical chemists, there is a critical need for us to develop higher resolving power techniques to continue to push the boundaries of biomolecular discovery. This presentation will focus on several strategies for improving the separation capacity of ion mobility, including (a) chemical reactions, (b) software/processing methods, and (c) hardware advances. Specifically, we will present a recently published analytical suite of simple, inexpensive reactions targeting steroid functional groups for significantly improved sensitivity, selectivity, and structural elucidation. Furthermore, we will discuss data processing stemming from multiplexed acquisition modes, in which high-resolution post-processing can eliminate noise, increase resolving power to >200, and reveal isomers/conformers otherwise undetectable. Lastly, we will showcase the recently commercialized Structures for Lossless Ion Manipulations (SLIM) IM-MS platform, which provides resolving powers of >200 with its 13 m separation path. These strategies will be applied to a range of small molecule applications including detection and quantification of performance-enhancing anabolic steroids, monitoring of endocrine hormones, and differentiation of opioid analogs.