Ion mobility mass spectrometry: A unique platform for glycan isomer characterization.

Ion mobility mass spectrometry (IMMS) is a rapid separation, detection, and identification technique that has experienced exponential growth in glycan research. Glycans, on the other hand, possess complex and unique stereochemical features, endowing them with distinguishing functions. This review article highlights recent developments in ion mobility as a separation technique coupled to MS detection configurations that enable additional dimensional separation and collision cross-section (CCS) measurements, providing value-added data to unambiguously identify glycans. Since our last review in 2008, four new methods of ion mobility separation have been introduced and used with mass spectrometry. They are (1) cyclotron ion mobility spectrometry (CIMS), (2) trapped ion mobility spectrometry (TIMS), (3) structures for lossless ion manipulations (SLIM), and (4) cyclic ion mobility spectrometry (cIMS). CIMS separates gas-phase ions by looping them through a circular, cyclotron-like drift tube rather than a traditional linear path. TIMS is a high-resolution front-end separator that separates gas-phase ions by size, shape, and charge by holding them stationary in a moving gas stream with a tunable electric field. SLIM is based on advanced ion-optics technology that uses patterned electrode arrays on parallel planar surfaces to guide, trap, and separate gas-phase ions via electric fields without contacting the surfaces. cIMS is a novel ultra-high-resolution IMS technology that separates gas-phase ions by size, shape, and charge by circulating them in a closed-loop, circular path. CIMS and TIMS measure CCS, whereas SLIM and cIMS do not. However, new research has recently been published that shows promise for cIMS or SLIM to measure CCS. Of all four new IMS technologies, cIMS has the highest resolving power. This review aims not only to provide a deeper understanding of developments in IMMS research towards structural elucidation of glycans but also to discuss the road ahead. 147 references on IMMS are provided.