Contemporary glycomic approaches using ion mobility-mass spectrometry

Characterization of complex oligosaccharides has historically required extensive sample handling and separations before analysis using nuclear magnetic resonance spectroscopy and electron impact mass spectra following hydrolysis, derivatization, and gas chromatographic separation. Advances in liquid chromatography separations and tandem mass spectrometry have expanded the range of intact glycan analysis, but carbohydrate structure and conformation - integral chemical characteristics - are often difficult to assess with minimal amounts of sample in a rapid fashion. Because ion mobility spectrometry (IMS) separates analytes based upon an effective 'size-to-charge' ratio, IMS is, by extension, highly applicable to glycomics. Furthermore, the speed of IMS, its growing levels of separation efficiency, and direct compatibility with all forms of mass spectrometry, illustrates is core role in the future of glycomics efforts. This review assesses the current state of ion mobility-mass spectrometry applied to glycan, glycoprotein, and glycoconjugate analysis. Currently, assessing optimal ion polarity and adduct type for a glycan class along with the appropriate tandem mass spectrometry technique underpin many of the current glycan analysis efforts using ion mobility-mass spectrometry (IMMS). Once determined, these parameters have enabled a growing and impressive range of glycomics campaigns employing this technique. Additionally, the combination of IMS with tandem mass spectrometry, and even spectroscopic methods, further expands the dimensionality of hybrid instrumentation to provide a more comprehensive assessment of glycan structure across a wide dynamic range. Continued computational efforts to complement experimental and instrumental advancements also serve as a core component of IMMS workflows applied to glycomics and promise to maximize the information gained from mobility separations.