Mass spectrometry hybridized with gas-phase InfraRed spectroscopy for glycan sequencing.

Precise structural differentiation of often isomeric glycans is important given their roles in numerous biological processes. Mass spectrometry (MS) (and tandem MS) is one of the analytical techniques at the forefront of glycan analysis given its speed, sensitivity in producing structural information as well as the fact it can be coupled to other orthogonal analytical techniques such as liquid chromatography (LC) and ion mobility spectrometry (IMS). This review describes another family of techniques that are more commonly being hybridized to MS(/MS) namely gas-phase infrared (IR) spectroscopy, whose rise is in part due to the development and improved accessibility of tunable IR lasers. Gas-phase IR can often differentiate fine isomeric differences ubiquitous within carbohydrates that MS may be 'blind' to. There are also examples of cryogenic gas-phase IR spectroscopy with much greater spectral resolution as well as hybridizing with separative methods (LC, IMS). Furthermore, collision-induced dissociation (CID) product ions can also be probed by IR, which may be beneficial to deconvolute spectra, aid analysis and build spectral libraries, thus generating novel opportunities for fragment-based approaches to analyze glycans.