Structurally informed metabolite measurements with ion mobility-mass spectrometry

Although ion mobility-mass spectrometry (IM-MS) is no longer a new technology, new developments in instrumentation and resources for structurally informed measurements are enabling the use of IM-MS in emerging metabolomic applications. Once limited by experimental measurements, the growth of machine-learning strategies to predict collision cross-section values is rapidly increasing the coverage of IM-MS information in metabolite databases. IM-MS instrumentation capable of high-resolution separations is bringing new depth to the level of structural annotation that can be achieved, while creative strategies to combine IM-MS with complementary analytical or chemical methods are further leveraging its ability to resolve small molecule isomers and isobars. This brief review highlights the recent developments of IM-MS for metabolomics with a focus on applications to mass spectrometry imaging, rapid multi-omics, and single-cell analyses.