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Background on Ion-mobility Mass Spectrometry

IMS-MS is a rapid gas-phase technique, whereby ions are separated on the basis of their mass to charge (m/z) and their sizes, shapes and charges. This technique provides a viable and complementary approach to ensemble-averaged, solution-phase methods. Separation in IMS-MS is performed on the order of milliseconds while conventional (solution-phase) chromatographic methods are on the order of minutes to hours. Collisional cross section (CCS) data from IMS-MS experiments can be directly compared with databases of CCSs and theoretical CCSs of model structures from NMR, X-ray crystallography, molecular dynamics, or from machine learning approaches. Advances in flow-compatible and miniaturized LC and molecular ion generation/transmission in MS significantly improve metabolite and peptide identification workflow. Coupling LC to the front-end simplifies the resultant spectra, mitigates analyte suppression and improves limit of detection (LOD) for techniques used in subsequent analysis. Each compound has a reproducible normalized retention time, enabling identification of components within a complex mixture. It also reduces the effect of ion suppression, as compounds are analyzed sequentially, and directly increases the number of compounds detected from complex mixtures, such as single cells. Since the separation greatly simplifies the matrix of compounds eluting from the column, quantification is robust and routine. Lastly, LC-IMS-MS facilitates the discovery of isobaric compounds in volume-limited samples. For additional background information, please read the following review articles (not written by us):

1) Lanucara et al. The power of ion mobility-mass spectrometry for structural characterization and the study of conformational dynamics.. Nature Chemistry, 2014, 6:281-294. PDF
2) Kalenius et al. Ion mobility–mass spectrometry of supramolecular complexes and assemblies.. Nature Reviews Chemistry, 2018, 3:4-14. PDF
3) Cumeras et al. Review on ion mobility spectrometry. Analyst, 2015, 140:1376-1410. Part I Part II


Single-Cell Analysis with Mass Spectrometry

A technique with a femtomole limit of detection used to analyze a 1,000 um3 cell (one picoliter; approximately the size of a typical mammalian cell) is only capable of detecting compounds at millimolar concentrations or above, which may be insufficient for most analytes. Several mass spectrometry techniques have been developed to perform analyses of metabolites, lipids, peptides, and proteins one single cell at a time. Currently, the fastest technique of this kind is microscopy-guided mass spectrometry (microMS) developed by the Sweedler group at Illinois. The data can be used to stratify seemingly-homogenous cell population into subtypes. For review articles, please read:

1) Comi et al. Categorizing cells on the basis of their chemical profiles: progress in single-cell mass spectrometry.Journal of the American Chemical Society, 2017, 28:1919-1928. PDF
2) Neumann et al. Exploring the Fundamental Structures of Life: Non‐Targeted, Chemical Analysis of Single Cells and Subcellular Structures.. Angewandte Chemie, 2019, 6:9348-9364. PDF