Structures for lossless ion manipulations (SLIM) is a recently developed ultrahigh resolution ion mobility-mass spectrometry (IM-MS) platform that has demonstrated significant gains in ion mobility resolution, sample throughput, and sensitivity. These improvements are achieved using serpentine ultralong path with extended routing (SUPER) separations to enable &gt;100 m pathlengths. The increased resolution afforded by this technique lessens the need for chromatographic separations, decreasing time of analysis and improving throughput. Lastly, the capability for in-SLIM module accumulation of &gt;10<sup>9</sup> ions overcomes limitations in conventional pre-IM trapping, significantly improving sensitivity in quantitative assays. In this presentation, applications to metabolomics and proteomics will be highlighted, with a focus on these figures of merit.<br/>SLIM IM-MS has demonstrated significant improvements in resolution of structurally similar metabolites, including separation of enantiomeric amino acid pairs achieved through complexation with chiral cyclodextrin adducts. Moreover, conjugated bile acid isomers that are unresolved using traditional negative mode LC-MS/MS protocols (e.g., four taurodeoxycholic acid isomers) can be successfully resolved using direct injection for higher sample throughput. In addition, separation of glycodeoxycholic acid, glycoursodeoxycholic acid, and glycochenodeoxycholic acid is improved through complexation with cyclodextrin adducts and implementation of a compression ratio ion mobility programming (CRIMP) step to minimize peak width to both improve sensitivity and increase resolution. Finally, although targeted proteomics is currently limited by challenges in sample throughput and differentiation of post-translational modification (PTM) location isomers, SLIM LC-IM-MS has been used to routinely separate PTM isomers with improved limits of detection for many peptides in a plasma digest, in comparison with a standard LC-SRM protocol. The significant reduction in chromatographic time (&gt;2x reduction) provides the potential for increased throughput. In conclusion, SLIM IM-MS is a powerful tool capable of expanding the role of ion mobility in metabolomics and proteomics.<br/>

Improvements in metabolomics and proteomics separations and quantitation using Structures for Lossless Ion Manipulations (SLIM) IM-MS

2019 Spring National Meeting

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