Leveraging Advancements in Ion Mobility Technology for Lipid Applications

Lipids play a critical role in many biological processes as well as acting as biomarkers of many metabolic disorders. The analysis of lipids is complicated by the presence of numerous structural isomers, which are challenging to fully characterize using traditional liquid chromatography-mass spectrometry (LC-MS) workflows. To aid in the resolution of these complex isomeric profiles, ion mobility has become an increasingly important separation technique in lipid-based workflows. However, conventional ion mobility platforms often lack the necessary resolving power to resolve biologically relevant lipid isomers with differences in collision cross section (CCS) of less than ~2%, which includes structural features such as double bond position isomers, cis/trans isomers, and some SN1/SN2 positional isomers. More recently, the introduction of high-resolution ion mobility (HRIM) analytical techniques such as those based on structures for lossless manipulations (SLIM) enables rapid, gas-phase separation of lipids with resolving powers over 250,potentially facilitating the separation and identification of biologically relevant lipid isomers never detected in prior analyses. Here, we provide an overview of capabilities of HRIM technology for lipid analysis, including resolution of challenging isomeric species, cases in which high throughput separations can be achieved without the use of LC, and example application spaces, such as the relative quantitation of ganglioside profiles in a GBA mouse model for Parkinson's disease. Finally, future applications of highly resolved lipid CCS measurements will be discussed, including the development of predictive informatics and the potential impact for discovery lipidomics.

• HRIM technology is compatible with both LC- and FIA-based workflows and enables  isomer separations with the highest single-pass resolving power available
• HRIM data is highly reproducible across multiple lipid classes, agnostic of workflow
• Collision  cross section (CCS) is a robust and reliable measurement and highly resolved CCS measurements can be utilized to develop of predictive  informatics to aid in discovery lipidomic workflows
• HRIM  provides significant utility for applications where greater isomeric discrimination is needed