PNNL

Abstract

Understanding the biological mechanisms related to lipids and glycolipids is challenging due to the vast number of possible isomers. Mass spectrometry (MS) measurements are currently the dominant approach for studying and providing detailed information on lipid and glycolipid structures. However, difficulties in distinguishing many structural isomers (e.g. distinct acyl chain positions, double bond locations, as well as glycan isomers) inhibit the understanding of their biological roles. Here we utilized ultra-high resolution ion mobility spectrometry (IMS) separations based upon the use of traveling waves in a serpentine long path length multi-pass Structures for Lossless Manipulations (SLIM) to enhance isomer resolution. The multi-pass arrangement allowed separations ranging from ~16 m (1 pass) to ~470 m (32 passes) to be investigated for the distinction of lipids and glycolipids with extremely small structural differences. These ultra-high resolution SLIM IMS-MS analyses provide a foundation for exploring and better understanding isomer specific biological and disease processes.