Development of a Miniature Mass Spectrometry System for Point-of-Care Analysis of Lipid Isomers Based on Ozone-Induced Dissociation

Disorder of lipid homeostasis is closely associated with a variety of diseases. Although mass spectrometry (MS) approaches have been well developed for the characterization of lipids, it still lacks an integrated and compact MS system that is capable of rapid and detailed lipid structural characterization and can be conveniently transferred into different laboratories. In this work, we describe a novel miniature MS system with the capability of both ozone-induced dissociation (OzID) and collision-induced dissociation (CID) for the assignment of sites of unsaturation and sn-positions in glycerolipids. A miniature ozone generator was developed, which can be operated at a relatively high pressure. By maintaining high-concentration ozone inside the linear ion trap, OzID efficiency was significantly improved for the identification of C=C locations in unsaturated lipids, with reaction times as short as 10 ms. Finally, the miniature OzID MS system was applied to the analysis of C=C locations and sn-positions of lipids from biological samples. Direct sampling and fast detection of changes in phospholipid isomers were demonstrated for the rapid discrimination of breast cancer tissue samples, showing the potential of the miniature OzID MS system for point-of-care analysis of lipid isomer biomarkers in complex samples.

In this work, a miniature OzID MS system for the identification of lipid isomers was developed. The OzID efficiency was improved for fatty acid esters and phospholipids using the miniature LIT configuration, with reaction time as short as 10 ms. Coupling CID with OzID, we also developed a strategy that can dissociate C=C of fatty acids in negative-ion mode. Under optimized OzID conditions, the miniature MS system was also demonstrated to identify both C=C locations and chain sn-positions of different GPs in biological samples. Finally, fast detection of phospholipid C=C isomer biomarkers in breast cancer tissue samples was realized by coupling the direct sampling method with the miniature OzID MS system. Results showed that the miniature OzID MS system is capable of identification of various lipid isomers in biological samples and has the potential for point-of-care analysis of lipid isomer biomarkers.