Triboelectric Nanogenerator Ion Mobility-Mass Spectrometry for In-Depth Lipid Annotation

Lipids play a critical role in cell membrane integrity, signaling, and energy storage. However, in-depth structural characterization of lipids is still challenging and not routinely possible in lipidomics experiments. Techniques such as collision-induced dissociation (CID) tandem mass spectrometry (MS/MS), ion mobility (IM) spectrometry, and ultrahigh-performance liquid chromatography are not yet capable of fully characterizing double-bond and sn-chain position of lipids in a high-throughput manner. Herein, we report on the ability to structurally characterize lipids using large-area triboelectric nanogenerators (TENG) coupled with time-aligned parallel (TAP) fragmentation IM-MS analysis. Gas-phase lipid epoxidation during TENG ionization, coupled to mobility-resolved MS3 via TAP IM-MS, enabled the acquisition of detailed information on the presence and position of lipid C=C double bonds, the fatty acyl sn-chain position and composition, and the cis/trans geometrical C=C isomerism. The proposed methodology proved useful for the shotgun lipidomics analysis of lipid extracts from biological samples, enabling the detailed annotation of numerous lipid isobars.

Automated summary

This study demonstrated the successful structural characterization and annotation of lipids using large-area triboelectric nanogenerators combined with time-aligned parallel fragmentation mass spectrometry analysis, providing detailed information on double bonds, sn-chain positions, and C=C isomerism. This methodology offers a new avenue for lipid analysis in biological samples.