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 MS 3 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.