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.