Mass spectrometry (MS) imaging of lipids in tissues with
high structure
specificity is challenging in the effective fragmentation of position-selective
structures and the sensitive detection of multiple lipid isomers.
Herein, we develop an MS3 imaging method for the simultaneous
analysis of phospholipid CC and sn-position
isomers by on-tissue photochemical derivatization, nanospray desorption
electrospray ionization (nano-DESI), and a dual-linear ion trap MS
system. A novel laser-based sensing probe is developed for the real-time
adjustment of the probe-to-surface distance for nano-DESI. This method
is validated in mouse brain and kidney sections, showing its capability
of sensitive resolving and imaging of the fatty acyl chain composition,
the sn-position, and the CC location of phospholipids
in an MS3 scan. MS3 imaging of phospholipids
has shown the capability of differentiation of cancerous, fibrosis,
and adjacent normal regions in liver cancer tissues.