Mobility-Modulated Sequential Dissociation Analysis Enables Structural Lipidomics in Mass Spectrometry Imaging.

Area of Science:

• Biochemistry
• Analytical Chemistry
• Molecular Biology

Background:

• Mass spectrometry imaging (MSI) is crucial for spatial lipidomics and biomarker discovery.
• Current MSI methods have limited structure-resolving capabilities due to insufficient multiplexed tandem mass spectrometry (MS/MS) analysis.
• Small sample amounts per pixel and poor ion usage in MS/MS hinder detailed lipid analysis.

Purpose of the Study:

• To develop a novel strategy for multiplex MS/MS imaging of distinct lipids in biological tissues.
• To overcome the limitations of current MSI techniques in resolving lipid structures.
• To advance spatial lipidomics by enabling detailed isomer analysis.

Main Methods:

• A mobility-modulated sequential dissociation (MMSD) strategy was developed.
• Ion mobility-enabled data-independent acquisition was employed.
• Automated spectrum deconvolution was utilized for MS/MS data analysis.

Main Results:

• MMSD enabled multiplex MS/MS imaging of 24 structurally distinct lipids in mouse brain tissue.
• The method revealed correlations of a specific phosphatidylethanolamine isomer (PE 18:1_18:1) in human hepatocellular carcinoma (HCC) tissue.
• Spatial mapping of structurally distinct lipid isomers was achieved without compromising imaging speed.

Conclusions:

• MMSD significantly enhances the structure-resolving capability of MSI.
• This technique makes detailed spatial lipidomics and isomer analysis feasible.
• The findings open new avenues for biomarker discovery and fundamental biological research using MSI.