Universal Photosensitizer for Isomer-Selective Lipid Imaging with High Molecular Coverage.

Area of Science:

• Analytical Chemistry
• Biochemistry
• Molecular Imaging

Background:

• Spatial lipidomics uses mass spectrometry imaging (MSI) to analyze lipid distribution.
• Isomer-selected MSI (iMSI) advances lipid analysis but is often limited to single ionization modes and variable derivatization efficiency.
• Comprehensive lipidome analysis requires methods that overcome these limitations.

Purpose of the Study:

• To develop a universal online derivatization strategy for dual-polarity isomer-selected mass spectrometry imaging (iMSI) of lipids.
• To enhance the detection of low-abundance and isomeric lipids in biological samples.
• To enable simultaneous imaging of diverse lipid classes and their isomers.

Main Methods:

• Utilized tetrakis(4-carboxyphenyl)porphyrin (TCPP) as a photosensitizer for online lipid derivatization via singlet oxygen reaction.
• Employed sodium fluoride (NaF) as a solvent dopant to boost signal intensity for low-abundance molecules.
• Integrated TCPP derivatization and NaF doping with nanospray desorption electrospray ionization (nano-DESI) for dual-polarity iMSI.

Main Results:

• Achieved simultaneous positive and negative ion mode iMSI in a single experiment.
• Successfully imaged low-abundance isomeric lipids previously undetectable.
• Demonstrated enhanced derivatization efficiency for unsaturated fatty acids using TCPP.
• Revealed distinct spatial distributions of various lipid classes and their isomers in tissue samples.

Conclusions:

• The developed TCPP-based dual-polarity iMSI method provides comprehensive lipidome coverage.
• This approach significantly improves the sensitivity and scope of lipid imaging in biological tissues.
• The technique facilitates detailed spatial mapping of complex lipid isomers, advancing our understanding of biological systems.