High-Specificity and Sensitivity Imaging of Neutral Lipids Using Salt-Enhanced MALDI TIMS

Area of Science:

• Lipidomics
• Mass Spectrometry Imaging
• Cellular Biology

Background:

• Neutral lipids play crucial roles in cellular functions and disease.
• Characterizing neutral lipids with MALDI IMS is difficult due to low ionization efficiency and complex isomer/isobar mixtures.

Purpose of the Study:

• To enhance neutral lipid detection and characterization in biological tissues using MALDI IMS.
• To improve the separation of neutral lipid isomers and isobars.

Main Methods:

• Incorporated isotonic metal-cation washes into the MALDI IMS sample preparation.
• Utilized trapped ion mobility spectrometry (TIMS) for enhanced separation.
• Tested the method on murine brain, rabbit adrenal gland, human colon, and human kidney tissues.

Main Results:

• Metal-cation washes improved neutral lipid detection sensitivity and specificity.
• Salt adducts formed by washes aided in separating neutral lipid isobars and isomers via TIMS.
• The Na+ carbonate buffer solution (CBS) wash demonstrated the most significant overall improvement in neutral lipid detection.

Conclusions:

• The developed method offers a robust framework for mapping neutral lipids in various tissues and disease states.
• This approach enables detailed characterization of neutral lipid isomers and isobars in complex biological samples.
• Tissue-specific salt washes optimize neutral lipid analysis for MALDI IMS.