Matrix-assisted laser desorption ionization (MALDI) remains the reference method to generate molecular images of proteins and lipids within thin tissue sections. However, traditional MALDI imaging mass spectrometry (IMS) suffers from low matrix homogeneity and high signal background in low mass range caused by matrix signals. To overcome these issues, alternative workflow and methods have been developed. Of these, metal-assisted laser desorption ionization (LDI) has become a reference technique to ionize low molecular weight compounds while allowing IMS at very high spatial resolutions with very low background signal in the low mass range. Silver and gold remain the two most used metals for the detection of neutral lipids including cholesterol, free fatty acids, and triglycerides. In this chapter, we demonstrate the potential of metal-assisted LDI IMS through the analysis of spinal cord and kidney thin tissue sections after silver and gold metal deposition. We also detail typical step-by-step workflows and discuss the strength of the methods.
Keywords: Cholesterol; Gold; Imaging MS; Laser desorption ionization; Metal sputter; Neutral lipids; SALDI; Silver; Spinal cord.
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