Intact lipid imaging of mouse brain samples: MALDI, nanoparticle-laser desorption ionization, and 40 keV argon cluster secondary ion mass spectrometry.

We have investigated the capability of nanoparticle-assisted laser desorption ionization mass spectrometry (NP-LDI MS), matrix-assisted laser desorption ionization (MALDI) MS, and gas cluster ion beam secondary ion mass spectrometry (GCIB SIMS) to provide maximum information available in lipid analysis and imaging of mouse brain tissue. The use of Au nanoparticles deposited as a matrix for NP-LDI MS is compared to MALDI and SIMS analysis of mouse brain tissue and allows selective detection and imaging of groups of lipid molecular ion species localizing in the white matter differently from those observed using conventional MALDI with improved imaging potential. We demonstrate that high-energy (40 keV) GCIB SIMS can act as a semi-soft ionization method to extend the useful mass range of SIMS imaging to analyze and image intact lipids in biological samples, closing the gap between conventional SIMS and MALDI techniques. The GCIB SIMS allowed the detection of more intact lipid compounds in the mouse brain compared to MALDI with regular organic matrices. The 40 keV GCIB SIMS also produced peaks observed in the NP-LDI analysis, and these peaks were strongly enhanced in intensity by exposure of the sample to trifluororacetic acid (TFA) vapor prior to analysis. These MS techniques for imaging of different types of lipids create a potential overlap and cross point that can enhance the information for imaging lipids in biological tissue sections. Graphical abstract Schematic of mass spectral imaging of a mouse brain tissue using GCIB-SIMS and MALDI techniques.