Imaging mass spectrometry increased resolution using 2-mercaptobenzothiazole and 2,5-diaminonaphtalene matrices: application to lipid distribution in human colon

Imaging mass spectrometry is becoming a reference technique in the field of lipidomics, due to its ability to map the distribution of hundreds of species in a single run, along a tissue section. The next frontier is now achieving increasing resolution powers to offer cellular (or even sub-cellular) resolution. Thus, the new spectrometers are equipped with sophisticated optical systems to decrease the laser spot to <30 μm. Here, we demonstrate that by using the correct matrix (i.e., a matrix that maximizes ion detection and forms small crystals) and a careful preparation, it is possible to achieve resolutions of ∼5–10 μm, even with spectrometers equipped with non-optimal optics, which produces laser spots of 50 μm or even larger. As a proof of concept, we present images of distributions of lipids, both in positive and negative ion mode, over human colon endoscopic sections, recorded using 2-mercaptobenzothiazole for positive ion mode and 2,5-diaminonaphtalene for negative ion mode and an LTQ-Orbitrap XL, equipped with a matrix-assisted laser desorption ionization (MALDI) source that produces astigmatic laser spots.