Mass spectrometry imaging of small molecules using matrix-enhanced surface-assisted laser desorption/ionization mass spectrometry (ME-SALDI-MS).

Surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS) uses inorganic particles or porous surfaces as the energy-mediating means to promote desorption and ionization of low-mass analytes of interest. With good stability during laser ablation, SALDI substrates exhibit reduced background in the low-mass region that is often crowded in conventional matrix-assisted laser desorption/ionization (MALDI) due to matrix fragmentation; a benefit renders SALDI-MS attractive in imaging low-mass species. Practical application of SALDI-MS, however, is hindered by its unsatisfied detection sensitivity for most compounds. With aims of improving MS imaging resolution and sensitivity of low-mass species, we describe an experimental protocol using a hybrid ionization method, termed matrix-enhanced SALDI (ME-SALDI), to detect crucial low-mass species with their spatial distribution in mouse brain tissue.