title: An investigation on the mechanism of sublimed DHB matrix on molecular ion yields in SIMS imaging of brain tissue.
abstract: We have characterized the use of sublimation to deposit matrix-assisted laser desorption/ionization (MALDI) matrices in secondary ion mass spectrometry (SIMS) analysis, i.e. matrix-enhanced SIMS (ME-SIMS), a common surface modification method to enhance sensitivity for larger molecules and to increase the production of intact molecular ions. We use sublimation to apply a thin layer of a conventional MALDI matrix, 2,5-dihydroxybenzoic acid (DHB), onto rat brain cerebellum tissue to show how this technique can be used to enhance molecular yields in SIMS while still retaining a lateral resolution around 2 μm and also to investigate the mechanism of this enhancement. The results here illustrate that cholesterol, which is a dominant lipid species in the brain, is decreased on the tissue surface after deposition of matrix, particularly in white matter. The decrease of cholesterol is followed by an increased ion yield of several other lipid species. Depth profiling of the sublimed rat brain reveals that the lipid species are de facto extracted by the DHB matrix and concentrated in the top most layers of the sublimed matrix. This extraction/concentration of lipids directly leads to an increase of higher mass lipid ion yield. It is also possible that the decrease of cholesterol decreases the potential suppression of ion yield caused by cholesterol migration to the tissue surface. This result provides us with significant insights into the possible mechanisms involved when using sublimation to deposit this matrix in ME-SIMS.
authors.affiliation: Department of Chemical and Chemical Engineering, Chalmers University of Technology, Kemigården 4, 41296, Gothenburg, Sweden.|National center for imaging mass spectrometry, Kemivägen 10, 41296, Gothenburg, Sweden.
authors.forename: Masoumeh
authors.initials: M
authors.lastname: Dowlatshahi Pour
authors.affiliation: Department of Chemical and Chemical Engineering, Chalmers University of Technology, Kemigården 4, 41296, Gothenburg, Sweden. malmper@chalmers.se.|National center for imaging mass spectrometry, Kemivägen 10, 41296, Gothenburg, Sweden. malmper@chalmers.se.
authors.forename: Per
authors.initials: P
authors.lastname: Malmberg
authors.affiliation: Department of Chemical and Chemical Engineering, Chalmers University of Technology, Kemigården 4, 41296, Gothenburg, Sweden. andrewe@chalmers.se.|National center for imaging mass spectrometry, Kemivägen 10, 41296, Gothenburg, Sweden. andrewe@chalmers.se.|Department of Chemistry and Molecular Biology, University of Gothenburg, Medicinaregatan 9C, 40530, Gothenburg, Sweden. andrewe@chalmers.se.
authors.forename: Andrew
authors.initials: A
authors.lastname: Ewing
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology*; D005841:Gentisates / Q000737:chemistry*; D008297:Male; D025341:Principal Component Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*
chemical_list: D005841:Gentisates
keywords: Cholesterol migration; ME-SIMS mechanism; MS imaging