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Improved Spatial Resolution of MALDI Imaging of Lipids in the Brain by Alkylated Derivatives of 2,5-Dihydroxybenzoic Acid
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    Matrix-assisted laser desorption/ionization (MALDI) is one of the major techniques for mass spectrometry imaging (MSI) of biological systems along with secondary-ion mass spectrometry (SIMS) and desorption electrospray mass spectrometry (DESI). The inherent variability of MALDI-MSI signals within intact tissues is related to the heterogeneity of both the sample surface and the matrix crystallization. To circumvent some of these limitations of MALDI-MSI, we have developed improved matrices for lipid analysis based on structural modification of the commonly used matrix 2,5-dihydroxybenzoic acid (DHB).|We have synthesized DHB containing -C6H13 and -C12H25 alkyl chains and applied these matrices to rat brain using a capillary sprayer. We utilized a Bruker Ultraflex II MALDI-TOF/TOF mass spectrometer to analyze lipid extracts and tissue sections, and examined these sections with polarized light microscopy and differential interference contrast microscopy.|O-alkylation of DHB yields matrices, which, when applied to brain sections, follow a trend of phase transition from crystals to an oily layer in the sequence DHB → DHB-C6H13 → DHB-C12H25 . MALDI-MSI images acquired with DHB-C12H25 exhibited a considerably higher density of lipids than DHB.|Comparative experiments with DHB and DHB-C12H25 are presented, which indicate that the latter matrix affords higher lateral resolution than the former.

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    ES020693/ES/NIEHS NIH HHS/United States
    ES021068/ES/NIEHS NIH HHS/United States
    NS061817/NS/NINDS NIH HHS/United States
    NS076511/NS/NINDS NIH HHS/United States
    OH008282/OH/NIOSH CDC HHS/United States
    P30CA047904/CA/NCI NIH HHS/United States
    R01 NS061817/NS/NINDS NIH HHS/United States
    R01 NS076511/NS/NINDS NIH HHS/United States
    U19 AI068021/AI/NIAID NIH HHS/United States
    U19AI068021/AI/NIAID NIH HHS/United States
    U54 GM103529 08/GM/NIGMS NIH HHS/United States
    UL1 TR000005/TR/NCATS NIH HHS/United States
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