Dowlatshahi Pour Masoumeh, Malmberg Per, Ewing Andrew
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.
Anal Bioanal Chem. 2016 May;408(12):3071-81. doi: 10.1007/s00216-016-9385-3. Epub 2016 Feb 27.
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.
我们已经对在二次离子质谱（SIMS）分析中使用升华法沉积基质辅助激光解吸/电离（MALDI）基质进行了表征，即基质增强SIMS（ME-SIMS），这是一种常见的表面改性方法，用于提高对较大分子的灵敏度并增加完整分子离子的产生。我们使用升华法将一层传统的MALDI基质2,5-二羟基苯甲酸（DHB）应用于大鼠脑小脑组织，以展示该技术如何用于提高SIMS中的分子产率，同时仍保持约2μm的横向分辨率，并研究这种增强的机制。此处的结果表明，胆固醇是脑中占主导地位的脂质种类，在沉积基质后，组织表面的胆固醇会减少，尤其是在白质中。胆固醇减少后，其他几种脂质种类的离子产率会增加。对升华后的大鼠脑进行深度剖析表明，脂质种类实际上被DHB基质提取并浓缩在升华基质的最顶层。脂质的这种提取/浓缩直接导致更高质量脂质离子产率的增加。胆固醇的减少也有可能降低胆固醇迁移到组织表面所导致的离子产率潜在抑制。这一结果为我们深入了解在ME-SIMS中使用升华法沉积该基质时可能涉及的机制提供了重要见解。
