Transmission-mode MALDI-2 mass spectrometry imaging of cells and tissues at subcellular resolution
Transmission-mode MALDI-2 mass spectrometry imaging of cells and tissues at subcellular resolution
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DOI：
10.1038/s41592-019-0536-2
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发表时间：
2019-09-01
期刊：
影响因子：
48
通讯作者：
Dreisewerd, K.
中科院分区：
文献类型：
--
作者：
Niehaus, M.;Soltwisch, J.;Dreisewerd, K.
透射模式几何结构中的基质辅助激光解吸电离质谱成像 (t-MALDI-MSI) 可以提供像素大小为 lum 或更小的分子信息，这使得这种无标记方法对于在（亚）细胞水平上表征组织和细胞的化学成分非常有趣。然而，该技术广泛应用的一个主要障碍是小像素尺寸下离子丰度的降低。在这里，我们通过使用激光诱导位置离子化 (MALDI-2) 以及将 t-MALDI-2 离子源适配到 Orbitrap 质量分析仪来缓解这个问题。我们通过可视化小鼠小脑和肾切片以及培养的 Vero B4 细胞中大量磷酸脂和糖脂的分布，证明了这种组合所实现的关键灵敏度和准确性的提升。对于脑组织，像素尺寸达到了 600 nm。我们的方法可以成为细胞生物学和生物医学研究的一个有价值的新工具。
Matrix-assisted laser desorption-ionization mass spectrometry imaging in transmission-mode geometry (t-MALDI-MSI) can provide molecular information with a pixel size of lum and smaller, which makes this label-free method highly interesting for characterizing the chemical composition of tissues and cells on a (sub)cellular level. However, a major hindrance for wider use of the technology is the reduced ion abundance at small pixel sizes. Here we mitigate this problem by use of laser-induced postionization (MALDI-2) and by adapting a t-MALDI-2 ion source to an Orbitrap mass analyzer. We demonstrate the crucial sensitivity and accuracy boosts that are achieved with this combination by visualizing the distribution of numerous phospho- and glycolipids in mouse cerebellum and kidney slices, and in cultured Vero B4 cells. With brain tissue, a pixel size of 600 nm was achieved. Our method could constitute a valuable new tool for research in cell biology and biomedicine.