Institute for Hygiene, University of Münster, Münster, Germany.
Interdisciplinary Center for Clinical Research, University of Münster, Münster, Germany.
Nat Methods. 2019 Sep;16(9):925-931. doi: 10.1038/s41592-019-0536-2. Epub 2019 Aug 26.
Matrix-assisted laser desorption-ionization mass spectrometry imaging in transmission-mode geometry (t-MALDI-MSI) can provide molecular information with a pixel size of 1 µm 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 post-ionization (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.
在透射模式几何结构下（t-MALDI-MSI）进行的基质辅助激光解吸电离质谱成像（Matrix-assisted laser desorption-ionization mass spectrometry imaging in transmission-mode geometry）可以提供具有 1 µm 或更小像素大小的分子信息，这使得这种无需标记的方法非常有兴趣用于在（亚）细胞水平上表征组织和细胞的化学成分。然而，该技术更广泛应用的一个主要障碍是小像素尺寸下的离子丰度降低。在这里，我们通过使用激光诱导后电离（MALDI-2）和将 t-MALDI-2 离子源适配到轨道阱质谱仪来缓解这个问题。我们通过在小鼠小脑和肾切片以及培养的 Vero B4 细胞中可视化众多磷酸化和糖脂的分布，证明了这种组合实现的关键灵敏度和准确性提升。在脑组织中，达到了 600nm 的像素大小。我们的方法可能成为细胞生物学和生物医学研究的有价值的新工具。
