Mass spectrometry imaging with high resolution in mass and space.

Mass spectrometry imaging with high resolution in mass and space.
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DOI:
10.1007/s00418-013-1097-6
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发表时间:
2013-06
影响因子:
2.3
通讯作者:
Spengler, Bernhard
Spengler, Bernhard
中科院分区:
生物学3区
文献类型:
--
作者:
Roempp, Andreas;Spengler, Bernhard

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质谱(MS)成像将分子信息与样品中分析物的空间分布联系起来。与大多数组织化学技术相比,质谱成像可以区分分子修饰,不需要标记目标化合物。我们最近推出了第一种质谱成像方法,可以在细胞维度(空间分辨率高)上提供高度特异性的分子信息(高分辨率和质量精度)。该方法是基于在大气压下工作的矩阵辅助激光解吸/电离(MALDI)成像源,该成像源与轨道俘获质谱仪耦合。在这里,我们给出了一些应用实例,并展示了质谱成像在质量和空间上具有高分辨率的好处。磷脂、多肽和药物化合物在许多组织样品中以5-10 μm的空间分辨率成像。组织上胰蛋白酶消化后,以50 μm分辨率分析蛋白质。其他应用包括单细胞和人类肺癌组织的分析,以及首次对3 μm像素大小的组织进行MALDI成像测量。所有实验的MS图像分析显示与组织学染色评价具有良好的相关性。事实证明,高质量分辨率(R = 30,000)和质量精度(通常为1 ppm)对于组织样品中特定图像的生成和分析物的可靠鉴定至关重要。将所需的高质量质量分析与单细胞范围内的空间分辨率相结合的能力是我们方法的独特之处。因此,它有可能补充经典的组织化学方案,并在细胞水平上提供关于分子过程的新见解。
Mass spectrometry (MS) imaging links molecular information and the spatial distribution of analytes within a sample. In contrast to most histochemical techniques, mass spectrometry imaging can differentiate molecular modifications and does not require labeling of targeted compounds. We have recently introduced the first mass spectrometry imaging method that provides highly specific molecular information (high resolution and accuracy in mass) at cellular dimensions (high resolution in space). This method is based on a matrix-assisted laser desorption/ionization (MALDI) imaging source working at atmospheric pressure which is coupled to an orbital trapping mass spectrometer. Here, we present a number of application examples and demonstrate the benefit of ‘mass spectrometry imaging with high resolution in mass and space.’ Phospholipids, peptides and drug compounds were imaged in a number of tissue samples at a spatial resolution of 5–10 μm. Proteins were analyzed after on-tissue tryptic digestion at 50-μm resolution. Additional applications include the analysis of single cells and of human lung carcinoma tissue as well as the first MALDI imaging measurement of tissue at 3 μm pixel size. MS image analysis for all these experiments showed excellent correlation with histological staining evaluation. The high mass resolution (R = 30,000) and mass accuracy (typically 1 ppm) proved to be essential for specific image generation and reliable identification of analytes in tissue samples. The ability to combine the required high-quality mass analysis with spatial resolution in the range of single cells is a unique feature of our method. With that, it has the potential to supplement classical histochemical protocols and to provide new insights about molecular processes on the cellular level.
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