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Direct imaging of single cells and tissue at sub-cellular spatial resolution using transmission geometry MALDI MS

机译:使用透射几何MALDI MS以亚细胞空间分辨率直接成像单细胞和组织

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摘要

The need of cellular and sub-cellular spatial resolution in laser desorption ionization (LDI)/matrix-assisted LDI (MALDI) imaging mass spectrometry (IMS) necessitates micron and sub-micron laser spot sizes at biologically relevant sensitivities, introducing significant challenges for MS technology. To this end, we have developed a transmission geometry vacuum ion source that allows the laser beam to irradiate the back side of the sample. This arrangement obviates the mechanical/ion optic complications in the source by completely separating the optical lens and ion optic structures. We have experimentally demonstrated the viability of transmission geometry MALDI MS for imaging biological tissues and cells with sub-cellular spatial resolution. Furthermore, we demonstrate that in conjunction with new sample preparation protocols, the sensitivity of this instrument is sufficient to obtain molecular images at sub-micron spatial resolution.
机译:激光解吸电离(LDI)/基质辅助LDI(MALDI)成像质谱(IMS)中对细胞和亚细胞空间分辨率的需求使微米和亚微米激光点的尺寸具有生物学相关的灵敏度,这给MS带来了重大挑战技术。为此,我们开发了一种透射几何形状的真空离子源,它可以使激光束照射到样品的背面。通过将光学透镜和离子光学结构完全分开,这种布置消除了源中的机械/离子光学复杂性。我们已经通过实验证明了透射几何MALDI MS能够对具有亚细胞空间分辨率的生物组织和细胞进行成像。此外,我们证明与新的样品前处理方案结合使用,该仪器的灵敏度足以获得亚微米空间分辨率的分子图像。

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