Imaging Mass Spectrometry of Biological Tissues

生物组织成像质谱法******质谱法是一种强大的分析工具，用于鉴定和定量样品中的化学分子。它的工作原理是分离和测量这些化学物质的分子质量。为了对生物组织进行基质辅助激光解吸/电离成像质谱分析（MALDI IMS），使用激光束将化学物质的采样聚焦到组织切片的一个非常小的区域（< 0.1 mm）。以逐点（或逐像素）的方式，记录组织上化学物质的丰度和质量。然后将数据集显示为热图，以揭示任何检测到的分子的二维分布。当与精心设计的样品处理相结合时，研究人员能够将分子分布的变化与生物功能联系起来。理想情况下，统计软件应该能够以非目标和无偏见的方式识别变化。实际上，化学噪声的存在，即不是直接来自分析物的信号，会掩盖分析物信号中的微小变化，使其无法被统计工具检测到。这对于低分子量（MW）化合物的IMS尤其成问题，因为促进分析物激光电离所需的化学基质会在低MW区域产生相当大的背景噪声。该区域包含许多重要的代谢物和信号分子，如生物胺和神经递质。因此，需要进一步的研究来改进IMS对这些小分析物的非靶向分析。******这项研究经费将支持探索三种方法来提高低毫瓦区域组织IMS的质量。首先，提出了一种新型材料作为激光吸收基质，以降低化学噪声。研究将集中在金属氧化物纳米颗粒的使用，以及它们在组织表面的均匀应用，以促进对大鼠脑组织中低毫瓦代谢物和神经递质的分析。第二种方法是用组织化学反应衍生分析物，以提高电离效率，并标记它们以与背景区分。最后，分析后的数据处理将去除与矩阵相关的背景噪声。用特殊同位素标记的基质化合物将有助于背景噪声信号的识别。总之，这三种提出的方法将显著提高组织中低分子量化学物质非靶向分析的IMS质量。

Imaging Mass Spectrometry of Biological Tissues******Mass spectrometry is a powerful analytical tool for the identification and quantification of chemical molecules from a sample. It operates by separating and measuring the molecular masses of these chemicals. To perform matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) of biological tissues, the sampling of chemicals is focused to a very small area of a tissue section (< 0.1 mm) using a laser beam. In a spot-by-spot (or pixel-by-pixel) fashion, the abundances and masses of the chemicals on the tissue are recorded. The data set is then displayed as heat maps to reveal the 2-dimensional distribution of any detected molecules. When combined with strategically designed sample treatment, researchers are able to correlate the changes in molecular distribution to biological functions. Ideally, statistical software should be able to identify changes in a non-targeted and unbiased manner. In practice, the presence of chemical noise, signals that do not directly originate from the analytes, can drown out small changes in analyte signals, making them undetectable by statistical tools. This is particularly problematic for the IMS of low molecular weight (MW) compounds, because the chemical matrix required to promote the laser ionization of analytes can generate a substantial level of background noise in the low-MW region. This region consists of many important metabolites and signaling molecules, such as biogenic amines and neurotransmitters. Hence, further research is needed to improve IMS for the non-targeted profiling of these small analytes. ******This research grant will support the exploration of three approaches to improve the quality of tissue IMS in the low-MW region. Firstly, novel materials are proposed as the laser absorbing matrices which will reduce chemical noise. Studies will focus on the use of metal oxide nanoparticles, and their uniform application on the tissue surfaces, to facilitate the analysis of low-MW metabolites and neurotransmitters in rat brain tissue. The second approach is to derivatize the analytes with on-tissue chemical reactions, to enhance the ionization efficiency, and to label them for differentiation from background. Finally, post-analysis data processing will remove the matrix-related background noise. Identification of background noise signals will be assisted with the use of matrix compounds labeled with special isotopes. Together, the three proposed approaches will significantly improve the quality of IMS in the non-targeted profiling low-MW chemicals in tissue.