Imaging Mass Spectrometry of Biological Tissues

生物组织的成像质谱分析

• 批准号: RGPIN-2017-05584
• 负责人: Yeung, Ken
• 金额: $ 2.04万
• 依托单位: University of Western Ontario
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=682438
• 关键词: Imaging; Mass; Spectrometry; Biological; Tissues

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.

生物组织的成像质谱学*质谱学是从样品中识别和量化化学分子的强大分析工具。它通过分离和测量这些化学物质的分子质量来运作。为了对生物组织进行基质辅助激光解吸/电离成像质谱学(MALDI IMS)，使用激光束将化学物质的采样聚焦到组织切片的非常小的区域(&lt；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。当与战略性设计的样本处理相结合时，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无针对性和不偏不倚的方式识别变化。在实践中，化学噪声的存在可能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。这对低分子量(MW)化合物的IMS尤其有问题，因为促进分析物激光电离所需的化学基质可能会在低分子量区域产生大量的背景噪声。这个区域由许多重要的代谢物和信号分子组成，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。*这项研究拨款将支持探索三种方法，以提高低兆瓦地区组织IMS的质量。首先，提出了新的材料作为激光吸收矩阵，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，以便于分析大鼠脑组织中的低分子代谢物和神经递质。第二种方法是用组织上的化学反应衍生分析物，提高电离效率，并标记它们以便与背景区分。最后对分析后的数据进行处理，去除与矩阵相关的背景噪声。通过使用标记有特殊同位素的基质化合物，将有助于识别背景噪声信号。总之，这三种建议的方法将显著提高IMS在非靶向分析组织中的低分子化学物质的质量。