Center for Nano-Bio Measurement, Korea Research Institute of Standards and Science (KRISS), Daejeon 34113, Korea.
Department of Nano Science, University of Science and Technology (UST), Daejeon 34113, Korea.
Anal Chem. 2022 Jul 5;94(26):9297-9305. doi: 10.1021/acs.analchem.2c00676. Epub 2022 Jun 13.
The importance of multi-omic-based approaches to better understand diverse pathological mechanisms including neurodegenerative diseases has emerged. Spatial information can be of great help in understanding how biomolecules interact pathologically and in elucidating target biomarkers for developing therapeutics. While various analytical methods have been attempted for imaging-based biomolecule analysis, a multi-omic approach to imaging remains challenging due to the different characteristics of biomolecules. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) is a powerful tool due to its sensitivity, chemical specificity, and high spatial resolution in visualizing chemical information in cells and tissues. In this paper, we suggest a new strategy to simultaneously obtain the spatial information of various kinds of biomolecules that includes both labeled and label-free approaches using ToF-SIMS. The enzyme-assisted labeling strategy for the targets of interest enables the sensitive and specific imaging of large molecules such as peptides, proteins, and mRNA, a task that has been, to date, difficult for any MS analysis. Together with the strength of the analytical performance of ToF-SIMS in the label-free tissue imaging of small biomolecules, the proposed strategy allows one to simultaneously obtain integrated information of spatial distribution of metabolites, lipids, peptides, proteins, and mRNA at a high resolution in a single measurement. As part of the suggested strategy, we present a sample preparation method suitable for MS imaging. Because a comprehensive method to examine the spatial distribution of multiple biomolecules in tissues has remained elusive, our strategy can be a useful tool to support the understanding of the interactions of biomolecules in tissues as well as pathological mechanisms.
多组学方法对于更好地理解包括神经退行性疾病在内的多种病理机制的重要性已经显现出来。空间信息对于理解生物分子如何在病理上相互作用以及阐明用于开发治疗方法的靶标生物标志物非常有帮助。虽然已经尝试了各种基于分析的方法来进行基于成像的生物分子分析，但由于生物分子的不同特性，基于成像的多组学方法仍然具有挑战性。飞行时间二次离子质谱 (ToF-SIMS) 是一种强大的工具，因为它具有灵敏度、化学特异性和在细胞和组织中可视化化学信息的高空间分辨率。在本文中，我们提出了一种新策略，使用 ToF-SIMS 同时获得包括标记和无标记方法在内的各种生物分子的空间信息。对于感兴趣的目标的酶辅助标记策略使对多肽、蛋白质和 mRNA 等大分子的敏感和特异性成像成为可能，这是任何 MS 分析迄今为止都难以完成的任务。结合 ToF-SIMS 在无标记组织中小分子生物分子的分析性能优势，该策略允许在单次测量中同时获得代谢物、脂质、肽、蛋白质和 mRNA 空间分布的综合信息，具有高分辨率。作为所提出策略的一部分，我们提出了一种适合 MS 成像的样品制备方法。由于仍然难以找到一种全面的方法来检查组织中多种生物分子的空间分布，因此我们的策略可以成为支持理解组织中生物分子相互作用以及病理机制的有用工具。
