State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Key Laboratory of Mass Spectrometry Imaging and Metabolomics (Minzu University of China), National Ethnic Affairs Commission, Beijing 100081, China.
Anal Chem. 2021 Nov 23;93(46):15373-15380. doi: 10.1021/acs.analchem.1c03118. Epub 2021 Nov 8.
The improvement of on-tissue chemical derivatization for mass spectrometry imaging (MSI) of low-abundance and/or poorly ionizable functional molecules in biological tissue without delocalization is challenging. Here, we developed a novel hydrogel-assisted chemical derivatization (HCD) approach coupled with airflow-assisted desorption electrospray ionization (AFADESI)-MSI, allowing for enhanced visualization of inaccessible molecules in biological tissues. The derivatization reagent Girard's P (GP) reagent was creatively packaged into a hydrogel to form HCD blocks that have reactivity to carbonyl compounds as well as the feasibility of "cover/uncover" contact mode with tissue sections. The HCD blocks provided a favorable liquid microenvironment for the derivatization reaction and reduced matrix effects from derivatization reagents and tissue without obvious molecular migration, thus improving the derivatization efficiency. With this methodology, unusual carbonyl metabolites, including 166 fatty aldehydes (FALs) and 100 oxo fatty acids (FAs), were detected and visualized in rat brain, kidney, and liver tissue. This study provides a new approach to enhance chemical labeling for in situ tissue submetabolome profiling and improves our knowledge of the molecular histology and complex metabolism of biological tissues.
提高组织内化学衍生化方法，以用于对生物组织中低丰度和/或不易离子化的功能分子进行质谱成像（MSI），同时避免分子离位，这是一个具有挑战性的问题。在此，我们开发了一种新型的水凝胶辅助化学衍生化（HCD）方法，与气流辅助解吸电喷雾电离（AFADESI）-MSI 相结合，从而可以增强对生物组织中不可接近分子的可视化。衍生化试剂吉拉德试剂 P（GP）被创造性地封装到水凝胶中，形成 HCD 块，这些 HCD 块具有与羰基化合物反应的能力，以及与组织切片进行“覆盖/揭开”接触模式的可行性。HCD 块为衍生化反应提供了有利的液体微环境，并减少了衍生化试剂和组织的基质效应，而没有明显的分子迁移，从而提高了衍生化效率。通过这种方法，在大鼠的脑、肾和肝组织中检测到并可视化了 166 种脂肪酸醛（FAL）和 100 种氧化脂肪酸（FA）等异常羰基代谢物。本研究为增强原位组织亚代谢组分析中的化学标记提供了一种新方法，并提高了我们对生物组织的分子组织学和复杂代谢的认识。
