Ouyang Dan, Wang Chuanzhe, Zhong Chao, Lin Juan, Xu Gang, Wang Guane, Lin Zian
Ministry of Education Key Laboratory of Analytical Science for Food Safety and Biology, Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food Safety, College of Chemistry, Fuzhou University Fuzhou Fujian 350108 China
State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences (CAS) Fuzhou Fujian 350002 China
Chem Sci. 2023 Nov 27;15(1):278-284. doi: 10.1039/d3sc05633c. eCollection 2023 Dec 20.
Metabolic analysis in biofluids based on laser desorption/ionization mass spectrometry (LDI-MS), featuring rapidity, simplicity, small sample volume and high throughput, is expected to be a powerful diagnostic tool. Nevertheless, the signals of most metabolic biomarkers obtained by matrix-assisted LDI-MS are too limited to achieve a highly accurate diagnosis due to serious background interference. To address this issue, nanomaterials have been frequently adopted in LDI-MS as substrates. However, the "trial and error" approach still dominates the development of new substrates. Therefore, rational design of novel LDI-MS substrates showing high desorption/ionization efficiency and no background interference is extremely desired. Herein, four few-layered organic metal chalcogenides (OMCs) were precisely designed and for the first time investigated as substrates in LDI-MS, which allowed a favorable internal energy and charge transfer by changing the functional groups of organic ligands and metal nodes. As a result, the optimized OMC-assisted platform satisfyingly enhanced the mass signal by ≈10 000 fold in detecting typical metabolites and successfully detected different saccharides. In addition, a high accuracy diagnosis of central precocious puberty (CPP) with potential biomarkers of 12 metabolites was realized. This work is not only expected to provide a universal detection tool for large-scale clinical diagnosis, but also provides an idea for the design and selection of LDI-MS substrates.
基于激光解吸/电离质谱(LDI-MS)的生物流体代谢分析具有快速、简便、样本量小和高通量等特点,有望成为一种强大的诊断工具。然而,由于严重的背景干扰,通过基质辅助LDI-MS获得的大多数代谢生物标志物的信号过于有限,无法实现高精度诊断。为了解决这个问题,纳米材料在LDI-MS中经常被用作基质。然而,新基质的开发仍然主要采用“试错”方法。因此,迫切需要合理设计具有高解吸/电离效率且无背景干扰的新型LDI-MS基质。在此,精确设计了四种少层有机金属硫族化物(OMC),并首次将其作为LDI-MS中的基质进行研究,通过改变有机配体和金属节点的官能团,实现了良好的内能和电荷转移。结果,优化后的OMC辅助平台在检测典型代谢物时令人满意地将质量信号增强了约10000倍,并成功检测到不同的糖类。此外,利用12种代谢物的潜在生物标志物实现了对中枢性性早熟(CPP)的高精度诊断。这项工作不仅有望为大规模临床诊断提供一种通用的检测工具,也为LDI-MS基质的设计和选择提供了思路。