Visualizing xenobiotics and metabolites in zebrafish by VUV-laser desorption post-ionization mass spectrometry imaging
摘要
Mass spectrometry imaging (MSI) enables spatial mapping of chemical distributions across complex surfaces, with broad applications spanning materials analysis, life sciences, and clinical diagnostics. However, conventional ionization sources often suffer from limited ionization efficiency, creating a trade-off between detection sensitivity and spatial resolution. Post-ionization technology addresses this constraint by incorporating a secondary ionization step, significantly enhancing ionization yield and establishing itself as a leading approach for advancing mass spectrometry techniques. In this study, we have independently developed a vacuum ultraviolet-laser desorption post-ionization mass spectrometry (VUV-LDPI-MS) system, which significantly enhances detection sensitivity through the implementation of post-ionization technology. By integrating low-photon-energy long-wavelength laser desorption with the soft-ionizing capability of VUV light, this technique enhances the detection of chemical species within biological tissues—including both exogenous drugs and endogenous metabolites. The method achieved a theoretical detection limit of 8.3 pg/spot for methylene blue (MB), while markedly reducing substrate effects and sample background interference. Imaging results revealed that endogenous compounds closely aligned with zebrafish tissue anatomy, whereas the spatial distribution of exogenous MB strongly correlated with optical images. Successful application to zebrafish tissue sections enabled clear visualization of both MB and intrinsic metabolites. VUV-LDPI-MSI offers superior ionization efficiency with minimal sample preparation, presenting a robust alternative to conventional LDI-MS approaches and holding considerable promise for future technological development.