MALDI Mass Spectrometry Imaging of Metal Ions and Metabolites in Tissues Using a Bifunctional Matrix

Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is a powerful technique for spatially resolved analysis of diverse molecular species within biological tissues. However, the simultaneous imaging of metal ions and small-molecule metabolites remains analytically challenging due to their distinct chemical properties and desorption/ionization behaviors. Herein, 5,6-diamino-1,10-phenanthroline (DAP) hydrochloride was introduced as a bifunctional matrix that enables concurrent MALDI-MS imaging of metal ions and endogenous metabolites from the same tissue section. In the positive ion mode, DAP forms stable chelation complexes with metal ions, enhancing their ionization efficiency while preserving spatial localization. In negative ion mode, DAP hydrochloride exhibits excellent matrix properties for the efficient desorption and ionization of a wide range of endogenous metabolites. This strategy was successfully applied to tissue sections, achieving high-quality imaging of both metal ions and metabolites without the need for additional matrix coating. Our results demonstrate that DAP hydrochloride serves as a versatile and efficient matrix for multimodal molecular imaging and offers a promising platform for investigating metal-metabolite interactions in situ.