Yolk-shell Ni/NiO anchored on N-doped graphene synthesized as dual-ion MALDI matrix for detecting and imaging bioactive small molecules

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is an attractive tool to analyze the bioactive small molecules but remains a great challenge owing to the serious background interference from conventional matrix with m/z < 1000. Herein, we reported a dual-ion MALDI matrix of yolk-shell Ni/NiO nanoparticles anchored on nitrogen-doped graphene (Ni/NiO/N-Gr) to enhance MALDI performance. The Ni/NiO/N-Gr was synthesized via the pyrolysis and controllable oxidation strategy based on the nanoscale regulation of Kirkendall effect. The novel matrix showed the superior behavior for the analysis of various small molecular metabolites (amino acids, saccharides, spermidine, creatinine, hippuric acid, dopamine, and ascorbic acid) with high sensitivity, excellent salt tolerance, and favorable reproducibility in dual-ion modes compared to the traditional α-cyano-4-hydroxycinnamic acid (CHCA) and control substances (Ni/N-Gr and NiO/N-Gr). Meanwhile, we have realized accurate quantitation of blood glucose in mice with a linearity concentration range of 0.2-7.5 mM and qualitative detection of various endogenous small molecular metabolites in mice serum and urine samples. Especially, the Ni/NiO/N-Gr assisted LDI MS imaging (MSI) has exhibited the excellent spatial distribution of lipids in hippocampus region of mice brain. These results may provide an approach to explore the MALDI MS and MSI applications in clinical diagnosis.