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 alpha-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. (C) 2021 Published by Elsevier Inc.

Automated summary

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a powerful tool for analyzing bioactive small molecules. However, background interference from conventional matrices has been a challenge. In this study, a dual-ion MALDI matrix composed of yolk-shell Ni/NiO nanoparticles anchored on nitrogen-doped graphene was developed to enhance MALDI performance. The novel matrix demonstrated superior sensitivity, salt tolerance, and reproducibility compared to traditional matrices. It was successfully applied for the quantitation of blood glucose and qualitative detection of endogenous small molecular metabolites in mice samples. Additionally, the matrix enabled excellent imaging of lipid distribution in the hippocampus region of mice brains, suggesting its potential applications in clinical diagnosis.