A single atom cobalt anchored MXene bifunctional platform for rapid, label-free and high-throughput biomarker...

Few of single-atom materials have been served as platform to analyze small molecules for surface assisted laser desorption/ionization mass spectrometry (SALDI-MS). Herein, a novel single Co atom-anchored MXene (Co-N-Ti₃C₂) is prepared to achieve enhanced SALDI-MS and mass spectrometry imaging (MSI) performance for the first time. The Co-N-Ti₃C₂ films were prepared by a simple in situ self-assembly strategy to generate an efficient SALDI-MS platform. Compared to typical inorganic/organic matrices, Co-N-Ti₃C₂ films exhibit superior performance in small molecules detection with ultra-high sensitivity (LOD at amol level), excellent repeatability (CV <4%), clean background and wide analyte coverage, enabling accurate quantitative analysis of various low-concentration metabolites from 1 μL biofluid in seconds. Its usage efficiently enhanced SALDI-MS detection of various small-molecule biomarkers such as amino acids, succinic acid, itaconic acid, arachidonic acid, citrulline, prostaglandin E2, creatinine, uric acid, glutamine, D-mannose, cholesterol and inositol in positive ion mode. The blood glucose level in humans was successfully determined from a linearity concentration range (0.25-10 mM). Notably, the Co-N-Ti₃C₂ assisted SALDI-MSI enables study the spatial distribution of small molecules covering the range central to metabolomics at a high resolution on a tissue section. Furthermore, Co-N-Ti₃C₂ platform revealed a specific peak profile that distinguishes osteoarthritis (OA) from rheumatoid arthritis (RA) tissue. Density functional theory theoretical investigation revealed that single Co atoms anchored on Ti₃C₂ could highly enhanced the ionization ability of metabolites, resulting in high-sensitivity and heterogeneous metabolome coverage.