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

ABSTRACT

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.