Development of N,S-doped carbon dots as a novel matrix for the analysis of small molecules by negative ion MALDI-TOF MS

Recently, MALDI-TOF MS has emerged as a popular analytical tool with the advantages of easy sample preparation and good salt tolerance, as well as fast and high throughput data acquisition ability. However, for the existing matrices, they were limited in detecting low-molecular-weight analytes due to the matrix-related peaks and low reproducibility. Therefore, the development of new matrices is highly desirable. Here, a new matrix N,S-CDs, for the first time, was synthesized and used for small molecule analysis. Comprehensive assessments of N,S-CDs were conducted including structural characterization, comparisons with conventional CHCA, 9-AA and N-CDs matrices in detecting amino acids, peptides, nucleosides and anticancer drugs in different ion modes. The results showed that N,S-CDs could be a sensational matrix which had good signal intensity of the analytes without matrix-related interference, especially in negative ion mode. What's more, the N,S-CDs matrix displayed good salt tolerance and signal reproducibility. In addition, the N,S-CDs matrix was further applied for serum detection, quantitative determination of endogenous glucose, and the classification of different subtypes of breast cancer cell lines. The detection of various endogenous metabolites in serum analysis and significantly distinguishing between two cell lines indicated the ability of our new matrix to be applied in complex biological samples. Furthermore, the ionization mechanism of the N,S-CDs as a matrix was also discussed comparing with N-CDs in the transformation of structure and composition. This work creates a new application branch for N,S-CDs and provides an improved MALDI matrix for small molecule analysis.