A novel high-entropy TiVCrMoC₃T_x assisted LDI MS for serum metabolic fingerprint in rheumatoid arthritis

Worldwide, rheumatoid diseases account for approximately 37.57/100,000 disability-adjusted life years (DALYs). Early diagnosis of rheumatoid arthritis (RA) can effectively reduce associated risks and improve quality of life. To achieve this, accurate and rapid advanced tools are required. Herein, TiVCrMoC₃, a novel high-entropy two-dimensional (2D) carbide MXene that exhibits excellent electrical conductivity, is prepared and applied to surface-assisted laser desorption ionization mass spectrometry (SALDI-MS) analysis for the first time. TiVCrMoC₃ demonstrates superior performance in small-molecule detection compared with typical inorganic and organic substrates. Moreover, its exhibits ultrahigh sensitivity (limit of detection (LOD) at the 10 pg/mL level), excellent repeatability (coefficient of variation (CV) <4%), excellent quantitative detection capability (coefficient of determination = 0.99987), clean background, and broad analyte coverage. Results showed that TiVCrMoC₃-assisted laser desorption ionization mass spectrometry (LDI-MS) is efficient in screening RA diseases, with the advantages of high throughput and low cost. It enables accurate and quantitative analysis of various low-concentration metabolites in 1 μL of biological fluid within seconds. Combined with machine learning, TiVCrMoC₃-assisted LDI-MS is used to accurately diagnose multiple RA samples. A total of 8 potential different small-molecule metabolites between individuals with osteoarthritis (OA) and RA were identified based on relative quantification methods, and their associated metabolic changes were discussed. TiVCrMoC₃-assisted LDI-MS provides a potential tool for the rapid diagnosis of RA and may pave the way for precision medicine.