Zr-MOF encapsulated-magnetic beads-based fast and efficient conjugation strategy for sensitive immunoassays and early diagnosis of rheumatoid arthritis

Anti-cyclic citrullinated peptide (anti-CCP) antibodies are key biomarkers for rheumatoid arthritis and vital for its early diagnosis and monitoring. Conventional chemiluminescence immunoassays (CLIA) rely on streptavidin-functionalized magnetic beads (SA-MBs), which suffer from limited binding capacity and require labor-intensive chemical conjugation steps. Here, we report a MBs carrier modified with zirconium (Zr)-based metal-organic frameworks (MB@MOF), enabling rapid and efficient SA functionalization via one-step physicochemical adsorption. Compared to the conventional EDC/NHS method, our approach shortens the modification time by at least sixfold and eliminates the need for chemical crosslinkers. The MB@MOF carrier was constructed by anchoring Zr-MOF nanoparticles, synthesized with TCPE as the organic ligand, onto MBs. This carrier supports stable and dense SA loading while preserving native SA activity, thereby allowing highly sensitive detect anti-CCP antibodies. The developed MB@MOF carrier-based CLIA method achieved a detection limit of 0.1 RU/mL and a linear range of 0.5–200 RU/mL. Clinical validation using 36 clinical serum samples showed strong agreement with results from standard clinical analyzers, achieving an overall diagnostic accuracy of 91.7 %. This strategy significantly simplifies the assay workflow and holds strong potential for high-performance and rapid diagnostics of rheumatoid arthritis in clinical application.