Magnetism-Functionalized Lanthanide MOF-on-MOF with Plasmonic Differential Signal Amplification for Ultrasensitive Fluorescence Immunoassays

The successful application of fluorescence immunoassays for clinical diagnosis requires stable photoluminescent materials and highly efficient signal amplification strategies. In this work, the magnetism-functionalized lanthanide MOF-on-MOF (Fe₃O₄@SiO₂@MOF-on-MOF) was synthesized through intermolecular (van der Waals) interaction-assisted growth and further homogeneous epitaxial growth, which significantly improved the fluorescence performances and uncovered the underlying mechanism. The quantum chemical theory calculation and experimental studies revealed that the introduced magnetic Fe₃O₄@SiO₂ not only endowed magnetic separation capability but also promoted fluorescence performances, which increased the energy transfer of the intersystem crossing process and suppressed the luminescence of ligands and aggregation-induced quenching. Furthermore, the plasmonic Ag/Au nanocages were developed as highly efficient fluorescence quenchers to improve the sensitivity of the fluorescence immunoassay. On the basis of the proposed differential signal amplification (DSA) strategy, the immunoassay displayed superior detection ability, with a limit of detection of 0.13 pg·mL^-1 for severe acute respiratory syndrome coronavirus 2 nucleocapsid protein. The designed magnetic lanthanide MOF-on-MOF and proposed DSA strategy give new insights into ultrasensitive fluorescence immunoassays.