Magnetism-Functionalized\nLanthanide MOF-on-MOF with\nPlasmonic Differential Signal Amplification for Ultrasensitive Fluorescence\nImmunoassays

The successful application of fluorescence immunoassays\nfor clinical\ndiagnosis requires stable photoluminescent materials and highly efficient\nsignal amplification strategies. In this work, the magnetism-functionalized\nlanthanide MOF-on-MOF (Fe<sub>3</sub>O<sub>4</sub>@SiO<sub>2</sub>@MOF-on-MOF) was synthesized through intermolecular (van der Waals)\ninteraction-assisted growth and further homogeneous epitaxial growth,\nwhich significantly improved the fluorescence performances and uncovered\nthe underlying mechanism. The quantum chemical theory calculation\nand experimental studies revealed that the introduced magnetic Fe<sub>3</sub>O<sub>4</sub>@SiO<sub>2</sub> not only endowed magnetic separation\ncapability but also promoted fluorescence performances, which increased\nthe energy transfer of the intersystem crossing process and suppressed\nthe luminescence of ligands and aggregation-induced quenching. Furthermore,\nthe plasmonic Ag/Au nanocages were developed as highly efficient fluorescence\nquenchers to improve the sensitivity of the fluorescence immunoassay.\nOn the basis of the proposed differential signal amplification (DSA)\nstrategy, the immunoassay displayed superior detection ability, with\na limit of detection of 0.13 pg·mL<sup>–1</sup> for severe\nacute respiratory syndrome coronavirus 2 nucleocapsid protein. The\ndesigned magnetic lanthanide MOF-on-MOF and proposed DSA strategy\ngive new insights into ultrasensitive fluorescence immunoassays.