Plasmon-Enhanced Fluorescence Paper Lateral Flow Strip\nfor Point-of-Care Testing of SARS-CoV‑2 Antigens

Currently\ncommercial colorimetric paper lateral flow immunoassays\nexhibit insufficient limit of detection (LOD) and limited clinical\nsensitivity toward the detection of SARS-CoV-2 antigens, which causes\na high false negative rate. To mitigate this issue, a new plasmon-enhanced\nfluorescence probe was developed for paper lateral flow strips (PLFSs).\nThe probe is made of a sandwich-structured\nAg-core@silica@dye@silica-shell nanoparticle in which fluorescent\ndyes are sandwiched between the plasmonic Ag core and the silica outer\nshell, and the separation distance between the Ag core and the dye\nmolecules is controlled by the silica space layer. At the optimal\nthickness of the silica space layer, plasmons can amplify fluorescence\nsignals via the Purcell effect. The PLFS with the optimized plasmonic\nfluorescence probes exhibits a LOD of 65.0 pg/mL toward detection\nof the SARS-CoV-2 nucleocapsid protein in a buffer solution, which\nis much lower than that (2.3 ng/mL) of the commercial colorimetric\ncounterpart. Furthermore, it has been used successfully for testing\nCOVID-19 clinical samples, which has achieved 100% clinical sensitivity\nand 94.2% specificity, while the commercial colorimetric PLFS exhibits\n75.7% sensitivity and 91.4% specificity. The results demonstrate that\nthe plasmonic fluorescence PLFS can reduce false negative results\nsignificantly. This device has great potential in helping with timely\nmedical intervention and prevention from COVID-19 transmission.