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

Currently commercial colorimetric paper lateral flow immunoassays exhibit insufficient limit of detection (LOD) and limited clinical sensitivity toward the detection of SARS-CoV-2 antigens, which causes a high false negative rate. To mitigate this issue, a new plasmon-enhanced fluorescence probe was developed for paper lateral flow strips (PLFSs). The probe is made of a sandwich-structured Ag-core@silica@dye@silica-shell nanoparticle in which fluorescent dyes are sandwiched between the plasmonic Ag core and the silica outer shell, and the separation distance between the Ag core and the dye molecules is controlled by the silica space layer. At the optimal thickness of the silica space layer, plasmons can amplify fluorescence signals via the Purcell effect. The PLFS with the optimized plasmonic fluorescence probes exhibits a LOD of 65.0 pg/mL toward detection of the SARS-CoV-2 nucleocapsid protein in a buffer solution, which is much lower than that (2.3 ng/mL) of the commercial colorimetric counterpart. Furthermore, it has been used successfully for testing COVID-19 clinical samples, which has achieved 100% clinical sensitivity and 94.2% specificity, while the commercial colorimetric PLFS exhibits 75.7% sensitivity and 91.4% specificity. The results demonstrate that the plasmonic fluorescence PLFS can reduce false negative results significantly. This device has great potential in helping with timely medical intervention and prevention from COVID-19 transmission.