Highly sensitive fluorescent lateral flow immunoassay based on core-shell PS@Dip@SiO2 microspheres for SARS-CoV-2 IgG detection.

A highly sensitive fluorescent lateral flow immunoassay (LFIA) was developed for SARS‑CoV‑2 IgG detection. Polystyrene (PS) microspheres were synthesized via emulsion polymerization, doped with dipyridamole (Dip), and coated with a protective silica (SiO2) shell through a sol-gel process. After amine functionalization, the SARS‑CoV‑2 nucleocapsid (N) protein was covalently immobilized onto the microsphere surface using EDC/NHS chemistry, yielding PS@Dip@SiO2-N fluorescent probes. The LFIA strip enabled one‑step detection within 15 min. Under optimized conditions (N protein conjugation concentration of 40 µg/mL), the strip showed excellent specificity with no cross‑reactivity against other human coronaviruses (NL63, OC43, 229E). Quantitative determination based on the T/C grayscale ratio fitted the Hill equation (R² = 0.9782). The detection limit for SARS‑CoV‑2 IgG was 10 ng/mL, approximately two orders of magnitude lower than that of a commercial colloidal gold‑based LFIA strip. This platform provides a rapid, sensitive, and low‑cost solution for point‑of‑care serological screening of COVID‑19.