A new antibody diagnostic assay with more rapid and robust properties is demanded to quantitatively evaluate anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunity in a large population. Here, we developed a nanometer-scale fluorescent biosensor system consisting of CdSe-ZnS quantum dots (QDs) coupled with the highly sensitive B-cell epitopes of SARS-CoV-2 that could remarkably identify the corresponding antibody with a detection limit of 100 pM. Intriguingly, we found that fluorescence quenching of QDs was stimulated more obviously when coupled with peptides than the corresponding proteins, indicating that the energy transfer between QDs and peptides was more effective. Compared to the traditional enzyme-linked immunosorbent assay (ELISA), the B-cell-epitope-based QD-biosensor could robustly distinguish coronavirus disease 2019 (COVID-19) antibody-positive patients from uninfected individuals with a higher sensitivity (92.3–98.1% positive rates by QD-biosensor vs. 78.3–83.1% positive rates by ELISAs in 207 COVID-19 patients’ sera) in a more rapid (5 min) and labor-saving manner. Taken together, the ‘QD-peptides’ biosensor provided a novel real-time, quantitative, and high-throughput method for clinical diagnosis and home-use tests.
B-Cell-Epitope-Based Fluorescent Quantum Dot Biosensors for SARS-CoV-2 Enable Highly Sensitive COVID-19 Antibody Detection