Rapid and reliable detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody can provide immunological evidence in addition to nucleic acid test for the early diagnosis and on-site screening of coronavirus disease 2019 (COVID-19). All-solid-state biosensor capable of rapid, quantitative SARS-CoV-2 antibody testing is still lacking. Herein, we propose an electronic labelling strategy of protein molecules and demonstrate SARS-CoV-2 protein biosensor employing colloidal quantum dots (CQDs)-modified electrode. The feature current peak corresponding to the specific binding reaction of SARS-CoV-2 antigen and antibody proteins was observed for the first time. The unique charging and discharging effect depending on the alternating voltage applied was ascribed to the quantum confinement, Coulomb blockade and quantum tunneling effects of quantum dots. CQDs-modified electrode could recognize the specific binding reaction between antigen and antibody and then transduce it into significant electrical current. In the case of serum specimens from COVID-19 patient samples, the all-solid-state protein biosensor provides quantitative analysis of SARS-CoV-2 antibody with correlation coefficient of 93.8% compared to enzyme-linked immunosorbent assay (ELISA) results. It discriminates patient and normal samples with accuracy of about 90%. The results could be read within 1 min by handheld testing system prototype. The sensitive and specific protein biosensor combines the advantages of rapidity, accuracy, and convenience, facilitating the implement of low-cost, high-throughput immunological diagnostic technique for clinical lab, point-of-care testing (POCT) as well as home-use test.

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.

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