B-Cell-Epitope-Based Fluorescent Quantum Dot Biosensors for SARS-CoV-2 Enable Highly Sensitive COVID-19 Antibody Detection

Yucheng Zheng; Kun Song; Kun Cai; Linlin Liu; Dixiao Tang; Wenbo Long; Bohui Zhai; Jianjun Chen; Yanbing Tao; Yunong Zhao; Simeng Liang; Qing Huang; Qianyun Liu; Qi Zhang; Yu Chen; Yingle Liu; Huayao Li; Ping Wang; Ke Lan; Huan Liu; Ke Xu

doi:10.3390/v14051031

B-Cell-Epitope-Based Fluorescent Quantum Dot Biosensors for SARS-CoV-2 Enable Highly Sensitive COVID-19 Antibody Detection

Viruses. 2022 May 12;14(5):1031. doi: 10.3390/v14051031.

Authors

Yucheng Zheng¹, Kun Song¹, Kun Cai², Linlin Liu², Dixiao Tang¹, Wenbo Long³, Bohui Zhai³, Jianjun Chen⁴, Yanbing Tao³, Yunong Zhao³, Simeng Liang¹, Qing Huang³, Qianyun Liu¹, Qi Zhang¹, Yu Chen^{1

5}, Yingle Liu^{1

5}, Huayao Li³, Ping Wang⁶, Ke Lan^{1

5}, Huan Liu³, Ke Xu^{1

5}

Affiliations

¹ State Key Laboratory of Virology, Institute for Vaccine Research, College of Life Sciences, Wuhan University, Wuhan 430072, China.
² Hubei Provincial Center for Diseases Control and Prevention, Wuhan 430079, China.
³ School of Optical and Electronic Information, Wuhan National Laboratory for Optoelectronics, Optics Valley Laboratory, Huazhong University of Science and Technology, 1037 Luoyu Road, Wuhan 430074, China.
⁴ Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.
⁵ Institute for Vaccine Research, Animal Biosafety Level 3 Laboratory, Wuhan University, Wuhan 430072, China.
⁶ Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.

Abstract

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.

Keywords: B-cell epitopes; SARS-CoV-2 diagnosis; nanometer-scale fluorescent biosensors; quantum dots.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antibodies
Biosensing Techniques*
COVID-19* / diagnosis
Epitopes, B-Lymphocyte
Humans
Peptides
Quantum Dots*
SARS-CoV-2

Substances

Antibodies
Epitopes, B-Lymphocyte
Peptides

Grants and funding

This work was supported in part by the National Natural Science Foundation of China (grants 31922004 to K.X. and 61922032 and 61861136004 to H.L.), Innovation Team Research Program of Hubei Province (2020CFA015 to K.X. and K.L.), Hubei Science and Technology Major Project (2021ACB0004 to K.C.), Application & Frontier Research Program of the Wuhan Government (2019020701011463 to K.X.), Open Research Fund of State Key Laboratory of Virology of Wuhan University (2022KF0009 to H.L.), and the Fundamental Research Funds for the Central Universities (No.2042020kf1067 to K.X. and COVID-19 Emergency Special Fund of Huazhong University of Science and Technology, No.2020kfyXGYJ076 to H.L.). We thank Program for HUST Academic Frontier Youth Team (2018QYTD06), and the Innovation Fund of WNLO for equipment supports. We thank the Analytical and Testing Center of HUST for the characterization support. We are grateful to Taikang Insurance Group Co., Ltd.; Beijing Taikang Yicai Foundation, Special Fund for COVID-19 Research of Wuhan University, and the Fundamental Research Funds for the Central Universities for their great support of this work.