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. 2020 Dec 29;64(3):739–747. doi: 10.1007/s40843-020-1577-y

An accurate, high-speed, portable bifunctional electrical detector for COVID-19

一种针对新型冠状病毒肺炎的准确、快速、便携式双功能电检测仪

Guojun Ke 1,2,#, Dingkai Su 2,#, Yu Li 2,#, Yu Zhao 3, Honggang Wang 3, Wanjian Liu 4, Man Li 5, Zhiting Yang 4, Fang Xiao 6, Yao Yuan 7, Fei Huang 1,✉, Fanyang Mo 3,✉, Peng Wang 5,✉, Xuefeng Guo 2,✉
PMCID: PMC7852050  PMID: 33552629

Abstract

Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has rapidly spread and caused a severe global pandemic. Because no specific drugs are available for COVID-19 and few vaccines are available for SARS-CoV-2, accurate and rapid diagnosis of COVID-19 has been the most crucial measure to control this pandemic. Here, we developed a portable bifunctional electrical detector based on graphene fieldeffect transistors for SARS-CoV-2 through either nucleic acid hybridization or antigen-antibody protein interaction, with ultra-low limits of detection of ~0.1 and ~1 fg mL−1 in phosphate buffer saline, respectively. We validated our method by assessment of RNA extracts from the oropharyngeal swabs of ten COVID-19 patients and eight healthy subjects, and the IgM/IgG antibodies from serum specimens of six COVID-19 patients and three healthy subjects. Here we show that the diagnostic results are in excellent agreement with the findings of polymerase chain reaction-based optical methods; they also exhibit rapid detection speed (~10 min for nucleic acid detection and ~5 min for immunoassay). Therefore, our assay provides an efficient, accurate tool for high-throughput point-of-care testing. graphic file with name 40843_2020_1577_Fig1_HTML.jpg

Electronic Supplementary Material

Supplementary material is available in the online version of this article at 10.1007/s40843-020-1577-y.

Keywords: COVID-19, biosensor, nucleic acid detection, immunoassay, point-of-care testing

Electronic Supplementary Material

40843_2020_1577_MOESM1_ESM.pdf (1MB, pdf)

An accurate, high-speed, portable bifunctional electrical detector for COVID-19

Acknowledgements

This work was supported by the National Key R&D Program of China (2017YFA0204901), the National Natural Science Foundation of China (21727806, 21772003 and 21933001), the Tencent Foundation through the XPLORER PRIZE, Guangdong Major Project of Basic and Applied Basic Research (2019B030302007), and Beijing National Laboratory for Molecular Sciences (BNLMS201901).

Author contributions

Guo X, Mo F, Wang P and Huang F conceived and designed the experiments; Ke G, Su D and Li Y fabricated the devices and performed the device measurements; Zhao Y, Wang H, Xiao F and Yuan Y designed and built the measurement machines; LiuWand Yang Z provided the antigen protein; Li M and Wang P provided the clinical samples; Guo X, Mo F, Wang P, Ke G and Su D analyzed the data and wrote the paper. All authors discussed the results and commented on the manuscript.

Footnotes

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary information

Experimental details and supporting data are available in the online version of this paper.

Guojun Ke received his BS degree in 2012 and PhD degree in 2017 from the School of Chemistry, Sun Yat-Sen University, respectively. From 2013 to 2016, he was a visiting student at the University of Basel. He is currently working as a postdoctoral fellow in South China University of Technology. His current research focuses on device physics of single-molecule junctions.

Dingkai Su received his BS degree in 2017 from the College of Nano Science and Technology, Soochow University. He is currently a PhD candidate at the College of Chemistry and Molecular Engineering, Peking University, under the guidance of Prof. Xuefeng Guo. His research interest focuses on single-molecule devices and dynamics.

Xuefeng Guo received his PhD degree in 2004 from the Institute of Chemistry, Chinese Academy of Sciences. From 2004 to 2007, he was a postdoctoral research scientist at the Columbia University Nanocenter. He joined the faculty as a professor under the “Peking 100-Talent” Program at Peking University in 2008. His research focuses on functional nanometer/molecular devices.

These authors contributed equally to this work.

Contributor Information

Fei Huang, Email: msfhuang@scut.edu.cn.

Fanyang Mo, Email: fmo@pku.edu.cn.

Peng Wang, Email: chinaroc001@126.com.

Xuefeng Guo, Email: guoxf@pku.edu.cn.

References

  • 1.Zhu N, Zhang D, Wang W, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020;382:727–733. doi: 10.1056/NEJMoa2001017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Wang C, Horby PW, Hayden FG, et al. A novel coronavirus outbreak of global health concern. Lancet. 2020;395:470–473. doi: 10.1016/S0140-6736(20)30185-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.de Wit E, van Doremalen N, Falzarano D, et al. SARS and MERS: Recent insights into emerging coronaviruses. Nat Rev Microbiol. 2016;14:523–534. doi: 10.1038/nrmicro.2016.81. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Lu R, Zhao X, Li J, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: Implications for virus origins and receptor binding. Lancet. 2020;395:565–574. doi: 10.1016/S0140-6736(20)30251-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.WHO Coronavirus Disease 2019 (COVID-19): Situation Report-52. https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200312-sitrep-52-covid-19.pdf?sfvrsn=e2bfc9c0_4
  • 6.WHO Coronavirus Disease (COVID-19) Dashboard. https://covid19.who.int
  • 7.Talebian S, Wallace GG, Schroeder A, et al. Nanotechnology-based disinfectants and sensors for SARS-CoV-2. Nat Nanotechnol. 2020;15:618–621. doi: 10.1038/s41565-020-0751-0. [DOI] [PubMed] [Google Scholar]
  • 8.Broughton JP, Deng X, Yu G, et al. CRISPR-Cas12-based detection of SARS-CoV-2. Nat Biotechnol. 2020;38:870–874. doi: 10.1038/s41587-020-0513-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Chan JFW, Yip CCY, To KKW, et al. Improved molecular diagnosis of COVID-19 by the novel, highly sensitive and specific COVID-19-RdRp/Hel real-time reverse transcription-PCR assay validated in vitro and with clinical specimens. J Clin Microbiol. 2020;58:e00310–20. doi: 10.1128/JCM.00310-20. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Real-time RT-PCR panel for detection 2019-nCoV (US Centers for Disease Control and Prevention, 2020). https://www.who.int/docs/default-source/coronaviruse/uscdcrt-pcr-panel-for-detection-instructions.pdf
  • 11.WHO Laboratory testing for coronavirus disease 2019 (Covid-19) in suspected human cases: Interim guidance, 2020. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technicalguidance/laboratory-guidance
  • 12.Xie X, Zhong Z, Zhao W, et al. Chest CT for typical coronavirus disease 2019 (COVID-19) pneumonia: Relationship to negative RT-PCR testing. Radiology. 2020;296:E41–E45. doi: 10.1148/radiol.2020200343. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Zhang Q, Zhao Q. BioRxiv. 2020. Inactivating porcine coronavirus before nuclei acid isolation with the temperature higher than 56°C damages its genome integrity seriously. [Google Scholar]
  • 14.Lu CH, Yang HH, Zhu CL, et al. A graphene platform for sensing biomolecules. Angew Chem Int Ed. 2009;48:4785–4787. doi: 10.1002/anie.200901479. [DOI] [PubMed] [Google Scholar]
  • 15.He G, Li J, Ci H, et al. Direct measurement of single-molecule DNA hybridization dynamics with single-base resolution. Angew Chem Int Ed. 2016;55:9036–9040. doi: 10.1002/anie.201603038. [DOI] [PubMed] [Google Scholar]
  • 16.Ke G, Duan C, Huang F, et al. Electrical and spin switches in single-molecule junctions. InfoMat. 2020;2:92–112. doi: 10.1002/inf2.12068. [DOI] [Google Scholar]
  • 17.Su D, Gu C, Guo X. Functional molecular electronic devices through environmental control. Sci China Mater. 2019;62:1–7. doi: 10.1007/s40843-018-9301-3. [DOI] [Google Scholar]
  • 18.Syu YC, Hsu WE, Lin CT. Review-Field-effect transistor biosensing: Devices and clinical applications. ECS J Solid State Sci Technol. 2018;7:Q3196–Q3207. doi: 10.1149/2.0291807jss. [DOI] [Google Scholar]
  • 19.Liang Y, Xiao M, Wu D, et al. Wafer-scale uniform carbon nanotube transistors for ultrasensitive and label-free detection of disease biomarkers. ACS Nano. 2020;14:8866–8874. doi: 10.1021/acsnano.0c03523. [DOI] [PubMed] [Google Scholar]
  • 20.Namdari P, Daraee H, Eatemadi A. Recent advances in silicon nanowire biosensors: Synthesis methods, properties, and applications. Nanoscale Res Lett. 2016;11:406. doi: 10.1186/s11671-016-1618-z. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Szunerits S, Boukherroub R. Graphene-based biosensors. Interface Focus. 2018;8:20160132. doi: 10.1098/rsfs.2016.0132. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Jia C, Li H, Jiang J, et al. Interface-engineered bistable [2]rotaxanegraphene hybrids with logic capabilities. Adv Mater. 2013;25:6752–6759. doi: 10.1002/adma.201302393. [DOI] [PubMed] [Google Scholar]
  • 23.Campos R, Borme J, Guerreiro JR, et al. Attomolar label-free detection of DNA hybridization with electrolyte-gated graphene field-effect transistors. ACS Sens. 2019;4:286–293. doi: 10.1021/acssensors.8b00344. [DOI] [PubMed] [Google Scholar]
  • 24.Seo G, Lee G, Kim MJ, et al. Rapid detection of COVID-19 causative virus (SARS-CoV-2) in human nasopharyngeal swab specimens using field-effect transistor-based biosensor. ACS Nano. 2020;14:5135–5142. doi: 10.1021/acsnano.0c02823. [DOI] [PubMed] [Google Scholar]
  • 25.Van Elslande J, Houben E, Depypere M, et al. Diagnostic performance of seven rapid IgG/IgM antibody tests and the Euroimmun IgA/IgG ELISA in COVID-19 patients. Clin Microbiol Infection. 2020;26:1082–1087. doi: 10.1016/j.cmi.2020.05.023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Tuaillon E, Bolloré K, Pisoni A, et al. Detection of SARS-CoV-2 antibodies using commercial assays and seroconversion patterns in hospitalized patients. J Infection. 2020;81:e39–e45. doi: 10.1016/j.jinf.2020.05.077. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Li Z, Yi Y, Luo X, et al. Development and clinical application of a rapid IgM-IgG combined antibody test for SARS-CoV-2 infection diagnosis. J Med Virol. 2020;92:1518–1524. doi: 10.1002/jmv.25727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Hou H, Wang T, Zhang B, et al. Detection of IgM and IgG antibodies in patients with coronavirus disease 2019. Clin Transl Immunol. 2020;9:e1136. doi: 10.1002/cti2.1136. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Malard LM, Pimenta MA, Dresselhaus G, et al. Raman spectroscopy in graphene. Phys Rep. 2009;473:51–87. doi: 10.1016/j.physrep.2009.02.003. [DOI] [Google Scholar]
  • 30.Ye J, Craciun MF, Koshino M, et al. Accessing the transport properties of graphene and its multilayers at high carrier density. Proc Natl Acad Sci USA. 2011;108:13002–13006. doi: 10.1073/pnas.1018388108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Xin N, Li X, Jia C, et al. Tuning charge transport in aromatic-ring single-molecule junctions via ionic-liquid gating. Angew Chem Int Ed. 2018;57:14026–14031. doi: 10.1002/anie.201807465. [DOI] [PubMed] [Google Scholar]
  • 32.Chen JH, Ishigami M, Jang C, et al. Printed graphene circuits. Adv Mater. 2007;19:3623–3627. doi: 10.1002/adma.200701059. [DOI] [Google Scholar]
  • 33.Xu S, Zhan J, Man B, et al. Real-time reliable determination of binding kinetics of DNA hybridization using a multi-channel graphene biosensor. Nat Commun. 2017;8:14902. doi: 10.1038/ncomms14902. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34.Cai B, Wang S, Huang L, et al. Ultrasensitive label-free detection of PNA-DNA hybridization by reduced graphene oxide field-effect transistor biosensor. ACS Nano. 2014;8:2632–2638. doi: 10.1021/nn4063424. [DOI] [PubMed] [Google Scholar]

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Supplementary Materials

40843_2020_1577_MOESM1_ESM.pdf (1MB, pdf)

An accurate, high-speed, portable bifunctional electrical detector for COVID-19

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