Human ACE2-Functionalized Gold “Virus-Trap” Nanostructures for Accurate Capture of SARS-CoV-2 and Single-Virus SERS Detection
Corresponding Author: Xiaoying Luo
Nano-Micro Letters,
Vol. 13 (2021), Article Number: 109
Abstract
The current COVID-19 pandemic urges the extremely sensitive and prompt detection of SARS-CoV-2 virus. Here, we present a Human Angiotensin-converting-enzyme 2 (ACE2)-functionalized gold “virus traps” nanostructure as an extremely sensitive SERS biosensor, to selectively capture and rapidly detect S-protein expressed coronavirus, such as the current SARS-CoV-2 in the contaminated water, down to the single-virus level. Such a SERS sensor features extraordinary 106-fold virus enrichment originating from high-affinity of ACE2 with S protein as well as “virus-traps” composed of oblique gold nanoneedles, and 109-fold enhancement of Raman signals originating from multi-component SERS effects. Furthermore, the identification standard of virus signals is established by machine-learning and identification techniques, resulting in an especially low detection limit of 80 copies mL−1 for the simulated contaminated water by SARS-CoV-2 virus with complex circumstance as short as 5 min, which is of great significance for achieving real-time monitoring and early warning of coronavirus. Moreover, here-developed method can be used to establish the identification standard for future unknown coronavirus, and immediately enable extremely sensitive and rapid detection of novel virus.
Highlights:
1 Extremely sensitive and prompt COVID-19 SERS biosensor to detect SARS-CoV-2 virus in the contaminated water at single-virus level.
2 SERS sensor features a low detection limit of 80 copies mL−1 for the simulated contaminated water by SARS-CoV-2 virus as short as 5 min.
3 ACE2-modified SERS sensor with machine-learning and identification standard enable rapid detection of novel yet-unknown coronaviruses.
Keywords
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- C.L. Huang, Y.M. Wang, X.W. Li, L.L. Ren, J.P. Zhao et al., Clinical features of patients infected with 2019 novel coronavirus in Wuhan. China. Lancet 395, 497–506 (2020). https://doi.org/10.1016/S0140-6736(20)30183-5
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- WHO Coronavirus Disease (COVID-19) Dashboard, data last updated: 2020/12/1, 7:08pm CEST. https://covid19.who.int/ (2020)
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- X.G. Zhang, X.L. Zhang, C.L. Luo, Z.Q. Liu, Y.Y. Chen et al., Volume-enhanced raman scattering detection of viruses. Small 15, 1805516 (2019). https://doi.org/10.1002/smll.201805516
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- M. Hoffmann, K.W. Hannah, S. Schroeder, N. Kruger, T. Herrler et al., SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 181(2), 271–280 (2020). https://doi.org/10.1016/j.cell.2020.02.052
- S. Watanabe, M. Sonobe, M. Arai, Y. Tazume, T. Matsuo et al., Enhanced optical sensing of anions with amide-functionalized gold nanoparticles. Chem. Commun. (2002). https://doi.org/10.1039/B205751D
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- R.H. Yan, Y.Y. Zhang, Y.N. Li, L. Xia, Y.Y. Guo et al., Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science 367, 1444–1448 (2020). http://science.sciencemag.org/content/367/6485/1444
- D. Nĕmĕcek, G.J. Thomas Raman Spectroscopy in Virus Structure Analysis. In: Handbook of Molecular Biophysics. Methods and Applications, 417–456 (2009)
- M. Keshavarz, B. Tang, K. Venkatakrishnan, Label-free SERS quantum semiconductor probe for molecular-level and in vitro cellular detection: a noble-metal-free methodology. ACS Appl. Mater. Interface 10, 34886–34904 (2018). https://doi.org/10.1021/acsami.8b10590
- R. Tuma, G.J. Thomas, Raman Spectroscopy of Viruses, in Handbook of Vibrational Spectroscopy. ed. by J.M. Chalmers, P.R. Griffiths (Wiley, Hoboken, 2006)
- R. Haldavnekar, K. Venkatakrishnan, B. Tang, Non plasmonic semiconductor quantum SERS probe as a pathway for in vitro cancer detection. Nat. Commun. 9, 3065 (2018). https://doi.org/10.1038/s41467-018-05237-x
- S. Krimm, J. Bandekar, Vibrational spectroscopy and conformation of peptides, polypeptides, and proteins. Adv. Protein Chem. 38(6), 181–364 (1986). https://doi.org/10.1016/S0065-3233(08)60528-8
- K.K. Chan, D. Dorosky, P. Sharma, S.A. Abbasi, J.M. Dye et al., Engineering human ACE2 to optimize binding to the spike protein of SARS coronavirus 2. Science 369, 1261–1265 (2020). https://doi.org/10.1126/science.abc0870
- J.Y. Lim, J.S. Nam, S.E. Yang, H. Shin, Y.H. Jang et al., Identification of newly emerging influenza viruses by surface-enhanced raman spectroscopy. Anal. Chem. 87, 11652–11659 (2015). https://doi.org/10.1021/acs.analchem.5b02661
References
C.L. Huang, Y.M. Wang, X.W. Li, L.L. Ren, J.P. Zhao et al., Clinical features of patients infected with 2019 novel coronavirus in Wuhan. China. Lancet 395, 497–506 (2020). https://doi.org/10.1016/S0140-6736(20)30183-5
F. Wu, S. Zhao, B. Yu, Y.M. Chen, W. Wang et al., A new coronavirus associated with human respiratory disease in China. Nature 579, 265–269 (2020). https://doi.org/10.1038/s41586-020-2008-3
WHO Coronavirus Disease (COVID-19) Dashboard, data last updated: 2020/12/1, 7:08pm CEST. https://covid19.who.int/ (2020)
S. Zheng, J. Fan, F. Yu, B.H. Feng, B. Lou et al., Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January–March 2020: retrospective cohort study. BMJ 369, m1443 (2020). https://doi.org/10.1136/bmj.m1443
L. Peng, J. Liu, W.X. Xu, Q.M. Luo, D.B. Chen et al., SARS-CoV-2 can be detected in urine, blood, anal swabs, and oropharyngeal swabs specimens. J. Med. Virol. (2020). https://doi.org/10.1002/jmv.25936
Y. Pan, D. Zhang, P. Yang, L.L.M. Poon, Q. Wang, Viral load of SARS-CoV-2 in clinical samples. Lancet Infect. Dis. 20, 411–412 (2020). https://doi.org/10.1016/S1473-3099(20)30113-4
L.R. Zou, F. Ruan, M.X. Huang, L.J. Liang, H.T. Huang et al., SARS-CoV-2 viral load in upper respiratory specimens of infected patients. N. Engl. J. Med. 382, 1177–1179 (2020). https://doi.org/10.1056/NEJMc2001737
E. Haramoto, B. Malla, O. Thakali, M. Kitajima, First environmental surveillance for the presence of SARS-CoV-2 RNA in wastewater and river water in Japan. Sci. Total Environ. 737, 140405 (2020). https://doi.org/10.1016/j.scitotenv.2020.140405
G. Orive, U. Lertxundi, D. Barcelo, Early SARS-CoV-2 outbreak detection by sewage-based epidemiology. Sci. Total Environ. 735, 139298 (2020). https://doi.org/10.1016/j.scitotenv.2020.139298
Y.Q. Li, B.W. Zhu, Y.G. Li, W.R. Leow, R. Goh et al., A synergistic capture strategy for enhanced detection and elimination of bacteria. Angew. Chem. Int. Ed. 53, 5837–5841 (2014). https://doi.org/10.1002/anie.201310135
N. Bhalla, Y.W. Pan, Z.G. Yang, A.F. Payam, Opportunities and challenges for biosensors and nanoscale analytical tools for pandemics: COVID-19. ACS Nano 14, 7783–7807 (2020). https://doi.org/10.1021/acsnano.0c04421
L. Yu, S. Wu, X. Hao, X. Dong, L. Mao et al., Rapid detection of COVID-19 coronavirus using a reverse transcriptional loop-mediated isothermal amplification (RT-LAMP) diagnostic platform. Clin. Chem. 66(7), 975–977 (2020). https://doi.org/10.1093/clinchem/hvaa102
J.P. Broughton, X.D. Deng, G.X. Yu, C.L. Fasching, V. Servellita et al., CRISPR-Cas12-based detection of SARS-CoV-2. Nat. Biotechnol. 38, 870–874 (2020). https://doi.org/10.1038/s41587-020-0513-4
X. Liu, C. Liu, G. Liu, W.X. Luo, N.S. Xia, COVID-19: Progress in diagnostics, therapy and vaccination. Theranostics 10, 7821–7835 (2020).
C. Zong, M.X. Xu, L.J. Xu, T. Wei, X. Ma et al., Surface-enhanced raman spectroscopy for bioanalysis: reliability and challenges. Chem. Rev. 118, 4946–4980 (2018). https://doi.org/10.1021/acs.chemrev.7b00668
S. Nie, S.R. Emory, Probing single molecules and single nanoparticles by surface-enhanced Raman scattering. Science 275, 1102–1106 (1997). https://doi.org/10.1126/science.275.5303.1102
H.X. Xu, E.J. Bjerneld, M. Kall, L. Borjesson, Spectroscopy of single hemoglobin molecules by surface enhanced Raman scattering. Phys. Rev. Lett. 83, 4357–4360 (1999). https://doi.org/10.1103/PhysRevLett.83.4357
Y. Zhang, Y.R. Zhen, O. Neumann, J.K. Day, P. Nordlander et al., Coherent anti-stokes raman scattering with single-molecule sensitivity using a plasmonic Fano resonance. Nat. Comm. 5, 4424 (2014). https://doi.org/10.1038/ncomms5424
J.Y. Chen, B. Wiley, Z.Y. Li, D. Campbell, F. Saeki et al., Gold nanocages: engineering their structure for biomedical applications. Adv. Mater. 17, 2255–2261 (2005). https://doi.org/10.1002/adma.200500833
J.R. Lombardi, Enhanced by organic surfaces. Nat. Mater. 16(9), 878–880 (2017). https://doi.org/10.1038/nmat4958
H.K. Yu, Y.S. Peng, Y. Yang, Z.Y. Li, Plasmon enhanced light-matter interaction: materials and structures. NPJ Comput. Mater. 5, 45 (2019). https://doi.org/10.1038/s41524-019-0184-1
Y. Yang, Z.Y. Li, K. Yamaguchi, M. Tanemura, Z.R. Huang et al., Controlled fabrication of silver nanoneedles array for SERS and their application in rapid detection of narcotics. Nanoscale 4, 2663–2669 (2012). https://doi.org/10.1039/C2NR12110G
L.L. Yang, Y.S. Peng, Y. Yang, J.J. Liu, H.L. Huang et al., A novel ultra-sensitive semiconductor SERS substrate boosted by the coupled resonance effect. Adv. Sci. 6, 1900310 (2019). https://doi.org/10.1002/advs.201900310
Y.S. Peng, C.L. Lin, L. Long, T. Masaki, M. Tang et al., Charge-transfer resonance and electromagnetic enhancement synergistically enabling MXenes with excellent SERS sensitivity for SARS-CoV-2 S protein detection. Nano-Micro Lett. 13, 52 (2021). https://doi.org/10.1007/s40820-020-00565-4
J.Y. Lim, J.S. Nam, H. Shin, J. Park, H.I. Song et al., Identification of newly emerging influenza viruses by detecting the virally infected cells based on surface enhanced raman spectroscopy and principal component analysis. Anal. Chem. 91, 5677–5684 (2019). https://doi.org/10.1021/acs.analchem.8b05533
S. Shanmukh, L. Jones, J. Driskell, Y.P. Zhao, R. Dluhy et al., Rapid and sensitive detection of respiratory virus molecular signatures using a silver nanorod array SERS substrate. Nano Lett. 6, 2630–2636 (2006). https://doi.org/10.1021/nl061666f
Y.T. Yeh, K. Gulino, Y.H. Zhanga, A. Sabestien, T.W. Chou et al., A rapid and label-free platform for virus capture and identification from clinical samples. PNAS 117, 895–901 (2020). https://doi.org/10.1073/pnas.1910113117
G. Eom, A. Hwang, H. Kim, S. Yang, D.K. Lee et al., Diagnosis of tamiflu-resistant influenza virus in human nasal fluid and saliva using surface-enhanced raman scattering. ACS Sens. 4, 2282–2287 (2019). https://doi.org/10.1021/acssensors.9b00697
X.G. Zhang, X.L. Zhang, C.L. Luo, Z.Q. Liu, Y.Y. Chen et al., Volume-enhanced raman scattering detection of viruses. Small 15, 1805516 (2019). https://doi.org/10.1002/smll.201805516
F. Shao, Z.C. Lu, C. Liu, H.Y. Han, K. Chen et al., Hierarchical nanogaps within bioscaffold arrays as a high-performance SERS substrate for animal virus biosensing. ACS Appl. Mater. Interface 6, 6281–6289 (2014). https://doi.org/10.1021/am4045212
D. Wrapp, N.S. Wang, K.S. Corbett, J.A. Goldsmith, C.L. Hsieh et al., Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science 367, 1260–1263 (2020). http://science.sciencemag.org/content/367/6483/1260
M. Hoffmann, K.W. Hannah, S. Schroeder, N. Kruger, T. Herrler et al., SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 181(2), 271–280 (2020). https://doi.org/10.1016/j.cell.2020.02.052
S. Watanabe, M. Sonobe, M. Arai, Y. Tazume, T. Matsuo et al., Enhanced optical sensing of anions with amide-functionalized gold nanoparticles. Chem. Commun. (2002). https://doi.org/10.1039/B205751D
B.R. Griffith, B.L. Allen, A.C. Rapraeger, L.L. Kiessling, A polymer scaffold for protein oligomerization. J. Am. Chem. Soc. 126, 1608–1609 (2004). https://doi.org/10.1021/ja037646m
R.H. Yan, Y.Y. Zhang, Y.N. Li, L. Xia, Y.Y. Guo et al., Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science 367, 1444–1448 (2020). http://science.sciencemag.org/content/367/6485/1444
D. Nĕmĕcek, G.J. Thomas Raman Spectroscopy in Virus Structure Analysis. In: Handbook of Molecular Biophysics. Methods and Applications, 417–456 (2009)
M. Keshavarz, B. Tang, K. Venkatakrishnan, Label-free SERS quantum semiconductor probe for molecular-level and in vitro cellular detection: a noble-metal-free methodology. ACS Appl. Mater. Interface 10, 34886–34904 (2018). https://doi.org/10.1021/acsami.8b10590
R. Tuma, G.J. Thomas, Raman Spectroscopy of Viruses, in Handbook of Vibrational Spectroscopy. ed. by J.M. Chalmers, P.R. Griffiths (Wiley, Hoboken, 2006)
R. Haldavnekar, K. Venkatakrishnan, B. Tang, Non plasmonic semiconductor quantum SERS probe as a pathway for in vitro cancer detection. Nat. Commun. 9, 3065 (2018). https://doi.org/10.1038/s41467-018-05237-x
S. Krimm, J. Bandekar, Vibrational spectroscopy and conformation of peptides, polypeptides, and proteins. Adv. Protein Chem. 38(6), 181–364 (1986). https://doi.org/10.1016/S0065-3233(08)60528-8
K.K. Chan, D. Dorosky, P. Sharma, S.A. Abbasi, J.M. Dye et al., Engineering human ACE2 to optimize binding to the spike protein of SARS coronavirus 2. Science 369, 1261–1265 (2020). https://doi.org/10.1126/science.abc0870
J.Y. Lim, J.S. Nam, S.E. Yang, H. Shin, Y.H. Jang et al., Identification of newly emerging influenza viruses by surface-enhanced raman spectroscopy. Anal. Chem. 87, 11652–11659 (2015). https://doi.org/10.1021/acs.analchem.5b02661