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Nano Research 2023, 16(5): 7304-7311 https://doi.org/10.1007/s12274-023-5386-7
Research Article | Issue | Published: 08 February 2023

An ultra-sensitive metasurface biosensor for instant cancer detection based on terahertz spectra

Show Author's Information Peiliang Wang1,2,3,4,  Jing Lou2,5,  Yun Yu2,8,  Lang Sun2,  Lan Sun6,7( ),  Guangyou Fang1,3,4( ),  Chao Chang2( )
Aerospace Information Research Institute, Chinese Academy of Sciences, Beijing 100094, China
Innovation Laboratory of Terahertz Biophysics, National Innovation Institute of Defense Technology, Beijing 100071, China
The Key Laboratory of Electromagnetic Radiation and Sensing Technology, Chinese Academy of Sciences, Beijing 100190, China
School of Electronic, Electrical and Communication Engineering, University of Chinese Academy of Sciences, Beijing 100049, China
Air and Missile Defense College, Air Force Engineering University, Xi’an 710051, China
Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing 100007, China
School of Psychological and Cognitive Sciences, Beijing Key Laboratory of Behavior and Mental Health, Peking University, Beijing 100871, China
School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, China
Keywords:
biosensor, terahertz, metasurface, cancer detection
Topics:
Nano biology
Cite this article:
Wang P, Lou J, Yu Y, et al. An ultra-sensitive metasurface biosensor for instant cancer detection based on terahertz spectra. Nano Research, 2023, 16(5): 7304-7311. https://doi.org/10.1007/s12274-023-5386-7
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Abstract Full text About this article

Metasurface biosensors have become the core label-free and rapid-detection technology in bioanalysis. Lung cancer and brain cancer are the first leading causes of cancer death among adults and adolescents, respectively, where poor early diagnosis results from expensive detection costs and time consumption. To tackle the above problems, here, we introduce a terahertz-domain metasurface biosensor for cancer diagnosis, relying on a perfectly symmetrical periodic surface structure, which significantly exhibits polarization-insensitivity at 2.05 THz and the high-sensitivity of 504 GHz/RIU (RIU = refractive index unit). According to the frequency shifts and transmittance variations, four cell types are successfully distinguished from each other. The minimum number of cells is required for thousands of cells to display the differences of spectra, which is 1/30 of clinical methods. Furthermore, the results were consistent with pathological results (the gold standard in clinic) by Gaussian curve fitting. The proposed biosensor has really achieved the characterization of cells in normal and cancerous state. This detection strategy dramatically reduced the cost of detection by reuse and time consumption was reduced to 1/20 of the pathology testing. In addition, it is flexible to set samples and easy to realize automatic operation due to the great polarization-insensitivity of the proposed biosensor, which can further reduce labor costs in the future. It is envisioned that the proposed biosensor will present immense potential in the fields of cancer detection, distinguishing different cancers, and identifying primary lesion cancer or metastatic cancer.


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About this article

An ultra-sensitive metasurface biosensor for instant cancer detection based on terahertz spectra

Show Author's information Peiliang Wang1,2,3,4, Jing Lou2,5, Yun Yu2,8, Lang Sun2, Lan Sun6,7( ), Guangyou Fang1,3,4( ), Chao Chang2( )
Aerospace Information Research Institute, Chinese Academy of Sciences, Beijing 100094, China
Innovation Laboratory of Terahertz Biophysics, National Innovation Institute of Defense Technology, Beijing 100071, China
The Key Laboratory of Electromagnetic Radiation and Sensing Technology, Chinese Academy of Sciences, Beijing 100190, China
School of Electronic, Electrical and Communication Engineering, University of Chinese Academy of Sciences, Beijing 100049, China
Air and Missile Defense College, Air Force Engineering University, Xi’an 710051, China
Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing 100007, China
School of Psychological and Cognitive Sciences, Beijing Key Laboratory of Behavior and Mental Health, Peking University, Beijing 100871, China
School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, China

Abstract

Metasurface biosensors have become the core label-free and rapid-detection technology in bioanalysis. Lung cancer and brain cancer are the first leading causes of cancer death among adults and adolescents, respectively, where poor early diagnosis results from expensive detection costs and time consumption. To tackle the above problems, here, we introduce a terahertz-domain metasurface biosensor for cancer diagnosis, relying on a perfectly symmetrical periodic surface structure, which significantly exhibits polarization-insensitivity at 2.05 THz and the high-sensitivity of 504 GHz/RIU (RIU = refractive index unit). According to the frequency shifts and transmittance variations, four cell types are successfully distinguished from each other. The minimum number of cells is required for thousands of cells to display the differences of spectra, which is 1/30 of clinical methods. Furthermore, the results were consistent with pathological results (the gold standard in clinic) by Gaussian curve fitting. The proposed biosensor has really achieved the characterization of cells in normal and cancerous state. This detection strategy dramatically reduced the cost of detection by reuse and time consumption was reduced to 1/20 of the pathology testing. In addition, it is flexible to set samples and easy to realize automatic operation due to the great polarization-insensitivity of the proposed biosensor, which can further reduce labor costs in the future. It is envisioned that the proposed biosensor will present immense potential in the fields of cancer detection, distinguishing different cancers, and identifying primary lesion cancer or metastatic cancer.

Keywords: biosensor, terahertz, metasurface, cancer detection

References(45)

[1]

Siegel, R. L.; Miller, K. D.; Fuchs, H. E.; Jemal, A. Cancer statistics, 2021. CA A Cancer J. Clin. 2021, 71, 7–33.
DOI Google Scholar
[2]

Miller, K. D.; Ostrom, Q. T.; Kruchko, C.; Patil, N.; Tihan, T.; Cioffi, G.; Fuchs, H. E.; Waite, K. A.; Jemal, A.; Siegel, R. L. et al. Brain and other central nervous system tumor statistics, 2021. CA A Cancer J Clin. 2021, 71, 381–406.
DOI Google Scholar
[3]

Herbst, R. S.; Morgensztern, D.; Boshoff, C. The biology and management of non-small cell lung cancer. Nature 2018, 553, 446–454.
DOI Google Scholar
[4]

Carter, B.; Zhao, K. J. The epigenetic basis of cellular heterogeneity. Nat. Rev. Genet. 2021, 22, 235–250.
DOI Google Scholar
[5]

He, Z. Y.; Chen, Z.; Tan, M. D.; Elingarami, S.; Liu, Y.; Li, T. T.; Deng, Y.; He, N. Y.; Li, S.; Fu, J. et al. A review on methods for diagnosis of breast cancer cells and tissues. Cell Proliferat. 2020, 53, e12822.
DOI Google Scholar
[6]

Min, L.; Wang, B. S.; Bao, H. R.; Li, X. R.; Zhao, L. B.; Meng, J. X.; Wang, S. T. Advanced nanotechnologies for extracellular vesicle-based liquid biopsy. Adv. Sci. (Weinh.) 2021, 8, 2102789.
DOI Google Scholar
[7]

Kang, K.; Park, J.; Kim, K.; Yu, K. J. Recent developments of emerging inorganic, metal and carbon-based nanomaterials for pressure sensors and their healthcare monitoring applications. Nano Res. 2021, 14, 3096–3111.
DOI Google Scholar
[8]
Zhang, D. Z.; Wang, M. Y.; Tang, M. C.; Song, X. S.; Zhang, X. X.; Kang, Z. J.; Liu, X. H.; Zhang, J. H.; Xue, Q. Z. Recent progress of diversiform humidity sensors based on versatile nanomaterials and their prospective applications. Nano Res., in press, https://doi.org/10.1007/s12274-022-4917-y.
[9]

Ahmed, M. U.; Saaem, I.; Wu, P. C.; Brown, A. S. Personalized diagnostics and biosensors: A review of the biology and technology needed for personalized medicine. Crit. Rev. Biotechnol. 2014, 34, 180–196.
DOI Google Scholar
[10]

Beruete, M.; Jáuregui-López, I. Terahertz sensing based on metasurfaces. Adv. Opt. Mater. 2020, 8, 1900721.
DOI Google Scholar
[11]

Hillenbrand, R.; Taubner, T.; Keilmann, F. Phonon-enhanced light–matter interaction at the nanometre scale. Nature 2002, 418, 159–162.
DOI Google Scholar
[12]

Qin, W.; Miranowicz, A.; Li, P. B.; Lü, X. Y.; You, J. Q.; Nori, F. Exponentially enhanced light–matter interaction, cooperativities, and steady-state entanglement using parametric amplification. Phys. Rev. Lett. 2018, 120, 093601.
DOI Google Scholar
[13]

Smith, D. R.; Pendry, J. B.; Wiltshire, M. C. K. Metamaterials and negative refractive index. Science 2004, 305, 788–792.
DOI Google Scholar
[14]
Zhao, Y. N.; Huang, J.; Huang, Q.; Tao, Y. B.; Gu, R. Q.; Li, H. Y.; Liu, H. Electrochemical biosensor employing PbS colloidal quantum dots/Au nanospheres-modified electrode for ultrasensitive glucose detection. Nano Res., in press, https://doi.org/10.1007/s12274-022-5138-0.
[15]
Lei, X. L.; Xu, X. X.; Liu, L. Q.; Xu, L. G.; Wang, L.; Kuang, H.; Xu, C. L. Gold-nanoparticle-based multiplex immuno-strip biosensor for simultaneous determination of 83 antibiotics. Nano Res., in press, https://doi.org/10.1007/s12274-022-4762-z.
[16]

Papasimakis, N.; Fedotov, V. A.; Savinov, V.; Raybould, T. A.; Zheludev, N. I. Electromagnetic toroidal excitations in matter and free space. Nat. Mater. 2016, 15, 263–271.
DOI Google Scholar
[17]

Kaelberer, T.; Fedotov, V. A.; Papasimakis, N.; Tsai, D. P.; Zheludev, N. I. Toroidal dipolar response in a metamaterial. Science 2010, 330, 1510–1512.
DOI Google Scholar
[18]

Gupta, M.; Singh, R. Toroidal metasurfaces in a 2D flatland. Rev. Phys. 2020, 5, 100040.
DOI Google Scholar
[19]

Ahmadivand, A.; Gerislioglu, B.; Ahuja, R.; Mishra, Y. K. Terahertz plasmonics: The rise of toroidal metadevices towards immunobiosensings. Mater. Today 2020, 32, 108–130.
DOI Google Scholar
[20]

Rodrigo, D.; Tittl, A.; Ait-Bouziad, N.; John-Herpin, A.; Limaj, O.; Kelly, C.; Yoo, D.; Wittenberg, N. J.; Oh, S. H.; Lashuel, H. A. et al. Resolving molecule-specific information in dynamic lipid membrane processes with multi-resonant infrared metasurfaces. Nat. Commun. 2018, 9, 2160.
DOI Google Scholar
[21]

Lawrence, M.; Barton, D. R.; Dixon, J.; Song, J. H.; Van De Groep, J.; Brongersma, M. L.; Dionne, J. A. High quality factor phase gradient metasurfaces. Nat. Nanotechnol. 2020, 15, 956–961.
DOI Google Scholar
[22]

Wu, D.; Liu, Y. M.; Yu, L.; Yu, Z. Y.; Chen, L.; Li, R. F.; Ma, R.; Liu, C.; Zhang, J. Q. N.; Ye, H. Plasmonic metamaterial for electromagnetically induced transparency analogue and ultra-high figure of merit sensor. Sci. Rep. 2017, 7, 45210.
DOI Google Scholar
[23]

Meng, F. Y.; Wu, Q.; Erni, D.; Wu, K.; Lee, J. C. Polarization-independent metamaterial analog of electromagnetically induced transparency for a refractive-index-based sensor. IEEE Trans. Microwave Theory Techn. 2012, 60, 3013–3022.
DOI Google Scholar
[24]

Wang, C. Q.; Jiang, X. F.; Zhao, G. M.; Zhang, M. Z.; Hsu, C. W.; Peng, B.; Stone, A. D.; Jiang, L.; Yang, L. Electromagnetically induced transparency at a chiral exceptional point. Nat. Phys. 2020, 16, 334–340.
DOI Google Scholar
[25]

Marangos, J. P. Electromagnetically induced transparency. J. Mod. Opt. 1998, 45, 471–503.
DOI Google Scholar
[26]

Xiang, Z. X.; Tang, C. X.; Chang, C.; Liu, G. Z. A new viewpoint and model of neural signal generation and transmission: Signal transmission on unmyelinated neurons. Nano Res. 2021, 14, 590–600.
DOI Google Scholar
[27]

Tan, X. X.; Wu, K. J.; Liu, S.; Yuan, Y. F.; Chang, C.; Xiong, W. Minimal-invasive enhancement of auditory perception by terahertz wave modulation. Nano Res. 2022, 15, 5235–5244.
DOI Google Scholar
[28]

Wang, K. C.; Wang, S. M.; Yang, L. X.; Wu, Z.; Zeng, B. Q.; Gong, Y. B. THz trapped ion model and THz spectroscopy detection of potassium channels. Nano Res. 2022, 15, 3825–3833.
DOI Google Scholar
[29]

Lou, J.; Xu, X.; Huang, Y. D.; Yu, Y.; Wang, J.; Fang, G. Y.; Liang, J. G.; Fan, C. H.; Chang, C. Optically controlled ultrafast terahertz metadevices with ultralow pump threshold. Small 2021, 17, 2104275.
DOI Google Scholar
[30]

Wang, P. L.; Lou, J.; Fang, G. Y.; Chang, C. Progress on cutting-edge infrared-terahertz biophysics. IEEE Trans. Microwave Theory Techn. 2022, 70, 5117–5140.
DOI Google Scholar
[31]

Ferguson, B.; Zhang, X. C. Materials for terahertz science and technology. Nat. Mater. 2002, 1, 26–33.
DOI Google Scholar
[32]

Zhang, X. C.; Shkurinov, A.; Zhang, Y. Extreme terahertz science. Nat. Photon. 2017, 11, 16–18.
DOI Google Scholar
[33]

Sengupta, K.; Nagatsuma, T.; Mittleman, D. M. Terahertz integrated electronic and hybrid electronic–photonic systems. Nat. Electron. 2018, 1, 622–635.
DOI Google Scholar
[34]

Song, B.; Shu, Y. S. Cell vibron polariton resonantly self-confined in the myelin sheath of nerve. Nano Res. 2020, 13, 38–44.
DOI Google Scholar
[35]

Siegel, P. H. Terahertz technology in biology and medicine. IEEE Trans. Microwave Theory Techn. 2004, 52, 2438–2447.
DOI Google Scholar
[36]

Dhillon, S. S.; Vitiello, M. S.; Linfield, E. H.; Davies, A. G.; Hoffmann, M. C.; Booske, J.; Paoloni, C.; Gensch, M.; Weightman, P.; Williams, G. P. et al. The 2017 terahertz science and technology roadmap. J. Phys. D Appl. Phys. 2017, 50, 043001.
DOI Google Scholar
[37]

Li, N.; Peng, D. L.; Zhang, X. J.; Shu, Y. S.; Zhang, F.; Jiang, L.; Song, B. Demonstration of biophoton-driven DNA replication via gold nanoparticle-distance modulated yield oscillation. Nano Res. 2021, 14, 40–45.
DOI Google Scholar
[38]

Lou, J.; Jiao, Y. N.; Yang, R. S.; Huang, Y. D.; Xu, X.; Zhang, L.; Ma, Z. F.; Yu, Y.; Peng, W. Y.; Yuan, Y. F. et al. Calibration-free, high-precision, and robust terahertz ultrafast metasurfaces for monitoring gastric cancers. Proc. Nat. l Acad. Sci. USA 2022, 119, e2209218119.
DOI Google Scholar
[39]

Yan, X.; Yang, M. S.; Zhang, Z.; Liang, L. J.; Wei, D. Q.; Wang, M.; Zhang, M.; Wang, T.; Liu, L. H.; Xie, J. H. et al. The terahertz electromagnetically induced transparency-like metamaterials for sensitive biosensors in the detection of cancer cells. Biosen. Bioelectron. 2019, 126, 485–492.
DOI Google Scholar
[40]

Keshavarz, A.; Vafapour, Z. Water-based terahertz metamaterial for skin cancer detection application. IEEE Sensors J. 2019, 19, 1519–1524.
DOI Google Scholar
[41]

Vafapour, Z.; Troy, W.; Rashidi, A. Colon cancer detection by designing and analytical evaluation of a water-based THz metamaterial perfect absorber. IEEE Sensors J. 2021, 21, 19307–19313.
DOI Google Scholar
[42]

Zhang, C. B.; Xue, T. J.; Zhang, J.; Liu, L. H.; Xie, J. H.; Wang, G. M.; Yao, J. Q.; Zhu, W. R.; Ye, X. D. Terahertz toroidal metasurface biosensor for sensitive distinction of lung cancer cells. Nanophotonics 2022, 11, 101–109.
DOI Google Scholar
[43]

Zhan, X. Y.; Yang, S.; Huang, G. R.; Yang, L. H.; Zhang, Y.; Tian, H. Y.; Xie, F. X.; De La Chapelle, M. L.; Yang, X.; Fu, W. L. Streptavidin-functionalized terahertz metamaterials for attomolar exosomal microRNA assay in pancreatic cancer based on duplex-specific nuclease-triggered rolling circle amplification. Biosens. Bioelectron. 2021, 188, 113314.
DOI Google Scholar
[44]

Soncin, I.; Sheng, J. P.; Chen, Q.; Foo, S.; Duan, K. B.; Lum, J.; Poidinger, M.; Zolezzi, F.; Karjalainen, K.; Ruedl, C. The tumour microenvironment creates a niche for the self-renewal of tumour-promoting macrophages in colon adenoma. Nat. Commun. 2018, 9, 582.
DOI Google Scholar
[45]

Wu, Y. Q.; Jiao, N.; Zhu, R. X.; Zhang, Y. D.; Wu, D. F.; Wang, A. J.; Fang, S.; Tao, L. W.; Li, Y. C.; Cheng, S.; et al. Identification of microbial markers across populations in early detection of colorectal cancer. Nat. Commun. 2021, 12, 3063.
DOI Google Scholar
Publication history
Copyright
Acknowledgements

Publication history

Received: 15 October 2022
Revised: 19 November 2022
Accepted: 04 December 2022
Published: 08 February 2023
Issue date: May 2023

Copyright

© Tsinghua University Press 2023

Acknowledgements

Acknowledgements

This work was financially supported by the National Natural Science Foundation of China (Nos. 12225511, T2241002, and 61988102, ) and XPLORER PRIZE of C. C.

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