Advertisement

Biomedical Microdevices

, 21:65 | Cite as

Sensitive detection of lung cancer biomarkers using an aptameric graphene-based nanosensor with enhanced stability

  • Zhuang Hao
  • Yunlu PanEmail author
  • Cong Huang
  • Ziran Wang
  • Xuezeng Zhao
Article
  • 43 Downloads

Abstract

We present an electrolyte-gated graphene field effect transistor (GFET) nanosensor using aptamer for rapid, highly sensitive and specific detection of a lung cancer biomarker interleukin-6 (IL-6) with enhanced stability. The negatively charged aptamer folds into a compact secondary conformation upon binding with IL-6, thus altering the carrier concentration of graphene and yielding a detectable change in the drain-source current Ids. Aptamer has smaller size than other receptors (e.g. antibodies), making it possible to bring the charged IL-6 more closely to the graphene surface upon affinity binding, thereby enhancing the sensitivity of the detection. Thanks to the higher stability of aptamer over antibodies, which degrade easily with increasing storage time, consistent sensing performance was obtained by our nanosensor over extended-time (>24 h) storage at 25 °C. Additionally, due to the GFET-enabled rapid transduction of the affinity recognition to IL-6, detection of IL-6 can be achieved in several minutes (<10 min). Experimental results indicate that this nanosensor can rapidly and specifically respond to the change in IL-6 levels with high consistency after extended-time storage and a detection limit (DL) down to 139 fM. Therefore, our nanosensor holds great potential for lung cancer diagnosis at its early stage.

Keywords

Graphene Lung cancer biomarker Aptamer Biosensing Interleukin-6 (IL-6) 

Notes

Acknowledgements

This work was supported by fundings from the National Natural Science Foundation of China (Grant Nos. 51505108 and 51475118). The author Zhuang Hao would like to gratefully thank Dr. Xuejun Wang from East China University of Science and Technology for technical supports and insightful discussions.

Supplementary material

10544_2019_409_MOESM1_ESM.docx (914 kb)
ESM 1 (DOCX 914 kb)

References

  1. F.M. Brichory, D.E. Misek, A.-M. Yim, M.C. Krause, T.J. Giordano, D.G. Beer, S.M. Hanash, Proc. Natl. Acad. Sci. 98, 9824 (2001)CrossRefGoogle Scholar
  2. J.E. Chang, D.S. Lee, S.W. Ban, J. Oh, M.Y. Jung, S.H. Kim, S.J. Park, K. Persaud, S. Jheon, Sensors Actuators B Chem. 255, 800 (2018)CrossRefGoogle Scholar
  3. P. Chen, M.T. Chung, W. McHugh, R. Nidetz, Y. Li, J. Fu, T.T. Cornell, T.P. Shanley, K. Kurabayashi, ACS Nano 9, 4173 (2015)CrossRefGoogle Scholar
  4. B.V. Chikkaveeraiah, A. Bhirde, R. Malhotra, V. Patel, Anal. Chem. 81, 9129 (2009)CrossRefGoogle Scholar
  5. T.H. Chou, C.Y. Chuang, C.M. Wu, Cytokine 51, 107 (2010)CrossRefGoogle Scholar
  6. G. Cizza, A.H. Marques, F. Eskandari, I.C. Christie, S. Torvik, M.N. Silverman, T.M. Phillips, E.M. Sternberg, Biol. Psychiatry 64, 907 (2008)CrossRefGoogle Scholar
  7. B.R. Clarkson, R. Chaudhuri, A. Schön, J.W. Cooper, L. Kueltzo, E. Freire, Anal. Biochem. 554, 61 (2018)CrossRefGoogle Scholar
  8. G. Gavelli, E. Giampalma, Cancer 89, 2453 (2000)CrossRefGoogle Scholar
  9. Z. Hao, Y. Zhu, X. Wang, P.G. Rotti, C. Dimarco, S.R. Tyler, X. Zhao, J.F. Engelhardt, J. Hone, Q. Lin, ACS Appl. Mater. Interfaces 9, 27504 (2017)CrossRefGoogle Scholar
  10. Z. Hao, Z. Wang, Y. Li, Y. Zhu, X. Wang, C.G. De Moraes, Y. Pan, X. Zhao, Q. Lin, Nanoscale 10, 21681 (2018)CrossRefGoogle Scholar
  11. Z. Hao, Y. Pan, W. Shao, Q. Lin, X. Zhao, Biosens. Bioelectron. (2019)Google Scholar
  12. C.-H. Huang, C. Zeng, Y.-C. Wang, H.-Y. Peng, C.-S. Lin, C.-J. Chang, H.-Y. Yang, Sensors 18, 2845 (2018)CrossRefGoogle Scholar
  13. X. Hun, Z. Zhang, Biosens. Bioelectron. 22, 2743 (2007)CrossRefGoogle Scholar
  14. G.C. Jensen, C.E. Krause, G.A. Sotzing, J.F. Rusling, Phys. Chem. Chem. Phys. 13, 4888 (2011)CrossRefGoogle Scholar
  15. Y. Jia, H. Cai, Q. Lin, J. Micro/Nanolithogr. MEMS MOEMS 024501, 15 (2016)Google Scholar
  16. R. Kapoor, C.W. Wang, Biosens. Bioelectron. 24, 2696 (2009)CrossRefGoogle Scholar
  17. D.J. Kim, I.Y. Sohn, J.H. Jung, O.J. Yoon, N.E. Lee, J.S. Park, Biosens. Bioelectron. 41, 621 (2013)CrossRefGoogle Scholar
  18. S.G. Kim, J.S. Lee, J. Jun, D.H. Shin, J. Jang, ACS Appl. Mater. Interfaces 8, 6602 (2016)CrossRefGoogle Scholar
  19. X. Li, W. Cai, J. An, S. Kim, J. Nah, D. Yang, L. Colombo, and R. S. Ruoff, 3893, 1312 (2009)Google Scholar
  20. H. Lilja, D. Ulmert, A.J. Vickers, Nat. Rev. Cancer 8, 268 (2008)CrossRefGoogle Scholar
  21. G. Liu, K. Zhang, A. Nadort, M.R. Hutchinson, E.M. Goldys, ACS Sensors 2, 218 (2017)CrossRefGoogle Scholar
  22. L. Luo, Z. Zhang, L. Hou, Anal. Chim. Acta 584, 106 (2007)CrossRefGoogle Scholar
  23. R. Malhotra, V. Patel, J.P. Vaqué, J.S. Gutkind, J.F. Rusling, Anal. Chem. 82, 3118 (2010)CrossRefGoogle Scholar
  24. S. Manohar, A.R. Mantz, K.E. Bancroft, C.Y. Hui, A. Jagota, D.V. Vezenov, Nano Lett. 8, 4365 (2008)CrossRefGoogle Scholar
  25. B.S. Munge, C.E. Krause, R. Malhotra, V. Patel, J. Silvio Gutkind, J.F. Rusling, Electrochem. Commun. 11, 1009 (2009)CrossRefGoogle Scholar
  26. R.D. Munje, S. Muthukumar, B. Jagannath, S. Prasad, Sci. Rep. 7, 1950 (2017)CrossRefGoogle Scholar
  27. K.I. Papamichael, M.P. Kreuzer, G.G. Guilbault, Sensors Actuators B Chem. 121, 178 (2007)CrossRefGoogle Scholar
  28. S.R. Pine, L.E. Mechanic, L. Enewold, A.K. Chaturvedi, H.A. Katki, Y.L. Zheng, E.D. Bowman, E.A. Engels, N.E. Caporaso, C.C. Harris, J. Natl. Cancer Inst. 103, 1112 (2011)CrossRefGoogle Scholar
  29. A.R. Ruslinda, V. Penmatsa, Y. Ishii, S. Tajima, H. Kawarada, Analyst 137, 1692 (2012)CrossRefGoogle Scholar
  30. C. Wang, Y. Li, Y. Zhu, X. Zhou, Q. Lin, M. He, Adv. Funct. Mater. 26, 8575 (2016)CrossRefGoogle Scholar
  31. T.I. Williams, K.L. Toups, D.A. Saggese, K.R. Kalli, W.A. Cliby, D.C. Muddiman, J. Proteome Res. 6, 2936 (2007)CrossRefGoogle Scholar
  32. Y. Xiao, A.A. Lubin, A.J. Heeger, K.W. Plaxco, Angew. Chem. Int. Ed. 44, 5456 (2005)CrossRefGoogle Scholar
  33. H. Yanagawa, S. Sone, Y. Takahashi, T. Haku, S. Yano, T. Shinohara, T. Ogura, Br. J. Cancer 71, 1095 (1995)CrossRefGoogle Scholar
  34. X. Zhong, D. Li, W. Du, M. Yan, Y. Wang, D. Huo, and C. Hou, 3671 (2018)Google Scholar
  35. Y. Zhu, Y. Hao, E.A. Adogla, J. Yan, D. Li, K. Xu, Q. Wang, J. Hone, Q. Lin, Nanoscale 8, 5815 (2016)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Zhuang Hao
    • 1
  • Yunlu Pan
    • 1
    Email author
  • Cong Huang
    • 1
  • Ziran Wang
    • 1
  • Xuezeng Zhao
    • 1
  1. 1.Key Laboratory of Micro-systems and Micro-structures Manufacturing, Ministry of Education and School of Mechatronics EngineeringHarbin Institute of TechnologyHarbinChina

Personalised recommendations