Skip to main content
Log in

Electrochemical biosensor utilizing dual-mode output for detection of lung cancer biomarker based on reduced graphene oxide-modified reduced-molybdenum disulfide multi-layered nanosheets

  • Article
  • Published:
Journal of Materials Research Aims and scope Submit manuscript

Abstract

Here, we present an electrochemical biosensor for sensitive, specific, and rapid detection of lung cancer biomarker, neuron-specific enolase by utilization of rGO-modified r-MoS2 multi-layered nanosheets as a matrix. Layered structures along with the synergetic effect of r-MoS2 and rGO allow easy grafting of two materials into one another. This empowers the sensor to have a heterogeneous rate transfer constant of 1.29 × 10–3 cm/s and an electroactive surface area of 27.83 mm2. Electrochemical impedance spectroscopy and cyclic voltammetry are used as dual modes for the detection of NSE, and the sensor exhibits a wide linear detection range. The sensor is found to be reproducible with a relative standard deviation of less than 5% along with an invariant response towards other endogenous interfering species found in human serum. The investigations done in this study will further help us to fabricate a device for rapid and early detection of lung cancer.

Graphical abstract

Drop casting of lung cancer biomarker (NSE) onto BSA/anti-NSE/r-MoS2-rGO/ITO bioelectrode and its electrochemical response using EIS and CV.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Scheme 1

Similar content being viewed by others

Data availability

Data related to the manuscript content will be made available upon request.

References

  1. F. Bray, J. Ferlay, I. Soerjomataram, R.L. Siegel, L.A. Torre, A. Jemal, Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer J Clin 68(6), 394 (2018)

    Google Scholar 

  2. H. Singh, J. Bernabe, J. Chern, M.J.J.M.R. Nath, Copper selenide as multifunctional non-enzymatic glucose and dopamine sensor. J. Mater. Res. 36(7), 1413–1424 (2021)

    Article  CAS  Google Scholar 

  3. H. Wang, S. Wu, T. Cao, B. Zhao, J. Ruan, J. Cao, Z. Tong, X.J.J.M.R. Zhang, Self-assembly behavior of layered titanium niobate and methylene blue cation and electrochemical detection of dopamine. J. Mater. Sci. 36, 1437 (2021)

    CAS  Google Scholar 

  4. J. Han, Y. Zhuo, Y.-Q. Chai, Y.-L. Yuan, R. Yuan, Novel electrochemical catalysis as signal amplified strategy for label-free detection of neuron-specific enolase. Biosens. Bioelectron. 31(1), 399 (2012)

    Article  CAS  Google Scholar 

  5. G. Yang, Z. Xiao, C. Tang, Y. Deng, H. Huang, Z. He, Recent advances in biosensor for detection of lung cancer biomarkers. Biosens. Bioelectron. 141, 111416 (2019)

    Article  CAS  Google Scholar 

  6. D. Carney, D. Ihde, M. Cohen, P. Marangos, P. Bunn Jr., J. Minna, A.J.T.L. Gazdar, Serum neuron-specific enolase: a marker for disease extent and response to therapy of small-cell lung cancer. The Lancet 319(8272), 583 (1982)

    Article  Google Scholar 

  7. C.-M. Xu, Y.-L. Luo, S. Li, Z.-X. Li, L. Jiang, G.-X. Zhang, L. Owusu, H.-L.J.B. Chen, Multifunctional neuron-specific enolase: its role in lung diseases. Biosci. Rep. 39(11), BSR20192732 (2019)

    Article  CAS  Google Scholar 

  8. A. Kalkal, S. Kadian, S. Kumar, G. Manik, P. Sen, S. Kumar, G.J.B. Packirisamy, Ti3C2-MXene decorated with nanostructured silver as a dual-energy acceptor for the fluorometric neuron specific enolase detection. Biosens. Bioelectron. 195, 113620 (2022)

    Article  CAS  Google Scholar 

  9. S. Yin, L. Zhao, Z. Ma, Label-free electrochemical immunosensor for ultrasensitive detection of neuron-specific enolase based on enzyme-free catalytic amplification. Anal. Bioanal. Chem. 410(4), 1279 (2018)

    Article  CAS  Google Scholar 

  10. Q. Zhang, X. Li, C. Qian, L. Dou, F. Cui, X. Chen, Label-free electrochemical immunoassay for neuron specific enolase based on 3D macroporous reduced graphene oxide/polyaniline film. Anal. Biochem. 540, 1 (2018)

    Google Scholar 

  11. H. Wang, Z. Ma, Amperometric immunoassay for the tumor marker neuron-specific enolase using a glassy carbon electrode modified with a nanocomposite consisting of polyresorcinol and of gold and platinum nanoparticles. Microchim. Acta 184(9), 3247 (2017)

    Article  CAS  Google Scholar 

  12. X. Fu, R. Huang, J. Wang, X. Feng, Platinum nanoflower-based catalysts for an enzyme-free electrochemical immunoassay of neuron-specific enolase. Anal. Methods 5(16), 3803 (2013)

    Article  CAS  Google Scholar 

  13. A. Mohammadi, E. Heydari-Bafrooei, M.M. Foroughi, M. Mohammadi, Electrochemical aptasensor for ultrasensitive detection of PCB77 using thionine-functionalized MoS2-rGO nanohybrid. Microchem. J. 155, 104747 (2020)

    Article  CAS  Google Scholar 

  14. A. Sinha, B. Tan, Y. Huang, H. Zhao, X. Dang, J. Chen, R. Jain, MoS2 nanostructures for electrochemical sensing of multidisciplinary targets: a review. TrAC Trends Anal. Chem. 102, 75 (2018)

    Article  CAS  Google Scholar 

  15. C. Anichini, W. Czepa, D. Pakulski, A. Aliprandi, A. Ciesielski, P. Samorì, Chemical sensing with 2D materials. Chem. Soc. Rev. 47(13), 4860 (2018)

    Article  CAS  Google Scholar 

  16. K. Kalantar-zadeh, J.Z. Ou, Biosensors based on two-dimensional MoS2. Acs Sens. 1(1), 5 (2016)

    Article  CAS  Google Scholar 

  17. V. Georgakilas, J.N. Tiwari, K.C. Kemp, J.A. Perman, A.B. Bourlinos, K.S. Kim, R. Zboril, Noncovalent functionalization of graphene and graphene oxide for energy materials, biosensing, catalytic, and biomedical applications. Chem. Rev. 116(9), 5464 (2016)

    Article  CAS  Google Scholar 

  18. H.-H. Huang, K.K.H. De Silva, G. Kumara, M. Yoshimura, Structural evolution of hydrothermally derived reduced graphene oxide. Sci. Rep. 8(1), 1 (2018)

    Google Scholar 

  19. H. Yang, J. Zhou, J. Bao, Y. Ma, J. Zhou, C. Shen, H. Luo, M. Yang, C. Hou, D. Huo, A simple hydrothermal one-step synthesis of 3D-MoS2/rGO for the construction of sensitive enzyme-free hydrogen peroxide sensor. Microchem. J. 162, 105746 (2021)

    Article  CAS  Google Scholar 

  20. S. Gao, Y. Zhang, Z. Yang, T. Fei, S. Liu, T.J.J.A. Zhang, Compounds: Electrochemical chloramphenicol sensors-based on trace MoS2 modified carbon nanomaterials: Insight into carbon supports. J. Alloys Compd. 872, 159687 (2021)

    Article  CAS  Google Scholar 

  21. O. Jalil, C.M. Pandey, D.J.B. Kumar, Highly sensitive electrochemical detection of cancer biomarker based on anti-EpCAM conjugated molybdenum disulfide grafted reduced graphene oxide nanohybrid. Bioelectrochemistry 138, 107733 (2021)

    Article  CAS  Google Scholar 

  22. R. Khatri, N.K. Puri, Electrochemical study of hydrothermally synthesised reduced MoS2 layered nanosheets. Vacuum 175, 109250 (2020)

    Article  CAS  Google Scholar 

  23. M.A.R. Anjum, H.Y. Jeong, M.H. Lee, H.S. Shin, J.S.J.A.M. Lee, Efficient hydrogen evolution reaction catalysis in alkaline media by all-in-one MoS2 with multifunctional active sites. Adv. Mater. 30(20), 1707105 (2018)

    Article  CAS  Google Scholar 

  24. F. Wang, M. Zheng, B. Zhang, C. Zhu, Q. Li, L. Ma, W.J.S. Shen, Ammonia intercalated flower-like MoS2 nanosheet film as electrocatalyst for high efficient and stable hydrogen evolution. Sci. Rep. 6(1), 1 (2016)

    CAS  Google Scholar 

  25. M. Li, D. Wang, J. Li, Z. Pan, H. Ma, Y. Jiang, Z.J.R. Tian, Facile hydrothermal synthesis of MoS 2 nano-sheets with controllable structures and enhanced catalytic performance for anthracene hydrogenation. RSC Adv. 6(75), 71534 (2016)

    Article  CAS  Google Scholar 

  26. M. Sreeramareddygari, M. Somasundrum, W.J.N.J.C. Surareungchai, In situ polymerization and covalent functionalisation of trithiocyanuric acid by MoS2 nanosheets resulting in a novel nanozyme with enhanced peroxidase activity. New J Chem 44(15), 5809 (2020)

    Article  CAS  Google Scholar 

  27. X. Xia, Z. Zheng, Y. Zhang, X. Zhao, C.J.I. Wang, Synthesis of MoS2-carbon composites with different morphologies and their application in hydrogen evolution reaction. Int. J. Hydogen Energy 39(18), 9638 (2014)

    Article  CAS  Google Scholar 

  28. M. Li, A. Addad, Y. Zhang, A. Barras, P. Roussel, M.A. Amin, S. Szunerits, R.J.C. Boukherroub, Flower-like nitrogen-co-doped MoS2@ RGO composites with excellent stability for supercapacitors. ChemElectroChem 8(15), 2903 (2021)

    Article  CAS  Google Scholar 

  29. H. Sun, H. Liu, Z. Hou, R. Zhou, X. Liu, J.-G.J.C.E.J. Wang, Edge-terminated MoS2 nanosheets with an expanded interlayer spacing on graphene to boost supercapacitive performance. Chem. Eng. J 387, 124204 (2020)

    Article  Google Scholar 

  30. X. Bai, Y. Du, X. Hu, Y. He, C. He, E. Liu, J. Fan, Synergy removal of Cr (VI) and organic pollutants over RP-MoS2/rGO photocatalyst. Appl. Catal. B 239, 204 (2018)

    Article  CAS  Google Scholar 

  31. W.-K. Jo, S. Kumar, M.A. Isaacs, A.F. Lee, S. Karthikeyan, Cobalt promoted TiO2/GO for the photocatalytic degradation of oxytetracycline and Congo Red. Appl. Catal. B 201, 159 (2017)

    Article  CAS  Google Scholar 

  32. H. Sun, S. Liu, G. Zhou, H.M. Ang, M.O. Tadé, S. Wang, Reduced graphene oxide for catalytic oxidation of aqueous organic pollutants. ACS Appl. Mater. Interfaces. 4(10), 5466 (2012)

    Article  CAS  Google Scholar 

  33. L. Chen, D. Ding, C. Liu, H. Cai, Y. Qu, S. Yang, Y. Gao, T. Cai, Degradation of norfloxacin by CoFe2O4-GO composite coupled with peroxymonosulfate: a comparative study and mechanistic consideration. Chem. Eng. J. 334, 273 (2018)

    Article  CAS  Google Scholar 

  34. J. Zhou, H. Xiao, B. Zhou, F. Huang, S. Zhou, W. Xiao, D. Wang, Hierarchical MoS2–rGO nanosheets with high MoS2 loading with enhanced electro-catalytic performance. Appl. Surf. Sci. 358, 152 (2015)

    Article  CAS  Google Scholar 

  35. S. Yang, X. Feng, S. Ivanovici, K. Müllen, Fabrication of graphene-encapsulated oxide nanoparticles: towards high-performance anode materials for lithium storage. Angew. Chem. Int. Ed. 49(45), 8408 (2010)

    Article  CAS  Google Scholar 

  36. H. Wang, J.T. Robinson, X. Li, H. Dai, Solvothermal reduction of chemically exfoliated graphene sheets. J. Am. Chem. Soc. 131(29), 9910 (2009)

    Article  CAS  Google Scholar 

  37. S. Stankovich, D.A. Dikin, R.D. Piner, K.A. Kohlhaas, A. Kleinhammes, Y. Jia, Y. Wu, S.T. Nguyen, R.S. Ruoff, Synthesis of graphene-based nanosheets via chemical reduction of exfoliated graphite oxide. Carbon 45(7), 1558 (2007)

    Article  CAS  Google Scholar 

  38. J. Zhang, L. Zhao, A. Liu, X. Li, H. Wu, C. Lu, Three-dimensional MoS2/rGO hydrogel with extremely high double-layer capacitance as active catalyst for hydrogen evolution reaction. Electrochim. Acta 182, 652 (2015)

    Article  CAS  Google Scholar 

  39. L. Lin, S. Zhang, Effective solvothermal deoxidization of graphene oxide using solid sulphur as a reducing agent. J. Mater. Chem. 22(29), 14385 (2012)

    Article  CAS  Google Scholar 

  40. T. Yang, L.-H. Liu, J.-W. Liu, M.-L. Chen, J.-H. Wang, Cyanobacterium metallothionein decorated graphene oxide nanosheets for highly selective adsorption of ultra-trace cadmium. J. Mater. Chem. 22(41), 21909 (2012)

    Article  CAS  Google Scholar 

  41. R. Vinoth, I.M. Patil, A. Pandikumar, B.A. Kakade, N.M. Huang, D.D. Dionysios, B. Neppolian, Synergistically enhanced electrocatalytic performance of an N-doped graphene quantum dot-decorated 3D MoS2–graphene nanohybrid for oxygen reduction reaction. ACS Omega 1(5), 971 (2016)

    Article  CAS  Google Scholar 

  42. G. Sun, X. Zhang, R. Lin, J. Yang, H. Zhang, P. Chen, Hybrid fibers made of molybdenum disulfide, reduced graphene oxide, and multi-walled carbon nanotubes for solid-state, flexible, asymmetric supercapacitors. Angew. Chem. 127(15), 4734 (2015)

    Article  Google Scholar 

  43. S. Kumar, V. Sharma, K. Bhattacharyya, V. Krishnan, Synergetic effect of MoS 2–RGO doping to enhance the photocatalytic performance of ZnO nanoparticles. New J. Chem. 40(6), 5185 (2016)

    Article  CAS  Google Scholar 

  44. N. Kumar, S. Kumar, R. Gusain, N. Manyala, S. Eslava, S.S. Ray, Polypyrrole-promoted rGO–MoS2 nanocomposites for enhanced photocatalytic conversion of CO2 and H2O to CO, CH4, and H2 products. ACS Appl. Energy Mater. 3(10), 9897 (2020)

    Article  CAS  Google Scholar 

  45. E.G. da Silveira Firmiano, A.C. Rabelo, C.J. Dalmaschio, A.N. Pinheiro, E.C. Pereira, W.H. Schreiner, E.R. Leite, Supercapacitor electrodes obtained by directly bonding 2D MoS2 on reduced graphene oxide. Adv. Energy Mater. 4(6), 1301380 (2014)

    Article  CAS  Google Scholar 

  46. Y.-L. Chen, Z.-A. Hu, Y.-Q. Chang, H.-W. Wang, Z.-Y. Zhang, Y.-Y. Yang, H.-Y.J.T.J.P.C.C. Wu, Zinc oxide/reduced graphene oxide composites and electrochemical capacitance enhanced by homogeneous incorporation of reduced graphene oxide sheets in zinc oxide matrix. J Phys. Chem. C 115(5), 2563 (2011)

    Article  CAS  Google Scholar 

  47. G. Wang, X. Shen, J. Yao, J.J.C. Park, Graphene nanosheets for enhanced lithium storage in lithium ion batteries. Carbon 47(8), 2049 (2009)

    Article  CAS  Google Scholar 

  48. L. Zhang, W. Fan, W.W. Tjiu, T. Liu, 3D porous hybrids of defect-rich MoS 2/graphene nanosheets with excellent electrochemical performance as anode materials for lithium ion batteries. RSC Adv. 5(44), 34777 (2015)

    Article  CAS  Google Scholar 

  49. V.K. Singh, S. Kumar, S.K. Pandey, S. Srivastava, M. Mishra, G. Gupta, B. Malhotra, R. Tiwari, A. Srivastava, Fabrication of sensitive bioelectrode based on atomically thin CVD grown graphene for cancer biomarker detection. Biosens. Bioelectron. 105, 173 (2018)

    Article  CAS  Google Scholar 

  50. S. Kumar, S. Kumar, S. Tiwari, S. Srivastava, M. Srivastava, B.K. Yadav, S. Kumar, T.T. Tran, A.K. Dewan, A. Mulchandani, Biofunctionalized nanostructured zirconia for biomedical application: a smart approach for oral cancer detection. Adv. Sci. 2(8), 1500048 (2015)

    Article  CAS  Google Scholar 

  51. M. Kukkar, A. Sharma, P. Kumar, K.-H. Kim, A. Deep, Application of MoS2 modified screen-printed electrodes for highly sensitive detection of bovine serum albumin. Anal. Chim. Acta 939, 101 (2016)

    Article  CAS  Google Scholar 

  52. J.-B. Jorcin, M.E. Orazem, N. Pébère, B.J.E.A. Tribollet, CPE analysis by local electrochemical impedance spectroscopy. Electrochim. Acta 51(8–9), 1473 (2006)

    Article  CAS  Google Scholar 

  53. B. Hirschorn, M.E. Orazem, B. Tribollet, V. Vivier, I. Frateur, M.J.J.T.E.S. Musiani, Constant-phase-element behavior caused by resistivity distributions in films: I. Theory 157(12), 452 (2010)

    Google Scholar 

  54. M. Farrokhnia, G. Amoabediny, M. Ebrahimi, M. Ganjali, M.J.T. Arjmand, Ultrasensitive early detection of insulin antibody employing novel electrochemical nano-biosensor based on controllable electro-fabrication process. Talanta 238, 122947 (2021)

    Article  CAS  Google Scholar 

  55. O. Jalil, C.M. Pandey, D.J.M.A. Kumar, Electrochemical biosensor for the epithelial cancer biomarker EpCAM based on reduced graphene oxide modified with nanostructured titanium dioxide. Microchim. Acta 187(5), 1 (2020)

    Article  CAS  Google Scholar 

  56. X. Xi, D. Wu, W. Ji, S. Zhang, W. Tang, Y. Su, X. Guo, R.J.A.F.M. Liu, Manipulating the sensitivity and selectivity of OECT-based biosensors via the surface engineering of carbon cloth gate electrodes. Adv. Funct. Mater. 30(4), 1905361 (2020)

    Article  CAS  Google Scholar 

  57. D. Sandil, S.C. Sharma, N.K. Puri, Protein-functionalized WO 3 nanorods–based impedimetric platform for sensitive and label-free detection of a cardiac biomarker. J. Mater. Res. 34(8), 1331 (2019)

    Article  CAS  Google Scholar 

  58. D. Chauhan, P.K. Gupta, P.R. Solanki, Electrochemical immunosensor based on magnetite nanoparticles incorporated electrospun polyacrylonitrile nanofibers for Vitamin-D3 detection. Mater. Sci. Eng. C 93, 145 (2018)

    Article  CAS  Google Scholar 

  59. S. Kumar, N. Gupta, B.D. Malhotra, Ultrasensitive biosensing platform based on yttria doped zirconia-reduced graphene oxide nanocomposite for detection of salivary oral cancer biomarker. Bioelectrochemistry 140, 107799 (2021)

    Article  CAS  Google Scholar 

  60. D.C. Marcano, D.V. Kosynkin, J.M. Berlin, A. Sinitskii, Z. Sun, A. Slesarev, L.B. Alemany, W. Lu, J.M. Tour, Improved synthesis of graphene oxide. ACS Nano 4(8), 4806 (2010)

    Article  CAS  Google Scholar 

  61. M. Saraf, K. Natarajan, A.K. Saini, S.M. Mobin, Small biomolecule sensors based on an innovative MoS 2–rGO heterostructure modified electrode platform: a binder-free approach. Dalton Trans. 46(45), 15848 (2017)

    Article  CAS  Google Scholar 

  62. Y. Li, H. Wang, L. Xie, Y. Liang, G. Hong, H. Dai, MoS2 nanoparticles grown on graphene: an advanced catalyst for the hydrogen evolution reaction. J. Am. Chem. Soc. 133(19), 7296 (2011)

    Article  CAS  Google Scholar 

Download references

Acknowledgments

Authors are highly obliged to Hon’ble Vice-Chancellor, Delhi Technological University, Delhi, India for promoting research and providing appropriate infrastructure and facilities.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Nitin K. Puri.

Ethics declarations

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 3715 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Khatri, R., Puri, N.K. Electrochemical biosensor utilizing dual-mode output for detection of lung cancer biomarker based on reduced graphene oxide-modified reduced-molybdenum disulfide multi-layered nanosheets. Journal of Materials Research 37, 1451–1463 (2022). https://doi.org/10.1557/s43578-022-00546-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1557/s43578-022-00546-w

Keywords

Navigation