Photoelectrochemical detection of breast cancer biomarker based on hexagonal carbon nitride tubes

  • Junjun Luo
  • Dong Liang
  • Xiaoqing Qiu
  • Minghui YangEmail author
Research Paper


Photoelectrochemical (PEC) sensor for sensitive detection of breast cancer biomarker human epidermal growth factor receptor 2 (HER2) utilizing hexagonal carbon nitride tubes (HCNT) as photoactive material is reported. The detection is based on suppression of the PEC current intensity of the sensor. HCNT were synthesized via a facile hydrothermal method with large specific surface area and low electron-hole recombination. Au nanoparticles (AuNPs) were deposited onto the surface of the HCNT, which enhanced the photocurrent intensity of the HCNT by one time. For HER2 detection, peptide specific to HER2 was immobilized on the AuNPs surface for capturing HER2 molecules. The following binding of HER2 with HER2 aptamer and the reaction of phosphate groups on aptamer with molybdate can form molybdophosphate precipitate, which sticks to the surface of HCNT and impedes electron transport. Thus, photocurrent intensity of the sensor was suppressed. Under optimal conditions, the linear relationship between the PEC intensity and the logarithm of HER2 concentration was from 0.5 to 1 ng mL−1 with low limit of detection (LOD) of 0.08 pg mL−1. Furthermore, the PEC sensor also displayed capability for detecting HER2 in human serum samples. This PEC sensor signal detection strategy can be easily adapted to other PEC sensors involving DNA and find wide applications.

Graphical abstract


Photoelectrochemistry Breast cancer Hexagonal carbon nitride tube Au nanoparticle Molybdophosphate 


Funding information

This work received support from the National Natural Science Foundation of China (No. 21575165).

Compliance with ethical standards

The authors declare that they have no competing interests. All experiments were in accordance with the guidelines of the National Institute of Health, China, and approved by the Institutional Ethical Committee (IEC) of the Second Xiangya Hospital that attached to Central South University. We also obtained informed consent for any experimentation with human serum samples.

Supplementary material

216_2019_2060_MOESM1_ESM.pdf (226 kb)
ESM 1 (PDF 225 kb)


  1. 1.
    Zhao W-W, Xu J-J, Chen H-Y. Photoelectrochemical aptasensing. Trends Anal Chem. 2016;82:307–15.CrossRefGoogle Scholar
  2. 2.
    Fan D, Bao C, Liu X, Wu D, Zhang Y, Wang H, et al. A novel label-free photoelectrochemical immunosensor based on NCQDs and Bi2S3 co-sensitized hierarchical mesoporous SnO2 microflowers for detection of NT-proBNP. J Mater Chem B. 2018;6(46):7634–42.CrossRefGoogle Scholar
  3. 3.
    Feng J, Li F, Li X, Ren X, Fan D, Wu D, et al. An amplification label of core–shell CdSe@CdS QD sensitized GO for a signal-on photoelectrochemical immunosensor for amyloid β-protein. J Mater Chem B. 2019;7(7):1142–8.CrossRefGoogle Scholar
  4. 4.
    Hao N, Lu J, Chi M, Xiong M, Zhang Y, Hua R, et al. A universal photoelectrochemical biosensor for dual microRNA detection based on two CdTe nanocomposites. J Mater Chem B. 2019;7(7):1133–41.CrossRefGoogle Scholar
  5. 5.
    Fan G-C, Zhu H, Shen Q, Han L, Zhao M, Zhang J-R, et al. Enhanced photoelectrochemical aptasensing platform based on exciton energy transfer between CdSeTe alloyed quantum dots and SiO2@Au nanocomposites. Chem Commun. 2015;51(32):7023–6.CrossRefGoogle Scholar
  6. 6.
    Shi X-M, Wang C-D, Zhu Y-C, Zhao W-W, Yu X-D, Xu J-J, et al. 3D semiconducting polymer/graphene networks: toward sensitive photocathodic enzymatic bioanalysis. Anal Chem. 2018;90(16):9687–90.CrossRefGoogle Scholar
  7. 7.
    Shi X-M, Mei L-P, Wang Q, Zhao W-W, Xu J-J, Chen H-Y. Energy transfer between semiconducting polymer dots and gold nanoparticles in a photoelectrochemical system: a case application for cathodic bioanalysis. Anal Chem. 2018;90(7):4277–81.CrossRefGoogle Scholar
  8. 8.
    Yang H, Zhang Y, Zhang L, Cui K, Ge S, Huang J, et al. Stackable lab-on-paper device with all-in-one Au electrode for high-efficiency photoelectrochemical cyto-sensing. Anal Chem. 2018;90(12):7212–20.CrossRefGoogle Scholar
  9. 9.
    Zhao M, Fan G-C, Chen J-J, Shi J-J, Zhu J-J. Highly sensitive and selective photoelectrochemical biosensor for Hg2+ detection based on dual signal amplification by exciton energy transfer coupled with sensitization effect. Anal Chem. 2015;87(24):12340–7.CrossRefGoogle Scholar
  10. 10.
    Qiu Z, Shu J, Tang D. Near-infrared-to-ultraviolet light-mediated photoelectrochemical aptasensing platform for cancer biomarker based on core-shell NaYF4:Yb,Tm@TiO2 upconversion microrods. Anal Chem. 2018;90(1):1021–8.CrossRefGoogle Scholar
  11. 11.
    Giampiccolo A, Tobaldi D, Leonardi S, Murdoch B, Seabra M, Ansell M, et al. Sol gel graphene/TiO2 nanoparticles for the photocatalytic-assisted sensing and abatement of NO2. Appl Catal B Environ. 2019;243:183–94.CrossRefGoogle Scholar
  12. 12.
    Wang C, Ye X, Wang Z, Wu T, Wang Y, Li C. Molecularly imprinted photo-electrochemical sensor for human epididymis protein 4 based on polymerized ionic liquid hydrogel and gold nanoparticle/ZnCdHgSe quantum dots composite film. Anal Chem. 2017;89(22):12391–8.CrossRefGoogle Scholar
  13. 13.
    Yu F, Wang Z, Zhang S, Ye H, Kong K, Gong X, et al. Molecular engineering of donor-acceptor conjugated polymer/g-C3N4 heterostructures for significantly enhanced hydrogen evolution under visible-light irradiation. Adv Funct Mater. 2018;28(47):1804512.CrossRefGoogle Scholar
  14. 14.
    Liu C, Qin H, Kang L, Chen Z, Wang H, Qiu H, et al. Graphitic carbon nitride nanosheets as a multifunctional nanoplatform for photochemical internalization-enhanced photodynamic therapy. J Mater Chem B. 2018;6(47):7908–15.CrossRefGoogle Scholar
  15. 15.
    Li X, Zhu L, Zhou Y, Yin H, Ai S. Enhanced photoelectrochemical method for sensitive detection of protein kinase a activity using TiO2/g-C3N4, PAMAM dendrimer, and alkaline phosphatase. Anal Chem. 2017;89(4):2369–76.CrossRefGoogle Scholar
  16. 16.
    Yan K, Zhu Y, Ji W, Chen F, Zhang J. Visible light-driven membraneless photocatalytic fuel cell toward self-powered aptasensing of PCB77. Anal Chem. 2018;90(16):9662–6.CrossRefGoogle Scholar
  17. 17.
    Wang Z, Chen M, Huang Y, Shi X, Zhang Y, Huang T, et al. Self-assembly synthesis of boron-doped graphitic carbon nitride hollow tubes for enhanced photocatalytic NOx removal under visible light. Appl Catal B Environ. 2018;239:352–61.CrossRefGoogle Scholar
  18. 18.
    Zhu Y-C, Zhang N, Ruan Y-F, Zhao W-W, Xu J-J, Chen H-Y. Alkaline phosphatase tagged antibodies on gold nanoparticles/TiO2 nanotubes electrode: a plasmonic strategy for label-free and amplified photoelectrochemical immunoassay. Anal Chem. 2016;88(11):5626–30.CrossRefGoogle Scholar
  19. 19.
    Zhao W-W, Yu PP, Shan Y, Wang J, Xu J-J, Chen H-Y. Exciton-plasmon interactions between CdS quantum dots and Ag nanoparticles in photoelectrochemical system and its biosensing application. Anal Chem. 2012;84(14):5892–7.CrossRefGoogle Scholar
  20. 20.
    Da P, Li W, Lin X, Wang Y, Tang J, Zheng G. Surface plasmon resonance enhanced real-time photoelectrochemical protein sensing by gold nanoparticle-decorated TiO2 nanowires. Anal Chem. 2014;86(13):6633–9.CrossRefGoogle Scholar
  21. 21.
    Li R, Yan R, Bao J, Tu W, Dai Z. A localized surface plasmon resonance-enhanced photoelectrochemical biosensing strategy for highly sensitive and scatheless cell assay under red light excitation. Chem Commun. 2016;52(79):11799–802.CrossRefGoogle Scholar
  22. 22.
    Shen C, Zeng K, Luo J, Li X, Yang M, Rasooly A. Self-assembled DNA generated electric current biosensor for HER2 analysis. Anal Chem. 2017;89(19):10264–9.CrossRefGoogle Scholar
  23. 23.
    Xiang W, Wang G, Cao S, Wang Q, Xiao X, Li T, et al. Coupling antibody based recognition with DNA based signal amplification using an electrochemical probe modified with MnO2 nanosheets and gold nanoclusters: application to the sensitive voltammetric determination of the cancer biomarker alpha fetoprotein. Microchim Acta. 2018;185(7):335.CrossRefGoogle Scholar
  24. 24.
    Chai Y, Li X, Yang M. Aptamer based determination of the cancer biomarker HER2 by using phosphate-functionalized MnO2 nanosheets as the electrochemical probe. Microchim Acta. 2019;186(5):316.CrossRefGoogle Scholar
  25. 25.
    Cao S, Wang Q, Xiao X, Li T, Yang M. Electrochemical immunoassay for the tumor marker CD25 by coupling magnetic sphere-based enrichment and DNA based signal amplification. Microchim Acta. 2019;186(6):352.CrossRefGoogle Scholar
  26. 26.
    Wang G, Wang H, Cao S, Xiang W, Li T, Yang M. Electrochemical determination of the activity and inhibition of telomerase based on the interaction of DNA with molybdate. Microchim Acta. 2019;186(2):96.CrossRefGoogle Scholar
  27. 27.
    Mahlknecht G, Maron R, Mancini M, Schechter B, Sela M, Yarden Y. Aptamer to ErbB-2/HER2 enhances degradation of the target and inhibits tumorigenic growth. PNAS. 2013;110(20):8170–5.CrossRefGoogle Scholar
  28. 28.
    Wang Z, Wang W, Bu X, Wei Z, Geng L, Wu Y, et al. Microarray based screening of peptide nano probes for HER2 positive tumor. Anal Chem. 2015;87(16):8367–72.CrossRefGoogle Scholar
  29. 29.
    Xue J, Ma S, Zhou Y, Zhang Z, He M. Facile photochemical synthesis of Au/Pt/g-C3N4 with plasmon-enhanced photocatalytic activity for antibiotic degradation. ACS Appl Mater Interfaces. 2015;7(18):9630–7.CrossRefGoogle Scholar
  30. 30.
    Yang C, Wang B, Zhang L, Yin L, Wang X. Synthesis of layered carbonitrides from biotic molecules for photoredox transformations. Angew Chem Int Ed. 2017;56(23):6727–31.CrossRefGoogle Scholar
  31. 31.
    Ma D, Wu J, Gao M, Xin Y, Ma T, Sun Y. Fabrication of Z-scheme g-C3N4/RGO/Bi2WO6 photocatalyst with enhanced visible-light photocatalytic activity. Chem Eng J. 2016;290:136–46.CrossRefGoogle Scholar
  32. 32.
    Du X, Zhang Z, Miao Z, Ma M, Zhang Y, Zhang C, et al. One step electrodeposition of dendritic gold nanostructures on beta-lactoglobulin-functionalized reduced graphene oxide for glucose sensing. Talanta. 2015;144:823–9.CrossRefGoogle Scholar
  33. 33.
    Tian S, Zeng K, Yang A, Wang Q, Yang M. A copper based enzyme-free fluorescence ELISA for HER2 detection. J Immunol Methods. 2017;451:78–82.CrossRefGoogle Scholar
  34. 34.
    Ravalli A, da Rocha C, Yamanaka H, Marrazza G. A label-free electrochemical affisensor for cancer marker detection: the case of HER2. Bioelectrochemistry. 2015;106:268–75.CrossRefGoogle Scholar
  35. 35.
    Yang S, You M, Zhang F, Wang Q, He P. A sensitive electrochemical aptasensing platform based on exonuclease recycling amplification and host-guest recognition for detection of breast cancer biomarker HER2. Sensors Actuators B Chem. 2018;258:796–802.CrossRefGoogle Scholar
  36. 36.
    Pacheco J, Rebelo P, Freitas M, Nouws H, Delerue-Matos C. Breast cancer biomarker (HER2-ECD) detection using a molecularly imprinted electrochemical sensor. Sensors Actuators B Chem. 2018;273:1008–14.CrossRefGoogle Scholar
  37. 37.
    Tallapragada S, Layek K, Mukherjee R, Mistry K, Ghosh M. Development of screen-printed electrode based immunosensor for the detection of HER2 antigen in human serum samples. Bioelectrochemistry. 2017;118:25–30.CrossRefGoogle Scholar
  38. 38.
    Carvajal S, Fera S, Jones A, Baldo T, Mosa I, Rusling J, et al. Disposable inkjet-printed electrochemical platform for detection of clinically relevant HER-2 breast cancer biomarker. Biosens Bioelectron. 2018;104:158–62.CrossRefGoogle Scholar
  39. 39.
    Loo L, Capobianco J, Wu W, Gao X, Shih W, Shih W-H, et al. Highly sensitive detection of HER2 extracellular domain in the serum of breast cancer patients by piezoelectric microcantilevers. Anal Chem. 2011;83(9):3392–7.CrossRefGoogle Scholar
  40. 40.
    Qureshi A, Gurbuz Y, Niazi J. Label-free capacitance based aptasensor platform for the detection of HER2/ErbB2 cancer biomarker in serum. Sensors Actuators B Chem. 2015;220:1145–51.CrossRefGoogle Scholar
  41. 41.
    Sharma S, Zapatero-Rodriguez J, Saxena R, O’Kennedy R, Srivastava S. Ultrasensitive direct impedimetric immunosensor for detection of serum HER2. Biosens Bioelectron. 2018;106:78–85.CrossRefGoogle Scholar
  42. 42.
    Hu L, Hu S, Guo L, Shen C, Yang M, Rasooly A. DNA generated electric current biosensor. Anal Chem. 2017;89(4):2547–52.CrossRefGoogle Scholar
  43. 43.
    Li X, Shen C, Yang M, Rasooly A. Polycytosine DNA electric-current-generated immunosensor for electrochemical detection of human epidermal growth factor receptor 2 (HER2). Anal Chem. 2018;90(7):4764–9.CrossRefGoogle Scholar
  44. 44.
    Shen C, Liu S, Li X, Zhao D, Yang M. Immunoelectrochemical detection of the human epidermal growth factor receptor 2 (HER2) via gold nanoparticle-based rolling circle amplification. Microchim Acta. 2018;185(12):547.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Junjun Luo
    • 1
  • Dong Liang
    • 1
  • Xiaoqing Qiu
    • 1
  • Minghui Yang
    • 1
    Email author
  1. 1.Key Laboratory of Hunan Province for Water Environment and Agriculture Product Safety, College of Chemistry and Chemical EngineeringCentral South UniversityChangshaChina

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