Skip to main content
SpringerLink
Log in

A sandwich-type electrochemical aptasensor for the carcinoembryonic antigen via biocatalytic precipitation amplification and by using gold nanoparticle composites

  • Original Paper
  • Published:
Microchimica Acta Aims and scope Submit manuscript

Abstract

A sandwich-type electrochemical aptasensor is described for detecting the carcinoembryonic antigen (CEA) with high sensitivity and accuracy. Two kinds of nanomaterials are used. The first was obtained by modifying gold nanoparticles with reduced graphene oxide and hemin (Hemin-rGO-AuNPs). The second consists of horseradish peroxidase-modified organic-inorganic hybrid nanoflowers linked to gold nanoparticles to obtain an architecture of type HRP-Cu3(PO4)2-HNF-AuNPs). These serve as carriers for two aptamers (apt1 and apt2) against CEA. Simultaneously, they were used to catalyze the precipitation reaction between 4-chloro-1-naphthol(4-CN) and H2O2. A sandwich-type assay linked to enzyme inhibition amplification was established for electrochemical determination of CEA. Under optimal experimental conditions and by using differential pulse voltammetry, the response peak currents (best measured at −0.34 V vs. Ag/AgCl) increases linearly with the logarithm of the CEA concentration in the range between 100 fg mL−1 and 100 ng mL−1. The detection limit is as low as 29 fg mL−1.

Schematic representation of the sandwich-type electrochemical aptasensor based on signal inhibition amplification from biocatalytic precipitation reaction. (HRP-Cu3(PO4)2 hybrid nanoflowers: Horseradish Peroxidase-Cu3(PO4)2 hybrid nanoflowers; AuNPs: Gold Nanoparticles; Hemin-rGO-AuNPs: Hemin-Reduced Graphene Oxide-Gold Nanoparticles; BSA: Bovine Serum Albumin; CEA: Carcinoembryonic Antigen; CEAapt1: 5′-SH-(CH2)6-ATA CCA GCT TAT TCA ATT-3′; CEAapt2: 5′-NH2-(CH2)6-AGG GGG TGA AGG GAT ACC C-3′; GCE: Glassy carbon electrode; 4-CN: 4-Chloro-1-naphthol; DPV: Differential pulse voltammetry).

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Scheme 1
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Gold P (1965) Demonstration of tumor-specific antigens in human colonic Carcinomata by immunological tolerance and absorption techniques. J Exp Med 121(3):439–462

    Article  CAS  Google Scholar 

  2. Shousha S, Lyssiotis T, Godfrey VM, Scheuer PJ (1979) Carcinoembryonic antigen in breast-cancer tissue: a useful prognostic indicator. Brit Med J 1(6166):777–779

    Article  CAS  Google Scholar 

  3. Malkin A, Kellen JA, Lickrish GM, Bush RS (2015) Carcinoembryonic antigen (CEA) and other tumor markers in ovarian and cervical cancer. Cancer 42(S3):1452–1456

    Article  Google Scholar 

  4. Millo R, Radillo L, Mandruzzato GP (1988) Tumoral markers (CA 125--CEA) in the screening of ovarian cancer. Eur J Gynaecol Oncol 9(6):485–489

    PubMed  Google Scholar 

  5. Ardakania MM, Ardakania ZT, Sahraeia N (2019) Seyed Mohammad Moshtaghioun fabrication of an ultrasensitive and selective electrochemical aptasensor to detect carcinoembryonic antigen by using a new nanocomposite. Biosens Bioelectron 129:1–6

    Article  Google Scholar 

  6. Huang J-Y, Zhao L, Lei W, Wen W, Wang YJ, Bao T, Xiong HY, Zhang XH, Wang SF (2018) A high-sensitivity electrochemical aptasensor of carcinoembryonic antigen based on graphene quantum dots-ionic liquid-nafion nanomatrix and DNAzyme-assisted signal amplification strategy. Biosens Bioelectron 99:28–33

    Article  CAS  Google Scholar 

  7. Nie G, Wang Y, Tang Y, Zhao D, Guo Q (2017) A graphene quantum dots based electrochemiluminescence immunosensor for carcinoembryonic antigen detection using poly(5-formylindole)/reduced graphene oxide nanocomposite. Biosens Bioelectron 101:123–128

    Article  Google Scholar 

  8. Wang D, Li Y, Lin Z, Qiu B, Guo L (2015)Surface-enhanced Electrochemiluminescence of Ru@SiO2 for ultrasensitive detection of carcinoembryonic antigen. Anal Chem 87(12):5966–5972

    Article  CAS  Google Scholar 

  9. Nie G, Tang Y, Zhang B, Wang Y, Guo Q (2018)Label-free photoelectrochemical immunosensing platform for detection of carcinoembryonic antigen through photoactive conducting poly(5-formylindole) nanocomposite. Biosens Bioelectron 116:60–66

    Article  CAS  Google Scholar 

  10. Li B, Lai GS, Zhang HL, Hu SL, Yu AM (2017) Copper chromogenic reaction based colorimetric immunoassay for rapid and sensitive detection of a tumor biomarker. Anal Chim Acta 963:106–111

    Article  CAS  Google Scholar 

  11. Wu K, Chu C, Ma C, Yang H, Yan M, Ge S, Yu J, Song X (2015) Immunoassay for carcinoembryonic antigen based on the Zn2+-enhanced fluorescence of magnetic-fluorescent nanocomposites. Sensors Actuators B Chem 206:43–49

    Article  CAS  Google Scholar 

  12. Chen ZH, Wu YS, Chen MJ, Hou JY, Ren ZQ, Sun D, Liu TC (2013) A novel homogeneous time-resolved fluoroimmunoassay for carcinoembryonic antigen based on water-soluble quantum dots. J Fluoresc 23(4):649–657

    Article  CAS  Google Scholar 

  13. Wu YM, Li GP, Zou LN, Lei S, Yu Q, Ye BX (2018) Highly active DNAzyme-peptide hybrid structure coupled porous palladium for high-performance electrochemical aptasensing platform. Sensors Actuators B Chem 259:372–379

    Article  CAS  Google Scholar 

  14. Huang JY, Zhao L, Lei W, Wen W, Wang YJ, Bao T, Xiong HY, Zhang XH, Wang SF (2018) A high-sensitivity electrochemical aptasensor of carcinoembryonic antigen based on graphene quantum dots-ionic liquid-nafion nanomatrix and DNAzyme-assisted signal amplification strategy. Biosens Bioelectron 99:28–33

    Article  CAS  Google Scholar 

  15. Cheng H, Xu LL, Zhang HL, Yu AM, Lai GS (2016) Enzymatically catalytic signal tracing by a glucose oxidase and ferrocene dually functionalized nanoporous gold nanoprobe for ultrasensitive electrochemical measurement of a tumor biomarker. Analyst 141(14):4381–4387

    Article  CAS  Google Scholar 

  16. Wu YM, Zou LN, Lei S, Yu Q, Ye BX (2017) Highly sensitive electrochemical thrombin aptasensor based on peptide-enhanced electrocatalysis of hemin/G-quadruplex and nanocomposite as nanocarrier. Biosens Bioelectron 97:317–324

    Article  CAS  Google Scholar 

  17. Zhang G, Liu Z, Fan L, Guo Y (2018) Electrochemical prostate specific antigen aptasensor based on hemin functionalized graphene-conjugated palladium nanocomposites. Microchim Acta 185(3):159

    Article  Google Scholar 

  18. Wang YH, Xia H, Huang KJ, Wu X, Ma YY, Deng R, Lu YF, Han ZW (2018) Ultrasensitive determination of thrombin by using an electrode modified with WSe2 and gold nanoparticles, aptamer-thrombin-aptamer sandwiching, redox cycling, and signal enhancement by alkaline phosphatase. Mirochim Acta 85(11):502

    Article  Google Scholar 

  19. Si ZZ, Xie B, Chen ZH, Tang C, Li T, Yang MH (2017) Electrochemical aptasensor for the cancer biomarker CEA based on aptamer induced current due to formation of molybdophosphate. Microchim Acta 184:3215–3221

    Article  CAS  Google Scholar 

  20. Wang QL, Cui HF, Song XJ, Fan SF, Chen LL, Li MM, Li ZY (2018) A label-free and lectin-based sandwich aptasensor for detection of carcinoembryonic antigen. Sensors Actuators B 260:48–54

    Article  CAS  Google Scholar 

  21. Ma C, Liu HY, Zhang LN, Lia H, Yan M, Song XR, Yu JH (2018) Multiplexed aptasensor for simultaneous detection of carcinoembryonic antigen and mucin-1 based on metal ion electrochemical labels and Ru(NH3)6 3+ electronic wires. Biosens Bioelectron 99:8–13

    Article  CAS  Google Scholar 

  22. Li WX, Shu D, Zhang DS, Ma ZF (2018)Multi-amplification of the signal of voltammetric immunosensors: highly sensitive detection of tumor marker. Sensors Actuators B Chem 262:50–56

    Article  CAS  Google Scholar 

  23. Du X, Kang T, Lu L et al (2017) An electrochemiluminescence sensor based on CdSe@CdS functionalized MoS2 and hemin/G-quadruplex-based DNAzyme biocatalytic precipitation for sensitive detection of Pb(II). Anal Methods 10:1039

    Google Scholar 

  24. Lai GS, Cheng H, Xin DH, Zhang HL, Yu AM (2016) Amplified inhibition of the electrochemical signal of ferrocene by enzyme-functionalized graphene oxide nanoprobe for ultrasensitive immunoassay. Anal Chim Acta 902:189–195

    Article  CAS  Google Scholar 

  25. Zhang KY, Lv SZ, Lin ZZ, Li MJ, Tang DP (2018)Bio-bar-code-based photoelectrochemical immunoassay for sensitive detection of prostate-specific antigen using rolling circle amplification and enzymatic biocatalytic precipitation. Biosens Bioelectron 101:159–166

    Article  CAS  Google Scholar 

  26. Zhu D, Liu W, Zhao D, Hao Q, Li J, Huang J, Shi J, Chao J, Su S, Wang L (2017)Label-free electrochemical sensing platform for MicroRNA-21 detection using Thionine and Gold nanoparticles co-functionalized MoS2 Nanosheet. ACS Appl Mater Interfaces 9(41):35597–35603

    Article  CAS  Google Scholar 

  27. Fu YM, Huang D, Li C, Zou LN, Ye BX (2018) Graphene blended with SnO2 and Pd-Pt nanocages for sensitive non-enzymatic electrochemical detection of H2O2 released from living cells. Anal Chim Acta 1014:10–18

    Article  CAS  Google Scholar 

  28. Yu Q, Wu Y, Liu Z, Lei S, Li G, Ye B (2018) Novel electrochemical biosensor based on cationic peptide modified hemin/G-quadruples enhanced peroxidase-like activity. Biosens Bioelectron 107:178–183

    Article  CAS  Google Scholar 

  29. Lv X, Weng J (2013) Ternary composite of hemin, gold nanoparticles and graphene for highly efficient decomposition of hydrogen peroxide. Sci Rep 3:3285

    Article  Google Scholar 

  30. Yang Z, Qian J, Yang X, Jiang D, Du X, Wang K, Mao H, Wang K (2015) A facile label-free colorimetric aptasensor for acetamiprid based on the peroxidase-like activity of hemin-functionalized reduced graphene oxide. Biosens Bioelectron 65:39–46

    Article  CAS  Google Scholar 

  31. Liu F, Tang J, Xu J, Shu Y, Xu Q, Wang H, Hu X (2016) Low potential detection of indole-3-acetic acid based on the peroxidase-like activity of hemin/reduced graphene oxide nanocomposite. Biosens Bioelectron 86:871–878

    Article  CAS  Google Scholar 

  32. Liu J, Cui M, Niu L, Zhou H, Zhang S (2016) Enhanced peroxidase-like properties of graphene-hemin-composite decorated with Au Nanoflowers as electrochemical aptamer biosensor for the detection of K562 leukemia Cancer cells. Chemistry 22(50):18001–18008

    Article  CAS  Google Scholar 

  33. Liu J, Cui M, Zhou H, Zhang S (2016) Efficient double-quenching of electrochemiluminescence from CdS:Eu QDs by hemin-graphene-Au nanorods ternary composite for ultrasensitive immunoassay. Sci Rep 6:30577

    Article  CAS  Google Scholar 

  34. Gu CJ, Kong FY, Chen ZD, Fan DH, Fang HL, Wang W (2016) Reduced graphene oxide-hemin-Au nanohybrids: facile one-pot synthesis and enhanced electrocatalytic activity towards the reduction of hydrogen peroxide. Biosens Bioelectron 78:300–307

    Article  CAS  Google Scholar 

  35. Yu Q, Wu YM, Liu Z, Lei S, Li GP, Ye BX (2018) Novel electrochemical biosensor based on cationic peptide modified hemin/G-quadruples enhanced peroxidase-like activity. Biosens Bioelectron 107:178–183

    Article  CAS  Google Scholar 

  36. Li J, Li X, Zhao Q, Jiang Z, Tadé M, Wang S, Liu S (2018)Polydopamine-assisted decoration of TiO2 nanotube arrays with enzyme to construct a novel photoelectrochemical sensing platform. Sensors Actuators B Chem 255:133–139

    Article  CAS  Google Scholar 

  37. Ge J, Lei J, Zare RN (2012)Protein-inorganic hybrid nanoflowers. Nature Nanotech 7(7):428–432

    Article  CAS  Google Scholar 

  38. Lin Z, Xiao Y, Yin Y, Hu W, Liu W, Yang H (2014) Facile synthesis of enzyme-inorganic hybrid nanoflowers and its application as a colorimetric platform for visual detection of hydrogen peroxide and phenol. ACS Appl Mater Interfaces 6(13):10775–10782

    Article  CAS  Google Scholar 

  39. Ye R, Zhu C, Song Y, Lu Q, Ge X, Yang X, Zhu MJ, Du D, Li H, Lin Y (2016) Bioinspired synthesis of all-in-oneorganic-inorganic hybrid Nanoflowers combined with a handheld pH meter for on-site detection of food pathogen. Small 12(23):3094–3100

    Article  CAS  Google Scholar 

  40. Liu Y, Chen J, Du M, Wang X, Ji X, He Z (2017) The preparation of dual-functional hybrid nanoflower and its application in the ultrasensitive detection of disease-related biomarker. Biosens Bioelectron 92:68–73

    Article  CAS  Google Scholar 

  41. Kong W, Wu D, Hu N, Li N, Dai C, Chen X, Suo Y, Li G, Wu Y (2018) Robust hybrid enzyme nanoreactor mediated plasmonic sensing strategy for ultrasensitive screening of anti-diabetic drug. Biosens Bioelectron 99:653–659

    Article  CAS  Google Scholar 

  42. Ambrosi A, Castaneda MT, Killard AJ et al (2007)Double-codified Gold Nanolabels for enhanced Immunoanalysis. Anal Chem 79(14):5232–5240

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors are sincerely grateful for the financial support from the National Natural Science Foundation of China (Grant no. 21575130; U1504216) and Startup Research Fund of Zhengzhou University (Grant no. 1511316006).

Author information

Authors and Affiliations

  1. College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou, 450001, People’s Republic of China

    Lingling Xu, Zi Liu, Sheng Lei, Di Huang, Lina Zou & Baoxian Ye

Authors
  1. Lingling Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zi Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sheng Lei
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Di Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lina Zou
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Baoxian Ye
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Lina Zou or Baoxian Ye.

Ethics declarations

The author(s) declare that they have no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(DOCX 820 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xu, L., Liu, Z., Lei, S. et al. A sandwich-type electrochemical aptasensor for the carcinoembryonic antigen via biocatalytic precipitation amplification and by using gold nanoparticle composites. Microchim Acta 186, 473 (2019). https://doi.org/10.1007/s00604-019-3542-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00604-019-3542-2

Keywords

Search

Navigation