Skip to main content
Log in

Photoelectrochemical assay for the detection of circulating tumor cells based on aptamer-Ag2S nanocrystals for signal amplification

  • Paper in Forefront
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

In this work, we developed a photoelectrochemical assay for circulating tumor cells (CTCs) detection based on hexagonal carbon-nitrogen tubes (HCNT) as visible light-sensitive materials. The MCF-7 cell was selected as the model CTC and was captured through specific recognition between epithelial cell adhesion molecules (EpCAM) on the cell surface and anti-EpCAM antibodies. Anti-EpCAM antibody-modified magnetic nanoparticles were used to enrich and separate MCF-7 cells from samples. The detection signal was amplified by Ag2S nanocrystals, which can compete with HCNTs for absorbing visible light, leading to a decrease of photocurrent intensity. The linear range of the assay for MCF-7 cells is from 10 to 5000 cells mL−1, with a detection limit of 3 cells mL−1 (S/D = 3). The assay has good selectivity for MCF-7 detection over HeLa cells. The assay was successfully applied for the detection of MCF-7 in human whole blood, which indicates the potential for clinical application.

Graphical abstract

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.

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

Similar content being viewed by others

References

  1. Haber DA, Velculescu VE. Blood-based analyses of cancer: circulating tumor cells and circulating tumor DNA. Cancer Discov. 2014;4(6):650–1.

    Article  CAS  Google Scholar 

  2. Manier S, Park J, Capelletti M, Bustoros M, Freeman SS, Ha G, et al. Whole-exome sequencing of cell-free DNA and circulating tumor cells in multiple myeloma. Nat Commun. 2018;9(1):1691.

    Article  CAS  Google Scholar 

  3. Davis AA, Zhang Q, Gerratana L, Shah AN, Zhan Y, Qiang W, et al. Association of a novel circulating tumor DNA next-generating sequencing platform with circulating tumor cells (CTCs) and CTC clusters in metastatic breast cancer. Breast Cancer Res. 2019;21(1):137.

    Article  CAS  Google Scholar 

  4. Nie LJ, Li FL, Huang XL, Aguilar ZP, Wang YA, Xiong YH, et al. Folic acid targeting for efficient isolation and detection of ovarian cancer CTCs from human whole blood based on two-step binding strategy. ACS Appl Mater Interfaces. 2018;10(16):14055–62.

    Article  CAS  Google Scholar 

  5. Wu XX, Xia YZ, Huang YJ, Li J, Ruan HM, Chen TX, et al. Improved SERS-active nanoparticles with various shapes for CTC detection without enrichment process with supersensitivity and high specificity. ACS Appl Mater Interfaces. 2016;8(31):19928–38.

    Article  CAS  Google Scholar 

  6. Safarpour H, Dehghani S, Nosrati R, Zebardast N, Alibolandi M, Mokhtarzadeh A, et al. Optical and electrochemical-based nano-aptasensing approaches for the detection of circulating tumor cells (CTCs). Biosens Bioelectron. 2020;148:111833.

    Article  CAS  Google Scholar 

  7. Zhong X, Zhang H, Zhu Y, Liang Y, Yuan Z, Li J, et al. Circulating tumor cells in cancer patients: developments and clinical applications for immunotherapy. Mol Cancer. 2020;19(1):15.

    Article  Google Scholar 

  8. Burinaru TA, Avram M, Avram A, Marculescu C, Tincu B, Tucureanu V, et al. Detection of circulating tumor cells using microfluidics. ACS Comb Sci. 2018;20(3):107–26.

    Article  CAS  Google Scholar 

  9. Yin JX, Deng JQ, Wang L, Du C, Zhang W, Jiang XY. Detection of circulating tumor cells by fluorescence microspheres-mediated amplification. Anal Chem. 2020;92(10):6968–76.

    Article  CAS  Google Scholar 

  10. Cao J, Zhao X-P, Younis MR, Li Z-Q, Xia X-H, Wang C. Ultrasensitive capture, detection, and release of circulating tumor cells using a nanochannel–ion channel hybrid coupled with electrochemical detection technique. Anal Chem. 2017;89(20):10957–64.

    Article  CAS  Google Scholar 

  11. Shen C, Liu S, Li X, Yang M. Electrochemical detection of circulating tumor cells based on DNA generated electrochemical current and rolling circle amplification. Anal Chem. 2019;91(18):11614–9.

    Article  CAS  Google Scholar 

  12. Parker SG, Yang Y, Ciampi S, Gupta B, Kimpton K, Mansfeld FM, et al. A photoelectrochemical platform for the capture and release of rare single cells. Nat Commun. 2018;9(1):2288.

    Article  Google Scholar 

  13. Shu J, Tang DP. Recent advances in photoelectrochemical sensing: from engineered photoactive materials to sensing devices and detection modes. Anal Chem. 2020;92(1):363–77.

    Article  CAS  Google Scholar 

  14. Li C, Chen S, Gao X, Zhang W, Wang Y. Fabrication, characterization and photoelectrochemical properties of CdS/CdSe nanofilm co-sensitized ZnO nanorod arrays on Zn foil subs. J Colloid Interface Sci. 2021;588:269–82.

    Article  CAS  Google Scholar 

  15. Eley C, Li T, Liao FL, Fairclough SM, Smith JM, Smith G, et al. Nanojunction-mediated photocatalytic enhancement in heterostructured CdS/ZnO, CdSe/ZnO, and CdTe/ZnO nanocrystals. Angew Chem Int Ed. 2014;53(30):7838–42.

    Article  CAS  Google Scholar 

  16. Khan AH, Bertrand GHV, Teitelboim A, Sekhar MC, Polovitsyn A, Brescia R, et al. CdSe/CdS/CdTe core/barrier/crown nanoplatelets: synthesis, optoelectronic properties, and multiphoton fluorescence upconversion. ACS Nano. 2020;14(4):4206–15.

    Article  CAS  Google Scholar 

  17. Jung K, Lee J, Kim YM, Kim J, Kim CU, Lee MJ. Influence of defects and nanoscale strain on the photovoltaic properties of CdS/CdSe nanocomposite co-sensitized ZnO nanowire solar cells. Electrochim Acta. 2016;220:500–10.

    Article  CAS  Google Scholar 

  18. Kumar SG, Rao KSRK. Comparison of modification strategies towards enhanced charge carrier separation and photocatalytic degradation activity of metal oxide semiconductors (TiO2, WO3 and ZnO). Appl Surf Sci. 2017;391:124–48.

    Article  CAS  Google Scholar 

  19. Luo JJ, Liang D, Zhao D, Yang MH. Photoelectrochemical detection of circulating tumor cells based on aptamer conjugated Cu2O as signal probe. Biosens Bioelectron. 2020;151:111976.

    Article  CAS  Google Scholar 

  20. Luo JJ, Liang D, Li XQ, Deng L, Wang ZX, Yang MH. Aptamer-based photoelectrochemical assay for the determination of MCF-7. Microchim Acta. 2020;187(5):257.

    Article  CAS  Google Scholar 

  21. Shin SR, Zhang YS, Kim DJ, Manbohi A, Avci H, Silvestri A, et al. Aptamer-based microfluidic electrochemical biosensor for monitoring cell-secreted trace cardiac biomarkers. Anal Chem. 2016;88(20):10019–27.

    Article  CAS  Google Scholar 

  22. Gao SX, Zheng X, Hu B, Sun MJ, Wu JH, Jiao BH, et al. Enzyme-linked, aptamer-based, competitive biolayer interferometry biosensor for palytoxin. Biosens Bioelectron. 2017;89:952–8.

    Article  CAS  Google Scholar 

  23. Xiang WW, Lv QX, Shi HX, Xie B, Gao L. Aptamer-based biosensor for detecting carcinoembryonic antigen. Talanta. 2020;214:120716.

    Article  CAS  Google Scholar 

  24. Zamiri R, Abbastabar Ahangar H, Zakaria A, Zamiri G, Shabani M, Singh B, et al. The structural and optical constants of Ag2S semiconductor nanostructure in the far-infrared. Chem Cent J. 2015;9(1):28.

    Article  Google Scholar 

  25. Hou Y, Zhu L, Hao H, Zhang Z, Ding C, Zhang G, et al. A novel photoelectrochemical aptamer sensor based on rare-earth doped Bi2WO6 and Ag2S for the rapid detection of Vibrio parahaemolyticus. Microchem J. 2021;165:106132.

    Article  CAS  Google Scholar 

  26. Zhang L, Li P, Feng L, Chen X, Jiang J, Zhang S, et al. Synergetic Ag2S and ZnS quantum dots as the sensitizer and recognition probe: a visible light-driven photoelectrochemical sensor for the “signal-on” analysis of mercury (II). J Hazard Mater. 2020;387:121715.

    Article  CAS  Google Scholar 

  27. Ding C, Zhang C, Cheng S, Xian Y. Multivalent aptamer functionalized Ag2S nanodots/hybrid cell membrane-coated magnetic nanobioprobe for the ultrasensitive isolation and detection of circulating tumor cells. Adv Funct Mater. 2020;30(16):1909781.

    Article  CAS  Google Scholar 

  28. Wu LL, Wen CY, Hu J, Tang M, Qi CB, Li N, et al. Nanosphere-based one-step strategy for efficient and nondestructive detection of circulating tumor cells. Biosens Bioelectron. 2017;94:219–26.

    Article  CAS  Google Scholar 

  29. Yang DD, Liu M, Xu J, Yang C, Wang XX, Lou YB, et al. Carbon nanosphere-based fluorescence aptasensor for targeted detection of breast cancer cell MCF-7. Talanta. 2018;185:113–7.

    Article  CAS  Google Scholar 

  30. Zheng TT, Zhang QF, Feng S, Zhu JJ, Wang Q, Wang H. Robust nonenzymatic hybrid nanoelectrocatalysts for signal amplification toward ultrasensitive electrochemical cytosensing. J Am Chem Soc. 2014;136(6):2288–91.

    Article  CAS  Google Scholar 

  31. Luo J, Liang D, Qiu X, Yang M. Photoelectrochemical detection of breast cancer biomarker based on hexagonal carbon nitride tubes. Anal Bioanal Chem. 2019;411:6889–97.

    Article  CAS  Google Scholar 

  32. Roshan H, Ravanan F, Sheikhi MH, Mirzaei A. High-detectivity near-infrared photodetector based on Ag2S nanocrystals. J Alloys Compd. 2021;852:156948.

    Article  CAS  Google Scholar 

  33. Ansari JR, Singh N, Mohapatra S, Ahmad R, Saha NR, Chattopadhyay D, et al. Enhanced near infrared luminescence in Ag@Ag2S core-shell nanoparticles. Appl Surf Sci. 2019;463:573–80.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors are thankful for the support of this work by the Hunan Provincial Science and Technology Plan Project, China (No. 2019TP1001) and Innovation-Driven Project of Central South University (2020CX002).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Minghui Yang or Xianggui Wang.

Ethics declarations

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 affiliated with Central South University.

Additional information

Publisher’s note

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

Supplementary Information

ESM 1

(PDF 235 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, Z., Luo, J., Yang, M. et al. Photoelectrochemical assay for the detection of circulating tumor cells based on aptamer-Ag2S nanocrystals for signal amplification. Anal Bioanal Chem 413, 5259–5266 (2021). https://doi.org/10.1007/s00216-021-03502-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-021-03502-5

Keywords

Navigation