Skip to main content
SpringerLink
Log in

Dually functional polyethylenimine-coated gold nanoparticles: a versatile material for electrode modification and highly sensitive simultaneous determination of four tumor markers

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

Abstract

A novel sandwich-type electrochemical multiplex immunoassay is described for simultaneous detection of the tumor biomarkers alpha fetoprotein (AFP), carcinoembryonic antigen (CEA), prostate-specific antigen (PSA) and interleukin-8 (IL-8). Polyethylenimine-coated gold nanoparticles (PEI-AuNPs) were used for both modification of a screen-printed carbon electrode (SPCE) and as labeling tags. The coated AuNPs can be easily adsorbed on the electrodes which also are loaded with the electroactive metal ions cadmium(II), lead(II) copper(II) and silver(I) and related secondary antibodies (Ab2). These give distinct voltammetric signals at −0.80, −0.55, −0.20 and + 0.05 V, respectively (vs Ag/AgCl). Four corresponding capture antibodies (Ab1) were then conjugated to one of the electrodes. After a sandwich-type structure was formed by binding of the analytes and the labeling AuNPs, the electrochemical signal responses were recorded. Under the optimized testing conditions, there is a linear relationship in range from 0.25–10 ng mL−1 for AFP, CEA and PSA, and from 0.50–100 pg mL−1 for IL-8. The corresponding detection limits are 1.7, 1.6, 0.9 and 1.0 fg mL−1, respectively. Cross reactivity, interferences and stability of the modified electrodes and of the signal nanotags are satisfying in that they can be stored for >4 weeks without significant signal reduction. The method was successfully applied to the determination of the biomarkers in spiked human serum.

Poly(ethylenimine)-coated gold nanoparticles were used in a sandwich-type multiplex electrochemical immunosensor. The coated gold nanoparticles were used for both electrode modification and as electrochemical nanotags. The resultingvmmunosensor exhibits excellent sensitivity for the four analytes studied, and also displays selectivity and long-term stability.

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

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

Similar content being viewed by others

References

  1. Yi H, Heng Z (2017) Protein array-based approaches for biomarker discovery in cancer. Genom Proteom Bioinf 15:73–81. https://doi.org/10.1016/j.gpb.2017.03.001

    Article  Google Scholar 

  2. Henry N, Hayes D (2012) Cancer biomarkers. Mol Oncol 6:140–146. https://doi.org/10.1016/j.molonc.2012.01.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Suraj S (2009) Tumor markers in clinical practice: general principles and guidelines. Indian J Med Paediatr Oncol 30:1–8. https://doi.org/10.4103/0971-5851.56328

    Article  CAS  Google Scholar 

  4. Rusling J, Kumar C, Gutkind J, Patele V (2010) Measurement of biomarker proteins for point-of-care early detection and monitoring of cancer. Analyst 135:2496–2511. https://doi.org/10.1039/c0an00204f

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Chang J, Kundranda M (2017) Novel diagnostic and predictive biomarkers in pancreatic adenocarcinoma. Int J Mol Sci 18:667–680. https://doi.org/10.3390/ijms18030667

    Article  CAS  PubMed Central  Google Scholar 

  6. Visintin I, Feng Z, Longton G, Ward D, Alvero A, Lai Y, Tenthorey J, Leiser A, Flores-Saaib R, Yu H, Azori M, Rutherford T, Schwartz P, Mor G (2008) Diagnostic markers for early detection of ovarian cancer. Clin Cancer Res 14:1065–1072. https://doi.org/10.1158/1078-0432.CCR-07-1569

    Article  CAS  PubMed  Google Scholar 

  7. Jayanthi V, Das A, Saxena U (2017) Recent advances in biosensor development for the detection of cancer biomarkers. Biosens Bioelectron 91:15–23. https://doi.org/10.1016/j.bios.2016.12.014

    Article  CAS  PubMed  Google Scholar 

  8. Jie W, Zhifeng F, Feng Y, Huangxian J (2007) Biomedical and clinical applications of immunoassays and immunosensors for tumor markers. Trends Anal Chem 26:679–688. https://doi.org/10.1016/j.trac.2007.05.007

    Article  CAS  Google Scholar 

  9. Bhaskara V, Ashwinkumar A, Nicole Y, Henry S, Xiaoyuan C (2012) Electrochemical immunosensors for detection of cancer protein biomarkers. ACS Nano 6:6546–6561. https://doi.org/10.1021/nn3023969

    Article  CAS  Google Scholar 

  10. Zonghua W, Jun L, Qionglin L, Yiming W, Guoan L (2002) Carbon nanotube-modified electrodes for the simultaneous determination of dopamine and ascorbic acid. Analyst 127:653–658. https://doi.org/10.1016/j.snb.2012.06.044

    Article  CAS  Google Scholar 

  11. Xinle J, Zhimin L, Na L, Zhanfang M (2014) A label-free immunosensor based on graphene nanocomposites for simultaneous multiplexed electrochemical determination of tumor markers. Biosens Bioelectron 53:160–166. https://doi.org/10.1016/j.bios.2013.09.050

    Article  CAS  Google Scholar 

  12. Zifeng W, Na L, Zhanfang M (2014) Platinum porous nanoparticles hybrid with metal ions as probes for simultaneous detection of multiplex cancer biomarkers. Biosens Bioelectron 53:324–329. https://doi.org/10.1016/j.bios.2013.10.009

    Article  CAS  Google Scholar 

  13. Zifeng W, Na L, Feng F, Zhanfang M (2015) Synthesis of cadmium, lead and copper alginate nanobeads as immunosensing probes for the detection of AFP, CEA and PSA. Biosens Bioelectron 70:98–105. https://doi.org/10.1016/j.bios.2015.03.015

    Article  CAS  Google Scholar 

  14. Joseph W, Guodong L, Arben M (2003) Electrochemical coding technology for simultaneous detection of multiple DNA targets. J Am Chem Soc 125:3214–3215. https://doi.org/10.1021/ja029668z

    Article  CAS  Google Scholar 

  15. De W, Ning G, Jing Z, Ping X, Yuting C, Tianhua L, Daodong P, Shan J (2014) Signal amplification for multianalyte electrochemical immunoassay with bidirectional stripping voltammetry using metal-enriched polymer nanolabels. Sens Actuat B-Chem 197:244–253. https://doi.org/10.1016/j.snb.2014.03.011

    Article  CAS  Google Scholar 

  16. Xinle J, Xia C, Jingman H, Jie M, Zhanfang M (2014) Triple signal amplification using gold nanoparticles, bienzyme and platinum nanoparticles functionalized graphene as enhancers for simultaneous multiple electrochemical immunoassay. Biosens Bioelectron 53:65–70. https://doi.org/10.1016/j.bios.2013.09.021

    Article  CAS  Google Scholar 

  17. Qiang Z, Yaqin C, Ruo Y, Ying Z (2013) Simultaneous detection of four biomarkers with one sensing surface based on redox probe tagging strategy. Anal Chim Acta 800:22–28. https://doi.org/10.1016/j.aca.2013.08.039

    Article  CAS  Google Scholar 

  18. Xiulan H, Ruo Y, Yaqin C, Ying Z, Yintao S (2007) A new antibody immobilization strategy based on electro-deposition of gold nanoparticles and prussian blue for label-free amperometric immunosensor. Biotechnol Lett 29:149–155. https://doi.org/10.1007/s10529-006-9211-7

    Article  CAS  Google Scholar 

  19. Qinfeng R, Feng F, Zhanfang M (2016) Metal ions doped chitosan–poly(acrylic acid) nanospheres: synthesis and their application in simultaneously electrochemical detection of four markers of pancreatic cancer. Biosens Bioelectron 75:148–154. https://doi.org/10.1016/j.bios.2015.08.041

    Article  CAS  Google Scholar 

  20. Xia C, Xinle J, Jingman H, Jie M, Zhanfang M (2013) Electrochemical immunosensor for simultaneous detection of multiplex cancer biomarkers based on graphene nanocomposites. Biosens Bioelectron 50:356–361. https://doi.org/10.1016/j.bios.2013.06.054

    Article  CAS  Google Scholar 

  21. Teng X, Xinle J, Xia C, Zhanfang M (2014) Simultaneous electrochemical detection of multiple tumor markers using metal ions tagged immunocolloidal gold. Biosens Bioelectron 56:174–179. https://doi.org/10.1016/j.bios.2014.01.006

    Article  CAS  Google Scholar 

  22. Xia C, Zhanfang M (2014) Multiplexed electrochemical immunoassay of biomarkers using chitosan nanocomposites. Biosens Bioelectron 55:343–349. https://doi.org/10.1016/j.bios.2013.12.037

    Article  CAS  Google Scholar 

  23. Wen-Jing S, Jin-Zhi D, Tian-Meng S, Pei-Zhuo Z, Jun W (2010) Gold nanoparticles capped with polyethyleneimine for enhanced siRNA delivery. Small 6:239–246. https://doi.org/10.1002/smll.200901513

    Article  CAS  Google Scholar 

  24. Yuhan L, Soo HL, Jee SK, Atsushi M, Xuesi C, Tae GP (2011) Controlled synthesis of PEI-coated gold nanoparticles using reductive catechol chemistry for siRNA delivery. J Control Release 155:3–10. https://doi.org/10.1016/j.jconrel.2010.09.009

    Article  CAS  Google Scholar 

  25. Erol PD, Sema B, ömer G, Süleyman P, Adil D (2001) Adsorption of heavy-metal ions on poly(ethylene imine)-immobilized poly(methyl methacrylate) microspheres. J Appl Polym Sci 81:197–205. https://doi.org/10.1002/app.1429

    Article  Google Scholar 

  26. Bríd MR, Sharon RP, Anil KC, Neil C, Curtis CH (2014) A combined prognostic serum Interleukin-8 and Interleukin-6 classifier for stage 1 lung Cancer in the prostate, lung, colorectal, and ovarian Cancer screening trial. J Thorac Oncol 9:1494–1503. https://doi.org/10.1097/JTO.0000000000000278

    Article  CAS  Google Scholar 

  27. Robert W. V, M. CRAIG M., Gang Z, Angela NG, Garry M. M, George L. W, Robert L. V, David R (1999) Interleukin-8 serum levels in patients with benign prostatic hyperplasia and prostate cancer. J Urol 53(1):139–147. https://doi.org/10.1016/S0090-4295(98)00455-5

    Article  CAS  Google Scholar 

  28. Worldwide cancer data: Global cancer statistics for the most common cancers. World Cancer Research Fund (American Institute for Cancer Research). https://www.wcrf.org/dietandcancer/cancer-trends/worldwide-cancer-data. Accessed 7 March 2019

  29. Kwan K, Hyang BL, Ji WL, Hyoung KP, Kuan SS (2008) Self-assembly of poly(ethylenimine)-capped au nanoparticles at a toluene−water interface for efficient surface-enhanced raman scattering. Langmuir 24:7178–7183. https://doi.org/10.1021/la800733x

    Article  CAS  Google Scholar 

  30. Jian DQ, Ru PL, Rui W, Li-XF, Yi WC, Xing HX (2009) A label-free amperometric immunosensor based on biocompatible conductive redox chitosan-ferrocene/gold nanoparticles matrix. Biosens Bioelectron 25:852–857. https://doi.org/10.1016/j.bios.2009.08.048

    Article  CAS  Google Scholar 

  31. Dexiang F, Lihua L, Junqing Z, Yuzhong Z (2015) Simultaneous electrochemical detection of multiple biomarkers using gold nanoparticles decorated multiwall carbon nanotubes as signal enhancers. Anal Biochem 482:48–54. https://doi.org/10.1016/j.ab.2015.04.018

    Article  CAS  Google Scholar 

  32. Dianping T, Li H, Reinhard N, Mingdi X, Zhuangqiang G, Dietmar K (2013) Multiplexed electrochemical immunoassay of biomarkers using metal sulfide quantum dot nanolabels and trifunctionalized magnetic beads. Biosens Bioelectron 46:37–43. https://doi.org/10.1016/j.bios.2013.02.027

    Article  CAS  Google Scholar 

  33. Teng X, Na L, Jing Y, Zhanfang M (2015) Triple tumor markers assay based on carbon-gold nanocomposite. Biosens Bioelectron 70:161–166. https://doi.org/10.1016/j.bios.2015.03.036

    Article  CAS  Google Scholar 

  34. Shilpi V, Anu S, Ajay S, Jyoti K, Kavita A, Jaime RV, Priti S, Surinder PS (2017) Anti-IL8/AuNPs-rGO/ITO as an immunosensing platform for noninvasive electrochemical detection of oral cancer. ACS Appl Mater Interfaces 9:27462–27474. https://doi.org/10.1021/acsami.7b06839

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This research work was financed by National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency (NSTDA) Grant No. P-1750196 (Thailand) and partially supported by Chiang Mai University. T.P. thanks an award of the Thailand Graduate Institute of Science and Technology (TGIST) PhD scholarship sponsored from the National Science and Technology Development Agency (Thailand). The authors gratefully acknowledge a Short-Term Research Fellowships in Overseas, the Graduate School (Chiang Mai University), Research Center on Chemistry for Development of Health Promoting Products from Northern Resources, Center of Excellence for Innovation in Chemistry (PERCH-CIC), Center of Excellence in Materials Science and Technology and Department of Chemistry, Faculty of Science, Chiang Mai University.

Author information

Authors and Affiliations

  1. Department of Chemistry, Faculty of Science, Chiang Mai University, Chiang Mai, 50200, Thailand

    Thitirat Putnin & Kontad Ounnunkad

  2. The Graduate School, Chiang Mai University, Chiang Mai, 50200, Thailand

    Thitirat Putnin

  3. Nanostructures and Functional Assembly Laboratory (NFA), National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency (NSTDA), Pathum thani, 12120, Thailand

    Aroonsri Ngamaroonchote, Natta Wiriyakun & Rawiwan Laocharoensuk

  4. Center of Excellence in Materials Science and Technology, Chiang Mai University, Chiang Mai, 50200, Thailand

    Kontad Ounnunkad

  5. Research Center on Chemistry for Development of Health Promoting Products from Northern Resources, Chiang Mai University, Chiang Mai, 50200, Thailand

    Kontad Ounnunkad

  6. Center of Excellence for Innovation in Chemistry (PERCH-CIC), Faculty of Science, Chiang Mai University, Chiang Mai, 50200, Thailand

    Kontad Ounnunkad

Authors
  1. Thitirat Putnin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Aroonsri Ngamaroonchote
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Natta Wiriyakun
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kontad Ounnunkad
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rawiwan Laocharoensuk
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Kontad Ounnunkad or Rawiwan Laocharoensuk.

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 5.52 mb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Putnin, T., Ngamaroonchote, A., Wiriyakun, N. et al. Dually functional polyethylenimine-coated gold nanoparticles: a versatile material for electrode modification and highly sensitive simultaneous determination of four tumor markers. Microchim Acta 186, 305 (2019). https://doi.org/10.1007/s00604-019-3370-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00604-019-3370-4

Keywords

Search

Navigation