Skip to main content
SpringerLink
Log in

Paper-based chemiluminescence immunodevice for the carcinoembryonic antigen by employing multi-enzyme carbon nanosphere signal enhancement

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

Abstract

A paper-based chemiluminescence (CL) immunodevice is described for sensitive determination of the carcinoembryonic antigen (CEA). Capture antibody (Ab1) was first immobilized on the paper-based chip after plasma treatment of the paper surface. Next, carbon nanospheres functionalized with horse radish peroxidase (HRP) were attached as a signal antibody label. Strongly enhanced CL was achieved from the HRP catalyzed luminol/H2O2 CL system when using a sandwich immunoassay format. CEA can be quantified with a lower detection limit of 3 pg·mL−1. The method displays an almost 10-fold increased sensitivity in comparison to a commercial Ab2-HRP based kit. Conceivably, this sensitive method may also be extended by designing sensitive assays for other biomarkers of interest in point-of-care diagnostics.

Schematic of a paper-based chemiluminescence (CL) immunodevice for the determination of the carcinoembryonic antigen (CEA) by applying a multi-enzyme carbon nanosphere signal enhancement strategy.

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. Yamada K, Henares TG, Suzuki K, Citterio D (2015) Paper-based inkjet-printed microfluidic analytical devices. Angew Chem Int Ed 54:5294–5310

    Article  CAS  Google Scholar 

  2. Martinez AW, Phillips ST, Butte MJ, Whitesides GM (2007) Patterned paper as a platform for inexpensive, low-volume, portable bioassays. Angew Chem Int Ed 46:1318–1320

    Article  CAS  Google Scholar 

  3. Martinez AW, Phillips ST, Whitesides GM, Carrilho E (2010) Diagnostics for the developing world: microfluidic paper-based analytical devices. Anal Chem 82:3–10

    Article  CAS  Google Scholar 

  4. Ahmed S, Bui MPN, Abbas A (2016) Paper-based chemical and biological sensors: engineering aspects. Biosens Bioelectron 77:249–263

    Article  CAS  Google Scholar 

  5. Mahato K, Srivastava A, Chandra P (2017) Paper-based diagnostics for personalized health care: emerging technologies and commercial aspects. Biosens Bioelectron 96:246–259

    Article  CAS  Google Scholar 

  6. Choi JR, Yong KW, Tang RH, Gong Y, Wen T, Li F, Pingguan-Murphy B, Bai D, Xu F (2017) Advances and challenges of fully integrated paper-based point-of-care nucleic acid testing. TrAC-Trends Anal Chem 93:37–50

    Article  CAS  Google Scholar 

  7. Glauco PDS, Cátia CC, Lauro TK (2018) A simple, sensitive and reduced cost paper-based device with low quantity of chemicals for the early diagnosis of plasmodium falciparum malaria using an enzyme-based colorimetric assay. Sensors Actuators B Chem 255:2113–2120

    Article  Google Scholar 

  8. Jokerst JC, Adkins JA, Bisha B, Mentele MM, Goodridge LD, Henry CS (2012) Development of a paper-based analytical device for colorimetric detection of select foodborne pathogens. Anal Chem 84:2900–2907

    Article  CAS  Google Scholar 

  9. Wu LD, Ma C, Zheng XX, Liu HY, Yu JH (2015) Paper-based electrochemiluminescence origami device for protein detection using assembled cascade DNA-carbon dots nanotags based on rolling circle amplification. Biosens Bioelectron 68:413–420

    Article  CAS  Google Scholar 

  10. Ge L, Yan JX, Song XR, Yan M, Ge SG, Yu JH (2012) Three-dimensional paper-based electrochemiluminescence immunodevice for multiplexed measurement of biomarkers and point-of-care testing. Biomaterials 33:1024–1031

    Article  CAS  Google Scholar 

  11. Zhang B, Ma WJ, Li FX, Gao WC, Zhao Q, Peng WP, Piao JF, Wu XL, Wang HJ, Gong XQ, Chang J (2017) Fluorescence quenching-based signal amplification on immunochromatography test strips for dual-mode sensing of two biomarkers of breast cancer. Nanoscale 9:18711–18722

    Article  CAS  Google Scholar 

  12. Das P, Krull UJ (2017) Detection of a cancer biomarker protein on modified cellulose paper by fluorescence using aptamer-linked quantum dots. Analyst 142:3132–3135

    Article  CAS  Google Scholar 

  13. Chen SM, Wan QQ, Badu-Tawiah AK (2016) Mass spectrometry for paper-based immunoassays: toward on-demand diagnosis. J Am Chem Soc 138:6356–6359

    Article  CAS  Google Scholar 

  14. Denk H, Tappeiner G, Eckerstorfer R, Holzner JH (1972) Carcinoembryonic antigen (CEA) in gastrointestinal and extragastrointestinal tumors and its relationship to tumor-cell differentiation. Int J Cancer 10:262–272

    Article  CAS  Google Scholar 

  15. Hasanzadeh M, Shadjou N (2017) Advanced nanomaterials for use in electrochemical and optical immunoassays for the carcinoembryonic antigen. A review. Microchim Acta 184:389–414

    Article  CAS  Google Scholar 

  16. Wang Y, Xu HR, Luo JP, Liu JT, Wang L, Fan Y, Yan S, Yang Y, Cai XX (2016) A novel label-free microfluidic paper-based immunosensor for highly sensitive electrochemical detection of carcinoembryonic antigen. Biosens Bioelectron 83:319–326

    Article  CAS  Google Scholar 

  17. Li L, Kong QK, Zhang Y, Dong CM, Ge SG, Yu JH (2015) A 3D electrochemical immunodevice based on a porous Pt-paper electrode and metal ion functionalized flower-like Au nanoparticles. J Mater Chem B 3:2764–2769

    Article  CAS  Google Scholar 

  18. Lan FF, Sun GQ, Liang LL, Ge SG, Yan M, Yu JH (2016) Microfluidic paper-based analytical device for photoelectrochemical immunoassay with multiplex signal amplification using multibranched hybridization chain reaction and PdAu enzyme mimetics. Biosens Bioelectron 79:416–422

    Article  CAS  Google Scholar 

  19. Qiu ZL, Shu J, Tang DP (2017) Bioresponsive release system for visual fluorescence detection of carcinoembryonic antigen from mesoporous silica nanocontainers mediated optical color on quantum dot-enzyme-impregnated paper. Anal Chem 89:5152–5160

    Article  CAS  Google Scholar 

  20. Zhang XR, Baeyenes WRG, Garcia CAM, Ouyang J (1999) Recent developments in chemiluminescence sensors. TrAC-Trends Anal Chem 18:384–391

    Article  CAS  Google Scholar 

  21. Ge L, Yu JH, Ge SG, Yan M (2014) Lab-on-paper-based devices using chemiluminescence and electrogenerated chemiluminescence detection. Anal Bioanal Chem 406:5613–5630

    Article  CAS  Google Scholar 

  22. Wang SM, Ge L, Song XR, Yu JH, Ge SG, Huang JD, Zeng F (2012) Paper-based chemiluminescence ELISA: lab-on-paper based on chitosan modified paper device and wax-screen-printing. Biosens Bioelectron 31:212–218

    Article  Google Scholar 

  23. Zhao M, Li HF, Liu W, Guo YM, Chu WR (2016) Plasma treatment of paper for protein immobilization on paper-based chemiluminescence immunodevice. Biosens Bioelectron 79:581–588

    Article  CAS  Google Scholar 

  24. Li N, Zhao P, Astruc D (2014) Anisotropic gold nanoparticles: synthesis, properties, applications, and toxicity. Angew Chem Int Ed 53:1756–1789

    Article  CAS  Google Scholar 

  25. Wang K, He X, Yang X, Shi H (2013) Functionalized silica nanoparticles: a platform for fluorescence imaging at the cell and small animal levels. Acc Chem Res 46:1367–1376

    Article  CAS  Google Scholar 

  26. Gan N, Jin H, Li T, Zheng L (2011) Fe3O4/Au magnetic nanoparticle amplification strategies for ultrasensitive electrochemical immunoassay of alfa-fetoprotein. Int J Nanomedicine 6:3259–3269

    Article  CAS  Google Scholar 

  27. Yang W, Ratinac KR, Ringer SP, Thordarson P, Gooding JJ, Braet F (2010) Carbon nanomaterials in biosensors: should you use nanotubes or graphene. Angew Chem Int Ed 49:2114–2138

    Article  CAS  Google Scholar 

  28. Lin MH, Liu YJ, Sun ZH, Zhang SL, Yang ZH, Ni CL (2012) Electrochemical immunoassay of benzo[a]pyrene based on dual amplification strategy of electron-accelerated Fe3O4/polyaniline platform and multi-enzyme-functionalized carbon sphere label. Anal Chim Acta 722:100–106

    Article  CAS  Google Scholar 

  29. Dong HF, Zhu Z, Ju HX, Yan F (2012) Triplex signal amplification for electrochemical DNA biosensing by coupling probe-gold nanoparticles-graphene modified electrode with enzyme functionalized carbon sphere as tracer. Biosens Bioelectron 33:228–232

    Article  CAS  Google Scholar 

  30. Gan CF, Sun ZH, Ling L, He ZY, Lei HT, Liu YJ (2016) Construction of portable electrochemical immunosensors based on grapheme hydrogel@polydopamine for microcystin-LR detection using multi-mesoporous carbon sphereenzyme labels. RSC Adv 6:51662–51669

    Article  CAS  Google Scholar 

  31. Liu W, Guo YM, Zhao M, Li HF, Zhang ZJ (2015) Ring-oven washing technique integrated paper-based immunodevice for sensitive detection of cancer biomarker. Anal Chem 87:7951–7957

    Article  CAS  Google Scholar 

  32. Luo YN, Asiri AM, Zhang X, Yang GH, Du D, Lin YH (2014) A magnetic electrochemical immunosensor for the detection of phosphorylated p53 based on enzyme functionalized carbon nanospheres with signal amplification. RSC Adv 4:54066–54071

    Article  CAS  Google Scholar 

  33. Jiao L, Zhang LH, Du WW, Liu SQ, Wei Q, Li H (2017) Robust enzyme-free electrochemical immunoassay of CEA enhanced by porous PdCu nanoparticles. Electrochim Acta 252:374–380

    Article  CAS  Google Scholar 

  34. Liu Q, Liu XP, Wei YP, Mao CJ, Niu HL, Song JM, Jin BK, Zhang SY (2017) Electrochemiluminescence immunoassay for the carcinoembryonic antigen using CdSe:Eu nanocrystals. Microchim Acta 184:1353–1360

    Article  CAS  Google Scholar 

  35. Babamiri B, Hallaj R, Salimi A, Akhtari K (2017) Potential-resolved electrochemiluminescence immunoassay for simultaneous determination of CEA and AFP tumor markers using dendritic nanoclusters and Fe3O4@SiO2 nanoparticles. Microchim Acta 184:3613–3623

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We are grateful to Shaanxi Province Science Foundation (No. 2015JM2066) for funding this work. The authors also thank the Fundamental Research Funds for the Central Universities (No.GK201603049, No.GK201701002) and Program for Innovative Research Team in Shaanxi Province (No. 2014KCT-28) for supporting this work.

Author information

Authors and Affiliations

  1. Key Laboratory of Analytical Chemistry for Life Science of Shaanxi Province, School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi’an, 710062, China

    Ying Chen, Weiru Chu, Wei Liu, Xiaoyan Guo, Yan Jin & Baoxin Li

Authors
  1. Ying Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Weiru Chu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wei Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiaoyan Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yan Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Baoxin Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wei Liu.

Ethics declarations

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

Electronic supplementary material

ESM 1

(DOC 2460 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chen, Y., Chu, W., Liu, W. et al. Paper-based chemiluminescence immunodevice for the carcinoembryonic antigen by employing multi-enzyme carbon nanosphere signal enhancement. Microchim Acta 185, 187 (2018). https://doi.org/10.1007/s00604-018-2726-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00604-018-2726-5

Keywords

Search

Navigation