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Manganese dioxide nanoparticle-based colorimetric immunoassay for the detection of alpha-fetoprotein

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Abstract

An immunoassay has been developed for the determination of alpha-fetoprotein (AFP). It is based (a) on the use of a detection reaction mediated by manganese dioxide nanoparticles (MnO2 NPs) because their good stability at room temperature, and (b) on tyramine signal amplification (TSA). The MnO2 NPs acts as an artificial peroxidase that causes the conversion of TMB to give a colored product, and the tyramine-triggered reaction is used for signal amplification to improve the detection limit. Combined with immuno-magnetic separation and enrichment, the response of this AFP immunoassay is linear from 6.25–400 ng mL−1, with a detection limit of 22 pg mL−1 (S/N = 3). This immunoassay was successfully applied to the quantification of AFP in serum samples, and gave excellent accuracy compared with the clinical results from a local hospital. The LOD and stability of this assay are better than those of the standard horseradish peroxidase-based ELISA. The strategy presented here is conceived to have a wider scope in that it may be extended to various other immunoassays.

Schematic of an immunoassay based on manganese dioxide nanoparticles (MnO2 NPs)-mediated enzyme reaction and tyramine-triggered signal amplification (TSA) to detect alpha-fetoprotein (AFP).

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References

  1. Tong QH, Tao T, Xie LQ, Lu HJ (2016) ELISA–PLA: a novel hybrid platform for the rapid, highly sensitive and specific quantification of proteins and post-translational modifications. Biosens Bioelectron 80:385–391

    Article  CAS  Google Scholar 

  2. Hu R, Liu T, Zhang XB, Yang YH, Chen T, Wu CC, Liu Y, Zhu GZ, Huan SY, Fu T, Tan WH (2015) DLISA: a DNAzyme-based ELISA for protein enzyme-free immunoassay of multiple analytes. Anal Chem 87:7746–7753

    Article  CAS  Google Scholar 

  3. Jin LY, Dong YM, Wu XM, Cao GX, Wang GL (2015) Versatile and amplified biosensing through enzymatic cascade reaction by coupling alkaline phosphatase in situ generation of photoresponsive nanozyme. Anal Chem 87:10429–10436

    Article  CAS  Google Scholar 

  4. Wang GL, Xu XF, Qiu L, Dong YM, Li ZJ, Zhang C (2014) Dual responsive enzyme mimicking activity of AgX (X = cl, Br, I) nanoparticles and its application for cancer cell detection. ACS Appl Mater Interfaces 6:6434–6442

    Article  CAS  Google Scholar 

  5. Lin YH, Ren JS, Qu XG (2014) Catalytically active nanomaterials: a promising candidate for artificial enzymes. Acc Chem Res 47:1097–1105

    Article  CAS  Google Scholar 

  6. Bracamonte MV, Melchionna M, Giuliani A, Nasi L, Tavagnacco C, Prato M, Fornasiero P (2017) H2O2 sensing enhancement by mutual integration of single walled carbon nanohorns with metal oxide catalysts: the CeO2 case. Sensors Actuators B Chem 239:923–932

    Article  CAS  Google Scholar 

  7. Mu JS, Zhang L, Zhao M, Wang Y (2014) Catalase mimic property of Co3O4 nanomaterials with different morphology and its application as a calcium sensor. ACS Appl Mater Interfaces 6:7090–7098

    Article  CAS  Google Scholar 

  8. Han L, Zeng LX, Wei MD, Li CM, Liu AH (2015) A V2O3-ordered mesoporous carbon composite with novel peroxidase-like activity towards the glucose colorimetric assay. Nano 7:11678–11685

    CAS  Google Scholar 

  9. Dutta AK, Maji SK, Srivastava DN, Mondal A, Biswas P, Paul P, Adhikary B (2012) Synthesis of FeS and FeSe nanoparticles from a single source precursor: a study of their photocatalytic activity, peroxidase-like behavior, and electrochemical sensing of H2O2. ACS Appl Mater Interfaces 4:1919–1927

    Article  CAS  Google Scholar 

  10. Cai Q, Lu SK, Liao F, Li YQ, Ma SZ, Shao MW (2014) Catalytic degradation of dye molecules and in situ SERS monitoring by peroxidase-like Au/CuS composite. Nano 6:8117–8123

    CAS  Google Scholar 

  11. Zhu X, Zhao HL, Niu XH, Liu TT, Shi LB, Lan MB (2016) A comparative study of carbon nanotube supported MFe2O4 spinels (M = Fe, Co, Mn) for amperometric determination of H2O2 at neutral pH values. Microchim Acta 183:2431–2439

    Article  CAS  Google Scholar 

  12. Zhang XN, Shen JZ, Ma HL, Jiang YX, Huang CY, Han E, Yao BS, He YY (2016) Optimized dendrimer-encapsulated gold nanoparticles and enhanced carbon nanotube nanoprobes for amplified electrochemical immunoassay of E. coli in dairy product based on enzymatically induced deposition of polyaniline. Biosens Bioelectron 80:666–673

    Article  CAS  Google Scholar 

  13. Kotov NA (2010) Inorganic nanoparticles as protein mimics. Science 330:188–189

    Article  CAS  Google Scholar 

  14. Wei H, Wang E (2013) Nanomaterials with enzyme-like characteristics (nanozymes): next-generation artificial enzymes. Chem Soc Rev 42:6060–6093

    Article  CAS  Google Scholar 

  15. Jiao L, Mu ZG, Miao LY, Du WW, Wei Q, Li H (2017) Enhanced amperometric immunoassay for the prostate specific antigen using Pt-Cu hierarchical trigonal bipyramid nanoframes as a label. Microchim Acta 184:423–429

    Article  CAS  Google Scholar 

  16. Campuzano S, Pedrero M, Nikoleli GP, Pingarrón JM, Nikolelis DP (2017) Hybrid 2D-nanomaterials-based electrochemical immunosensing strategies for clinical biomarkers determination. Biosens Bioelectron 89:269–279

    Article  CAS  Google Scholar 

  17. Xu SH, Ouyang WJ, Xie PS, Lin Y, Qiu B, Lin ZY, Chen GN, Guo LH (2017) Highly uniform gold nanobipyramids for ultrasensitive colorimetric detection of influenza virus. Anal Chem 89:1617–1623

    Article  CAS  Google Scholar 

  18. Revathi C, Mohan RG, Ramasamy K, Rajendra T (2015) Synthesis and electrocatalytic properties of manganese dioxide for non-enzymatic hydrogen peroxide sensing. Mater Sci Semicond Process 31:709–714

    Article  Google Scholar 

  19. Liu X, Wang Q, Zhao HH, Zhang LC, Su YY, Lv Y (2012) BSA-templated MnO2 nanoparticles as both peroxidase and oxidase mimics. Analyst 137:4552–4558

    Article  CAS  Google Scholar 

  20. Pei XM, Zhang B, Tang J, Liu BQ, Lai WQ, Tang DP (2013) Sandwich-type immunosensors and immunoassays exploiting nanostructure labels: a review. Anal Chim Acta 758:1–18

    Article  CAS  Google Scholar 

  21. Yuan L, Xu LL, Liu SQ (2012) Integrated tyramide and polymerization-assisted signal amplification for a highly-sensitive immunoassay. Anal Chem 84:10737–10744

    Article  CAS  Google Scholar 

  22. Bhattacharya D, Bhattacharya R, Dhar T (1999) A novel signal amplification technology for ELISA based on catalyzed reporter deposition. Demonstration of its applicability for measuring aflatoxin B1. J Immunol Methods 230:71–86

    Article  CAS  Google Scholar 

  23. Meany DL, Hackler L, Zhang H, Chan DW (2011) Tyramide signal amplification for antibody-overlay lectin microarray: a strategy to improve the sensitivity of targeted glycan profiling. J Proteome Res 10:1425–1431

    Article  CAS  Google Scholar 

  24. Bobrow M, Shaughnessy K, Litt G (1991) Catalyzed reporter deposition, a novel method of signal amplification: II. Application to membrane immunoassays. J Immunol Methods 137:103–112

    Article  CAS  Google Scholar 

  25. Anderson G, Taitt C (2008) Amplification of microsphere-based microarrays using catalyzed reporter deposition. Biosens Bioelectron 24:324–328

    Article  CAS  Google Scholar 

  26. Stack EC, Wang CC, Roman KA, Hoyt CC (2014) Multiplexed immunohistochemistry, imaging, and quantitation: a review, with an assessment of tyramide signal amplification, multispectral imaging and multiplex analysis. Methods 70:46–58

    Article  CAS  Google Scholar 

  27. Wang N, Gibbons C, Freeman R (2011) Novel immunohistochemical techniques using discrete signal amplification systems for human cutaneous peripheral nerve fiber imaging. J Histochem Cytochem 59:382–390

    Article  CAS  Google Scholar 

  28. Zhou J, Tang J, Chen GN, Tang DP (2014) Layer-by-layer multienzyme assembly for highly sensitive electrochemical immunoassay based on tyramine signal amplification strategy. Biosens Bioelectron 54:323–328

    Article  CAS  Google Scholar 

  29. Hou L, Tang Y, Xu MD, Gao ZQ, Tang DP (2014) Tyramine-based enzymatic conjugate repeats for ultrasensitive immunoassay accompanying tyramine signal amplification with enzymatic biocatalytic precipitation. Anal Chem 86:8352–8358

    Article  CAS  Google Scholar 

  30. Montini T, Melchionna M, Monai M, Fornasiero P (2016) Fundamentals and catalytic applications of CeO2-based materials. Chem Rev 116:5987–6041

    Article  CAS  Google Scholar 

  31. Asati A, Santra S, Kaittanis C, Nath S, Perez JM (2009) Oxidase like activity of polymer-coated cerium oxide nanoparticles. Angew Chem Int Ed 48:2308–2312

    Article  CAS  Google Scholar 

  32. Xie QF, Weng XH, Lu LJ, Lin ZY, Xu XW, Fu CL (2015) A sensitive fluorescent sensor for quantification of alpha-fetoprotein based on immunosorbent assay and click chemistry. Biosens Bioelectron 77:46–50

    Article  Google Scholar 

  33. Liu XX, Song XD, Dong ZY, Meng XT, Chen YP, Yang L (2017) Photonic crystal fiber-based immunosensor for high-performance detection of alpha fetoprotein. Biosens Bioelectron 91:431–435

    Article  CAS  Google Scholar 

  34. Liu N, Feng F, Liu ZM, Ma ZF (2015) Porous platinum nanoparticles and PdPt nanocages for use in an ultrasensitive immunoelectrode for the simultaneous determination of the tumor markers CEA and AFP. Microchim Acta 182:1143–1151

    Article  CAS  Google Scholar 

  35. Guo JJ, Wang JC, Zhang JJ, Zhang WJ, Zhang YZ (2017) Ultrasensitive non enzymatic multiple immunosensor for tumor markers detection by coupling DNA hybridization chain reaction with intercalated molecules. Biosens Bioelectron 90:159–165

    Article  CAS  Google Scholar 

  36. Liu ZR, Yang B, Chen BB, He M, Hu B (2017) Upconversion nanoparticle as elemental tag for the determination of alpha-fetoprotein in human serum by inductively coupled plasma mass spectrometry. Analyst 142:197–205

    Article  CAS  Google Scholar 

  37. Jo NR, Lee KJ, Shin YB (2016) Enzyme-coupled nanoplasmonic biosensing of cancer markers in human serum. Biosens Bioelectron 81:324–333

    Article  CAS  Google Scholar 

  38. Wright LM, Kreikemeier JT, Fimmel CJ (2007) A concise review of serum markers for hepatocellular cancer. Cancer Detect Prev 31:35–44

    Article  CAS  Google Scholar 

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Acknowledgements

We acknowledge financial support from NSFC (21505027)

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Correspondence to Yiping Chen, Yu Wang or Mengxia Xie.

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Li, Y., Wu, J., Zhang, C. et al. Manganese dioxide nanoparticle-based colorimetric immunoassay for the detection of alpha-fetoprotein. Microchim Acta 184, 2767–2774 (2017). https://doi.org/10.1007/s00604-017-2303-3

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  • DOI: https://doi.org/10.1007/s00604-017-2303-3

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