Analytical and Bioanalytical Chemistry

, Volume 411, Issue 29, pp 7807–7815 | Cite as

An ultrasensitive fluorescent aptasensor based on truncated aptamer and AGET ATRP for the detection of bisphenol A

  • Zhuangzhuang Guo
  • Jinfa Tang
  • Manman Li
  • Yanju LiuEmail author
  • Huaixia YangEmail author
  • Jinming KongEmail author
Research Paper


Given the gigantic harmfulness of bisphenol A (BPA), a novel and ultrasensitive aptasensor, which employs the truncated BPA aptamer, click chemistry, and activators generated by electron transfer for atom transfer radical polymerization (AGET ATRP), was developed herein for the quantitative determination of BPA. Firstly, hairpin DNAs (hairpins) with a thiol at the 5′ end and an azide group at the 3′ end were conjugated with aminated magnetic beads (MBs) through heterobifunctional cross-linkers. BPA truncated aptamer (ssDNA-A) hybridizes with its complementary single-stranded DNA (ssDNA-B) to form double-stranded DNA. In the presence of BPA, ssDNA-A specifically captures BPA, and then ssDNA-B is released. Subsequently, the ssDNA-B hybridizes with hairpins to expose the azide group near the surface of the MBs. Then, propargyl-2-bromoisobutyrate (PBIB), the initiator of AGET ATRP containing alkynyl group, was conjugated with azide group of hairpins via the Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC). Consequently, a large number of fluorescein-o-acrylate (FA) were introduced to the MBs through AGET ATRP, resulting in that the fluorescence intensity was increased dramatically. Obviously, the fluorescence intensity was especially sensitive to the change of BPA concentration, and this method can be used in quantitative determination of BPA. Under optimal conditions, a broad liner range from 100 fM to 100 nM and a low limit of detection (LOD) of 6.6 fM were obtained. Moreover, the method exhibits not only excellent specificity for BPA detection over BPA analogues but high anti-interference ability in real water sample detection, indicating that it has huge application prospect in food safety and environment monitoring.


Bisphenol A Truncated Aptamer AGET ATRP Aptasensor 


Funding information

This work was supported by the project of tackling of key scientific and technical problems in Henan Province (192102310033) and the National Natural Science Foundation of China (21575066).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.


  1. 1.
    Rochester JR. Bisphenol A and human health: a review of the literature. Reprod Toxicol. 2013;42:132–55.Google Scholar
  2. 2.
    Yildirim N, Long F, He M, et al. A portable optic fiber aptasensor for sensitive, specific and rapid detection of bisphenol-A in water samples. Environ Sci: Processes Impacts. 2014;16(6):1379–86.Google Scholar
  3. 3.
    Vogel SA. The politics of plastics: the making and unmaking of bisphenol a “safety”. Am J Public Health. 2009;99(S3):S559–66.PubMedPubMedCentralGoogle Scholar
  4. 4.
    Flint S, Markle T, Thompson S, et al. Bisphenol A exposure, effects, and policy: a wildlife perspective. J Environ Manag. 2012;104:19–34.Google Scholar
  5. 5.
    Guida M, Troisi J, Ciccone C, et al. Bisphenol A and congenital developmental defects in humans. Mutat Res Fundam Mol Mech Mutagen. 2015;774:33–9.Google Scholar
  6. 6.
    Tharp AP, Maffini MV, Hunt PA, et al. Bisphenol A alters the development of the rhesus monkey mammary gland. Proc Natl Acad Sci. 2012;109(21):8190–5.PubMedGoogle Scholar
  7. 7.
    Lehmler HJ, Liu B, Gadogbe M, et al. Exposure to bisphenol A, bisphenol F, and bisphenol S in US adults and children: the national health and nutrition examination survey 2013–2014. ACS omega. 2018;3(6):6523–32.PubMedPubMedCentralGoogle Scholar
  8. 8.
    Huysman S, Van Meulebroek L, Janssens O, et al. Targeted quantification and untargeted screening of alkylphenols, bisphenol A and phthalates in aquatic matrices using ultra-high-performance liquid chromatography coupled to hybrid Q-Orbitrap mass spectrometry. Anal Chim Acta. 2019;1049:141–51.PubMedGoogle Scholar
  9. 9.
    Rezaee M, Yamini Y, Shariati S, et al. Dispersive liquid–liquid microextraction combined with high-performance liquid chromatography-UV detection as a very simple, rapid and sensitive method for the determination of bisphenol A in water samples. J Chromatogr A. 2009;1216(9):1511–4.PubMedGoogle Scholar
  10. 10.
    Goeury K, Duy SV, Munoz G, et al. Analysis of Environmental Protection Agency priority endocrine disruptor hormones and bisphenol A in tap, surface and wastewater by online concentration liquid chromatography tandem mass spectrometry. J Chromatogr A. 2019;1591:87–98.PubMedGoogle Scholar
  11. 11.
    Liu A, Shen Z, Yuan L, et al. High-performance thin-layer chromatography coupled with HPLC-DAD/HPLC-MS/MS for simultaneous determination of bisphenol A and nine brominated analogs in biological samples. Anal Bioanal Chem. 2019;411(3):725–34.PubMedGoogle Scholar
  12. 12.
    Deceuninck Y, Bichon E, Marchand P, et al. Determination of bisphenol A and related substitutes/analogues in human breast milk using gas chromatography-tandem mass spectrometry. Anal Bioanal Chem. 2015;407(9):2485–97.PubMedGoogle Scholar
  13. 13.
    Xiao Y, Lubin AA, Heeger AJ, et al. Label-free electronic detection of thrombin in blood serum by using an aptamer-based sensor. Angew Chem. 2010;117(34):5592–5.Google Scholar
  14. 14.
    Munzar JD, Ng A, Juncker D. Duplexed aptamers: history, design, theory, and application to biosensing. Chem Soc Rev. 2019;48(5):1390–419.PubMedGoogle Scholar
  15. 15.
    Kwon YS, Raston NHA, Gu MB. An ultra-sensitive colorimetric detection of tetracyclines using the shortest aptamer with highly enhanced affinity. Chem Commun. 2014;50(1):40–2.Google Scholar
  16. 16.
    Abnous K, Danesh NM, Ramezani M, et al. A novel electrochemical sensor for bisphenol A detection based on nontarget-induced extension of aptamer length and formation of a physical barrier. Biosens Bioelectron. 2018;119:204–8.PubMedGoogle Scholar
  17. 17.
    Jo M, Ahn JY, Lee J, et al. Development of single-stranded DNA aptamers for specific bisphenol A detection. Oligonucleotides. 2011;21(2):85–91.PubMedPubMedCentralGoogle Scholar
  18. 18.
    Zhu Y, Cai Y, Xu L, et al. Building an aptamer/graphene oxide FRET biosensor for one-step detection of bisphenol A. ACS Appl Mater Interfaces. 2015;7(14):7492–6.PubMedGoogle Scholar
  19. 19.
    Lee ES, Kim GB, Ryu SH, et al. Fluorescing aptamer-gold nanosensors for enhanced sensitivity to bisphenol A. Sensors Actuators B Chem. 2018;260:371–9.Google Scholar
  20. 20.
    Deiminiat B, Rounaghi GH, Arbab-Zavar MH, et al. A novel electrochemical aptasensor based on f-MWCNTs/AuNPs nanocomposite for label-free detection of bisphenol A. Sensors Actuators B Chem. 2017;242:158–66.Google Scholar
  21. 21.
    Xue F, Wu J, Chu H, et al. Electrochemical aptasensor for the determination of bisphenol A in drinking water. Microchim Acta. 2013;180(1–2):109–15.Google Scholar
  22. 22.
    Marks HL, Pishko MV, Jackson GW, et al. Rational design of a bisphenol A aptamer selective surface-enhanced Raman scattering nanoprobe. Anal Chem. 2014;86(23):11614–9.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Gao P, Wang H, Li P, et al. In-site synthesis molecular imprinting Nb2O5–based photoelectrochemical sensor for bisphenol A detection. Biosens Bioelectron. 2018;121:104–10.PubMedGoogle Scholar
  24. 24.
    Mei Z, Chu H, Chen W, Xue F, Liu J, Xu H, et al. Ultrasensitive one-step rapid visual detection of bisphenol A in water samples by label-free aptasensor. Biosens Bioelectron. 2013;39(1):26–30.PubMedGoogle Scholar
  25. 25.
    Lee EH, Lim HJ, Lee SD, et al. Highly sensitive detection of bisphenol A by NanoAptamer assay with truncated aptamer. ACS Appl Mater Interfaces. 2017;9(17):14889–98.PubMedGoogle Scholar
  26. 26.
    Sun H, Qiu Y, Liu Q, Wang Q, et al. Ultrasensitive DNA biosensor based on electrochemical atom transfer radical polymerization. Biosens Bioelectron. 2019;131:193–9.PubMedGoogle Scholar
  27. 27.
    Hu Q, Kong J, Han D, Zhang Y, Bao Y, Zhang X, et al. Electrochemically controlled RAFT polymerization for highly sensitive electrochemical biosensing of protein kinase activity. Anal Chem. 2019;91(3):1936–43.PubMedGoogle Scholar
  28. 28.
    Yun W, Wu H, Chen L, Yang L. Dual enzyme-free amplification strategy for ultra-sensitive fluorescent detection of bisphenol A in water. Anal Chim Acta. 2018;1020:104–9.PubMedGoogle Scholar
  29. 29.
    Azizi M, Zaferani M, Cheong SH, et al. Pathogenic bacteria detection using RNA-based loop-mediated isothermal-amplification-assisted nucleic acid amplification via droplet microfluidics. ACS Sens. 2019;4(4):841–8.PubMedGoogle Scholar
  30. 30.
    Chen J, Zhou S. Label-free DNA Y junction for bisphenol A monitoring using exonuclease III-based signal protection strategy. Biosens Bioelectron. 2016;77:277–83.PubMedGoogle Scholar
  31. 31.
    Min K, Gao H, Matyjaszewski K. Preparation of homopolymers and block copolymers in miniemulsion by ATRP using activators generated by electron transfer (AGET). J Am Chem Soc. 2005;127(11):3825–30.PubMedGoogle Scholar
  32. 32.
    Werner A, Schmitt V, Sèbe G, et al. Convenient synthesis of hybrid polymer materials by AGET-ATRP polymerization of pickering emulsions stabilized by cellulose nanocrystals grafted with reactive moieties. Biomacromolecules. 2018;20(1):490–501.PubMedGoogle Scholar
  33. 33.
    Vidiella del Blanco M, Gomez V, Keplinger T, et al. Solvent-controlled spatial distribution of SI-AGET-ATRP grafted polymers in lignocellulosic materials. Biomacromolecules. 2018;20(1):336–46.PubMedGoogle Scholar
  34. 34.
    Liu X, Chen Q, Yang G, et al. Magnetic nanomaterials with near-infrared pH-activatable fluorescence via iron-catalyzed AGET ATRP for tumor acidic microenvironment imaging. J Mater Chem B. 2015;3(14):2786–800.Google Scholar
  35. 35.
    Wang C, Li Y, Wei Y. A sandwich boronate affinity sorbent assay for glucose detection facilitated by boronic acid-terminated fluorescent polymers. Sensors Actuators B Chem. 2017;247:595–601.Google Scholar
  36. 36.
    Lei YM, Zhou J, Chai YQ, et al. SnS2 quantum dots as new emitters with strong electrochemiluminescence for ultrasensitive antibody detection. Anal Chem. 2018;90(20):12270–7.PubMedGoogle Scholar
  37. 37.
    Zhao Z, Zhang M, Hogle JM, et al. DNA-corralled nanodiscs for the structural and functional characterization of membrane proteins and viral entry. J Am Chem Soc. 2018;140(34):10639–43.PubMedPubMedCentralGoogle Scholar
  38. 38.
    Yu J, Lu C, Wang C, Wang J, Fan Y, Chu F. Sustainable thermoplastic elastomers derived from cellulose, fatty acid and furfural via ATRP and click chemistry. Carbohydr Polym. 2017;176:83–90.PubMedGoogle Scholar
  39. 39.
    Navarro LA, French DL, Zauscher S. Synthesis of modular brush polymer–protein hybrids using diazotransfer and copper click chemistry. Bioconjug Chem. 2018;29(8):2594–605.PubMedGoogle Scholar
  40. 40.
    Pan X, Fantin M, Yuan F, Matyjaszewski K. Externally controlled atom transfer radical polymerization. Chem Soc Rev. 2018;47(14):5457–90.PubMedGoogle Scholar
  41. 41.
    Wu Y, Liu S, He L. Electrochemical biosensing using amplification-by-polymerization. Anal Chem. 2009;81(16):7015–21.PubMedGoogle Scholar
  42. 42.
    Fantin M, Isse AA, Gennaro A, Matyjaszewski K. Understanding the fundamentals of aqueous ATRP and defining conditions for better control. Macromolecules. 2015;48(19):6862–75.Google Scholar
  43. 43.
    Xu J, Lee ES, Gye MC, Kim YP. Rapid and sensitive determination of bisphenol A using aptamer and split DNAzyme. Chemosphere. 2019;228:110–6.PubMedGoogle Scholar
  44. 44.
    Mo F, Xie J, Wu T, et al. A sensitive electrochemical sensor for bisphenol A on the basis of the AuPd incorporated carboxylic multi-walled carbon nanotubes. Food Chem. 2019;292:253–9.PubMedGoogle Scholar
  45. 45.
    Li Q, Bai J, Ren S, Wang J, Gao Y, Li S, et al. An ultrasensitive sensor based on quantitatively modified upconversion particles for trace bisphenol A detection. Anal Bioanal Chem. 2019;411(1):171–9.PubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Pharmacy CollegeHenan University of Chinese MedicineZhengzhouChina
  2. 2.The First Affilicated Hospital of Henan University of Chinese MedicineZhengzhouChina
  3. 3.School of Environmental and Biological EngineeringNanjing University of Science and TechnologyNanjingChina

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