Advertisement

Microchimica Acta

, 186:233 | Cite as

A fluorometric turn-on aptasensor for mucin 1 based on signal amplification via a hybridization chain reaction and the interaction between a luminescent ruthenium(II) complex and CdZnTeS quantum dots

  • Zheng Li
  • Guobin Mao
  • Mingyuan Du
  • Songbai Tian
  • Longqing Niu
  • Xinghu Ji
  • Zhike HeEmail author
Original Paper
  • 144 Downloads

Abstract

A fluorometric method is described for the determination of the tumor biomarker mucin 1 (MUC1). It is based on signal amplification of the hybridization chain reaction (HCR), and the interaction between a luminescent ruthenium(II) complex and CdZnTeS quantum dots (QDs). If MUC1 bind to the biotin-labeled aptamer, it will initiate HCR with hairpins H1 and H2 to form a long-range dsDNA. The long nucleic acid chains are then linked on the surface of streptavidin-modified magnetic microparticles (MMPs) through streptavidin-biotin interaction. The luminescent ruthenium(II) complex is then embedded in the long dsDNA linked to the MMPs. Hence, there is little Ru complex in the supernatant after magnetic separation, and the fluorescence of the CdZnTeS QDs (best measured at excitation/emission wavelengths of 350/530 nm) is only slightly quenched. In the absence of target, the fluorescence of the CdZnTeS QDs is strongly quenched. Fluorescence increases linearly in the 0.2–100 ng·mL−1 MUC1 concentration range, and the LOD is 0.13 ng·mL−1 (at S/N = 3). The method was applied to the determination of MUC1 in spiked human serum samples.

Graphical abstract

A fluorometric turn-on aptasensor for mucin 1 is described that is based on the interaction between a Ru(II) complex and quantum dots (QDs). The detection system includes biotin-labeled aptamer-H0, hairpins H1 and H2, streptavidin-modified magnetic microparticles (MMPs), Ru(bpy)2(dppx)2+ and CdZnTeS QDs.

Keywords

Mucin 1 aptamer Quenching HCR amplification Magnetic microparticles 

Notes

Acknowledgements

This work was supported by the National Natural Science Foundation of China (21675119) and National Major Science and Technology Projects (2018ZX10301405).

Compliance with ethical standards

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

Supplementary material

604_2019_3347_MOESM1_ESM.doc (122 kb)
ESM 1 (DOC 122 kb)

References

  1. 1.
    Donald WK (2009) Mucins in cancer: function, prognosis and therapy. Nat Rev Cancer 9:874–885CrossRefGoogle Scholar
  2. 2.
    Singh R, Bandyopadhyay D (2007) MUC1: a target molecule for cancer therapy. Cancer Biol Ther 6:481–486CrossRefGoogle Scholar
  3. 3.
    Chinen AB, Guan CM, Ferrer JR, Barnaby SN, Merkel TJ, Mirkin CA (2015) Nanoparticle probes for the detection of cancer biomarkers, cells, and tissues by fluorescence. Chem Rev 115:10530–10574CrossRefGoogle Scholar
  4. 4.
    Chikkaveeraiah BV, Bhirde A, Morgan NY, Eden HS, Chen XY (2012) Electrochemical immunosensors for detection of cancer protein biomarkers. ACS Nano 6:6546–6561CrossRefGoogle Scholar
  5. 5.
    Falahat R, Wiranowska M, Gallant ND, Toomey R, Hill R, Alcantar N (2015) A cell ELISA for the quantification of MUC1 mucin (CD227) expressed by cancer cells of epithelial and neuroectodermal origin. Cell Immunol 298:96–103CrossRefGoogle Scholar
  6. 6.
    Feng JJ, Wu XL, Ma W, Kuang H, Xu LG, Xu CL (2015) A SERS active bimetallic core–satellite nanostructure for the ultrasensitive detection of Mucin-1. Chem Commun 51:14761–14763CrossRefGoogle Scholar
  7. 7.
    Wang N, Zhang MM, Chen XJ, Ma XX, Li C, Zhang Z, Tang JL (2017) Mapping the interaction sites of mucin 1 and DNA aptamer by atomic force microscopy. Analyst 142:3800–3804CrossRefGoogle Scholar
  8. 8.
    Ma C, Liu HY, Tian T, Song XR, Yu JH, Yan M (2016) A simple and rapid detection assay for peptides based on the specific recognition of aptamer and signal amplification of hybridization chain reaction. Biosens Bioelectron 83:15–18CrossRefGoogle Scholar
  9. 9.
    He Y, Lin Y, Hong HW, Pang DW (2012) A graphene oxide-based fluorescent aptasensor for the turn-on detection of epithelial tumor marker mucin 1. Nanoscale 4:2054–2059CrossRefGoogle Scholar
  10. 10.
    Hu R, Wen W, Wang QL, Xiong HY, Zhang XH, Gu HS, Wang SF (2014) Novel electrochemical aptamer biosensor based on an enzyme–gold nanoparticle dual label for the ultrasensitive detection of epithelial tumour marker MUC1. Biosens Bioelectron 53:384–389CrossRefGoogle Scholar
  11. 11.
    Liu CY, Liu X, Qin Y, Deng CY, Xiang J (2016) A simple regenerable electrochemical aptasensor for the parallel and continuous detection of biomarkers. RSC Adv 6:58569–58476Google Scholar
  12. 12.
    Deng CY, Pi XM, Qian P, Chen XQ, Wu WM, Xiang J (2017) High-performance ratiometric electrochemical method based on the combination of signal probe and inner reference probe in one hairpin-structured DNA. Anal Chem 89:966–973CrossRefGoogle Scholar
  13. 13.
    Jiang XY, Wang HJ, Wang HJ, Zhuo Y, Yuan R, Chai YQ (2017) Electrochemiluminescence biosensor based on 3-D DNA nanomachine signal probe powered by protein-aptamer binding com- plex for ultrasensitive mucin 1 detection. Anal Chem 89:4280–4286CrossRefGoogle Scholar
  14. 14.
    Guo QJ, Li XZ, Shen CC, Zhang SB, Qi HZ, Li T, Yang MH (2015) Electrochemical immunoassay for the protein biomarker mucin 1 and for MCF-7 cancer cells based on signal enhancement by silver nanoclusters. Microchim Acta 182:1483–1489CrossRefGoogle Scholar
  15. 15.
    Yazdanparast S, Benvidi A, Banaei M, Nikukar H, Tezerjani MD, Azimzadeh M (2018) Dual-aptamer based electrochemical sandwich biosensor for MCF-7 human breast cancer cells using silver nanoparticle labels and a poly(glutamic acid)/MWNT nanocomposite. Microchim Acta 185:405CrossRefGoogle Scholar
  16. 16.
    Ma N, Jiang WT, Li T, Zhang ZQ, Qi HZ, Yang MH (2015) Fluorescence aggregation assay for the protein biomarker mucin 1 using carbon dot-labeled antibodies and aptamers. Microchim Acta 182:443–447CrossRefGoogle Scholar
  17. 17.
    Jr MB, Moronne M, Gin P, Weiss S, Alivisatos AP (1998) Semiconductor nanocrystals as fluorescent biological labels. Science 281:2013–2016CrossRefGoogle Scholar
  18. 18.
    Peng ZA, Peng XG (2001) Formation of high-quality CdTe, CdSe, and CdS nanocrystals using CdO as precursor. J Am Chem Soc 123:183–184CrossRefGoogle Scholar
  19. 19.
    Liu ZY, Tang A, Wang M, Yang CH, Teng F (2015) Heating-up synthesis of cadimum-free and color-tunable quaternary and five-component Cu–In–Zn–S-based semiconductor nanocrystals. J Mater Chem C 3:10114–10120CrossRefGoogle Scholar
  20. 20.
    Mao GB, Cai Q, Wang FB, Luo CL, Ji XH, He ZK (2017) One-step synthesis of Rox-DNA functionalized CdZnTeS quantum dots for the visual detection of hydrogen peroxide and blood Gl- ucose. Anal Chem 89:11628–11635CrossRefGoogle Scholar
  21. 21.
    Mao GB, Liu C, Du MY, Zhang YW, Ji XH, He ZK (2018) One-pot synthesis of the stable CdZnTeS quantum dots for the rapid and sensitive detection of copper-activated enzyme. Talanta 185:123–131CrossRefGoogle Scholar
  22. 22.
    Zhao D, Chan WH, He ZK, Qiu T (2009) Quantum dot-ruthenium complex dyads: recognition of double-Strand DNA through dual-color fluorescence detection. Anal Chem 81:3537–3543CrossRefGoogle Scholar
  23. 23.
    Xiang X, Chen L, Zhuang QG, Ji XH, He ZK (2012) Real-time luminescence-based colorimetric determination of double-strand DNA in droplet on demand. Biosens Bioelectron 32:43–49CrossRefGoogle Scholar
  24. 24.
    Liu YF, Luo M, Yan J, Xiang X, Ji XH, Zhou GH, He ZK (2013) An ultrasensitive biosensor for DNA detection based on hybridization chain reaction coupled with the efficient quenching of a ruthenium complex to CdTe quantum dots. Chem Commun 49:7424–7426CrossRefGoogle Scholar
  25. 25.
    Zhang Z, Xiang X, Huang FH, Zheng MM, Xia XY, Han L (2018) Mercury ion-mediated “molecular beacon” integrating with hybridization chain reaction: application to fluorescence turn-on detection of glutathione by using quantum dots and Ru complex. Sensors Actuators B Chem 273:159–166CrossRefGoogle Scholar
  26. 26.
    Liu SW, Xu NH, Tan CY, Fang W, Tan Y (2018) A sensitive colorimetric aptasensor based on trivalent peroxidasemimic DNAzyme and magnetic nanoparticles. Anal Chim Acta 1018:86–93CrossRefGoogle Scholar
  27. 27.
    Huang J, Wu YR, Chen Y, Zhu Z, Yang XH, Yang CYJ (2011) Pyrene-excimer probes based on the hybridization chain reaction for the detection of nucleic acids in complex biological fluids. Angew Chem Int Ed 50:401–404CrossRefGoogle Scholar
  28. 28.
    Ling LS, He ZK, Song GW, Yuan D, Zeng YE (2000) A novel method for determination of DNA by use of molecular ‘light switch’ complex of Ru(bipy)2(dppx)2+. Anal Chim Acta 403:209–217CrossRefGoogle Scholar
  29. 29.
    Zhao D, Fang Y, Wang HY, He ZK (2011) Synthesis and characterization of high-quality water-soluble CdTe: Zn2+ quantum dots capped by N-acetyl-L-cysteine via hydrothermal method. J Mater Chem 21:13365–13370CrossRefGoogle Scholar
  30. 30.
    Ferreira CSM, Matthews CS, Missailidis S (2006) DNA aptamers that bind to MUC1 tumor marker: design and characterization of MUC1-binding single-stranded DNA aptamers. Tumour Biol 27:289–301CrossRefGoogle Scholar
  31. 31.
    Yu WW, Qu LH, Guo WZ, Peng XG (2003) Experimental determination of the extinction coefficient of CdTe, CdSe, and CdS nanocrystals. Chem Mater 15:2854–2860CrossRefGoogle Scholar

Copyright information

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

Authors and Affiliations

  • Zheng Li
    • 1
  • Guobin Mao
    • 1
  • Mingyuan Du
    • 1
  • Songbai Tian
    • 1
  • Longqing Niu
    • 1
  • Xinghu Ji
    • 1
  • Zhike He
    • 1
    Email author
  1. 1.Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular SciencesWuhan UniversityWuhanPeople’s Republic of China

Personalised recommendations