Simultaneously responsive microfluidic chip aptasensor for determination of kanamycin, aflatoxin M1, and 17β-estradiol based on magnetic tripartite DNA assembly nanostructure probes

Microchimica Acta volume 187, Article number: 176 (2020) Cite this article

Abstract

The authors describe a microfluidic chip-based aptasensor platform combined with magnetic tripartite DNA structure-functionalized nanocomposites to achieve simultaneous determination of kanamycin (KANA), aflatoxin M1 (AFM1), and 17β-estradiol (E2) in milk. The two-duplex tripartite DNA nanostructure was first assembled on the surface of magnetic beads. When the aptamer on the probes recognized the specific target, the aptamer-target would be released into the supernatant. The pre-primer@circular DNA template structure initiates rolling circle amplification (RCA) by phi29 polymerase. After magnetic separation, the magnetic nanocomposites were added into a solution containing three different lengths of complementary strands to the RCA products. The number of complementary strands significantly decrease, and this can be quantitated by the microfluidic chip. Further, the employment of magnetic nanocomposites and microfluidic chip not only resolve the complex matrix interference, but also dramatically enhances the determination selectivity and sensitivity. This aptasensor allows for determination of KANA, AFM1, and E2 with limits of detection as low as 0.32 pg mL−1, 0.95 pg mL−1, and 6.8 pg mL−1, respectively. This novel method exhibits the advantages of excellent stability and fast response time (< 3 min on microfluidic chip platform) for simultaneous determination of KANA, AFM1, and E2 in milk samples and ensures food safety.

Graphical abstract

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

US$ 39.95

Tax calculation will be finalised during checkout.

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

References

  1. 1.

    Rather IA, Koh WY, Paek WK, Lim J (2017) The sources of chemical contaminants in food and their health implications. Front Pharmacol 8

  2. 2.

    Qin XL, Yin Y, Yu HJ, Guo WJ, Pei MS (2016) A novel signal amplification strategy of an electrochemical aptasensor for kanamycin, based on thionine functionalized graphene and hierarchical nanoporous PtCu. Biosens Bioelectron 77:752–758

    CAS  PubMed  Article  Google Scholar 

  3. 3.

    Khoshfetrat SM, Bagheri H, Mehrgardi MA (2018) Visual electrochemiluminescence biosensing of aflatoxin M1 based on luminol-functionalized, silver nanoparticle-decorated graphene oxide. Biosens Bioelectron 100:382–388

    CAS  PubMed  Article  Google Scholar 

  4. 4.

    Gao RX, Cui XH, Hao Y, Zhang LL, Liu DC, Tang YH (2016) A highly-efficient imprinted magnetic nanoparticle for selective separation and detection of 17 beta-estradiol in milk. Food Chem 194:1040–1047

    CAS  PubMed  Article  Google Scholar 

  5. 5.

    Dasenaki ME, Thomaidis NS (2015) Multi-residue determination of 115 veterinary drugs and pharmaceutical residues in milk powder, butter, fish tissue and eggs using liquid chromatography-tandem mass spectrometry. Anal Chim Acta 880:103–121

    CAS  PubMed  Article  Google Scholar 

  6. 6.

    Sutton AT, Fraige K, Leme GM, Bolzani VD, Hilder EF, Cavalheiro AJ, Arrua RD, Funari CS (2018) Natural deep eutectic solvents as the major mobile phase components in high-performance liquid chromatography-searching for alternatives to organic solvents. Anal Bioanal Chem 410(16):3705–3713

    CAS  PubMed  Article  Google Scholar 

  7. 7.

    Liu L, Li T, Zhang SW, Song P, Guo BY, Zhao YL, Wu HC (2018) Simultaneous quantification of multiple cancer biomarkers in blood samples through DNA-assisted nanopore sensing. Angew Chem Int Ed 57(37):11882–11887

    CAS  Article  Google Scholar 

  8. 8.

    Shen P, Li W, Liu Y, Ding Z, Deng Y, Zhu XR, Jin YH, Li YC, Li JL, Zheng TS (2017) High-throughput low-background g-quadruplex aptamer chemiluminescence assay for ochratoxin A using a single photonic crystal microsphere. Anal Chem 89(21):11862–11868

    CAS  PubMed  Article  Google Scholar 

  9. 9.

    Pavski V, Le XC (2001) Detection of human immunodeficiency virus type 1 reverse transcriptase using aptamers as probes in affinity capillary electrophoresis. Anal Chem 73(24):6070–6076

    CAS  PubMed  Article  Google Scholar 

  10. 10.

    Hao N, Lu JW, Zhou Z, Hua R, Wang K (2018) A pH-resolved colorimetric biosensor for simultaneous multiple target detection. ACS Sens 3(10):2159–2165

    CAS  PubMed  Article  Google Scholar 

  11. 11.

    Dai Z, Gao Q, Cheung MC, Leung HM, Lau TCK, Sleiman HF, Lai KWC, Lo PK (2016) A highly versatile platform based on geometrically well-defined 3D DNA nanostructures for selective recognition and positioning of multiplex targets. Nanoscale 8(43):18291–18295

    CAS  PubMed  Article  Google Scholar 

  12. 12.

    Xu HY, Liao C, Zuo P, Liu ZW, Ye BC (2018) Magnetic-based microfluidic device for on-chip isolation and detection of tumor-derived exosomes. Anal Chem 90(22):13451–13458

    CAS  PubMed  Article  Google Scholar 

  13. 13.

    Wang CH, Chang CP, Lee GB (2016) Integrated microfluidic device using a single universal aptamer to detect multiple types of influenza viruses. Biosens Bioelectron 86:247–254

    CAS  PubMed  Article  Google Scholar 

  14. 14.

    Mazaafrianto DN, Maeki M, Ishida A, Tani H, Tokeshi M (2018) Recent microdevice-based aptamer sensors. Micromachines-Basel 9(5)

    PubMed Central  Article  Google Scholar 

  15. 15.

    Liao ZR, Zhang Y, Li YR, Miao YF, Gao SM, Lin FK, Deng YL, Geng LN (2019) Microfluidic chip coupled with optical biosensors for simultaneous detection of multiple analytes: a review. Biosens Bioelectron 126:697–706

    CAS  PubMed  Article  Google Scholar 

  16. 16.

    Zhou LY, Gan N, Zhou Y, Li TH, Cao YT, Chen YJ (2017) A label-free and universal platform for antibiotics detection based on microchip electrophoresis using aptamer probes. Talanta 167:544–549

    CAS  PubMed  Article  Google Scholar 

  17. 17.

    He LY, Shen ZP, Cao YT, Li TH, Wu DZ, Dong YR, Gan N (2019) A microfluidic chip based ratiometric aptasensor for antibiotic detection in foods using stir bar assisted sorptive extraction and rolling circle amplification. Analyst 144(8):2755–2764

    CAS  PubMed  Article  Google Scholar 

  18. 18.

    Zhang K, Gan N, Hu FT, Chen XX, Li TH, Cao JX (2018) Microfluidic electrophoretic non-enzymatic kanamycin assay making use of a stirring bar functionalized with gold-labeled aptamer, of a fluorescent DNA probe, and of signal amplification via hybridization chain reaction. Microchim Acta 185(3)

  19. 19.

    Liu M, Zhang WQ, Zhang Q, Brennan JD, Li YF (2015) Biosensing by tandem reactions of structure switching, nucleolytic digestion, and DNA amplification of a DNA assembly. Angew Chem Int Ed 54(33):9637–9641

    CAS  Article  Google Scholar 

  20. 20.

    Ali MM, Li F, Zhang ZQ, Zhang KX, Kang DK, Ankrum JA, Le XC, Zhao WA (2014) Rolling circle amplification: a versatile tool for chemical biology, materials science and medicine. Chem Soc Rev 43(10):3324–3341

    CAS  PubMed  Article  Google Scholar 

  21. 21.

    Ma J, Wu L, Li ZH, Lu ZC, Yin WM, Nie AX, Ding F, Wang BR, Han HY (2018) Versatile electrochemiluminescence assays for PEDV antibody based on rolling circle amplification and Ru-DNA nanotags. Anal Chem 90(12):7415–7421

    CAS  PubMed  Article  Google Scholar 

  22. 22.

    Liu M, Hui CY, Zhang Q, Gu J, Kannan B, Jahanshahi-Anbuhi S, Filipe CDM, Brennan JD, Li YF (2016) Target-induced and equipment-free DNA amplification with a simple paper device. Angew Chem Int Ed 55(8):2709–2713

    Article  Google Scholar 

  23. 23.

    Hu J, Liu MH, Zhang CY (2018) Integration of isothermal amplification with quantum dot- based fluorescence resonance energy transfer for simultaneous detection of multiple microRNAs. Chem Sci 9(18):4258–4267

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  24. 24.

    Zhang Y, Luo FF, Zhang YT, Zhu LQ, Li Y, Zhao SL, He PG, Wang QJ (2018) A sensitive assay based on specific aptamer binding for the detection of salmonella enterica serovar Typhimurium in milk samples by microchip capillary electrophoresis. J Chromatogr A 1534:188–194

    CAS  PubMed  Article  Google Scholar 

  25. 25.

    Song KM, Cho M, Jo H, Min K, Jeon SH, Kim T, Han MS, Ku JK, Ban C (2011) Gold nanoparticle-based colorimetric detection of kanamycin using a DNA aptamer. Anal Biochem 415(2):175–181

    CAS  PubMed  Article  Google Scholar 

  26. 26.

    Zhou LY, Gan N, Hu FT, Li TH, Cao YT, Wu DZ (2018) Microchip electrophoresis array-based aptasensor for multiplex antibiotic detection using functionalized magnetic beads and polymerase chain reaction amplification. Sensor Actuators B Chem 263:568–574

    CAS  Article  Google Scholar 

  27. 27.

    Klein S, Harreiss C, Menter C, Hummer J, Distel LVR, Meyer K, Hock R, Kryschi C (2018) NOBF4-functionalized au-Fe3O4 nanoheterodimers for radiation therapy: synergy effect due to simultaneous reactive oxygen and nitrogen species formation. ACS Appl Mater Interfaces 10(20):17071–17080

    CAS  PubMed  Article  Google Scholar 

  28. 28.

    Chowdhury AD, Agnihotri N, Doong RA, De A (2017) Label-free and nondestructive separation technique for isolation of targeted DNA from DNA-protein mixture using magnetic au-Fe3O4 nanoprobes. Anal Chem 89(22):12244–12251

    Article  Google Scholar 

  29. 29.

    Wang JR, Lu ZX, Tang HL, Wu L, Wang ZX, Wu MH, Yi XY, Wang JX (2017) Multiplexed electrochemical detection of MiRNAs from sera of glioma patients at different stages via the novel conjugates of conducting magnetic microbeads and diblock oligonucleotide-modified gold nanoparticles. Anal Chem 89(20):10834–10840

    CAS  PubMed  Article  Google Scholar 

  30. 30.

    Liu CB, Lu CX, Tang ZG, Chen X, Wang GH, Sun FX (2015) Aptamer-functionalized magnetic nanoparticles for simultaneous fluorometric determination of oxytetracycline and kanamycin. Microchim Acta 182:2567–2575

    CAS  Article  Google Scholar 

  31. 31.

    Wang Y, Gan N, Zhou Y, Li TH, Hu FT, Cao YT, Chen YJ (2017) Novel label-free and high-throughput microchip electrophoresis platform for multiplex antibiotic residues detection based on aptamer probes and target catalyzed hairpin assembly for signal amplification. Biosens Bioelectron 97:100–106

    CAS  PubMed  Article  Google Scholar 

  32. 32.

    Sharma A, Catanante G, Hayat A, Istamboulie G, Ben Rejeb I, Bhand S, Marty JL (2016) Development of structure switching aptamer assay for detection of aflatoxin M1 in milk sample. Talanta 158:35–41

    CAS  PubMed  Article  Google Scholar 

  33. 33.

    Chaisuwan N, Xu H, Wu GY, Liu JS (2013) A highly sensitive differential pulse anodic stripping voltammetry for determination of 17 beta-estradiol (E2) using CdSe quantum dots based on indirect competitive immunoassay. Biosens Bioelectron 46:150–154

    CAS  PubMed  Article  Google Scholar 

Download references

Acknowledgments

The authors thank LetPub (www.letpub.com) for its linguistic assistance during the preparation of this manuscript.

Funding

This work was supported by the National Natural Science Foundation of China (No.21974074), the Natural Science Foundation of Zhejiang (LY19B050001, LY17C200007, LGN18H300001), and K. C. Wong Magna Fund in Ningbo University.

Author information

Affiliations

  1. Faculty of Materials Science and Chemical Engineering, Ningbo University, Ningbo, 315211, People’s Republic of China

    Liyong He, Zhipeng Shen, Jiaqi Wang, Jin Zeng, Wenhai Wang & Ning Gan

  2. The Art Institute of Ningbo University, Ningbo, 315211, People’s Republic of China

    Huihui Wu

  3. Institute of Pharmaceutical Analysis, College of Pharmacy, Jinan University, Guangzhou, 510632, People’s Republic of China

    Qiqin Wang

Authors
  1. Liyong He
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zhipeng Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jiaqi Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jin Zeng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wenhai Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Huihui Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Qiqin Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ning Gan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Qiqin Wang or Ning Gan.

Ethics declarations

Conflict of interest

The authors 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 1.98 mb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

He, L., Shen, Z., Wang, J. et al. Simultaneously responsive microfluidic chip aptasensor for determination of kanamycin, aflatoxin M1, and 17β-estradiol based on magnetic tripartite DNA assembly nanostructure probes. Microchim Acta 187, 176 (2020). https://doi.org/10.1007/s00604-020-4155-5

Download citation

Keywords

  • Multiclass chemical contaminants
  • Rolling circle amplification
  • Au-Fe3O4 nanocomposites
  • Complementary strands signal tags
  • Milk safety