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Microchimica Acta

, 186:699 | Cite as

A vertical flow microarray chip based on SERS nanotags for rapid and ultrasensitive quantification of α-fetoprotein and carcinoembryonic antigen

  • Di Zhang
  • Li Huang
  • Bing Liu
  • Qinyu Ge
  • Jian Dong
  • Xiangwei ZhaoEmail author
Original Paper
  • 138 Downloads

Abstract

A vertical flow microarray chip is described that uses core-shell SERS nanotags as tags for ultrasensitive quantification of the tumor markers α-fetoprotein (AFP) and carcinoembryonic antigen (CEA) by detecting the intensity of the specific Raman bands at 592 cm−1. The nanotags warrant high sensitivity, and the use of porous nitrocellulose warrants a high surface-to-volume ratio. The linear dynamic ranges are 0.1 ng mL−1 - 10 μg mL−1 for both AFP and CEA, and the limits of detection) are 0.27 pg mL−1 and 0.96 pg mL−1, respectively. Quantification is rapid and can be performed without preconcentration.

Graphical abstract

Schematic representation of a vertical flow microarray chip using AuNBA@Ag SERS nanotags (where NBA stands for Nile blue A) as labels for rapid, ultrasensitive, and simultaneous detection of tumor biomarkers CEA and AFP.

Keywords

CEA AFP Tumor biomarkers POCT Nile blue A Broad linear dynamic range Portable Raman spectrometer Silver Gold 

Notes

Acknowledgements

This work was financially supported by the National Key Research and Development Program of China (2018YFF0215200, 2017YFA0205700), National Natural Science Foundation of China (Grants 61850410528, 81827901, and 21327902), the Natural Science Foundation of Jiangsu Province (BK2014021828, BE2016002, and BK20170907), China Postdoctoral Science Foundation funded project (2018 M642132), the Fundamental Research Funds for the Central Universities, Six Talent Peaks Project of Jiangsu Province, the Collaboration Research Fund of Southeast University and Nanjing Medical University (Grant 2242017K3DN26), Fundamental Research Project of Shenzhen Science & Technology Innovation Committee (201803063001075).

Compliance with ethical standards

Conflict of interest

The authors declare no competing financial interest.

Supplementary material

604_2019_3792_MOESM1_ESM.docx (23 kb)
ESM 1 (DOCX 22.5 kb)

References

  1. 1.
    Zarei M (2017) Advances in point-of-care technologies for molecular diagnostics. Biosens Bioelectron 98:494–506CrossRefGoogle Scholar
  2. 2.
    Yetisen AK, Akram MS, Lowe CR (2013) Paper-based microfluidic point-of-care diagnostic devices. Lab Chip 13(12):2210–2251CrossRefGoogle Scholar
  3. 3.
    Luppa PB, Müller C, Schlichtiger A, Schlebusch H (2011) Point-of-care testing (POCT): current techniques and future perspectives. TrAC Trend Anal Chem 30(6):887–898CrossRefGoogle Scholar
  4. 4.
    Farzin L, Shamsipur M, Sheibani S, Samandari L, Hatami Z (2019) A review on nanomaterial-based electrochemical, optical, photoacoustic and magnetoelastic methods for determination of uranyl cation. Microchim Acta 186(5):289CrossRefGoogle Scholar
  5. 5.
    Zhang D, Huang L, Liu B, Ni H, Sun L, Su E, Chen H, Gu Z, Zhao X (2018) Quantitative and ultrasensitive detection of multiplex cardiac biomarkers in lateral flow assay with core-shell SERS nanotags. Biosens Bioelectron 106:204–211CrossRefGoogle Scholar
  6. 6.
    Wang R, Kim K, Choi N, Wang X, Lee J, Jeon JH, G-e R, Choo J (2018) Highly sensitive detection of high-risk bacterial pathogens using SERS-based lateral flow assay strips. Sens Actuator B-Chem 270:72–79CrossRefGoogle Scholar
  7. 7.
    Cheng Z, Choi N, Wang R, Lee S, Moon KC, Yoon SY, Chen L, Choo J (2017) Simultaneous detection of dual prostate specific antigens using surface-enhanced Raman scattering-based immunoassay for accurate diagnosis of prostate cancer. ACS Nano 11(5):4926–4933CrossRefGoogle Scholar
  8. 8.
    Xie Y, Chang H, Zhao K, Li J, Yang H, Mei L, Xu S, Deng A (2015) A novel immunochromatographic assay (ICA) based on surface-enhanced Raman scattering for the sensitive and quantitative determination of clenbuterol. Anal Methods 7(2):513–520CrossRefGoogle Scholar
  9. 9.
    Shi Q, Huang J, Sun Y, Deng R, Teng M, Li Q, Yang Y, Hu X, Zhang Z, Zhang G (2018) A SERS-based multiple immuno-nanoprobe for ultrasensitive detection of neomycin and quinolone antibiotics via a lateral flow assay. Microchim Acta 185(2):84CrossRefGoogle Scholar
  10. 10.
    Fu X, Chu Y, Zhao K, Li J, Deng A (2017) Ultrasensitive detection of the β-adrenergic agonist brombuterol by a SERS-based lateral flow immunochromatographic assay using flower-like gold-silver core-shell nanoparticles. Microchim Acta 184(6):1711–1719CrossRefGoogle Scholar
  11. 11.
    Zhang F, Zhu J, Li JJ, Zhao JW (2015) A promising direct visualization of an au@ ag nanorod-based colorimetric sensor for trace detection of alpha-fetoprotein. J Mater Chem C 3(23):6035–6045CrossRefGoogle Scholar
  12. 12.
    Zeng H, Agyapong DAY, Li C, Zhao R, Yang H, Wu C, Jiang Y, Liu Y (2015) A carcinoembryonic antigen optoelectronic immunosensor based on thiol-derivative-nanogold labeled anti-CEA antibody nanomaterial and gold modified ITO. Sens Actuator B-Chem 221:22–27CrossRefGoogle Scholar
  13. 13.
    Clarke OJ, Goodall BL, Hui HP, Vats N, Brosseau CL (2017) Development of a SERS-based rapid vertical flow assay for point-of-care diagnostics. Anal Chem 89(3):1405–1410CrossRefGoogle Scholar
  14. 14.
    Reutersward P, Gantelius J, Andersson Svahn H (2015) An 8 minute colorimetric paper-based reverse phase vertical flow serum microarray for screening of hyper IgE syndrome. Analyst 140(21):7327–7334CrossRefGoogle Scholar
  15. 15.
    Nunes Pauli GE, de la Escosura-Muniz A, Parolo C, Helmuth Bechtold I, Merkoci A (2015) Lab-in-a-syringe using gold nanoparticles for rapid immunosensing of protein biomarkers. Lab Chip 15(2):399–405CrossRefGoogle Scholar
  16. 16.
    Guarrotxena N, Bazan GC (2014) Antitags: SERS-encoded nanoparticle assemblies that enable single-spot multiplex protein detection. Adv Mater 26(12):1941–1946CrossRefGoogle Scholar
  17. 17.
    de Lange V, Voros J (2014) Twist on protein microarrays: layering wax-patterned nitrocellulose to create customizable and separable arrays of multiplexed affinity columns. Anal Chem 86(9):4209–4216CrossRefGoogle Scholar
  18. 18.
    Chinnasamy T, Segerink LI, Nystrand M, Gantelius J, Andersson Svahn H (2014) Point-of-care vertical flow allergen microarray assay: proof of concept. Clin Chem 60(9):1209–1216CrossRefGoogle Scholar
  19. 19.
    Zhang D, Huang L, Liu B, Su E, Chen H-Y, Gu Z, Zhao X (2018) Quantitative detection of multiplex cardiac biomarkers with encoded SERS nanotags on a single T line in lateral flow assay. Sens Actuator B-Chem 277:502–509CrossRefGoogle Scholar
  20. 20.
    Frens G (1973) Controlled nucleation for the regulation of the particle size in monodisperse gold suspensions. Nat Phys Sci 241:20–22CrossRefGoogle Scholar
  21. 21.
    Liu B, Zhang D, Ni H, Wang D, Jiang L, Fu D, Han X, Zhang C, Chen H, Gu Z, Zhao X (2018) Multiplex analysis on a single porous hydrogel bead with encoded SERS nanotags. ACS Appl Mater Interfaces 10(1):21–26CrossRefGoogle Scholar
  22. 22.
    Liu B, Ni H, Zhang D, Wang D, Fu D, Chen H, Gu Z, Zhao X (2017) Ultrasensitive detection of protein with wide linear dynamic range based on core-shell SERS nanotags and photonic crystal beads. ACS Sens 2(7):1035–1043CrossRefGoogle Scholar
  23. 23.
    Lim DK, Jeon KS, Hwang JH, Kim H, Kwon S, Suh YD, Nam JM (2011) Highly uniform and reproducible surface-enhanced Raman scattering from DNA-tailorable nanoparticles with 1-nm interior gap. Nat Nanotechnol 6(7):452–460CrossRefGoogle Scholar
  24. 24.
    Oh JW, Lim DK, Kim GH, Suh YD, Nam JM (2014) Thiolated DNA-based chemistry and control in the structure and optical properties of plasmonic nanoparticles with ultrasmall interior nanogap. J Am Chem Soc 136(40):14052–14059CrossRefGoogle Scholar
  25. 25.
    Kang JW, So PT, Dasari RR, Lim DK (2015) High resolution live cell Raman imaging using subcellular organelle-targeting SERS-sensitive gold nanoparticles with highly narrow intra-nanogap. Nano Lett 15(3):1766–1772CrossRefGoogle Scholar
  26. 26.
    Gandra N, Singamaneni S (2013) Bilayered Raman-intense gold nanostructures with hidden tags (BRIGHTs) for high-resolution bioimaging. Adv Mater 25(7):1022–1027CrossRefGoogle Scholar
  27. 27.
    Krug JT, Wang GD, Emory SR, Nie S (1999) Efficient Raman enhancement and intermittent light emission observed in single gold nanocrystals. J Am Chem Soc 121(39):9208–9214CrossRefGoogle Scholar
  28. 28.
    de Lange V, Habegger M, Schmidt M, Voros J (2017) Improving FoRe: a new inlet design for filtering samples through individual microarray spots. ACS Sens 2(3):339–345CrossRefGoogle Scholar
  29. 29.
    Zhang C, Gao Y, Yang N, You T, Chen H, Yin P (2018) Direct determination of the tumor marker AFP via silver nanoparticle enhanced SERS and AFP-modified gold nanoparticles as capturing substrate. Microchim Acta 185(2):90CrossRefGoogle Scholar
  30. 30.
    Park J, Lee S, Kim Y, Choi A, Lee H, Lim J, Kim Y, Han K, Oh EJ (2018) Comparison of four automated carcinoembryonic antigen immunoassays: ADVIA centaur XP, ARCHITECT I2000sr, Elecsys E170, and Unicel dxi800. Ann Lab Med 38(4):355–361CrossRefGoogle Scholar

Copyright information

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

Authors and Affiliations

  • Di Zhang
    • 1
    • 2
    • 3
  • Li Huang
    • 1
    • 2
    • 4
  • Bing Liu
    • 1
    • 2
  • Qinyu Ge
    • 1
    • 2
  • Jian Dong
    • 1
    • 2
  • Xiangwei Zhao
    • 1
    • 2
    Email author
  1. 1.State Key Laboratory of Bioelectronics, School of Biological Science and Medical EngineeringSoutheast UniversityNanjingChina
  2. 2.National Demonstration Center for Experimental Biomedical Engineering EducationSoutheast UniversityNanjingChina
  3. 3.Department of Biomedical EngineeringYale UniversityNew HavenUSA
  4. 4.Getein Biotechnology Co., Ltd.NanjingChina

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