Skip to main content
Log in

Advancements in DNA-assisted Immunosensors

  • Review Article
  • Published:
BioChip Journal Aims and scope Submit manuscript

Abstract

Several types of biosensors have been developed to detect a wide variety of human diseases. Immunosensors are classified as the most representative of all biosensors. They are based on antibodies that selectively recognize specific analytes and have high specificity and sensitivity. However, there are limitations to the types of substances that can be detected, and it is sometimes difficult to achieve sufficient sensitivity without additional amplification steps. To overcome these problems, novel immunosensors are being developed that combine DNA-based high signal amplification systems. These technologies ameliorate the low sensitivity of existing immunosensors by using DNA probes that can bind directly to targets as bioreceptors or act as signal amplifiers. In this review, we will discuss immunodetection methods that use DNA-based technologies on laboratory-scale and advanced point-of-care testing (POCT) that employ these technologies for high performance analyses.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

References

  1. Vigneshvar, S., Sudhakumari, C. C., Senthilkumaran, B. & Prakash, H. Recent advances in biosensor technology for potential applications — an overview. Front. Bioeng. Biotechnol.4, 1–9 (2016).

    Google Scholar 

  2. Turner, A. P. F. Biosensors: Sense and sensibility. Chem. Soc. Rev.42, 3184–3196 (2013).

    CAS  PubMed  Google Scholar 

  3. Kim, T. Y., Lim, M. C., Woo, M. A. & Jun, B. H. Radial flow assay using gold nanoparticles and rolling circle amplification to detect mercuric ions. Nanomaterials8, 1–13 (2018).

    Google Scholar 

  4. Lee, S.H., Park, S.M., Kim, B.N., Kwon, O.S., Rho, W.Y. & Jun, B.H. Emerging ultrafast nucleic acid amplification technologies for next-generation molecular diagnostics. Biosens. Bioelectron.141, 111448 (2019).

    CAS  PubMed  Google Scholar 

  5. Chen, Y., Lu, S., Zhang, S., Li, Y., Qu, Z., Chen, Y., Lu, B., Wang, X. & Feng, X. Skin-like biosensor system via electrochemical channels for noninvasive blood glucose monitoring. Sci. Adv.3, 1–8 (2017).

    Google Scholar 

  6. Kim, J., Campbell, A.S., de Ávila, B.E.F. & Wang, J. Wearable biosensors for healthcare monitoring. Nat. Biotechnol.37, 389–406 (2019).

    CAS  PubMed  Google Scholar 

  7. Bhalla, N., Jolly, P., Formisano, N. & Estrela, P. Introduction to biosensors. Essays Biochem.60, 1–8 (2016).

    PubMed  PubMed Central  Google Scholar 

  8. Ermolaeva, T., Farafonova, O. & Karaseva, N. Possibilities and prospects of immunosensors for a highly sensitive pesticide detection in vegetables and fruits: A review. Food Anal. Methods12, 2785–2801 (2019).

    Google Scholar 

  9. Nguyen, H.H., Lee, S.H., Lee, U.J., Fermin, C.D. & Kim, M. Immobilized enzymes in biosensor applications. Materials (Basel).12, 1–34 (2019).

    Google Scholar 

  10. Liu, Y., Wang, H., Chen, J., Liu, C., Li, W., Kong, J., Yang, P. & Liu, B. A sensitive microchip-based immunosensor for electrochemical detection of low-level biomarker s100b. Electroanalysis25, 1050–1055 (2013).

    CAS  Google Scholar 

  11. Juzgado, A., Soldà, A., Ostric, A., Criado, A., Valenti, G., Rapino, S., Conti, G., Fracasso, G., Paolucci, F. & Prato, M. Highly sensitive electrochemiluminescence detection of a prostate cancer biomarker. J. Mater. Chem. B5, 6681–6687 (2017).

    CAS  PubMed  Google Scholar 

  12. Song, C.K., Oh, E., Kang, M.S., Shin, B.S., Han, S.Y., Jung, M., Lee, E.S., Yoon, S.Y., Sung, M.M., Ng, W.B., Cho, N.J. & Lee, H. Fluorescence-based immunosensor using three-dimensional CNT network structure for sensitive and reproducible detection of oral squamous cell carcinoma biomarker. Anal. Chim. Acta1027, 101–108 (2018).

    CAS  PubMed  Google Scholar 

  13. Choi, D.H., Lee, S.K., Oh, Y.K., Bae, B.W., Lee, S.D., Kim, S., Shin, Y.B. & Kim, M.G. A dual gold nanoparticle conjugate-based lateral flow assay (LFA) method for the analysis of troponin I. Biosens. Bioelectron.25, 1999–2002 (2010).

    CAS  PubMed  Google Scholar 

  14. Han, G.R. & Kim, M.G. Design, synthesis, and evaluation of gold nanoparticle-antibody-horseradish peroxidase conjugates for highly sensitive chemiluminescence immunoassay (hs-CLIA). Biotechnol. Bioprocess Eng.24, 206–214 (2019).

    CAS  Google Scholar 

  15. Bi, S., Zhou, H. & Zhang, S. Multilayers enzymecoated carbon nanotubes as biolabel for ultrasensitive chemiluminescence immunoassay of cancer biomarker. Biosens. Bioelectron.24, 2961–2966 (2009).

    CAS  PubMed  Google Scholar 

  16. Hong, S.Y., Park, Y.M., Jang, Y.H., Min, B.H. & Yoon, H.C. Quantitative lateral-flow immunoassay for the assessment of the cartilage oligomeric matrix protein as a marker of osteoarthritis. Biochip J.6, 213–220 (2012).

    CAS  Google Scholar 

  17. Oh, H.K., Kim, J.W., Kim, J.M. & Kim, M.G. High sensitive and broad-range detection of cortisol in human saliva using a trap lateral flow immunoassay (trapLFI) sensor. Analyst143, 3883–3889 (2018).

    CAS  PubMed  Google Scholar 

  18. Ali, J., Najeeb, J., Asim Ali, M., Farhan Aslam, M. & Raza, A. Biosensors: Their fundamentals, designs, types and most recent impactful applications: A review. J. Biosens. Bioelectron.08, 1–9 (2017).

    CAS  Google Scholar 

  19. Monošík, R., Stred’anský, M. & Šturdík, E. Biosensors — classification, characterization and new trends. Acta Chim. Slovaca5, 109–120 (2012).

    Google Scholar 

  20. Cosnier, S. Affinity biosensors based on electropolymerized films. Electroanalysis17, 1701–1715 (2005).

    CAS  Google Scholar 

  21. Seo, H. Bin & Gu, M.B. Aptamer-based sandwichtype biosensors. J. Biol. Eng.11, 1–7 (2017).

    Google Scholar 

  22. Nezlin, R. Use of aptamers in immunoassays. Mol. Immunol.70, 149–154 (2016).

    CAS  PubMed  Google Scholar 

  23. Lee, S.J., Park, J.W., Kim, I.A., Youn, B.S. & Gu, M.B. Sensitive detection of adipokines for early diagnosis of type 2 diabetes using enzyme-linked antibody-aptamer sandwich (ELAAS) assays. Sens. Actuators, B Chem.168, 243–248 (2012).

    CAS  Google Scholar 

  24. Tran, H.V., Piro, B., Reisberg, S., Nguyen, L.H., Nguyen, T.D., Duc, H.T. & Pham, M.C. An electrochemical ELISA-like immunosensor for miRNAs detection based on screen-printed gold electrodes modified with reduced graphene oxide and carbon nanotubes. Biosens. Bioelectron.62, 25–30 (2014).

    CAS  PubMed  Google Scholar 

  25. Darmostuk, M., Rimpelova, S., Gbelcova, H. & Ruml, T. Current approaches in SELEX: An update to aptamer selection technology. Biotechnol. Adv.33, 1141–1161 (2014).

    Google Scholar 

  26. Wu, W., Li, J., Pan, D., Li, J., Song, S., Rong, M., Li, Z., Gao, G. & Lu, J. Gold nanoparticle-based enzyme-linked antibody-aptamer sandwich assay for detection of salmonella typhimurium. ACS Appl. Mater. Interfaces6, 16974–16981 (2014).

    CAS  PubMed  Google Scholar 

  27. Santiago-Felipe, S., Tortajada-Genaro, L.A., Puchades, R. & Maquieira, A. Recombinase polymerase and enzyme-linked immunosorbent assay as a DNA amplification-detection strategy for food analysis. Anal. Chim. Acta811, 81–87 (2014).

    CAS  PubMed  Google Scholar 

  28. Zhou, Y., Zhang, H., Liu, L., Li, C., Chang, Z., Zhu, X., Ye, B. & Xu, M. Fabrication of an antibody-aptamer sandwich assay for electrochemical evaluation of levels of β-amyloid oligomers. Sci. Rep.6, 1–8 (2016).

    Google Scholar 

  29. Aswani Kumar, Y.V.V., Renuka, R.M., Achuth, J., Venkataramana, M., Ushakiranmayi, M. & Sudhakar, P. Development of hybrid IgG-aptamer sandwich immunoassay platform for aflatoxin B1 detection and its evaluation onto various field. Front. Pharmacol.9, 271 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Kang, J., Yeom, G., Ha, S.J. & Kim, M.G. Development of a DNA aptamer selection method based on the heterogeneous sandwich form and its application in a colorimetric assay for influenza A virus detection. New J. Chem.43, 6883–6889 (2019).

    CAS  Google Scholar 

  31. Yeom, G., Kang, J., Jang, H., Nam, H.Y., Kim, M.G. & Park, C.J. Development of DNA Aptamers against the nucleocapsid protein of severe fever with thrombocytopenia syndrome virus for diagnostic application: Catalytic signal amplification using replication protein A-conjugated liposomes. Anal. Chem.91, 13772–13779 (2019).

    CAS  PubMed  Google Scholar 

  32. Schweitzer, B., Roverts, S., Grimwade, B., Shao, W., Wang, M., Fu, Q., Shu, Q., Laroche, I., Zhou, Z., Tchernev, V.T., Christiansen, J., Velleca, M. & Kingsmore, S.F. Multiplexed protein profiling on microarrays by rolling-circle amplification. Nat. Biotechnol.20, 359–365 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. He, J., Evers, D.L., O’Leary, T.J. & Mason, J.T. Immunoliposome-PCR: A generic ultrasensitive quantitative antigen detection system. J. Nanobiotechnology10, 1 (2012).

    Google Scholar 

  34. Nussbaum, O., Bar Oz, M., Tilayov, T., Atiya, H. & Dagan, S. A signal amplification probe enhances sensitivity of antibodies and aptamers based Immunodiagnostic assays. J. Immunol. Methods448, 85–90 (2017).

    CAS  PubMed  Google Scholar 

  35. Navrátil, V., Schimer, J., Tykvart, J., Knedlík, T., Vik, V., Majer, P., Konvalinka, J., Šácha, P. DNA-linked Inhibitor Antibody Assay (DIANA) for sensitive and selective enzyme detection and inhibitor screening. Nucleic Acids Res.45, e10 (2017).

    PubMed  Google Scholar 

  36. Byun, J.Y., Lee, K.H., Shin, Y.B. & Kim, D.M. Cascading amplification of immunoassay signal by cell-free expression of firefly luciferase from detection antibody-conjugated DNA in an escherichia coli extract. ACS Sens.4, 93–99 (2019).

    CAS  PubMed  Google Scholar 

  37. Fischer, C., Wessels, H., Paschke-Kratzin, A. & Fischer, M. Aptamers: Universal capture units for lateral flow applications. Anal. Biochem.522, 53–60 (2017).

    CAS  PubMed  Google Scholar 

  38. Posthuma-Trumpie, G.A., Korf, J. & Van Amerongen, A. Lateral flow (immuno)assay: Its strengths, weaknesses, opportunities and threats. A literature survey. Anal. Bioanal. Chem.393, 569–582 (2009).

    CAS  PubMed  Google Scholar 

  39. Liu, C.C., Yeung, C.Y., Chen, P.H., Yeh, M.K. & Hou, S.Y. Salmonella detection using 16S ribosomal DNA/RNA probe-gold nanoparticles and lateral flow immunoassay. Food Chem.141, 2526–2532 (2013).

    CAS  PubMed  Google Scholar 

  40. Adhikari, M., Strych, U., Kim, J., Goux, H., Dhamane, S., Poongavanam, M.V., Hagström, A.E.V., Kourentzi, K., Conrad, J.C. & Willson, R.C. Aptamer-phage reporters for ultrasensitive lateral flow assays. Anal. Chem.87, 11660–11665 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Zhu, X., Kou, F.K., Xu, H., Lin, L., Yang, G. & Lin, Z. A highly sensitive aptamer-immunoassay for vascular endothelial growth factor coupled with portable glucose meter and hybridization chain reaction. Sens. Actuators, B253, 660–665 (2017).

    CAS  Google Scholar 

  42. Kang, J., Yeom, G., Jang, H., Oh, J., Park, C.J. & Kim, M.G. Development of replication protein A-conjugated gold nanoparticles for highly sensitive detection of disease biomarkers. Anal. Chem.91, 10001–10007 (2019).

    CAS  PubMed  Google Scholar 

  43. Frohnmeyer, E., Tuschel, N., Sitz, T., Hermann, C., Dahl, G. T., Schulz, F., Baeumner, A.G. & Fischer, M. Aptamer lateral flow assays for rapid and sensitive detection of cholera toxin. Analyst144, 1840–1849 (2019).

    CAS  PubMed  Google Scholar 

  44. Phillips, E.A., Moehling, T.J., Bhadra, S., Ellington, A.D. & Linnes, J.C. Strand displacement probes combined with isothermal nucleic acid amplification for instrument-free detection from complex samples. Anal. Chem.90, 6580–6586 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Fredriksson, S., Gullberg, M., Jarvius, J., Olsson, C., Pietras, K., Gústafsdóttir, S.M., Ostman, A. & Landegren, U. Protein detection using proximity-dependent DNA Ligation Assays. Nat. Biotechnol.20, 473–477 (2002).

    CAS  PubMed  Google Scholar 

  46. Hinman, S.S., McKeating, K.S. & Cheng, Q. DNA Linkers and Diluents for Ultrastable Gold Nanoparticle Bioconjugates in Multiplexed Assay Development. Anal. Chem.89, 4272–4279 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Roskos, K., Hickerson, A.I., Lu, H.-W., Ferguson, T.M., Shinde, D.N., Klaue, Y. & Niemz, A. Simple system for isothermal DNA amplification coupled to lateral flow detection. PLoS One8, e69355 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Du, X., Zang, Y., Liu, H., Li, P. & Wang, S. Rapid detection of staphylococcus aureus via recombinase polymerase amplification combined with lateral flow strip. Food Anal. Methods11, 2296–2306 (2018).

    Google Scholar 

  49. Lundberg, M., Thorsen, S.B., Assarsson, E., Villablanca, A., Tran, B., Gee, N., Knowles, M., Nielsen, B.S., Couto, E.G., Martin, R., Nilsson, O., Fermer, C., Schlingemann, J., Christensen, I.J., Nielsen, H.J., Ekström, B., Andersson, C., Gustafsson, M., Brunner, N., Stenvang, J. & Fredriksson, S. Multiplexed homogeneous proximity ligation assays for high-throughput protein biomarker research in serological material. Mol. Cell. Proteomics10, 1–11 (2011).

    Google Scholar 

  50. Kang, Y., Feng, K.J., Chen, J.W., Jiang, J.H., Shen, G.L. & Yu, R.Q. Electrochemical detection of thrombin by sandwich approach using antibody and aptamer. Bioelectrochemistry73, 76–81 (2008).

    CAS  PubMed  Google Scholar 

  51. Guo, L. & Kim, D.H. LSPR biomolecular assay with high sensitivity induced by aptamer-antigen-antibody sandwich complex. Biosens. Bioelectron.31, 567–570 (2012).

    CAS  PubMed  Google Scholar 

  52. Pultar, J., Sauer, U., Domnanich, P. & Preininger, C. Aptamer-antibody on-chip sandwich immunoassay for detection of CRP in spiked serum. Biosens. Bioelectron.24, 1456–1461 (2009).

    CAS  PubMed  Google Scholar 

  53. Huang, Y., Nie, X.M., Gan, S.L., Jiang, J.H., Shen, G.L. & Yu, R. Q. Electrochemical immunosensor of platelet-derived growth factor with aptamer-primed polymerase amplification. Anal. Biochem.382, 16–22 (2008).

    CAS  PubMed  Google Scholar 

  54. Qureshi, A., Gurbuz, Y. & Niazi, J. H. Capacitive aptamer-antibody based sandwich assay for the detection of VEGF cancer biomarker in serum. Sens. Actuators, B209, 645–651 (2015).

    CAS  Google Scholar 

  55. Kim, D., Jetson, R.R. & Krusemark, C.J. A DNA-assisted immunoassay for enzyme activity: Via a DNA-linked, activity-based probe. Chem. Commun.53, 9474–9477 (2017).

    CAS  Google Scholar 

  56. Maerle, A.V. Simonova, M.A., Pivovarov, V.D., Voronina, D.V., Drobyazina, P.E., Trofimov, D.Y., Alekseev, L.P., Zavriev, S.K., & Ryazantsev, D.Y. Development of the covalent antibody-DNA conjugates technology for detection of IgE and IgM antibodies by immuno-PCR. PLoS One14, e0209860 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Chen, R., Sun, Y., Huo, B., Yuan, S., Sun, X., Zhang, M., Yin, N., Fan, L., Yao, W., Wang, J., Han, D., Li, S., Pen, Y., Bai, J., Ning, B., Liang, J., Gao, Z. Highly sensitive detection of ochratoxin A based on bio-barcode immunoassay and catalytic hairpin assembly signal amplification. Talanta208, 120405 (2020).

    CAS  PubMed  Google Scholar 

  58. Shen, G., Zhang, S. & Hu, X. Signal enhancement in a lateral flow immunoassay based on dual gold nanoparticle conjugates. Clin. Biochem.46, 1734–1738 (2013).

    CAS  PubMed  Google Scholar 

  59. Hansen, C.H., Yang, D., Koussa, M.A. & Wong, W.P. Nanoswitch-linked immunosorbent assay (NLISA) for fast, sensitive, and specific protein detection. Proc. Natl. Acad. Sci. U. S. A.114, 10367–10372 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This research was supported by the GIST (Gwangju Institute of Science and Technology), Korea, under the Practical Research and Development support program supervised by the GTI (GIST Technology Institute), Samsung Research Funding & Incubation Center of Samsung Electronics under Project Number SRFC-IT1702-10.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Min-Gon Kim.

Ethics declarations

Conflict of Interests The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kang, J., Kim, MG. Advancements in DNA-assisted Immunosensors. BioChip J 14, 18–31 (2020). https://doi.org/10.1007/s13206-020-4103-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13206-020-4103-9

Keywords

Navigation