Skip to main content
SpringerLink
Log in

Fluorescence Signal Amplification for Ultrasensitive DNA Detection

  • Chapter
Book cover Reviews in Fluorescence 2007

Part of the book series: Reviews in Fluorescence ((RFLU,volume 2007))

Abstract

Ultrasensitive and reliable DNA detection tools are currently needed for the diagnostic of infectious and genetic diseases. To achieve the required sensitivity, one can amplify either the target DNA or the signal generated by each target molecule detected. Since enzymatic amplification of DNA is prone to contamination or inhibition, sensors that can benefit from signal amplification are usually more robust. Several approaches have been developed to obtain an amplification of the fluorescence signal generated by some biosensors upon DNA detection. Some among them feature the use of conjugated polymers as biosensors; due to their collective system response, they offer an amplification of the signal as compared to the response of individual monomers. Other approaches feature the use of efficient Förster energy transfer schemes. The use of fluorophore encapsulation, to increase the number of fluorophores reporting a detection event and to protect them from quenching species, can also be used to obtain an amplified fluorescence signal. The purpose of this review is to point out and discuss how these different methods achieve the observed fluorescence signal amplification, in order to relate them to what is known about fluorescence emission and energy transfer.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Daar, A. S., Thorsteinsdottir, H., Martin, D. K., Smith, A. C., Nast, S., Singer, P. A., Top ten biotechnologies for improving health in developing countries. Nature Genetics, 32(2), 229–232, (2002).

    Article  CAS  PubMed  Google Scholar 

  2. Piunno, P. A. E., Krull, U. J., Trends in the development of nucleic acid biosensors for medical diagnostics. Analytical and Bioanalytical Chemistry, 381(5), 1004–1011, (2005).

    Article  CAS  PubMed  Google Scholar 

  3. Thomas, S. W., Joly, G. D., Swager, T. M., Chemical sensors based on amplifying fluorescent conjugated polymers. Chemical Reviews, 107(4), 1339–1386, (2007).

    Article  CAS  PubMed  Google Scholar 

  4. Ihara, T., Mukae, M., Homogeneous DNA-detection based on the non-enzymatic reactions promoted by target DNA. Analytical Sciences, 23(6), 625–629, (2007).

    Article  CAS  PubMed  Google Scholar 

  5. Altschuh, D., Oncul, S., Demchenko, A. P., Fluorescence sensing of intermolecular interactions and development of direct molecular biosensors. Journal of Molecular Recognition, 19(6), 459–477, (2006).

    Article  CAS  PubMed  Google Scholar 

  6. Boissinot, M., Bergeron Michel, G., Toward rapid real-time molecular diagnostic to guide smart use of antimicrobials. Current Opinion in Microbiology, 5(5), 478–82, (2002).

    Article  PubMed  Google Scholar 

  7. Cao YunWei, C., Jin, R., Mirkin Chad, A., Nanoparticles with Raman spectroscopic fingerprints for DNA and RNA detection. Science, 297(5586), 1536–40, (2002).

    Article  PubMed  Google Scholar 

  8. Dubertret, B., Calame, M., Libchaber, A. J., Single-mismatch detection using gold-quenched fluorescent oligonucleotides. Nature Biotechnology, 19(4), 365–370, (2001).

    Article  CAS  PubMed  Google Scholar 

  9. Elghanian, R., Storhoff, J. J., Mucic, R. C., Letsinger, R. L., Mirkin, C. A., Selective colorimetric detection of polynucleotides based on the distance-dependent optical properties of gold nanoparticles. Science, 277(5329), 1078–1081, (1997).

    Article  CAS  PubMed  Google Scholar 

  10. Gaylord, B. S., Heeger, A. J., Bazan, G. C., DNA detection using water-soluble conjugated polymers and peptide nucleic acid probes. Proceedings of the National Academy of Sciences of the United States of America, 99(17), 10954–10957, (2002).

    Google Scholar 

  11. Gaylord, B. S., Heeger, A. J., Bazan, G. C., DNA Hybridization detection with water-soluble conjugated polymers and chromophore-labeled single-stranded DNA. Journal of the American Chemical Society, 125(4), 896–900, (2003).

    Article  CAS  PubMed  Google Scholar 

  12. Taton, T. A., Mirkin, C. A., Letsinger, R. L., Scanometric DNA array detection with nanoparticle probes. Science, 289(5485), 1757–1760, (2000).

    Article  CAS  PubMed  Google Scholar 

  13. Wang, J., Polsky, R., Merkoci, A., Turner, K. L., “Electroactive beads" for ultrasensitive DNA detection. Langmuir, 19(4), 989–991, (2003).

    Article  CAS  Google Scholar 

  14. Saghatelian, A., Guckian, K. M., Thayer, D. A., Ghadiri, M. R., DNA Detection and signal amplification via an engineered allosteric enzyme. Journal of the American Chemical Society, 125(2), 344–345, (2003).

    Article  CAS  PubMed  Google Scholar 

  15. Swager, T. M., The molecular wire approach to sensory signal amplification. Accounts of Chemical Research, 31(5), 201–207, (1998).

    Article  CAS  Google Scholar 

  16. KorriYoussoufi, H., Garnier, F., Srivastava, P., Godillot, P., Yassar, A., Toward bioelectronics: Specific DNA recognition based on an oligonucleotide-functionalized polypyrrole. Journal of the American Chemical Society, 119(31), 7388–7389, (1997).

    Article  CAS  Google Scholar 

  17. Ho, H. A., Boissinot, M., Bergeron, M. G., Corbeil, G., Dore, K., Boudreau, D., Leclerc, M., Colorimetric and fluorometric detection of nucleic acids using cationic polythiophene derivatives. Angewandte Chemie-International Edition, 41(9), 1548–1551, (2002).

    Article  CAS  Google Scholar 

  18. Ho, H. A., Najari, A., Leclerc, M., Optical detection of DNA and proteins with cationic polythiophenes. Accounts of Chemical Research, 41(2), 168–178, (2008).

    Article  CAS  PubMed  Google Scholar 

  19. Dore, K., Dubus, S., Ho, H. A., Levesque, I., Brunette, M., Corbeil, G., Boissinot, M., Boivin, G., Bergeron, M. G., Boudreau, D., Leclerc, M., Fluorescent polymeric transducer for the rapid, simple, and specific detection of nucleic acids at the zeptomole level. Journal of the American Chemical Society, 126(13), 4240–4244, (2004).

    Article  CAS  PubMed  Google Scholar 

  20. Nilsson, K. P. R., Inganas, O., Chip and solution detection of DNA hybridization using a luminescent zwitterionic polythiophene derivative. Nature Materials, 2(6), 419–U10, (2003).

    Google Scholar 

  21. Ho, H. A., Dore, K., Boissinot, M., Bergeron, M. G., Tanguay, R. M., Boudreau, D., Leclerc, M., Direct molecular detection of nucleic acids by fluorescence signal amplification. Journal of the American Chemical Society, 127(36), 12673–12676, (2005).

    Article  CAS  PubMed  Google Scholar 

  22. Klimov, A. I., Rocha, E., Hayden, F. G., Shult, P. A., Roumillat, L. F., Cox, N. J., Prolonged shedding of amantadine-resistant influenza—a viruses by immunodeficient patients – detection by polymerase chain-reaction – restriction analysis. Journal of Infectious Diseases, 172(5), 1352–1355, (1995).

    CAS  PubMed  Google Scholar 

  23. Karlsson, K. F., Asberg, P., Nilsson, K. P. R., Inganas, O., Interactions between a zwitterionic polythiophene derivative and oligonucleotides as resolved by fluorescence resonance energy transfer. Chemistry of Materials, 17(16), 4204–4211, (2005).

    Article  CAS  Google Scholar 

  24. Chen, L. H., McBranch, D. W., Wang, H. L., Helgeson, R., Wudl, F., Whitten, D. G., Highly sensitive biological and chemical sensors based on reversible fluorescence quenching in a conjugated polymer. Proceedings of the National Academy of Sciences of the United States of America, 96(22), 12287–12292, (1999).

    Article  CAS  PubMed  Google Scholar 

  25. Herland, A., Inganas, O., Conjugated polymers as optical probes for protein interactions and protein conformations. Macromolecular Rapid Communications, 28(17), 1703–1713, (2007).

    Article  CAS  Google Scholar 

  26. Kushon, S. A., Ley, K. D., Bradford, K., Jones, R. M., McBranch, D., Whitten, D., Detection of DNA hybridization via fluorescent polymer superquenching. Langmuir, 18(20), 7245–7249, (2002).

    Article  CAS  Google Scholar 

  27. Jones, R. M., Bergstedt, T. S., McBranch, D. W., Whitten, D. G., Tuning of superquenching in layered and mixed fluorescent polyelectrolytes. Journal of the American Chemical Society, 123(27), 6726–6727, (2001).

    Article  CAS  PubMed  Google Scholar 

  28. Kumaraswamy, S., Bergstedt, T., Shi, X. B., Rininsland, F., Kushon, S., Xia, W. S., Ley, K., Achyuthan, K., McBranch, D., Whitten, D., Fluorescent-conjugated polymer superquenching facilitates highly sensitive detection of proteases. Proceedings of the National Academy of Sciences of the United States of America, 101(20), 7511–7515, (2004).

    Article  CAS  PubMed  Google Scholar 

  29. Lakowicz, J. R., Principles of Fluorescence Spectroscopy. 2nd ed., Kluwer Academic/Plenum: New York, p xxiii, 698, (1999).

    Google Scholar 

  30. Tyagi, S., Kramer, F. R., Molecular beacons: probes that fluoresce upon hybridization. Nature biotechnology, 14(3), 303–308, (1996).

    Article  CAS  PubMed  Google Scholar 

  31. Xu, Q. H., Gaylord, B. S., Wang, S., Bazan, G. C., Moses, D., Heeger, A. J., Time-resolved energy transfer in DNA sequence detection using water-soluble conjugated polymers: The role of electrostatic and hydrophobic interactions. Proceedings of the National Academy of Sciences of the United States of America, 101(32), 11634–11639, (2004).

    Article  CAS  PubMed  Google Scholar 

  32. Wang, S., Gaylord, B. S., Bazan, G. C., Fluorescein provides a resonance gate for FRET from conjugated polymers to DNA intercalated dyes. Journal of the American Chemical Society, 126(17), 5446–5451, (2004).

    Article  CAS  PubMed  Google Scholar 

  33. Xu, Q. H., Wang, S., Korystov, D., Mikhailovsky, A., Bazan, G. C., Moses, D., Heeger, A. J., The fluorescence resonance energy transfer (FRET) gate: A time-resolved study. Proceedings of the National Academy of Sciences of the United States of America, 102(3), 530–535, (2005).

    Article  CAS  PubMed  Google Scholar 

  34. St-Louis, M., Tanguay, R. M., Mutations in the fumarylacetoacetate hydrolase gene causing hereditary tyrosinemia type I: Overview. Human Mutation, 9(4), 291–299, (1997).

    Article  CAS  PubMed  Google Scholar 

  35. Dore, K., Leclerc, M., Boudreau, D., Investigation of a fluorescence signal amplification mechanism used for the direct molecular detection of nucleic acids. Journal of Fluorescence, 16(2), 259–265, (2006).

    Article  CAS  PubMed  Google Scholar 

  36. Lee, K., Povlich, L. K., Kim, J., Label-free and self-signal amplifying molecular DNA sensors based on bioconjugated polyelectrolytes. Advanced Functional Materials, 17(14), 2580–2587, (2007).

    Article  CAS  Google Scholar 

  37. Zhou, X. C., Zhou, J. Z., Improving the signal sensitivity and photostability of DNA hybridizations on microarrays by using dye-doped core-shell silica nanoparticles. Analytical Chemistry, 76(18), 5302–5312, (2004).

    Article  CAS  PubMed  Google Scholar 

  38. Yan, J. L., Estevez, M. C., Smith, J. E., Wang, K. M., He, X. X., Wang, L., Tan, W. H., Dye-doped nanoparticles for bioanalysis. Nano Today, 2(3), 44–50, (2007).

    Article  Google Scholar 

  39. Lian, W., Litherland, S. A., Badrane, H., Tan, W. H., Wu, D. H., Baker, H. V., Gulig, P. A., Lim, D. V., Jin, S. G., Ultrasensitive detection of biomolecules with fluorescent dye-doped nanoparticles. Analytical Biochemistry, 334(1), 135–144, (2004).

    Article  CAS  PubMed  Google Scholar 

  40. Bagwe, R. P., Zhao, X. J., Tan, W. H., Bioconjugated luminescent nanoparticles for biological applications. Journal of Dispersion Science and Technology, 24(3–4), 453–464, (2003).

    Article  CAS  Google Scholar 

  41. Soto, C. M., Blum, A. S., Vora, G. J., Lebedev, N., Meador, C. E., Won, A. P., Chatterji, A., Johnson, J. E., Ratna, B. R., Fluorescent signal amplification of carbocyanine dyes using engineered viral nanoparticles. Journal of the American Chemical Society, 128(15), 5184–5189, (2006).

    Article  CAS  PubMed  Google Scholar 

  42. Dalgarno, S. J., Tucker, S. A., Bassil, D. B., Atwood, J. L., Fluorescent guest molecules report ordered inner phase of host capsules in solution. Science, 309(5743), 2037–2039, (2005).

    Article  CAS  PubMed  Google Scholar 

  43. Chen, L. H., Xu, S., McBranch, D., Whitten, D., Tuning the properties of conjugated polyelectrolytes through surfactant complexation. Journal of the American Chemical Society, 122(38), 9302–9303, (2000).

    Article  CAS  Google Scholar 

  44. Sautter, A., Kaletas, B. K., Schmid, D. G., Dobrawa, R., Zimine, M., Jung, G., van Stokkum, I. H. M., De Cola, L., Williams, R. M., Wurthner, F., Ultrafast energy-electron transfer cascade in a multichromophoric light-harvesting molecular square. Journal of the American Chemical Society, 127(18), 6719–6729, (2005).

    Article  CAS  PubMed  Google Scholar 

  45. Vallotton, P., Tairi, A. P., Wohland, T., Friedrich-Benet, K., Pick, H., Hovius, R., Vogel, H., Mapping the antagonist binding site of the serotonin type 3 receptor by fluorescence resonance energy transfer. Biochemistry, 40(41), 12237–12242, (2001).

    Article  CAS  PubMed  Google Scholar 

  46. Gaylord, B. S., Wang, S. J., Heeger, A. J., Bazan, G. C., Water-soluble conjugated oligomers: Effect of chain length and aggregation on photoluminescence-quenching efficiencies. Journal of the American Chemical Society, 123(26), 6417–6418, (2001).

    Article  CAS  PubMed  Google Scholar 

  47. Lavigne, J. J., Broughton, D. L., Wilson, J. N., Erdogan, B., Bunz, U. H. F., “Surfactochromic" conjugated polymers: Surfactant effects on sugar-substituted PPEs. Macromolecules, 36(20), 7409–7412, (2003).

    Article  CAS  Google Scholar 

  48. Kwakye, S., Baeumner, A., A microfluidic biosensor based on nucleic acid sequence recognition. Analytical and Bioanalytical Chemistry, 376(7), 1062–1068, (2003).

    Article  CAS  PubMed  Google Scholar 

  49. Dore, K., Neagu-Plesu, R., Leclerc, M., Boudreau, D., Ritcey, A. M., Characterization of superlighting polymer-DNA aggregates: A fluorescence and light scattering study. Langmuir, 23(1), 258–264, (2007).

    Article  CAS  PubMed  Google Scholar 

  50. Myers, D., Surfaces, Interfaces, and Colloids: Principles and Applications. Wiley-VCH, New York, 433 pp (1991).

    Google Scholar 

  51. Ishizu, K., Toyoda, K., Furukawa, T., Sogabe, A., Electrostatic interaction of anionic/nonionic polyelectrolyte prototype copolymer brushes with cationic linear polyelectrolyte. Macromolecules, 37(10), 3954–3957, (2004).

    Article  CAS  Google Scholar 

  52. Appell, J., Porte, G., An investigation on the micellar shape using angular dissymmetry of light scattered by solutions of cetylpyridinium bromide. Journal of Colloid and Interface Science, 81(1), 85–90, (1981).

    Article  CAS  Google Scholar 

  53. Fuetterer, T., Nordskog, A., Hellweg, T., Findenegg, G. H., Foerster, S., Dewhurst, C. D., Characterization of polybutadiene-poly(ethyleneoxide) aggregates in aqueous solution: A light-scattering and small-angle neutron-scattering study. Physical Review E, 70(4), (2004).

    Google Scholar 

  54. Hiemenz, P. C., Rajagopalan, R. (Editors), Principles of Colloid and Surface Chemistry, 3rd ed., Revised and Expanded. Taylor & Francis, New York, p. 688 , (1997).

    Google Scholar 

  55. Park, L. C., Maruyama, T., Goto, M., DNA hybridization in reverse micelles and its application to mutation detection. Analyst, 128(2), 161–165, (2003).

    Article  CAS  PubMed  Google Scholar 

  56. Peng, Q., Xie, M. Q., Huang, Y., Lu, Z. Y., Cao, Y., Novel supramolecular polymers based on zinc-salen chromophores for efficient light-emitting diodes. Macromolecular Chemistry and Physics, 206(23), 2373–2380, (2005).

    Article  CAS  Google Scholar 

  57. Drolet, N., Morin, J. F., Leclerc, N., Wakim, S., Tao, Y., Leclerc, M., 2,7-carbazolenevinylene-based oligomer thin-film transistors: High mobility through structural ordering. Advanced Functional Materials, 15(10), 1671–1682 (2005).

    Article  CAS  Google Scholar 

  58. Scholes, G. D., Long-range resonance energy transfer in molecular systems. Annual Review of Physical Chemistry, 54, 57–87, (2003).

    Article  CAS  PubMed  Google Scholar 

  59. Zhang, J., Lakowicz, J. R., A model for DNA detection by metal-enhanced fluorescence from immobilized silver nanoparticles on solid substrate. Journal of Physical Chemistry B, 110(5), 2387–2392, (2006).

    Article  CAS  Google Scholar 

  60. Lessard-Viger, M., Saiveng Live, L., Dupont-Therrien, O., Boudreau, D., Reduction of self-quenching in fluorescent silica-coated nanoparticles. Plasmonics, 3, 33–40, (2008).

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Centre de Recherche Université Laval Robert-Giffard (CRULRG), Unité de neurobiologie cellulaire, G1J2G3, 2601 Ch. Canardière, Québec, QC, Canada

    Kim Doré

  2. Centre de recherche sur la science et l’ingénierie des matériaux (CERSIM), and Département de chimie, Université Laval, G1K 7P4, Québec, QC, Canada

    Mario Leclerc

  3. Département de chimie, Université Laval, G1K 7P4, Québec, QC, Canada

    Denis Boudreau

Authors
  1. Kim Doré
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mario Leclerc
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Denis Boudreau
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Doré, K., Leclerc, M., Boudreau, D. (2009). Fluorescence Signal Amplification for Ultrasensitive DNA Detection. In: Reviews in Fluorescence 2007. Reviews in Fluorescence, vol 2007. Springer, New York, NY. https://doi.org/10.1007/978-0-387-88722-7_9

Download citation

Publish with us

Policies and ethics

Search

Navigation