Control of enhanced Raman scattering using a DNA-based assembly process of dye-coded nanoparticles

Article metrics


Enhanced Raman scattering from metal surfaces has been investigated for over 30 years1. Silver surfaces are known to produce a large effect, and this can be maximized by producing a roughened surface, which can be achieved by the aggregation of silver nanoparticles2,3,4. However, an approach to control this aggregation, in particular through the interaction of biological molecules such as DNA, has not been reported. Here we show the selective turning on of the surface enhanced resonance Raman scattering5 effect on dye-coded, DNA-functionalized, silver nanoparticles through a target-dependent, sequence-specific DNA hybridization assembly that exploits the electromagnetic enhancement mechanism for the scattering. Dye-coded nanoparticles that do not undergo hybridization experience no enhancement and hence do not give surface enhanced resonance Raman scattering. This is due to the massive difference in enhancement from nanoparticle assemblies compared with individual nanoparticles. The electromagnetic enhancement is the dominant effect and, coupled with an understanding of the surface chemistry, allows surface enhanced resonance Raman scattering nanosensors to be designed based on a natural biological recognition process.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Schematic representation of the synthesis of Raman dye-functionalized DNA silver nanoparticle conjugates.
Figure 2: UV-vis analysis of dye-coded DNA-functionalized silver nanoparticles.
Figure 3: SERRS spectra of DNA-functionalized Raman dye-coded silver nanoparticles.
Figure 4: Selective enhancement of specific Raman signals through DNA hybridization.


  1. 1

    Fleishman, M., Hendra, P. J. & McQuillan, A. J. Raman spectra of pyridine adsorbed at a silver electrode. Chem. Phys. Lett. 26, 163–166 (1974).

  2. 2

    Munro, C. H., Smith, W. E., Garner, M., Clarkson, J. & White, P. C. Characterization of the surface of a citrate-reduced colloid optimized for use as a substrate for surface-enhanced resonance Raman scattering. Langmuir 11, 3712–3720 (1995).

  3. 3

    Nie, S. & Emory, S. R. Probing single molecules and single nanoparticles by surface-enhanced Raman scattering. Science 275, 1102–1106 (1997).

  4. 4

    Faulds, K., Littleford, R. E., Graham, D., Dent, G. & Smith, W. E. A comparison of surface enhanced resonance Raman scattering (SERRS) from unaggregated and aggregated nanoparticles. Anal. Chem. 76, 592–598 (2004).

  5. 5

    Stacy, A. M. & Van Duyne, R. P. Surface enhanced Raman and resonance Raman spectroscopy in a non-aqueous electrochemical environment: Tris(2,2′-bipyridine)ruthenium(II) adsorbed on silver from acetonitrile. Chem. Phys. Lett. 102, 365 (1983).

  6. 6

    Stokes, R. J. et al. Quantitative enhanced Raman scattering of labeled DNA from gold and silver nanoparticles. Small 3, 1593–1604 (2007).

  7. 7

    Jeanmarie, D. L. & Van Duyne, R. P. Surface Raman spectroelectrochemistry, part 1: Heterocyclic, aromatic, and aliphatic amines adsorbed on the anodized silver electrode. J. Electroanal. Chem. 84, 1–20 (1977).

  8. 8

    Kneipp, K., Kneipp, H., Itzkan, I., Dasari, R. R. & Feld, M. S. Ultrasensitive chemical analysis by Raman spectroscopy. Chem. Rev. 99, 2957–2976 (1999).

  9. 9

    Cunningham, D. et al. Practical control of SERRS enhancement. Faraday Discuss. 132, 135–145 (2006).

  10. 10

    McHugh, C. J., Docherty, F. T., Graham, D. & Smith, W. E. SERRS dyes. Part 2. Synthesis and evaluation of dyes for multiple labelling for SERRS. Analyst 129, 69–72 (2004).

  11. 11

    Michaels, A. M., Jiang, J. & Brus, L. Ag nanocrystal junctions as the site for surface-enhanced Raman scattering of single Rhodamine 6G molecules. J. Phys. Chem. B 104, 11965–11971 (2000).

  12. 12

    Faulds, K., Smith, W. E., Graham, D. & Lacey, R. J. Assessment of silver and gold substrates for the detection of amphetamine sulfate by surface enhanced Raman scattering (SERS). Analyst 127, 282–286 (2002).

  13. 13

    Alivastos, A. P. et al. Organization of ‘nanocrystal molecules’ using DNA. Nature 382, 609–611 (1996).

  14. 14

    Huang, C. C., Huang, Y. F., Cao, Z., Tan, W. & Chang, H. T. Aptamer-modified gold nanoparticles for colorimetric determination of platelet-derived growth factors and their receptors Anal. Chem. 77, 5735–5741 (2005).

  15. 15

    Mirkin, C. A., Letsinger, R. L., Mucic, R. C. & Storhoff, J. J. A DNA-based method for rationally assembling nanoparticles into macroscopic materials. Nature 382, 607–609 (1996).

  16. 16

    Braun, G. et al. Surface-enhanced Raman spectroscopy for DNA detection by nanoparticle assembly onto smooth metal films. J. Am. Chem. Soc. 129, 6378–6379 (2007).

  17. 17

    Cao, Y. C., Jin, R. & Mirkin, C. A. Nanoparticles with Raman spectroscopic fingerprints for DNA and RNA detection. Science 297, 1536–1540 (2002).

  18. 18

    McAnally, G. et al. SERRS dyes. Part I. Synthesis of benzotriazole monoazo dyes as model analytes for surface enhanced resonance Raman scattering. Analyst 127, 838–841 (2002).

  19. 19

    Storhoff, J. J., Elghanian, R., Mucic, R. C., Mirkin, C. A. & Letsinger, R. L. One-pot colorimetric differentiation of polynucleotides with single base imperfections using gold nanoparticle probes. J. Am. Chem. Soc. 120, 1959–1964 (1998).

  20. 20

    Demers, L. M. et al. A fluorescence-based method for determining the surface coverage and hybridization efficiency of thiol-capped oligonucleotides bound to gold thin films and nanoparticles. Anal. Chem. 72, 5535–5541 (2000).

Download references


The authors wish to thank the Analytical Trust Fund of the Royal Society of Chemistry for the award of the Analytical Grand Prix to D.G.

Author information

All authors discussed the results and commented on the manuscript. D.G.T. performed all the experiments.

Correspondence to Duncan Graham.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Further reading