A molecular ruler based on plasmon coupling of single gold and silver nanoparticles


Förster Resonance Energy Transfer has served as a molecular ruler that reports conformational changes and intramolecular distances of single biomolecules1,2,3,4. However, such rulers suffer from low and fluctuating signal intensities, limited observation time due to photobleaching, and an upper distance limit of 10 nm. Noble metal nanoparticles have plasmon resonances in the visible range and do not blink or bleach. They have been employed as alternative probes to overcome the limitations of organic fluorophores5,6, and the coupling of plasmons in nearby particles has been exploited to detect particle aggregation by a distinct color change in bulk experiments7,8,9. Here we demonstrate that plasmon coupling can be used to monitor distances between single pairs of gold and silver nanoparticles. We followed the directed assembly of gold and silver nanoparticle dimers in real time and studied the kinetics of single DNA hybridization events. These 'plasmon rulers' allowed us to continuously monitor separations of up to 70 nm for >3,000 s.

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Figure 1: Color effect on directed assembly of DNA-functionalized gold and silver nanoparticles.
Figure 2: Effect of buffer exchange.
Figure 3: Spectral shift upon DNA hybridization.


  1. 1

    Weiss, S. Fluorescence spectroscopy of single biomolecules. Science 283, 1676–1683 (1999).

  2. 2

    Zhuang, X. et al. A single-molecule study of RNA catalysis and folding. Science 288, 2048–2051 (2000).

  3. 3

    Yildiz, A. et al. Myosin V walks hand-over-hand: Single fluorophore imaging with 1.5-nm localization. Science 300, 2061–2065 (2003).

  4. 4

    Blanchard, S.C., Kim, H.D., Gonzalez, R.L., Puglisi, J.D. & Chu, S. tRNA dynamics on the ribosome during translation. Proc. Natl. Acad. Sci. USA 101, 12893–12898 (2004).

  5. 5

    Yguerabide, J. & Yguerabide, E.E. Light-scattering submicroscopic particles as highly fluorescent analogs and their use as tracer labels in clinical and biological applications - II. Experimental characterization. Anal. Biochem. 262, 157–176 (1998).

  6. 6

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

  7. 7

    Storhoff, J.J., Lucas, A.D., Garimella, V., Bao, Y.P. & Muller, U.R. Homogeneous detection of unamplified genomic DNA sequences based on colorimetric scatter of gold nanoparticle probes. Nat. Biotechnol. 22, 883–887 (2004).

  8. 8

    Li, H. & Rothberg, L. Colorimetric detection of DNA sequences based on electrostatic interactions with unmodified gold nanoparticles. Proc. Natl. Acad. Sci. USA 101, 14036–14039 (2004).

  9. 9

    Dragnea, B., Chen, C., Kwak, E.S., Stein, B. & Kao, C.C. Gold nanoparticles as spectroscopic enhancers for in vitro studies on single viruses. J. Am. Chem. Soc. 125, 6374–6375 (2003).

  10. 10

    Siedentopf, H. & Zsigmondy, R. Über Sichtbarmachung und Größenbestimmung ultramikroskopischer Teilchen, mit besonderer Anwendung auf Goldrubingläser. Annalen der Physik 10, 1–39 (1903).

  11. 11

    Mie, G. Beiträge zur Optik trüber Medien speziell kolloidaler Metallösungen. Annalen der Physik 25, 377–445 (1908).

  12. 12

    Moskovits, M. Surface-Enhanced Spectroscopy. Rev. Mod. Phys. 57, 783–826 (1985).

  13. 13

    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, 1078–1081 (1997).

  14. 14

    McFarland, A.D. & Van Duyne, R.P. Single silver nanoparticles as real-time optical sensors with zeptomole sensitivity. Nano Lett. 3, 1057–1062 (2003).

  15. 15

    Raschke, G. et al. Biomolecular recognition based on single gold nanoparticle light scattering. Nano Lett. 3, 935–938 (2003).

  16. 16

    Kreibig, U. & Vollmer, M. Optical Properties of Metal Clusters Vol. 25 (Springer-Verlag, Berlin, 1995).

  17. 17

    Wei, Q.H., Su, K.H., Durant, S. & Zhang, X. Plasmon resonance of finite one-dimensional Au nanoparticle chains. Nano Lett. 4, 1067–1071 (2004).

  18. 18

    Su, K.H. et al. Interparticle coupling effects on plasmon resonances of nanogold particles. Nano Lett. 3, 1087–1090 (2003).

  19. 19

    Rechberger, W. et al. Optical properties of two interacting gold nanoparticles. Opt. Commun. 220, 137–141 (2003).

  20. 20

    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).

  21. 21

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

  22. 22

    Smith, S.B., Cui, Y.J. & Bustamante, C. Overstretching B-DNA: The elastic response of individual double-stranded and single-stranded DNA molecules. Science 271, 795–799 (1996).

  23. 23

    Singh-Zocchi, M., Dixit, S., Ivanov, V. & Zocchi, G. Single-molecule detection of DNA hybridization. Proc. Natl. Acad. Sci. USA 100, 7605–7610 (2003).

  24. 24

    Hagan, M.F. & Chakraborty, A.K. Hybridization dynamics of surface immobilized DNA. J. Chem. Phys. 120, 4958–4968 (2004).

  25. 25

    Sönnichsen, C. et al. Drastic reduction of plasmon damping in gold nanorods. Phys. Rev. Lett. 88, 077402 (2002).

  26. 26

    Park, S.J., Lazarides, A.A., Storhoff, J.J., Pesce, L. & Mirkin, C.A. The structural characterization of oligonucleotide-modified gold nanoparticle networks formed by DNA hybridization. J. Phys. Chem. B 108, 12375–12380 (2004).

  27. 27

    Tinoco, I. Force as a useful variable in reactions: Unfolding RNA. Annu. Rev. Biophys. Biomol. Struct. 33, 363–385 (2004).

  28. 28

    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).

  29. 29

    Itoh, H. et al. Mechanically driven ATP synthesis by F-1-ATPase. Nature 427, 465–468 (2004).

  30. 30

    Kanaras, A.G., Wang, Z.X., Bates, A.D., Cosstick, R. & Brust, M. Towards multistep nanostructure synthesis: Programmed enzymatic self-assembly of DNA/gold systems. Angew. Chem. Int. Ed. 42, 191–194 (2003).

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We acknowledge financial support through the Alexander von Humboldt Foundation (C.S.), the Otto A. Wipprecht Foundation (B.M.R.), Deutsche Forschungsgemeinschaft (B.M.R.), US Department of Energy contracts DE-AC03-76SF00098 and W-7405-ENG-36.

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Correspondence to Jan Liphardt or A Paul Alivisatos.

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The authors declare no competing financial interests.

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Sönnichsen, C., Reinhard, B., Liphardt, J. et al. A molecular ruler based on plasmon coupling of single gold and silver nanoparticles. Nat Biotechnol 23, 741–745 (2005). https://doi.org/10.1038/nbt1100

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