An ideal surface-enhanced Raman scattering (SERS) nanostructure for sensing and imaging applications should induce a high signal enhancement, generate a reproducible and uniform response, and should be easy to synthesize. Many SERS-active nanostructures have been investigated, but they suffer from poor reproducibility of the SERS-active sites, and the wide distribution of their enhancement factor values results in an unquantifiable SERS signal. Here, we show that DNA on gold nanoparticles facilitates the formation of well-defined gold nanobridged nanogap particles (Au-NNP) that generate a highly stable and reproducible SERS signal. The uniform and hollow gap (∼1 nm) between the gold core and gold shell can be precisely loaded with a quantifiable amount of Raman dyes. SERS signals generated by Au-NNPs showed a linear dependence on probe concentration (R2 > 0.98) and were sensitive down to 10 fM concentrations. Single-particle nano-Raman mapping analysis revealed that >90% of Au-NNPs had enhancement factors greater than 1.0 × 108, which is sufficient for single-molecule detection, and the values were narrowly distributed between 1.0 × 108 and 5.0 × 109.
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Cao, Y. C., Jin, R. & Mirkin, C. A. Nanoparticles with Raman spectroscopic fingerprints for DNA and RNA detection. Science 297, 1536–1540 (2002).
Bingham, J. M., Willets, K. A., Shah, N. C., Andrews, D. Q. & Van Duyne, R. P. Localized surface plasmon resonance imaging: simultaneous single nanoparticle spectroscopy and diffusional dynamics. J. Phys. Chem. C 113, 16839–16842 (2009).
Medley, C. D., Smith, J. E., Tang, Z., Wu, Y. & Tan, W. Gold nanoparticle-based colorimetric assay for the direct detection of cancerous cells. Anal. Chem. 80, 1067–1072 (2008).
Atwater, H. A. & Polman, A. Plasmonics for improved photovoltaic devices. Nature Mater. 9, 205–213 (2010).
Park, H-G. et al. A wavelength-selective photonic-crystal waveguide coupled to a nanowire light source. Nature Photon. 2, 622–626 (2008).
Sonnichsen, C., Reinhard, B. M., Liphardt, J. & Alivisatos, A. P. A molecular ruler based on plasmon coupling of single gold and silver nanoparticles. Nature Biotechnol. 6, 741–745 (2005).
Qian, X-M. & Nie, S. M. Single-molecule and single-nanoparticle SERS: from fundamental mechanisms to biomedical applications. Chem. Soc. Rev. 37, 912–920 (2008).
Jiang, J., Bosnick, K., Maillard, M. & Brus, L. Single molecule Raman spectroscopy at the junctions of large Ag nanocrystals. J. Phys. Chem. B 107, 9964–9972 (2003).
Li, W., Camargo, P. H. C., Lu, X. & Xia, Y. Dimers of silver nanosheres: facile synthesis and their use as hot spots for surface-enhanced Raman scattering. Nano Lett. 9, 485–490 (2009).
Graham, D., Thompson, D. G., Smith, W. E. & Faulds, K. Control of enhanced Raman scattering using a DNA-based assembly process of dye-coded nanoparticles. Nature Nanotech. 3, 548–551 (2008).
Lee, S. J., Morrill, A. R. & Moskovits, M. Hot spots in silver nanowire bundles for surface-enhanced Raman spectroscopy. J. Am. Chem. Soc. 128, 2200–2201 (2006).
Tripp, R. A., Dluhy, R. A. & Zhao, Y. Novel nanostructures for SERS biosensing. Nanotoday 3, 31–37 (2008).
Ward, D. R. et al. Electromigrated nanoscale gaps for surface-enhanced Raman spectroscopy. Nano Lett. 7, 1396–1400 (2007).
Zuloaga, J., Prodan, E., Nordlander, P. Quantum description of the plasmon resonances of a nanoparticle dimer. Nano Lett. 9, 887–891 (2009).
Etchegoin, P. G. & Le Ru, E. C. A perspective on single molecule SERS: current status and future challenges. Phys. Chem. Chem. Phys. 10, 6079–6089 (2008).
Park, W-H. & Kim, Z. H. Charge transfer enhancement in the SERS of a single molecule. Nano Lett. 10, 4040–4048 (2010).
Fang, Y., Seong, N-H. & Dlott, D. D. Measurement of the distribution of site enhancements in surface-enhanced Raman scattering. Science 321, 388–392 (2008).
Im, H., Bantz, K. C., Lindquist, N. C., Haynes, C. L. & Oh, S-H. Vertically oriented sub-10-nm plasmonic nanogap arrays. Nano Lett. 10, 2231–2236 (2010).
Kubo, W. & Fujikawa, S. Au double nanopillars with nanogap for plasmonic sensor. Nano Lett. 11, 8–15 (2011).
Jesse, T., Pavaskar, P., Echternach, P. M., Muller, R. E. & Cronin, S. B. Plasmonic nanoparticle arrays with nanometer separation for high-performance SERS substrates. Nano Lett. 10, 2749–2754 (2010).
Qin, L. et al. Designing, fabricating, and imaging Raman hot spots. Proc. Natl Acad. Sci. USA 103, 13300–13303 (2006).
Qian, X et al. In vivo tumor targeting and spectroscopic detection with surface-enhanced Raman nanoparticle tags. Nature Biotechnol. 26, 83–90 (2008).
Zavaleta, C. L. et al. Multiplexed imaging of surface-enhanced Raman scattering nanotags in living mice using noninvasive Raman spectroscopy. Proc. Natl Acad. Sci. USA 106, 13511–13516 (2009).
Lim, D-K., Jeon, K-S., Kim, H. M., Nam, J-M. & Suh, Y. D. Nanogap-engineerable Raman-active nanodumbbells for single-molecule detection. Nature Mater. 9, 60–67 (2010).
Kneipp, J., Kneipp, H., McLaughlin, M., Brown, D. & Kneipp, K. In vivo molecular probing of cellular compartments with gold nanoparticles and nanoaggregates. Nano Lett. 6, 2225–2231 (2006).
Brown, K. R. & Natan, M. J. Hydroxylamine seeding of colloidal Au nanoparticles in solution and on surfaces. Langmuir 14, 726–728 (1998).
Ma, Z. & Sui, S. Naked-eye sensitive detection of immunoglubulin G by enlargement of Au nanoparticles in vitro. Angew Chem. Int. Ed. 41, 2176–2179 (2002).
Wustholz, K. L. et al. Structure–activity relationships in gold nanoparticle dimers and trimers for surface-enhanced Raman spectroscopy. J. Am. Chem. Soc. 132, 10903–10910 (2010).
Anil, K., Kodali, A. K., Llorad, X. & Bhargava, R. Optimally designed nanolayered metal–dielectric particles as probes for massively multiplexed and ultrasensitive molecular assays. Proc. Natl Acad. Sci. USA 107, 13620–13625 (2009).
Sonnefraud, Y. et al. Experimental realization of subradiant, superradiant, and Fano resonance in ring/disk plasmonic nanocavities. ACS Nano 4, 1664–1670 (2010).
Zhang, P. & Guo, Y. Surface-enhanced Raman scattering inside metal nanoshells. J. Am. Chem. Soc. 131, 3808–3809 (2009).
Stokes, R. J. et al. Quantitative enhanced Raman scattering of labeled DNA from gold and silver nanoparticles. Small 3, 1593–1601 (2007).
Prodan, E., Radloff, C., Halas, N. J. & Nordlander, P. A hybridization model for the plasmon response of complex nanostructures. Science 302, 419–422 (2003).
Bardhan, R. et al. Nanosphere-in-a-nanoshell: a simple nanomatryushka. J. Phys. Chem. C 114, 7378–7383 (2010).
Shen, A. et al. Triplex Au–Ag–C core–shell nanoparticles as a novel Raman label. Adv. Funct. Mater. 20, 969–975 (2010).
Küstner, B. et al. SERS labels for red laser excitation: silica-encapsulated SAMs on tunable gold/silver nanoshells. Angew Chem. Int. Ed. 48, 1950–1953 (2009).
Zhang, Z. et al. Manipulating nanoscale light fields with the asymmetric bowtie nano-colorsorter. Nano Lett. 9, 4505–4509 (2009).
Faulds, K., Smith, W. E. & Graham, D. Evaluation of surface-enhanced resonance Raman scattering for quantitative DNA analysis. Anal. Chem. 76, 412–417 (2004).
Schlücker, S. SERS microscopy: nanoparticle probes and biomedical applications. ChemPhysChem 10, 1344–1354 (2009).
Murphy, C. J. et al. Gold nanoparticles in biology: beyond toxicity to cellular imaging. Acc. Chem. Res. 41, 1721–1730 (2008).
Hurst, S. J., Lytton-Jean, A. K. R. & Mirkin, C. A. Maximizing DNA loading on a range of gold nanoparticle sizes. Anal. Chem. 78, 8313–8318 (2006).
Y.D.S. was supported by KRICT (KK-0904-02, SI-1110), the Nano R&D Program (No. 2009-0082861), the Pioneer Research Center Program of NRF (No. 2009-0081511), the Development of Advanced Scientific Analysis Instrumentation Project of KRISS by MEST and the Eco-technopia 21 Project by KME. J-M.N. was supported by the 21C Frontier Functional Proteomics Project (FPR08-A2-150) and the Nano R&D program (2008-02890) through the National Research Foundation of Korea (NRF) from the Ministry of Education, Science and Technology. The authors would also like to acknowledge financial support from the Industrial Core Technology Development Program of the Ministry of Knowledge Economy (nos 10033183 and 10037397) and the KRICT OASIS Project from the Korea Research Institute of Chemical Technology. D-K.L. acknowledges financial support from the CJ Pharmaceutical Research Institute. K-S.J. acknowledges support by the Public Welfare & Safety Research Program through NRF funded by MEST (2010-0020-795).
The authors declare no competing financial interests.
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Lim, DK., Jeon, KS., Hwang, JH. et al. Highly uniform and reproducible surface-enhanced Raman scattering from DNA-tailorable nanoparticles with 1-nm interior gap. Nature Nanotech 6, 452–460 (2011). https://doi.org/10.1038/nnano.2011.79
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