Single-molecule detection with nanodumbbells

(Nanowerk Spotlight) Surface-enhanced Raman scattering (SERS) offers enormous potential for chemical sensing, even though the large nonlinearity of the effect makes reproducible sensing difficult. SERS relies upon a fundamental phenomenon in physics called the Raman effect – the change in the frequency of monochromatic light, such as a laser, when it passes through a substance.
Properly harnessed, Raman scattering can identify specific molecules by detecting their characteristic spectral fingerprints. A novel DNA-based assembly technique developed by scientists in South Korea (Jwa-Min Nam from Seoul National University and Yung Doug Suh from Korea Research Institute of Chemical Technology) now offers a means of precise engineering of gap distances in nanoparticle dumbbells for a robust surface-enhanced Raman sensing of DNA and RNA molecules.
"We have demonstrated a high-yield synthetic strategy to obtain gap-tailorable gold-silver core-shell nanodumbbells (GSNDs) and subsequent hot SERS-based single-molecule detection with structurally reproducible dimetric nanostructures," Jwa-Min Nam, an assistant professor in the Department of Chemistry at Seoul National University tells Nanowerk. "We believe that our method and findings could lead to a high cross section-based SERS sensing and single DNA detection in a highly reproducible fashion. Since our DNA-based nanostructure fabrication synthetic strategy is pretty flexible and many other nanostructures could be generated for various other applications, this work could be a breakthrough for the field."
Reporting their findings in the December 13, 2009 online edition of Nature Materials ("Nanogap-engineerable Raman-active nanodumbbells for single-molecule detection") a team from Seoul National University and Korea Research Institute of Chemical Technology showed that these Raman-active GSNDs have single-molecule sensitivity with high structural reproducibility. The authors of this paper include Dong-Kwon Lim, Ki-Seok Jeon and Hyung Min Kim along with the leading authors, Jwa-Min Nam and Yung Doug Suh.
To fabricate their single-molecule detector, the researchers first modified gold nanoparticles with two different kinds of DNA sequence – a protecting sequence and a target-capture sequence. One gold nanoparticle with a diameter of 20 nm (probe A) was functionalized with two kinds of 3'-thiol-modified DNA sequence; a second, 30 nm gold nanoparticle (probe B) was functionalized by two kinds of 5'-thiol-modified DNA sequence. By modifying the molar ratios of the two kinds of sequence, the target-capture DNA per probe could be modified. A Raman-active dye (Cy3) was pre-conjugated to the target-capture sequence (probe B alone) so that the dye could be located at the junction of the single-DNA interconnected probes A and B.
With the Cy3-modified DNA was located at the junction site between the DNA-tethered particles – the distance between the gold nanoparticles is 3-4 nm – the structure was coated with silver by means of a nanoscale silver-shell deposition process on the gold nanoparticle surface to form the GSNDs.
high-yield synthetic scheme and nanogap engineering for single-DNA-tethered core-shell nanodumbbells
The high-yield synthetic scheme and nanogap engineering for single-DNA-tethered heterodimeric GSNDs and AFM-correlated nano-Raman spectroscopic measurement of individual GSND particles. a, A high-yield synthetic scheme for the Au nanoparticle heterodimers using stoichiometric DNA modification and magnetic purification. b, Nanometer-scale silver-shell growth-based gap-engineering in the formation of the SERS-active GSND. c, AFM-correlated nano-Raman spectroscopy set-up (laser focal diameter is 250 nm) for the detection of a Raman signal from a single GSND particle. (Reprinted with permission from Nature Publishing Group)
Nam explains that his team's results are important for several reasons. "First, our DNA-directed and magnetic separation-based nanostructure synthetic scheme opens opportunities in the high-yield synthesis of specific nanostructures for materials science and bio-detection applications.
Second, unlike the conventional strong electrolyte-induced nonspecific nanoparticle aggregation, our DNA-directed nanodimer assembly method can be easily scalable to produce targeted SERS-active nanoprobes.
Third, we established a silver-shell coating-based nanogap-engineering method.
Fourth, the nanogap-engineering of GSNDs allows for exploring hot SERS structures in an efficient and straightforward fashion.
Fifth, our synthetic and detection strategies provide new ways of overcoming long-standing problems in Raman and materials-research societies about controlling the nanometer-gap, nanogeometry and dye position and environment with high reliability and reproducibility."
The Korean scientists point out that many critical problems in Raman – especially, single molecule sensing, increasing cross section area, and quantitative Raman for eventual, practical applications of SERS – could be studied and addressed by using their method and nanodumbbells. Additionally, other optical properties including fluorescence and plasmonic coupling effect could also be studied.
"Finally" says Nam, "this could lead to a highly sensitive – ideally single-molecule sensitive – and quantitative biomolecule detection with great multiplexing capability. Eventually, straightforward, faster, and more accurate disease diagnosis at a lower cost could be possible using our approach."
According to the team, clinical test and trials are already underway.
Michael Berger By – Michael is author of three books by the Royal Society of Chemistry:
Nano-Society: Pushing the Boundaries of Technology,
Nanotechnology: The Future is Tiny, and
Nanoengineering: The Skills and Tools Making Technology Invisible
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