Nanodumbbells' Single-Molecule Detection Capability Could Aid Future Disease Diagnosis

December 17, 2009

3 Min Read
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A DNA-based assembly technique developed by South Korean scientists can precisely engineer gap distances in nanoparticle dumbbells to optimize the sensing capability of DNA and RNA molecules using surface-enhanced Raman scattering (SERS). "This could lead to a highly sensitive--ideally single-molecule-sensitive--and quantitative biomolecule detection with great multiplexing capability," comments Jwa-Min Nam, an assistant professor in the department of chemistry at Seoul National University. Eventually, straightforward, faster, and more-accurate disease diagnosis at a lower cost could be possible using our approach."Relying on the Raman effect--the change in the frequency of monochromatic light, such as a laser, when it passes through a substance--SERS can identify specific molecules by detecting their characteristic spectral fingerprints. However, while the technology has great potential for chemical sensing, the large nonlinearity of the effect makes reproducible SERS sensing difficult, according to an article at Nanowerk.Reporting their findings in "Nanogap-Engineerable Raman-Active Nanodumbbells for Single-Molecule Detection," the team of researchers show that Raman-active gap-tailorable gold-silver core-shell nanodumbbells (GSNDs) have single-molecule sensitivity with high structural reproducibility. To fabricate a single-molecule detector, the scientists first modified gold nanoparticles with two different kinds of DNA sequences--a protecting one and a target-capture one. A gold nanoparticle with a diameter of 20 nm (probe A) was functionalized with two kinds of a 3'-thiol-modified DNA sequence. Another one, a 30-nm gold nanoparticle (probe B), was functionalized by two kinds of a 5'-thiol-modified DNA sequence. By modifying the molar ratios of the two kinds of sequences, the target-capture DNA per probe can be modified. Cy3, a Raman-active dye, was preconjugated 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 located at the junction site between the DNA-tethered gold nanoparticles--a distance of 3 to 4 nm--the gold nanoparticle surface was coated with silver by means of a nanoscale silver-shell deposition process to form the GSNDs."We believe that our method and findings could lead to high cross section-based SERS sensing and single DNA detection in a highly reproducible fashion," Nam comments. "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."Nam explains that his team's results are important for several reasons. First, the DNA-directed and magnetic separation-based nanostructure synthetic scheme opens opportunities in the high-yield synthesis of specific nanostructures for materials science and biodetection applications. Second, unlike the conventional strong electrolyte-induced nonspecific nanoparticle aggregation, the DNA-directed nanodimer assembly method can be easily scalable to produce targeted SERS-active nanoprobes. Third, the scientists 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, the synthetic and detection strategies provide new ways of overcoming long-standing problems in controlling the nanometer gap, nanogeometry, dye position, and environment in Raman and materials research."

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