Sensitive System Detects Individual Molecules for Medical Diagnostics

To construct their golden trap, the scientists chose DNA. Its thread-like strands can be folded into different objects with arbitrary dimensions using multiple shorter DNA segments. This technique, known as DNA origami, is based on the chemical binding of complementary bases; the DNA strands essentially interlock like the two rows of a zipper.

The scientists arranged two tiny gold particles onto a substrate at predetermined distances. Next, they anchored molecules of a dye called carboxytetramethylrhodamine (TAMRA) within these gaps. They then irradiated the sample using laser light, which yielded what is known as a Raman spectrum. This optical method involves laser light that is scattered from the molecule, which produces a spectrum that is like a fingerprint for the particular substance. Surface-enhanced Raman spectroscopy (SERS) spectra were recorded using a confocal Raman microscope (WITec; Ulm, Germany) equipped with an upright optical microscope.

They attached a pair of naked gold nanoparticles to a DNA triangle and connected three single dye molecules to the DNA using additional anchors that were localized directly within the hot spots. Similarly, in these Raman spectra, the dye's signal could easily be identified. Finally, they inserted only a single dye molecule into the gap between the two gold particles. Even this minuscule amount of TAMRA could still be detected. The surface illuminated by the laser beam contained a total of 17 DNA triangles showing the signal originated from 17 single molecules.

The scientists plan to attach an anchor in the gap between the gold particles, capable of binding a molecule of interest, such as a protein, for instance. This way, any type of biomolecule could be analyzed: DNA, ribonucleic acid (RNA), or proteins. Since every class of molecule produces characteristic Raman signals, the scientists can test for the presence of several substances at the same time using specially prepared DNA triangles. Therefore, this detection method could also be integrated into a chip and used in medical diagnostics. The study was published on November 19, 2013, in the Journal of Physical Chemical Letters.

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