"We measure a small current through the molecules using a setup developed in our lab." said Tao. "It's a conceptually simple setup. You just bring two electrodes together, separate them apart, make the measurement and repeat."
In the technique, chemical linker groups that form a tight bond with gold electrodes are attached to the ends of DNA. A drop of a DNA solution is then placed between the two electrodes. The DNA sticks to the surface of the electrodes spontaneously.
As the tip is pulled away and the two electrodes teased apart, the molecules of DNA are eventually dispersed to the point of measuring the current of a single DNA molecule.
For a proof of concept of the potential for measuring SNPs, the group used DNA of 11 or 12 bases in length dissolved in a physiologically relevant saline solution. From one electrode tip, a small current, or bias is used to probe the internal electronic states of DNA. By measuring the conductance, the team was able to understand the sequence information in the DNA and whether there was a mismatch in comparison to a normal DNA sequence.
What they found was that just a single base pair mutation in a DNA molecule, such as substituting an A for a G, can cause a significant change in the conductance of the molecule. The measurement is extremely sensitive, as the alteration of a single base in the DNA stack can either increase or decrease the conductivity of a DNA helix, depending on the type of mismatched base.
Not only was the group the first measure SNPs in this manner, but they were also the first to make the measurement in a water environment relevant to that found in biological systems.
How the current flows through the DNA molecule is st
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Contact: Joe Caspermeyer
joseph.caspermeyer@asu.edu
480-727-0369
Arizona State University
8-Dec-2005