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Electron Tunneling-Based DNA Reader Developed

An electron tunneling-based technology for accurately reading the base sequence of DNA molecules has been developed by an Arizona State University (ASU) research team headed by Dr. Stuart Lindsay. This is the first tunneling-based DNA reader that can discriminate among DNA's four bases in one tunnel gap. If the technology can be perfected, DNA sequencing could be performed much more quickly than by current technologies, and at a fraction of the cost. The ASU work was supported, in part, by funding from the National Human Genome Research Institute’s “$1000 Genome” initiative, which is intended to make DNA genome sequencing as widespread as a routine medical checkup, thus helping to usher in the era of “personalized medicine.” The new technology relies on a scanning tunneling microscope and an atomic force microscope, to make its measurements. The microscopes have a delicate electrode tip that is held very close to the DNA sample. In its current innovation over earlier versions, Dr. Lindsay's team made two gold electrodes, one on the end of the microscope probe, and another on the surface, that had their tiny ends chemically modified to attract and catch the DNA between a gap, like a pair of chemical tweezers. The gap between these functionalized electrodes had to be adjusted to find the hydrogen-bonding sweet spot, so that when a single chemical base of DNA passed through a tiny, 2.5-nanometer opening between the two electrodes, it momentarily sticks to the electrodes and a small increase in the current is detected. Any smaller, and the molecules would be able to bind in many configurations, confusing the readout; any larger and smaller bases would not be detected. "What we did was to narrow the number of types of bound configurations to just one per DNA base," said Dr. Lindsay. "The beauty of the approach is that all the four bases just fit the 2.5 nanometer gap, so it is one size fits all, but only just so!" At this scale, which is just a few atomic diameters wide, quantum phenomena are at play where the electrons can actually leak from one electrode to the other, tunneling through the DNA bases in the process. Each of the chemical bases of the DNA genetic code gives a unique electrical signature as the bases pass between the gap in the electrodes. By trial and error, and a bit of serendipity, the team discovered that just a single chemical modification to both electrodes allowed the system to distinguish among all four DNA bases.

According to the authors, “The present work shows that two major impediments to sequence readout by tunneling—a wide range of molecular orientations and a large contact resistance—can be overcome using functionalized electrodes.”

"We've now made a generic DNA sequence reader and are the first group to report the detection of all four DNA bases in one tunnel gap," said Dr. Lindsay. "Also, the control experiments show that there is a certain (poor) level of discrimination with even bare electrodes (the control experiments) and this is in itself, a first too. We were quite surprised about binding to bare electrodes because, like many physicists, we had always assumed that the bases would just tumble through. But actually, any surface chemist will tell you that the bases have weak chemical interactions with metal surfaces."

Dr. Lindsay's group is now hard at work trying to adapt the reader to work in water-based solutions (as opposed to the organic solutions used in these experiments), a critically practical step for DNA sequencing applications. Also, the team would like to combine the reader capabilities with carbon nanotube technology to work on reading short stretches of DNA.

This work was published on February 8, 2010 in Nano Letters.
[Press release] [Nano Letters article]