The Rapid Micro Blog


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A New Read on DNA Sequencing


I came across a very interesting article on gene sequencing. Biophysicist Stuart Lindsay, of the Biodesign Institute at Arizona State University, has demonstrated a technique that may lead to rapid, low cost reading of whole genomes, through recognition of the basic chemical units, the nucleotide bases that make up the DNA double helix. His group's research appears in the current issue of the journal Nature Nanotechnology.

Lindsay's technique for reading the DNA code relies on a fundamental property of matter known as quantum tunneling, which operates at the subatomic scale. According to quantum theory, elementary particles like electrons can do some very strange and counter-intuitive things, in defiance of classical laws of physics. Such sub-atomic, quantum entities possess both a particle and a wave-like nature. Part of the consequence of this is that an electron has some probability of moving from one side of a barrier to the other, regardless of the height or width of such a barrier. Remarkably, an electron can accomplish this feat, even when the potential energy of the barrier exceeds the kinetic energy of the particle. Such behavior is known as quantum tunneling, and the flow of electrons is a tunneling current. Tunneling is confined to small distances, so small that a tunnel junction should be able to read one DNA base at a time without interference from flanking bases. But the same sensitivity to distance means that vibrations of the DNA, or intervening water molecules, ruin the tunneling signal. So the Lindsay group has developed "recognition molecules" that "grab hold" of each base in turn, clutching the base against the electrodes that read out the signal. They call this new method "recognition tunneling."

To read longer lengths of DNA, Lindsay's group is working to couple the tunneling readout to a nanopore -- a tiny hole through which DNA is dragged, one base at a time, by an electric field. Sequencing through recognition tunneling, if proven successful for whole genome reading, could represent a substantial savings in cost and hopefully, in time as well. Existing methods of DNA sequencing typically rely on cutting the full molecule into thousands of component bits, snipping apart the ladder of complementary bases and reading these fragments. Later, the pieces must be meticulously re-assembled, with the aid of massive computing power.

Lindsay stresses much work remains to be done before the application of sequencing by recognition can become a clinical reality. "Right now, we can only read two or three bases as the tunneling probe drifts over them, and some bases are more accurately identified than others," he says. However, the group expects this to improve as future generations of recognition molecules are synthesized.

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