DNA Sequencers Get Tech Savvy

Sequencing's future?
An array of 16 transistors sequences DNA with single base resolution.

T. Sakata and Y. Miyahara, Angew. Chem. International Edition, 45 (2006)

The computer chip and DNA sequencing revolutions have finally merged. A pair of Japanese researchers report that they've developed the first all-electronic sequencing approach, one that harnesses the same kind of transistors that are at the heart of computer technology. If it can be scaled up, the strategy could dramatically increase the speed and reduce the cost of sequencing, enabling a new generation of personalized medical care.

Current sequencing machines chop DNA up, copy it, and unzip it into single strands. An enzyme called DNA polymerase then begins rebuilding each strand's double helix, using nucleotide bases as building blocks. Every once in a while, the polymerase inserts a base with a fluorescent tag, which terminates the rebuilding process for that strand. In the final step, the machine sorts all of the strands by length, and a laser reads the fluorescent bases. Further analysis then links multiple chopped fragments together to reveal the full sequence of starting DNA.

As successful as this technology is, it remains about 100 to 1000 times too expensive to be used for widespread medical diagnostics. Hoping to simplify things, bioelectronics experts Toshiya Sakata and Yuji Miyahara of the National Institute for Materials Science in Tsukuba focused on devices called field effect transistors, which form the heart of computer circuitry. These transistors switch from off to on when a burst of electric charge is sent to a "gate" electrode. This alters the conductivity of an electronic pathway nearby, allowing charges to flow freely through it between two other electrodes.

In this case, Sakata and Miyahara topped the gates on their electrodes with identical snippets of single stranded DNA. They then dunked the chip in a bath containing one of the four nucleotides of DNA--abbreviated A, G, C, and T--and added DNA polymerase to the mix. As the polymerase attaches negatively charged bases to the DNA, the strand becomes more negatively charged. This translates to a change in voltage, which turns on the transistor and thereby signals that the base was added to the chain. The process is then repeated to identify other bases. Because the technique does away with fluorescent tags and optical microscopes, it has the potential to be far simpler than current sequencing technology, Sakata and Miyahara report 27 March in Angewandte Chemie, International Edition in English.

"This paper is very early and exciting," says sequencing pioneer George Church of Harvard University. Church notes that in order for the approach to become a viable sequencing technology, it must be scaled up to work on thousands of DNA strands in parallel. Also, Church says, researchers must find a way to reuse their sequencing chips over and over. If they can manage that, DNA sequencing may eventually become as easy as working at a computer.

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