Just as silicon-based technology has fended off challengers for decades, it's proving very difficult to unseat the current method for decoding genomes, known as Sanger sequencing. Now a new study shows that Sanger sequencing still has plenty of room for improvement, which could make it more difficult for a host of emerging sequencing technologies to gain a toehold in the market.
Modern genome sequencing grew out of work in the mid 1970s by Fred Sanger at the Medical Research Council in the United Kingdom. Almost every lab that does sequencing uses the Sanger method, yet it remains expensive. Sequencing a mammalian genome, for example, currently costs about $22 million. Researchers around the globe are working furiously to come up with cheaper technologies and hope to ultimately drop the price to about $1000 for a complete genome.
Richard Mathies, a chemist at the University of California (UC), Berkeley, and his colleagues decided to see how far they could push down the costs of Sanger sequencing. To do so, they used microchip engineering technologies to shrink the current refrigerator-sized sequencing machine down to a 10 centimeter-wide plate of glass and plastic.
According to Mathies, this is the first lab-on-a-chip device that can carry out all of the many chemical steps needed to sequence DNA, including copying DNA fragments, purifying them, and adding fluorescent tags. Moreover, he says, unlike many upstart technologies troubled by poor accuracy or limited to very short DNA fragments, the new chip sequences DNA with nearly the same fidelity and long fragment lengths as conventional machines. The upshot, Mathies says, is that the chips' small size and integration should reduce reagent and personnel costs to the point where it should be possible to sequence a complete genome for as little as $50,000. Mathies, whose team publishes its work online this week in Proceedings of the National Academy of Sciences, says UC Berkeley has licensed patents on the technology to Microchip Biotechnologies of Dublin, California.
"It's a very elegant piece of microfabrication," says Norm Dovichi, a genome sequencing technology expert at the University of Washington, Seattle. Dovichi says it remains to be seen whether companies that commercialize the technology will ultimately integrate all the steps that the Berkeley team has put together on their chips, since most of the work goes into preparing DNA samples rather than sequencing them. Nevertheless, he says, it looks like Sanger sequencing won't relinquish its command of the sequencing field without a fight.
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