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A device that reads the sequence of DNA using semiconductor technology could bring the power of sequencing to a much broader swath of the science world. The desktop machine, developed by a startup called Ion Torrent, is slated to go on sale this month and will cost $50,000, about one-tenth of the cost of other sequencing machines on the market.

“It takes the democratization of sequencing to the next level,” says Chad Nusbaum, codirector of the genome sequencing and analysis program at the Broad Institute of MIT and Harvard, who has been testing the device. “Virtually anyone with good grant funding can buy one.”

Nusbaum and others say the biggest advantage of the new technology is its speed; it can sequence a sample of DNA in a couple of hours, rather than the week or more required by most of the machines now on the market. That could make the technology particularly useful for genetic diagnostics, which require a quick turnaround.

Life Technologies, a major player in the genomics industry, bought Ion Torrent for $375 million in cash and stock last August. Ion Torrent’s founder, Jonathan Rothberg, says that Life Technologies was particularly interested in his technology because of the potential diagnostic applications, though he is careful to note that the machine is only meant for research use at the moment.

The new device reads a much smaller amount of DNA than larger, more expensive machines. The current version analyzes 10 to 20 million bases per run, while the human genome is 3 billion bases. (Machines made by genomics giant Illumina, in contrast, can sequence about 250 billion bases of DNA in a weeklong run.) However, diagnostic and other applications only require analysis of limited stretches of DNA.

At the heart of Ion Torrent’s technology is a semiconductor chip manufactured in the same foundries as computer and cell-phone microprocessors. The chip holds an array of 1.5 million sensors, each topped with a small well designed to hold a single-stranded fragment of DNA. To sequence a strand of DNA, the machine synthesizes a complementary strand, sequentially attempting to add each of the four bases that make up DNA one by one to the well. When the correct base is incorporated into the growing sequence, it triggers a chemical reaction that releases a positively charged hydrogen atom, which is detected by the sensor. A computer stitches together the sequence by integrating these signals with knowledge of when each base was flowed through the chip.

The device is so much cheaper than other machines because of its simplicity; the chip itself detects the sequence, and it does so electronically. Other devices use optical systems, which require lasers, cameras, and microscopes. (These devices also read DNA sequence by synthesizing a complementary strand—but chemicals used in the reaction have to be modified to fluoresce when added to the growing piece of DNA; a camera detects the flashes of light.) “It’s a simple system to implement,” says Nusbaum of Ion Torrent’s technology. “Not just the machine, but also the infrastructure around it.”

While Ion Torrent’s machines are cheap, the cost of sequencing per base pair is higher than for other instruments because each chip can only be used once, and the disposable chip currently costs about $250. But Rothberg says that, as with standard microprocessors, the price will drop with larger volumes of chips. “Every time we make 10 times as many chips in these factories, the cost drops in half,” he says. And because they are manufactured using standard semiconductor fabrication methods, he says it will be easy to scale up the chips to contain 10 to 100 times as many sensors.

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Credit: Ion Torrent

Tagged: Biomedicine, sequencing, semiconductor, DNA sequenced, Ion Torrent

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