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.
Reading DNA: Ion Torrent’s chip, built using semiconductor technology, can read DNA sequence directly, without the optical systems used by other sequencing machines.
"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.
Rothberg likens the evolution of sequencing technology to that of the computer industry. "The original computers were expensive; [they were] hard to build, ship, and set up; and they required a special environment to operate." DNA sequencing was similarly once limited to the realm of large sequencing centers, but new technologies on the market over the last five years have greatly expanded its purview. These machines brought down the cost of sequencing dramatically, largely by reading millions of DNA sequencing reactions in parallel.
Within this scheme, Rothberg equates Ion Torrent's machines to personal computers. Thousands of labs across the globe will now have access to sequencing machines that can fit on a standard lab bench, but as Harvard geneticist George Church points out, the machines are still out of reach for the average consumer. Furthermore, while many labs will have the capacity to buy a $50,000 sequencer, it's not yet clear that they will. "Lots of labs are outsourcing these days," says Church. "But I do think a lot of people want their own device. They don't want to be in queue. If they have a sample, they want an answer immediately."
It's also difficult to predict how Ion Torrent will compete with other high-profile companies with new sequencing technologies on the market, most notably Pacific Biosciences. That company raised $200 million through an initial public offering in October of this year.
John Iafrate and Long Le, pathologists at Massachusetts General Hospital, plan to put the diagnostic potential of Ion Torrent's technology to the test. Their proposal to use the machine to analyze cancer-linked genes in tumor cells won the pair a free sequencer in a competition sponsored by the company last June. MGH currently screens so-called hotspots—regions of the genome known to harbor many cancer-linked mutations—in some incoming cancer patients. "This would allow us to move from the hotspot approach to cast a wider net; there are probably about 200 genes we are interested in," says Iafrate. "We want to understand every patient's cancer comprehensively enough [for them] to be given drugs or directed into the appropriate clinical trials."
He adds that both the speed and the cost of the machine will make it attractive to clinical genetics labs. "In a clinical setting, it's very important to turn around tests quickly," he says. "Outside of genome centers, it's hard to get capital funding for [sequencing instruments], so reducing the cost to $50,000 makes it very attractive. All of those factors make entry into the clinical arena a tractable problem."
By Emily Singer
From Technology Review