At a time when the longtime goal of a $1,000 genome is still just out of reach, a Harvard University physicist is promising an even cheaper price–the ability to sequence a human genome for just $30. David Weitz and his team are adapting microfluidics technology that uses tiny droplets, a strategy developed in his lab, to DNA sequencing. While the researchers have not yet sequenced DNA, they have successfully demonstrated parts of the process and formed a startup, GnuBio, to commercialize the technology. Weitz presented the findings at the Consumer Genomics Conference in Boston last week.
Weitz’s team had previously developed a way to create picoliter droplets of water, which act as tiny test tubes. The droplets can be precisely moved around on a microfluidics chip, injected with chemicals and sorted based on color. (The technology has been commercialized by RainDance Technologies, which Weitz cofounded in 2004. The company markets the droplet technology to amplify select regions of DNA.)
Because the droplets are so small, they require much smaller volumes of the chemicals used in the sequencing reaction than do current technologies. These reagents comprise the major cost of sequencing, and most estimates of the cost to sequence a human genome with a particular technology are calculated using the cost of the chemicals. Based solely on reagents, Weitz estimates that they will be able to sequence a human genome 30 times for $30. (Because sequencing is prone to errors, scientist must sequence a number of times to generate an accurate read.)
The cost of sequencing has dropped exponentially over the last five years, enabling much broader application of the technology to study human health and disease, agriculture, and microbial diversity. The current cost to sequence a human genome is just a few thousand dollars, though companies that perform the service charge $20,000 to $48,000. A number of companies are racing to develop even cheaper technologies.
In Weitz’s approach, droplets are injected with short strands of DNA of a known sequence, and these strands are labeled with an optical bar code. Pieces of the sample with an unknown sequence are also injected into the droplets–if the sample has a stretch of sequence complementary to the known strand, the two pieces will bind, triggering a change in color. Repeat this 1,000 times with 1,000 different known strands and you can generate the sequence of 1,000 letters of DNA, says Weitz.
Both the optical bar code and the color change are detected using a microscope and camera with automated detection software. Weitz says they can produce and process a million drops per second.
Thus far, the team has had little funding to develop the technology. For this reason, they have done only some steps of the process, such as the hybridization reaction described above.
GnuBio is currently securing venture funding, according to cofounder John Boyce, formerly head of business development at Helicos, another Cambridge-based sequencing company. GnuBio researchers aim to deliver a beta version of the technology to two customers later this year. “It won’t be able to sequence a human genome, but shorter sequences are still of value,” says Weitz. Priced at $45,000, the instrument will be significantly cheaper than others on the market.
Translating the research-stage technology into a commercial product will likely be a major challenge. George Church, a pioneer in sequencing technology at Harvard, who serves on GnuBio’s science advisory board, predicts that the biggest hurdles will be integrating the different steps of sequencing, such as sample preparation, and creating good, user-friendly software. Unlike competitor Complete Genomics, which offers sequencing as a service and can therefore rely on experts to do the work, GnuBio plans to sell machines.
Jonathan Rothberg, who cofounded RainDance with Weitz, says the company considered pursuing sequencing when it first started. “But we made a business decision there were other things for us to do,” he says.
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