AUTOMATION · With robotics and innovative sample tagging, GenVault offers DNA archiving with no freezer burn

BY MARK D. UEHLING

October 14, 2004 | In the movies, DNA is stored in gleaming steel vials, neatly arranged in a way that would make Martha Stewart smile. In real labs, Mitch Eggers knows, the situation is different.

"You'll find labels that have peeled off the tubes and are just lying at the bottom of the freezer," says Eggers, GenVault co-founder and CEO. "You'll extract a tube, and it'll be written on with a Sharpie and you can't understand whether that 6 is a B — or who actually wrote it. If you ask any experienced researcher who is extracting samples from a freezer, they'll tell you this is a problem."

With a few customers, including the U.S. National Institute on Aging and the Centers for Disease Control and Prevention (CDC), GenVault is hoping to wean customers from storing DNA in glass vials. "There has been a lack of attention to the upstream management of the samples," Eggers says. "That's really becoming the bottleneck in the genomics era. These discoveries are dependent on the samples, and the cost-effective analysis and management of the samples."


Wet Lab, Dry DNA 
GenVault says its technology is no cheaper than using cryogenic freezers, liquid nitrogen, and special shipping. The company's plates cost approximately $65 each to process, before volume discounts. But the company still believes its platform is well suited for medical research institutions and drug discovery. That's because GenVault can use whole genome amplification to divide a single DNA sample into a 384-well plate. The easy duplication of a particular sample, Eggers believes, will facilitate sharing of samples between academic centers and industrial partners previously wary of shipping off a precious biological resource that might be needed years later. So will GenShare, a Web interface that allows GenVault customers and third parties to search, swap, or sell DNA samples.

PAPER PLATES: GenVault's GenPlate (above), with 6mm elements of Whatman paper in each well, allows samples to be stored at room temperature.

GenVault's storage requires virtually no energy and far less volume than conventional approaches. "We can store 400,000 samples in the footprint of a two-car garage," says Eggers, who founded and ran Genometrix after serving on the faculties of Rice University and MIT's Lincoln Laboratory. Each well of a GenVault plate can store 10 µl of whole-blood DNA.

GenVault's first intersection with drug discovery may be via the CDC's National Health and Nutrition Examination Survey (NHANES) project, the only longitudinal evaluation of the overall health of the U.S. population; DNA from those samples is later made available to industry. This time, with GenVault technology, the minivan-based surveyors working for the CDC will not have to worry about preserving vials of blood.

The company uses a microarray with a twist — 6mm discs of absorbent paper that stores genetic material at room temperature. The dry DNA samples pose no biohazard and can languish within the shipping process indefinitely with no degradation. That requires a change in outlook for technicians conditioned to agonizing about samples safely making their way into a freezer halfway across the country. Of course, the $300-million cryogenic storage industry, with companies such as SPX, Thermo Forma, Revco Technologies, and Chart Industries, won't go away tomorrow. Nor will outfits such as Qiagen, which makes the kits and reagents to process DNA.


Double-Tagged Samples 
But GenVault has raised $18 million for the battle. Its approach synthesizes IT, automation, and cutting-edge genetics in a way that could simplify high-throughput processing of thousands of DNA samples at a time. An identifying genetic tag is grafted inside each sample's DNA. The tag can be scanned and read as a number even if the sample is returned to a liquid state. Another related machine-readable bar code helps robots retrieve 200 GenVault microarrays per hour, far faster than a technician rummaging through Volkswagen-sized freezer vats.

GenVault's system was set up to be simple to operate, both at its Carlsbad, Calif., headquarters and on the sites of customers who are more protective of their samples. Based on the company's pricing for storage (about $30 per plate per year), customers with more than 10,000 plates may want to build their own robotic storage facilities. Two robotically driven systems store the plates, and one of those systems has unlimited expansion capacity.

Either way, far less manpower is required to run a GenVault system than a typical DNA extraction facility. "Typically, it is just one person that can man the entire archive system," Eggers says. "In those cases where rapid access to the samples is important, there is about a factor-of-10 savings in terms of the labor."

And will the DNA stored in this manner last? The technique has been pioneered by others and has been validated in the peer-reviewed literature; Whatman filter papers handle the job. Eggers notes that there is a literature of reliable extraction of DNA from paper that occurred 14 years and more after the original sample was collected. "Some of those studies have indicated good, stable DNA outwards of 40 years," he says. "This is going to be long-term storage in terms of decades as opposed to years."