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Slow Supply Chain is the Mother of Invention--and the Mother of All DNA Magnets

SAN FRANCISCO, June 21 - The Joint Genome Institute has built a new way of turning dirty DNA into the pure stuff needed for gene sequencing.


The new tool is a hybrid magnet, believed to be the strongest of its kind commercially available, which was designed to provide the holding power needed for high-throughput sequencing.


Now the JGI and one of its parents, the Lawrence Berkeley National Laboratory, are in negotiations with a number of companies to license the patent-pending technology, which has been shown to blow that lids off traditional technology while saving labs money.


But what creatively astute planning mechanism pushed the emergence of the technology?




"The whole magnet thing got started because we had trouble getting them from vendors," explained Martin Pollard, instrumentation group leader at the JGI. "We needed 5,000 doughnut magnets, not 10, because we were high throughput.

Faced with an unacceptable six-week delivery time, Pollard pointed out that JGI had the resource to make in-house what it wasn't prepared to wait for. That resource was David Humphries, a staff engineer at JGI and Lawrence Berkeley and a former designer of magnets for particle accelerators.


Not your mother's fridge magnet


"I can do better than this," Humphries remembered thinking when looking over the commercial magnets used to hold DNA during the multiple washing and reaction cycles needed to purify genetic material before sequencing.


And so he reached back into his 15 years of experience designing magnets and came up with a design that sandwiched ferromagnetic materials like iron and steel to permanent magnets. He had a prototype built in several weeks, he said, and realized higher fields and stronger gradients than magnets that were currently available.


That was an understatement. The pull of Humphries' magnet was 70 percent stronger at its surface than even the most powerful commercial magnet, according to Lawrence Berkeley. Greater attraction meant a tighter hold on DNA as it was being washed, leading to purer samples. A stronger pull also meant there was less chance that the robotic pipette tips sucking fluid from wells would clog with magnetic beads, said Pollard.


Within two months the magnets were in production.


Humphries estimated that the new magnet design played an important role in JGI's ability to go from sequencing 20 million base pairs per day using a 96-well plate system to 40 million base pairs with a 384-well plate set up. He does acknowledge, though, that the new technology, while important in offering greater system stability as wells and samples shrink in size, is only one in a series of innovations.


"The magnet is not doing anything by itself; it's part of a long complex process," said Humphries.


Pollard agrees. "There's a lot of factors in ultimate-read length and pass rates." Since using the magnets, JGI sequencing has risen to 630 base pairs per read length compared to an industry average of 500 high-quality base pairs per cycle, according to Lawrence Berkeley.


The attraction


The magnets represent "a significant step forward" for allowing increased sequencing at decreased cost, according to Pollard. They offer an "advantage in a high-throughput environment to get that extra edge for incremental improvement," he said.


Humphries estimates that the magnets, in contributing to JGI's transition from 96 wells to 384, helped lead to a 30-percent reduction in personnel involved in the sequencing operation, thus reducing costs.


And while competing technologies exist to hold DNA during washing cycles--such as Qiagen's use of filters--scaling up may favor a magnetic approach, said Pollard.


"As an instruments person, I've said if you want me to automate a filter system I can, but I was told, 'No, consumables [filter plates] are too expensive,'" said Pollard. As the industry attempts to scale up to 1,536 well plates, use of larger quantities of consumables will become a more significant cost factor, he said.


Lawrence Berkeley is currently negotiating with several biotech companies to license the magnet technology, said Humphries, who declined to offer company names.


Humphries and his colleagues are now setting their sights on adapting the magnets to 1,536 well plates, functional-genomics applications, and for use in separating proteins.

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