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DASH-Based Technology Promises Genotypes for 1 Penny Apiece

COLD SPRING HARBOR, NY, May 8 - Researchers in Sweden claim they can crank out 1 million genotypes per week per assay device for significantly less than 1 cent per call--a lead-ball drop from the $.35 it costs today.


The team from the Karolinska Institute in Stockholm initially tweaked dynamic allele-specific hybridization to arrive at their results, which they say can answer "a desperate need" for cheap and flexible SNP genotyping. At its essence, the development is based on the principle of dynamically tracking DNA denaturation while a target and probe duplex is slowly heated.


Led by Anthony Brookes, vice chairman and coordinator of clinical genomics, the researchers knew that DASH alone can handle around 10,000 genotypes per week at roughly $.35 per call. A pair of innovations devised in Brookes' lab helped to create a second-generation DASH that now boasts 100-fold utility and implies 1 million individual genotypes per week for about $1,000 in reagent and consumable costs.


The team claims using this technology can "instantly create high-density macroarrays by centrifugal transfer of PCR-reaction products onto membranes for virtually zero cost, and an improved form of FRET signal generation that yields fluorescence intensities around 40 times stronger that the norm."


Brookes' team has now developed prototype components that can transfer a series of multiplexed PCRs in 1,536-well plates directly to membrane arrays. They then process the membranes and place them on a heating surface beneath a CCD camera for DASH analysis.


The research falls nicely with Brookes' belief that sometimes technological advances can be superfluous and unduly expensive.


"The [genomics] field has followed a trend over the last five years of becoming more and more high tech," Brookes said in an interview with GenomeWeb during the 2002 Cold Spring Harbor Lab's Genome Sequencing & Biology meeting here today. "More robotics, more gizmos, more microfluidics and microfabrications. More really high-tech solutions."


Brookes said he saw that trend filter down to genotyping. "Everyone said 'Oh, well, hybridization isn't good enough for genotyping.' So they said 'Let's do a sequencing step,' or 'Let's do a ligation step. Let's do something else after we've ligated our probe into place.'


"But we didn't follow that route," he said. "We thought that maybe hybridization is enough, but we need to be a little bit smarter."


Genotypes for sale, real cheap


Brookes, a softspoken Englishman, said the next step is to market the innovations of his five-person team. But he'll do that his way, too. Having shown venture capitalists the door, Brookes said he'd rather pen a licensing deal of some kind with a genomics tool shop or a biotech company rather than take the technology to the next level himself.


"A much better deal for me is to strike up a partnership with a company that's already making machines, that already knows the subject, already has advertising, the manpower to take our prototypes to market, to promote them, and to support them," Brookes said.


He said he has spoken with six companies and has two or three biotech firms lined up. He declined to name any of the companies he's spoken with but Applied Biosystems and Motorola came up on many occasions as ideal potential partners.