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NIST awards fund DNA diagnostic efforts
The National Institute of Standards and Technology (NIST; Gaithersburg, MD) has announced the list of companies that will receive grants under its annual Advanced Technology Program (ATP) com- petition. The ATP is intended to further commercial applications of scientific research and provide financial aid to companies that are developing cutting-edge technologies.
As in previous years, the 1999 program includes a category focused on the creation of tools for molecular diagnostics. The main goal of the DNA diagnostics program is to develop low-cost assays and automation equipment for the healthcare industry as well as the agricultural and environmental industries.
Although the primary function of the ATP competition is to provide funding to the selected companies, ATP program director Rosemarie Hunsacker admits that "there are a few unofficial benefits. Being chosen for government grants has a halo effect on the companies. With government endorsement, companies can appear more attractive to venture capitalists."
The selected companies specialize in all facets of DNA diagnostics from sample preparation and probe development to automation and analysis. In addition, many of this year's winning proposals involve partnerships with secondary sponsors, including both academic institutions and other industry firms. Following is a rundown of the principal sponsors and their grant-winning proposals.
DNA chips by Clinical Micro Sensors Inc. (Pasadena, CA) contain electrically active pads connected to specific DNA probes. Hybridization to a probe will send a signal that can be detected and quantified with a handheld unit. One hurdle for the company's technology will be to make the system sensitive enough to analyze whole blood and obviate costly amplification steps.
Axys Pharmaceuticals Inc. (South San Francisco, CA) and Luminex Corp. (Austin, TX) sponsored a proposal based on the core technology of Axys's liquid arrays, which incorporate DNA probes into polystyrene microspheres. On a flow cytometer, the microspheres can be distinguished by a unique combination of fluorescent dyes. Planning to manufacture up to a million different types of microspheres in a 1536-well microplate format, the partners envision a plate that could perform 1.5 billion assays simultaneously.
Caliper Technologies Corp. (Palo Alto, CA) is working to integrate DNA separation, purification, and analysis onto a single microfluidic chip, and hopes to reduce assay costs to a tenth of their current levels. "Hair-sized channels in the chips will partition nanoscale volumes of reagents and samples to allow any chemical or biochemical conversion," says Michael Knapp, Caliper's vice president for science and technology. High-throughput genotype screening will be the first application developed, "but as with most assays, ours should go to the bedside eventually," he adds.
Orchid Biocomputer Inc. (Baltimore) is seeking to develop a "universal processor" that will contain short DNA probes of four to six nucleotides in all possible combinations. "DNA does not hybridize to the probes," points out project leader Russ Graznow. "Binding is a homology event where a polymerase adds a fluorescently labeled base. Using all combinations of 4-mers, a single mutation will change eight of the 256 spots on the chip." Orchid hopes to minimize sample preparation and reduce costs to less than $1 per genotype.
Pharmaseq Inc. (Libertyville, IL) is using a unique approach that involves reusable, light-activated microtransponders coupled with DNA probes. "The detection instrument resembles a flow cytometer," says project leader Wlodek Mandecki. "Fluorescently labeled sample DNA binds to the probe. As the probe-transponder passes the laser, fluorescence is detected and the light powers the transponder to send a radio signal." Specific probes are identified by their unique radio frequency. One of the company's main goals is to further miniaturize the transponders, which are already only hundreds of micrometers on a side. The transponders are designed for a multiplex platform, says Mandecki. "We can easily pack 50,000 transponders in a tube of 1.5 ml." The technology could be ready by late 1999, but FDA approval could take another four years, he estimates.
Aclara Biosciences Inc. (Hayward, CA) is focusing on automated DNA specimen preparation, including every step from extraction to amplification. The company envisions a disposable plastic card containing microfluidics and all necessary reagents to prepare DNA for analysis.
PE Applied Biosystems (Foster City, CA) is also developing an integrated DNA preparation device that can accept samples from such varied sources as bacteria, plant cells, and mammalian cells. The company's goal is to produce an automated chip that can prepare at least 100 samples at once. Depositing single cells into the reaction chambers is one hurdle; membrane and enzyme technologies will be pursued for the subsequent purification, selection, and amplification processes.
Representatives from the winning companies are required to participate in an ATP-sponsored workshop. "ATP is prohibited from disclosing proprietary information, but the unofficial interactions during the workshop often lead to the various companies getting to know each other and sharing information," says ATP's Hunsacker.—Gary Woo
