CHICAGO, Feb. 25, 2002 — Wouldn’t it be great if your doctor could figure out within a few minutes not only what kind of infection you have, but also which antibiotics are still effective against it? Within the next few years, a nanoscale technology developed by a team at Northwestern University may yield a handheld device that does just that, and potentially much more.
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Writing in the February 22 issue of Science, researchers from Northwestern’s Institute for Nanotechnology describe a new method of DNA detection that uses gold nanoparticle probes and microarrays of electrodes. It’s 10 times more sensitive (causing fewer false negatives) and 100,000 times more selective (causing far fewer false positives) than current methods.
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The nanoprobes are coated with a synthesized string of nucleotides that complement one end of a target sequence in the sample being analyzed, so they can “grab” it if it’s there. Another set of nucleotides, complementing the other end of the target, is attached to a surface between two electrodes. If the target sequence is present in the sample, it attaches to both the nanoprobes and the sequences on the surface between the electrodes, so that the nanoprobes are anchored to the surface like a cluster of little balloons. When they’re treated with a silver solution, they create a bridge between the electrodes and produce a charge.
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The technology could theoretically be used to detect any disease or condition with a unique genomic fingerprint. For example, it could differentiate between various antibiotic-resistant strains of strep, or detect cancerous cells, or quickly identify HIV or biological weapons agents like anthrax. A single chip could contain electrode pairs to test for thousands of biological targets at once. And because an electrical charge is either present or absent, there’s no ambiguity in the results.
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The head of the research team is Chad Mirkin, director of the institute and co-founder of Nanosphere Inc., Northbrook, Ill., which is licensed to begin commercial development of the technology. “Nanotechnology can be used to get better results in all categories that are important in DNA detection — sensitivity, selectivity, cost, ease of use and speed,” he said. “The electrical DNA detection method that we have invented excels in all of these areas and has a good chance to become a truly disruptive technology.”
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Nanosphere is already developing DNA detection systems based on an earlier method invented by Mirkin’s team, also using gold nanoprobes, that causes a color change in a solution when a particular DNA sequence is detected. The first of those products is scheduled to be in beta testing by the end of the year.
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Vijaya Vasista, Nanosphere’s chief operating officer, says the new method described in the Science paper will be better suited to developing a handheld device that can be used in physicians’ offices, at a hospital bedside or on the battlefield. She estimates that such a device could be ready for testing and approval by the U.S. Food and Drug Administration in as little as three years. The company is planning to hire a regulatory specialist this year to shepherd its products through the intricate and rigorous process. Vasista anticipates that the company’s products will be marketed first in Europe, where approvals come more quickly.
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The first hurdle in developing the electrode-based detector will be to create a simple process for preparing the DNA samples for testing, Vasista says. For example, blood samples must now be prepared by separating out the white blood cells (the only ones that contain DNA), and then treating them to isolate the genetic material. “We need a miniature way to do that,” she said.
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Using figures from several industry analysts, including Merrill Lynch, Salomon Smith Barney and Credit Suisse First Boston, Nanosphere estimates this year’s total genomics market opportunity at about $4.3 billion, mostly in clinical research laboratory expenditures and in-vitro diagnostics. The company projects that the market will grow to more than $7 billion by 2005.
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If Nanosphere’s technology yields a device that fulfills its promise technically, it’s likely to find an eager market, said analyst Raylene Ballard of ECRI, Plymouth Meeting, Pa., a nonprofit organization that evaluates medical technology for health care providers. “These kinds of applications have a direct relation to quality of care,” she said. “There’s an obvious benefit in being able to get a result on the spot instead of waiting for two days.”
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Whether potential popularity translates into financial success will depend on a number of factors beyond Nanosphere’s control, Ballard added. “They have to be able to manufacture it fairly cheaply, and the government and insurance companies have to be willing to reimburse providers for its use. And you have to convince the medical community to use it, which is sometimes a slow process. But I don’t think it will be that hard to do if the device clearly works.”
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“If it delivers as advertised, it would be a really worthwhile thing,” said James Holman, senior vice president of medical affairs at Carilion Health System, a network of 10 hospitals headquartered in Roanoke, Va. “For an infectious disease, response time is critical.” Carilion routinely evaluates new technologies based on whether they’re an improvement over what’s already being used, and whether they’re the best use of scarce dollars.
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ECRI’s Ballard says many companies, including Nanogen Inc. in San Diego and Cepheid in Sunnyvale, Calif., are working on miniaturized DNA analysis. Cepheid announced in January that it had shipped field-ready DNA test kits for anthrax, botulism, plague, and tularemia to the U.S. Army Medical Research Institute of Infectious Diseases.
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Larger diagnostics companies like Roche, Bayer and Johnson & Johnson are also likely working toward the same goal, Ballard added. “They don’t like to talk about R&D until they’re ready to announce a product,” she said. “But they also may let some small company do the research and then swoop down and buy it. That’s very common in diagnostics.”