Biochip Technology Quickly Identifies TB Strain, Promises More Precise Treatment

Quick analysis leading to more effective treatment for tuberculosis and other diseases is the goal of biochips developed by Argonne and the Russian Academy of Science’s Englehardt Institute of Molecular Biology.

Biochips are glass slides to which are affixed microscopic, three-dimensional pads of a gel. Each pad acts as a mini test tube. A single chip can host thousands of biological reactions in a few seconds. Technology permits construction of biochips with a very large number of gel pads, though those in use generally have from 100 to 5,000.

Antibiotic use and misuse have created bacteria through natural selection that defy some of the same wonder drugs that once promised to end humankind’s most deadly diseases. TB is an example. Once on the wane, new strains have evolved that resist one or more of the antibiotics that were once effective in treating the disease.

When there’s a TB outbreak, particularly in poorer parts of the world, traditional tests can take days or months to determine which drugs will knock the disease out. In that time, people die. The World Health Organization says TB today kills more youth and adults than any other infectious disease, including AIDS and malaria combined.

Biochip technology promises to quickly and easily identify specific TB strains and the most effective treatment. Researchers at Argonne and in Russia have verified that biochips can identify mutant TB bacteria by testing strains categorized by traditional methods. Each biochip was prepared with probes to identify 29 mutations that account for 97 percent of the resistant bacteria currently active in patients.

Early tests done on sputum from chronic patients found that 20 of 28 samples contained mutations. Conventional tests later confirmed that these 20 strains were drug resistant.

Working with eight tuberculosis-related institutions in Russia, the researchers began clinical trials in Moscow, St. Petersburg, Novosibirsk and Irkutsk in 1999. They expect the tests to provide initial epidemiological information to help track the spread of mutant strains from one geographical area to another.

HOW BIOCHIPS DETECT TB
The pads on biochips for tuberculosis carry short synthesized strands corresponding to DNA of different TB strains. Each pad contains multiple samples of a single sequence of nucleotides—the four molecular bases that make up DNA, denoted as A, C, T and G. Testing uses the nucleotides’ natural pairing tendency. A and C always bond to one another, as do T and G.

A treated sample of single strands of unknown TB DNA is spread on the slide. Matches with complementary known short strands identify the bacterium and point doctors to the drugs that will work against it. The biochip test, which takes only a few hours, could replace the standard time-consuming series of TB diagnostic procedures. These include a skin test, a chest X-ray and a throat culture. The bacteria grow slowly, and preparing a culture typically takes two months. While they wait, patients are treated with a mixture—or “cocktail”—of antibiotics, an approach that is too expensive to be practical in the poor areas where TB is most prevalent.

By using DNA samples from different bacteria in the gel pads, the Argonne/Englehardt technique can quickly and efficiently diagnose a vast range of diseases. The greater number of reaction sites on Argonne slides makes them more sensitive than conventional biochips. Plus, they can be cleansed and reused up to 10 times, making them much more economical than similar products.

For more information please contact Richard Greb at 630-252-5565

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