‘MICRO-GEL’ TECHNOLOGY COULD HELP FIGHT
DRUG-RESISTANT STRAINS OF TUBERCULOSIS

By Candace Stuart
Small Times Senior Writer

June 19, 2001 — Not every scientist gets to assist his homeland in a time of need, but Andrei Mirzabekov has adapted a small tech tool he helped invent at Argonne National Laboratory to attack tuberculosis in his native Russia.

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Andrei Mirzabekov
believes Argonne’s
biochip will be
helpful in his
native Russia.
Meanwhile, his colleagues in the lab near Chicago are working to make their biochip versatile and affordable, finding ways to do more on less. They’ve already taken biochips into a new direction – out from the surface of the chip.

Motorola Inc. and Packard BioScience Co. are midway into a five-year, $18 million research agreement with Argonne and its Russian partner, the Engelhardt Institute of Molecular Biology, to develop the biochip technology for commercial uses. Motorola and Packard licensed 19 Argonne technologies related to the biochip.

Argonne initiated the biochip project in 1995. Like most biochips, the system anchors segments of real or synthesized DNA to a chip. If the same DNA is in a prepared sample, the two snippets will lock together. A fluorescent tag that is attached to the sample will light up when the binding occurs. The chip is inserted into a reader, which can detect the light and pinpoint which DNA strand is involved.

But Mirzabekov and his team improved on that basic design by developing a “micro-gel” technology that allowed the segments to poke out from the chip. In that way, they could fit more “probes” on the surface, and expose more of the DNA to the sample.

That lets them offer more probes per sampling – up to 100,000 – with more likelihood of a hit if any of the target DNA is in the sample.

“We have some very significant advantages,” said Lawrence Hill, an associate laboratory director in Argonne’s energy and environmental science technology division, where the biochip research is conducted.

Mirzabekov recognized that a technology such as Argonne’s biochip would be especially helpful in Russia, where increasingly drug-resistant strains of tuberculosis had emerged. The biochip would help doctors identify the strain of bacteria involved and prescribe specific therapies.

With Mirzabekov taking the lead, Argonne and Englehardt Institute identified 29 mutations in the TB bacteria’s genome that accounted for 97 percent of the drug-resistant bacteria. In 1999, they collaborated with eight health institutions in Russia to conduct clinical trials in Moscow, St. Petersburg, Novosibirsk and Irkutsk.

Their results are expected to save lives, time and money. Patients will get drugs designed to attack their specific strain of tuberculosis, allowing for a quicker recuperation and less likelihood that the bacteria will develop yet more drug resistance. The biochip test offers results in mere hours. And prescriptions requiring one specific drug will cost less than the traditional “cocktail” approaches.

“The tuberculosis (project) was something that came up later” in their work, Hill said. “It was a particular bent of Dr. Mirzabekov.”

Mirzabekov returned to Russia to devote himself to the project. His colleagues at Argonne are now looking at ways to improve the biochip and lower costs at the same time.

Besides using DNA probes, the researchers have adapted to biochip to use any probe made of protein. That would allow researchers to attach an antibody, for instance, which could be used to detect the specific cause for infections.

“Ours is particularly flexible,” Hill said. The chip is reusable, and has remained workable through 50 tests. They’ve gotten the cost per chip down to less than $20, Hall said, who estimates mass production will reduce that figure to mere cents.


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CONTACT THE AUTHOR:
Candace Stuart at [email protected] or call 734-994-1106, ext. 233.

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