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Lab-on-a-Chip Offers Potential for Fast Diagnosis of the Flu

Imagine: A traveler, while en route from China to the United States, comes down with a high fever, severe body aches, and diarrhea, symptoms that resemble those experienced by individuals recently infected with H5N1 avian flu. Is she the next case?

If Ronald Larson, Ph.D., professor of chemical engineering at the University of Michigan, has his way, some day health officials will have an answer roughly an hour after the plane lands.

Dr. Larson and his multidisciplinary research team are developing a small, portable device that can quickly decipher the genetic make-up of any influenza virus. Not only could the instrument, called a Genotyper, help diagnose flu in a patient, it could also be used to quickly ascertain if a new human flu strain has emerged. Further down the road, says Dr. Larson, a network of Genotypers could be wirelessly connected, enabling health officials to track the spread of certain flu strains worldwide.

“We believe it’s possible, and our efforts are to further that goal—to make that day come more quickly,” he says.

Diagram of the Genotyper, a DNA lab condensed to a silicon chip, may one day be able to quickly decipher different strains of influenza.
The Genotyper, a DNA lab condensed to a silicon chip, may one day be able to quickly decipher different strains of influenza.
Credit: Dr. Larson

The Genotyper is based on a technology developed by a team led by University of Michigan collaborators Mark Burns, Ph.D., professor of chemical and biochemical engineering, and David Burke, Ph.D., associate professor of human genomics, in which processes conducted in a typical DNA lab are condensed onto one small silicon chip.

About the size of a TV remote control, the Genotyper would employ some of the same techniques used by scientists to determine an organism’s genome. When the system is fully functional, a throat swab from the patient will be placed into the device, which removes the sample’s genetic material—in the case of flu virus, RNA—converts it into DNA, and copies it many times over.

To determine the flu strain, one version of the device uses “restriction enzymes,” enzymes that recognize certain sequences of DNA, clipping the DNA at those sites. Samples that share the same signature sequence as a given flu strain will be clipped at those points; samples that don’t will remain intact. (The team is initially focusing on the HA gene, but they eventually hope to include other genes as well.)

The DNA fragments are then run through an electrophoresis gel, which separates them out by size. Small fragments move farther and faster through the gel than large fragments. The resulting fluorescent read-out reveals the sample’s genetic make-up. In this way, the researchers can tell if a sample matches a common flu virus strain or pinpoint if the HA gene has deviated from the norm, making the virus potentially more dangerous.

In October 2005, Dr. Larson and his colleagues reported that the device accurately distinguished between two strains of flu by detecting variations in the strains’ hemagglutinin gene.

Reference

Pal R et al. An integrated microfluidic device for influenza and other genetic analysesLab Chip. 2005 Oct;5(10):1024-32. Epub 2005 Aug 18.

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Last Updated August 12, 2010