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New gene sorting technique slashes world speed records

ANAHEIM, Calif.—University of Michigan chemists have discovered a simple, inexpensive way to sort and separate long segments of DNA at speeds more than 10 times faster than is possible with current methods.

New techniques for rapid, inexpensive DNA sequencing could lead to instant " diagnosis-on-a-microchip" devices in physician's offices and an end to long delays in criminal trials waiting for results of DNA forensics testing.

"We hold the world's speed record for long-chain DNA separations," said Michael D. Morris, U-M professor of chemistry. " With our capillary techniques, we can map large segments of DNA, up to 1,500,000 base pairs, in just under four minutes. Using traditional technology, it can take up to eight hours. "

Within six months, Morris believes he will be able to cut his separation time for 50,000 base-pair DNA from just under four minutes to one minute, and for 1,500,000 base pairs to under two minutes.

Morris described the U-M research project in a presentation at the American Chemical Society meeting held here April 2-6. During his presentation, Morris showed the first fluorescence microscopy images and video of DNA separations as they occur in high-speed systems.

Sorting DNA fragments by size is a common procedure in molecular biology and the first step in DNA forensics testing, gene mapping and diagnosis of genetic diseases, Morris explained. After enzymes split the long chains of DNA into sections containing individual genes, they go through a size sorting process called electrophoresis.

Driven by an electric current, genes make their way through the electrophoresis gel—a thick jellylike solution filled with interlocking threadlike polymer molecules. "It's like swimming upstream through molasses," Morris said. "The shorter the piece of DNA, the faster it can pass through the solution. "

The explanation for how electrophoresis separates and sorts DNA fragments by size was based on theories developed by the Nobel Prize-winning physicist Pierre DeGennes in the early 1970s. Ever since then, scientists have assumed a gel or thick, tangled mat of polymers was crucial to the procedure's success.

But Morris and his graduate students—replicating experiments first conducted by scientists at the University of California-Berkeley—discovered that a dilute solution containing just a few widely dispersed polymer molecules separates long DNA fragments just as well and much faster than the thick solution.

"Instead of being a gel, the ultradilute solution is only slightly more viscous than water, so DNA segments pass through much more quickly," Morris said. Although the exact separation mechanism is still unclear, according to Morris, " polymers appear to collide with, elongate and slow down the DNA segments as they pass sort of like seaweed hitting ropes that mark off a swimming area. "

By periodically reversing the flow of electrical current across the ultradilute solution—a technique first developed and tested at U-M, Morris was able to separate large segments of DNA, up to 1,500,000 base pairs long, as well as small segments.

"The implications of this technology are just beginning to dawn on people," Morris said. " Being able to cut the time it takes to perform these basic procedures by one or two orders of magnitude could have a major impact in all areas of biotechnology, genetic engineering and molecular biology. "

U-M post-doctoral fellow Xuelong Shi and graduate students Richard Hammond, Yong Seong Kim and Michael Navin assisted with the research effort. The work was supported with grants from the National Institutes of Health.