Mar. 26, 1999 ATLANTA -- It could be a scene from a movie: A doctor puts a drop of blood into a small hand-held device and instantly reads out a complete DNA analysis. But it would have to be a science fiction movie, because in real life machines that analyze DNA are about the size of a refrigerator. And hundreds of them, working for the past 10 years, haven't been able to map the equivalent of one person's DNA.
But Cornell University researchers are working on a "biochip" -- an "artificial gel" made of silicon -- that might be a step toward the science fiction dream.
Stephen Turner, a graduate student working under Harold Craighead, Cornell professor of applied and engineering physics, described his biochip research in a talk, "DNA Motion in Nanofabricated Artificial Gels," today (March 25) at the centennial meeting of the American Physical Society in the Georgia World Congress Center.
The global scientific community has set itself the goal of sequencing all of the DNA in the human genome. But to date only about 10 percent of the total has been mapped. Largely, Cornell researchers say, this is because the process being used, gel electrophoresis, is cumbersome and time-consuming.
In gel electrophoresis, the DNA to be analyzed is first duplicated to make thousands of copies. Enzymes chop the DNA chains into many pieces of varying lengths. The sample is placed at one end of a column of an organic gel and an electric field is applied to the column to make the pieces migrate toward the opposite end. Short pieces move farther and faster than long pieces, so that after a few hours a map is formed showing how the lengths are distributed. Various systems are used to identify the base at the end of each piece, and from this, researchers can identify every position in the chain where each base appears. For accuracy the process must be repeated many times.
Craighead and his students hope to speed up and automate sequencing by replacing the organic gel with a tiny solid-state device, called an artificial gel. Electrophoresis gels consist of a maze of interlocking polymer molecules that leave many tiny openings through which moving DNA molecules must navigate. Using the same techniques used to make electronic circuits, tiny passageways can be carved on a silicon chip,
Turner's artificial gels are forests of vertical pillars with sizes down to 100 nanometers (nm) thick and 100 nm apart. (A nanometer is one billionth of a meter.) They are smaller, Craighead believes, than earlier versions of artificial sieves, an achievement made possible by using the Cornell Nanofabrication Facility's electron-beam lithography tools, which can lay out features much smaller than those used so far in commercial integrated circuits. Ordinarily such devices are made by etching a cavity in the silicon, then gluing on a cover to create a channel through which the DNA sample can flow. Turner used a new technique in which the channel is filled with a "sacrificial layer" that can be etched out after a covering layer is deposited. This allows much more precise control of the height of the channel, he explained.
The researchers are still at an early stage, running DNA samples through the biochip to see how fragments of different lengths can be identified. They mount the chips between two microscope slides, glue small reservoirs to each end to hold a few drops of a water-DNA mixture, place the slides on a microscope stage and apply an electric field, then watch and measure what happens, tagging DNA molecules with fluorescent dyes to make them visible.
While the artificial gel could lead to faster and cheaper methods for sequencing DNA, Turner said, his interest is in learning more about how DNA molecules move through restricted spaces. In water, DNA chains coil into a roughly spherical shape; the longer the chain, the larger the diameter of the sphere. Generally these spheres are larger than the passages through the gel, so the molecule must uncoil at least partially to snake through the openings.
An advantage of the artificial gel, Turner said, is that its openings are of uniform size and distribution, rather than random as in organic gels. This makes it possible to measure the velocity with which molecules of varying sizes move and compare the results with theoretical predictions. He is conducting tests over a range of different electric field strengths and different sieve dimensions.
The research is supported by The National Institutes of Health.
Related World Wide Web sites: The following sites provide additional information on this news release. Some might not be part of the Cornell University community, and Cornell has no control over their content or availability.
-- Craighead research group: http://www.hgc.cornell.edu/biofab/gel.htm
-- APS 1999 Centennial meeting, Atlanta, meeting program index: http://www.aps.org/meet/CENT99/BAPS/index.html
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