Purdue University researcher Fred Regnier has developed a way to take specialized instruments from the chemistry lab and shrink them one thousand to one million times and put them on a computer chip.
The unique design, which has been patented by Purdue and PerSeptive Biosystems Inc. of Boston, will allow scientists to pack dozens or hundreds of "laboratories" -- each fully capable of carrying out complex chemical analyses -- on a single silicon chip, reducing the cost and boosting the efficiency of many chemical and medical analyses.
"We now have the ability to do chemistry on a chip and carry out large numbers of experiments at the same time," says Regnier, professor of chemistry at Purdue and co-founder and chief technical officer of PerSeptive Biosystems. "Instead of having one chemistry lab to do experiments or chemical analyses, you can now have many labs all doing experiments at the same time."
The laboratory chips should be available in three to five years, Regnier says, and may allow physicians and medical professionals to perform chemical analyses that currently are done at specialized laboratories.
Details of the miniature laboratories were presented June 27 at the International Symposium on Column Liquid Chromatography in Birmingham, England.
The miniature laboratories can be used to perform capillary chromatography and capillary electrophoresis, both chemical techniques used to separate mixtures into pure chemical components. These types of analytical separations frequently are used in clinical analyses of blood and tissue samples, medical research, and drug discovery.
In standard chromatography, a solution to be separated is poured through a tube or column packed with various particles that are coated with a chemical compound. The different components of the solution are attracted to the particles with different affinity, and as the mixture flows through the column, it separates into a series of zones, each containing a pure substance.
The miniature laboratories employ the same principle. The difference is in their size and the way they are made.
Channels and microscopic "particles" are created using photolithography and chemical etching, the same technologies that are used to build semiconductors. The entire laboratory -- with chemical reaction vessels the size of a speck of dust and chromatography columns the size of a human hair -- is cut from a single piece of silicon, similar to the creation of a sculpture. Liquids are moved on the chip by voltage applied at the ends of the channels.
"What makes this device unique from similar devices under development is that we have found a way to create tiny, rectangular 'particles' within the channels," Regnier says. "These monolith structures, etched into the column as a single unit, serve the same purpose as the packing materials used in conventional chromatography columns, and they allow the miniature laboratory to perform more complex procedures."
Despite their diminutive size, the laboratories on a chip can obtain accurate measurements using only a fraction of a drop of liquid.
"Instead of using microliters of liquid, as is normally done, we use picoliters, volumes that are a million times smaller," Regnier says. "Using these tiny amounts of sample, measurements can still be made to within a few percent accuracy."
The mini-laboratories also differ from standard chromatographs because they contain no moving parts.
"Because it has no moving or machined parts, it's a much simpler device and is much less expensive to build than conventional laboratory equipment," Regnier says. "A standard liquid pumping system and column, for example, may cost $15,000, but a chip can be fabricated for $400, and we can line up 10 to 100 mini-laboratories on a single chip.
"That's the beauty of the microfabricated devices. In microfabrication, it's just as easy to create a large number of laboratories as it is to create just one, because they're all etched into the silicon chip at once as a single unit."
Using microfabrication techniques also will make it easy to create different versions for different applications, Regnier says.
The ability to fabricate specialized instruments at low cost and to connect large numbers of them together could have a major impact on areas of science such as clinical analysis and drug discovery, Regnier says.
"This effort parallels what happened in computers 30 years ago when scientists realized that by making semiconductors very, very small, they could put large numbers of them in a small space and do a huge number of calculations at once," he says.
The new technology may be particularly useful in pharmaceutical laboratories where scientists analyze thousands of natural and synthetic compounds in search of new drug candidates, Regnier says.
Other applications may include clinical settings such as a doctor's office, where the miniature laboratory could be used by medical professionals to perform diagnostic procedures. For simple diagnostic procedures, laboratories could be designed to work in a fashion similar to pregnancy test kits.
However, the miniature laboratories will be much more sophisticated, and will be able to perform in either a single-channel mode -- such as single test kits now do -- or to perform large numbers of different tests, or large numbers of the same test.
"Those types of tests currently are done in central laboratory facilities," Regnier says. "This technology might allow a clinical laboratory to be compacted into a single chip."
Though the tiny laboratories will be able to perform many of the same functions as standard chromatographs, their miniature stature does limit their capacity, Regnier says.
"Standard chromatographs are sometimes used to purify products, such as human growth hormone," he says. "Because of the minute amounts of liquid used in these mini-labs, it would not be feasible to use them to purify products. These devices are designed to analyze, and that they can do very well."
The research at Purdue was funded by the National Institutes of Health and the National Science Foundation. PerSeptive Biosystems has been developing microfluidic technologies for the diagnostics and pharmaceutical industries since 1993 and plans to commercialize devices and services based on the "lab on a chip" chromotography technology.
smg/Regnier.labchips/9706f15
Source: Fred Regnier, (765) 494-3878; e-mail, fregnier@purdue.edu Writer: Susan Gaidos, (765) 494-2081; e-mail, susan_gaidos@uns.purdue.edu
Photo caption:
Purdue researcher Fred Regnier (right) and Bing Ho, a doctoral
student in chemistry, stand next to a liquid chromatograph, an
instrument used to separate chemical compounds, as they examine a
silicon disk that contains a scaled-down version of the device. The
mini-laboratory is capable of carrying out many of the same types of
chemical separations as the full-sized instrument. Regnier has
developed a way to place multiple mini-labs on a single silicon disk.
(Purdue News Service Photo by David Umberger)
Color photo, electronic transmission, and Web and ftp download available. Photo ID: Regnier/Labchips.
NOTE TO JOURNALISTS: Fred Regnier will be in Europe for the last half of June, so journalists who wish to interview him should contact him at Purdue before June 14 or after June 30. A color photo of researchers examining a microfabricated laboratory is available. The photo is called "Regnier/labchips."
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