Mar. 30, 1998 An ingenious new use for liquid crystal displays being developed at the University of California, Davis, might one day make complex chemical analyses almost as easy as checking the time on your wristwatch.
In contrast to the slow, costly, laboratory-dependent tests now used for hundreds of jobs in medicine, industry and research, the Davis "liquid crystal assay" could give results in minutes for less than a dollar, virtually anywhere.
The only supplies needed would be the chemical sample, the stamp-size test chip, a few drops of liquid crystal and enough ambient light for the person running the test to read the result. The test doesn't even require electricity.
"The nicest thing about this approach is that the procedure used to perform the detection is very, very simple, " said Nicholas Abbott, the UC Davis associate professor who led the chip's development. "What we're proposing is comparable to the level of sophistication in a liquid-crystal watch and, as we all know, that technology has been very successful."
In this Friday's issue of the journal Science, Abbott and his colleagues will report their construction of a prototype liquid crystal assay and describe the chemical and physical principles that make it work.
Liquid crystals are a state of matter, just like the better-known states of liquid, solid and gas. Like solid crystals, liquid crystals can bend light and change its color. And as their name suggests, they can flow like a liquid.
Wristwatch displays and computer screens employ this light-bending yet fluid quality. With electrical fields, they direct the orientation of the rod-shaped molecules within liquid crystals. The orientation determines how the crystals will transmit light, and that in turn produces the images we perceive as numbers on a watch face or pictures on a computer screen.
Abbott's group oriented liquid crystals to produce an image that would be viewed by the user but did it in a different way. In this case, a change in surface topography, not an applied electrical field, directs the orientation.
The researchers set an experimental goal: to create a liquid crystal assay that would report whether an antibody -- a molecule like those produced by the human body in response to an infection -- was present in a test sample.
First the researchers spread an ultrathin layer of gold atop an inch-square glass plate, creating a microscopic landscape of gentle, parallel hills and valleys.
Within that landscape they placed a field of molecular receptors with a particular affinity for the target antibodies. Now the assay was built.
Then the sample solution was poured over the assay. The molecular receptors grabbed the antibodies and held tight. When the solution ebbed away, the landscape was left irreversibly changed: It was studded with antibodies, like big boulders.
Finally, a few drops of liquid crystal were oozed across the landscape and allowed to settle.
Had there been no antibodies in the test solution -- no boulders -- the liquid crystal molecules would have aligned in parallel along the hills and valleys. In that orientation, they would have transmitted no light. The tester would have seen just a black square.
But because there were antibodies, the liquid crystals were forced to bend around them. Light caromed crazily through the these contorted crystals, creating psychedelic patterns of yellow, orange and red, or fluorescent pink and green.
"It was striking," Abbott said, recalling his first sight of the finished test. "It was an exciting result, because it was so clear-cut that it would have been understood by any onlooker."
"What the Davis group has done is very, very clever," said Curtis Frank, the William M. Keck Sr. professor of engineering at Stanford University. Stanford and UC Davis are partners, with IBM Almaden, in the Center for Polymer Interfaces and Macromolecular Assemblies, a federally funded research program.
"The approach is very simple, but it's elegant," Frank said. "And that combination often yields many really nice inventions. This should have a large number of applications as a diagnostic tool."
For instance, Abbott said, this sort of "lab on a chip" technology could allow a crime scene investigator to check quickly for illegal drugs or explosives. Rural health-care workers could do bedside blood tests. Air or water pollution could be detected on-site. Pharmaceutical developers could quickly screen large numbers of drug candidates for desired qualities.
Abbott is working now on the next challenge -- making the test give more than a "yes" or "no" answer.
"Right now, the assay can detect a threshold concentration -- it can say whether the target material is there or not. But it can't yet tell us how much of the material is there," he said.
His current idea is to construct another landscape. This one would consist of a patchwork of fields, each field studded with a different density of molecular receptors. The test result would appear as a grid of bright and dark squares that would tell the user how much of the targeted material was present.
Abbott's collaborators on the Science paper were Vinay Gupta, Timothy Dubrovsky and Justin Skaife. Until recently, Gupta and Dubrovsky were post-doctoral researchers in Abbott's lab. Gupta is now an assistant professor of chemical engineering at the University of Illinois, Urbana, and Dubrovsky is a research scientist with Roche Diagnostic Systems in Somerville, N.J. Skaife is a graduate student at Davis.
Abbott is the Joe and Essie Smith Endowed Professor of chemical engineering and materials science at UC Davis. In 1994, he was named one of 20 of the most promising science and engineering researchers by the David and Lucile Packard Foundation and awarded $100,000 annually for five years. In 1997, he was one of 60 young researchers to be given Presidential Early Career Awards For Scientists and Engineers (PECASE) and will receive $500,000 over five years.
The research described here was funded by the National Science Foundation through the Center for Polymer Interfaces and Macromolecular Assemblies and by Abbott's Presidential Early Career Award.
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