HOUSTON, Oct. 26, 2001 - A University of Houston scientist has developed a chemical process for building a device that could help doctors predict a patient's response to drugs or screen patients for thousands of genetic mutations and diseases, all with one simple lab test. The DNA chip - similar to a computer chip but imbedded with DNA molecules instead of electronic circuitry - is designed to probe a biological sample for genetic information that indicates whether the person has a genetic predisposition for certain diseases or conditions.
"We have put thousands of strands of DNA onto a chip that can screen for the genes linked to breast cancer, cystic fibrosis or prostate cancer, for example," says Xiaolian Gao, a professor of biochemistry at the University of Houston. "This highly parallel technology allows us to do thousands or tens of thousands of experiments all at once."
Gao says there currently are many other biochip technologies available or in development, and the ultimate applications of biochips are similar - genetic screening, disease diagnosis and new drug development, for example. But the various devices differ in the technology used to fabricate the chips. She says the quality, suitability and cost of biochip products need to be significantly improved before most researchers or doctors can afford to use them.
"The advantage to our biochip is that we bring to the field a flexible, high quality and more cost efficient technology for DNA chips," she says. "Our novel platform technology will allow scientists to make custom-designed biochips containing not only DNA, but other types of molecules, such as RNA, peptides or libraries of organic molecules. Other prevalent technologies do not have the same potential and capabilities as ours." Gao and her team plan to make the biochips available for fields such as genomics, proteomics, chemical genetics and other new areas. Gao will present information about the versatility of the UH biochip technology Oct. 31 at the International Business Communication's Annual Biochip Technologies Conference, Chips to Hits, in San Diego.
Gao collaborated with two University of Michigan researchers - Xiaochuan Zhou, a research scientist, and Erdogan Gulari, a chemical engineering professor - and established a company called Xeotron in Houston to manufacture and commercialize their biochip products. The company licensed the technology from UH and UM and has begun producing DNA chips for testing. Initially, researchers in biological and biomedical fields will use the Xeotron-produced chips in labs to understand gene-related questions, but the eventual goal is to bring the chips to market for use by doctors, possibly in three years, Gao says. She estimates the market potential for the biochip to be in the hundreds of millions to billions of dollars.
"Our ambition is to become the Intel of the biochip market," Gao says.
The process Gao, Zhou and Gulari developed to make the DNA chip involves the use of thousands of micromirrors to project tiny light patterns - less than the diameter of a human hair - onto each postage stamp-sized DNA chip. Micromirror devices are commercially available and are used in some home theater projectors. Each micromirror can be individually manipulated to reflect light onto an exact location on the DNA chip.
Controlled by a computer, the light hits the chip at different spots, where it triggers a chemical reaction. Individual DNA strands are then built up on these locations one by one in a grid-like pattern, and the computer keeps track of information such as where each DNA strand is on the chip.
The strands of DNA affixed on the surface of Gao's chip act as probes, each strand corresponding to a specific gene or a DNA sequence where a complementary strand in biological samples will bind. The DNA contained in a blood or a tissue sample can be placed on the chip, and the person's DNA would then match up with the appropriate probe, like two pieces of Velcro attaching to each other. A detection device indicates which probes found their mark.
"If we put specific probes on the chip, we can tell if a person has or doesn't have these genetic codes present, and we can screen for thousands or tens of thousands of genes at once," Gao says. "Also, your genetic code may determine whether you have the ability to degrade a certain drug, or how well you will respond to a certain drug. Some people have better responses than others to hypertension drugs, or chemotherapy, for example.
"Using the chip, we also look at drugs that bind to DNA or RNA. This drug screening process can help tell us why a drug is more effective than another. In this case, we know a drug molecule binds to a region in the DNA or RNA probe, but we don't know why," Gao says. "We have interesting observations, and if we knew the mechanisms of binding, we could potentially design new molecules, new drugs that work better and are more specific." Gao is investigating molecular recognition using a technique called nuclear magnetic resonance spectroscopy, which allows researchers to look at the three-dimensional structure of molecules and DNA binding sites at the atomic level.
Gao's research has been funded by the National Institutes of Health, the Welsh Foundation, the Texas Higher Education Coordinating Board, the National Foundation for Cancer Research and the Merck Genomic Research Institute, a non-profit funding agency. In addition, Gao, along with Zhou and Gulari, recently received a grant from the Defense Advanced Research Projects Agency.
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