The University Record, June 11, 1996

U-M researchers try to create DNA-analyzing microchip

By Sally Pobojewski
News and Information Services

This silicon wafer contains three of five components fabricated for use in one integrated microchip for DNA analysis currently being developed at the U-M with funding from the National Institutes of Health.

Photo by Mark Burns

An inexpensive, disposable microchip based on technology developed by U-M biomedical engineering researchers could one day eliminate much of the anxiety, uncertainty and expense involved in current medical diagnostic and genetic testing procedures.

Using just a small blood sample, your doctor may be able to scan your DNA with the U-M device and get immediate answers to questions as serious as "Will my baby be born healthy?" or as simple as "Will an antibiotic help my sore throat?"

The current analysis technique for DNA---the molecule that stores our unique genetic "blueprint" in chemical codes called genes---requires a time-consuming process involving the polymerase chain reaction (PCR). "Sequencing genes with PCR requires a complete molecular biology laboratory and at least 10 individual procedures performed by highly skilled technicians in a process that can take days," says David T. Burke, assistant professor of human genetics.

"Our goal is to automate the process by, in essence, shrinking the lab to fit on one silicon microchip," Burke says. "Integrating everything on one chip minimizes the need for human interaction and maximizes efficiency and processing speed."

In an article published in the May 28 issue of the Proceedings of the National Academy of Sciences, Burke and his colleagues reported initial test results on five microfabricated components and their preliminary integration into a DNA-analyzing chip just three centimeters (about one inch) long and one-half-centimeter wide.

"The heart of the device is a thermocapillary pump which uses surface tension, rather than valves or moving parts, to mix drops of pure DNA with an enzyme solution and drive the DNA through five different components on the microchip," says Mark A. Burns, associate professor of chemical engineering.

The DNA solution forms discrete drops with curved surfaces inside a series of narrow channels on the U-M device. "Using microscopic heaters built into the chip, we heat just one side of a drop, which reduces the surface tension and increases the internal pressure on that side," explains Timothy S. Sammarco, a graduate student. "The pressure difference pushes the drop through the channel towards the direction of lower pressure."

In recent developments, the U-M team has moved samples through all five processing steps on one substrate to produce DNA separations, which were visible through a microscope, according to Burns. Work is currently under way to reduce the size of the microchip to about one square centimeter.

Because the device is fabricated with conventional photolithography and silicon micromachining techniques, it should be inexpensive and easy to produce in large quantities, says Carlos H. Mastrangelo, assistant professor of electrical engineering and computer science. Mastrangelo cautioned, however, that significant technical problems related to handling such small amounts of liquid, and interactions between liquids and materials in the chip remain to be solved.

Once the device is perfected, Burke said its low production cost should make it cost-effective for a company to market disposable, single-use microchips reducing the chances of DNA sample cross-contamination, a common problem with current laboratory tests.

"We are building technological expertise into the device itself, so everyone involved in DNA analysis doesn't have to be an expert," Burke explains. Cutting the cost, time and technical skill required for DNA analysis could open up the technology to wider applications in population-based genetic studies, self-testing kits, forensics testing, water analysis, agriculture and biology, Burke adds.

The DNA-analyzing microchip research program is supported by the National Institutes of Health. Initial funding was provided by the Office of the Vice President for Research, College of Engineering, Medical School and Genome Center.