November 14, 2002

'Laboratories On A Chip' Get Super-Small, Super-Smart Plumbing

If a crime scene yields only a single drop of blood as evidence, how can a forensics lab perform the dozens of necessary tests on it? What if a doctor finds a suspicious bacterium, but a patient can't wait for the days needed to grow a large colony for testing?

University of Rochester researchers are working on a new way to move and distribute microscopic amounts of fluid around a chip, essentially mimicking the work of scientists testing dozens of samples in a laboratory. The research is in response to a growing demand for "laboratories on a chip," programmable devices that automatically perform the multiple tests on much smaller amounts of material-on site and more efficiently than ever before. Researchers around the world are already working to develop chips that will allow instant glucose monitoring, DNA testing, drug manufacturing, and environmental monitoring.

In order to work, all of these chips need some sort of plumbing system to move liquid. Thomas B. Jones, professor of electrical engineering, and his team have developed a way to use the electrostatic attraction of water to electric fields, called dielectrophoresis, to divide a single drop of water into dozens of incredibly tiny droplets and move them to designated sites on a chip. The droplets can be mixed with specialized testing chemicals or biological fluids, or positioned for diagnostic tests with lasers or electrical pulses. Essentially, any laboratory test that can be shrunk to fit on a chip will be able to be serviced by the new plumbing system.

"Microchemical analysis is a rapidly advancing field, but while there are ways to test minuscule liquid volumes, no one has yet come up with a practical way to dispense and move these liquid samples around a chip," says Jones. "We're hoping to change all that. We've been able to take a single drop of water and split it up into as many as 30 droplets of specific sizes, route them around corners, send different droplets to different points on a chip and even mix different drops together."

Other microfluidic schemes use tiny channels and passages machined into substrates, but these are not only hard to make, but the pressure needed to move the fluid inside means that the slightest defect in fabrication could produce leaks. Jones' system uses narrow electrodes etched onto glass-so thin that they're almost invisible to the naked eye. AC voltage at about 60 kilohertz is applied to the electrodes and the resulting electrical force causes a "finger" to project from the drop. The finger stretches out along the electrode until it reaches the end, sort of a widened cul-de-sac. When the voltage is then switched off, the surface tension of the water itself pulls about half of the finger of water back toward the initial drop while half is left to form the droplets. This cul-de-sac can be quite a distance away across the chip-close to a centimeter in Jones' laboratory-and the path to it can even take sharp turns with ease.

Mixing different droplets together is as simple as setting the cul-de-sacs of two paths next to each other and then changing the electrical connections so that the droplets are attracted toward each other. To produce multiple droplets from a single finger, Jones widens the wires at certain areas along the path, making the finger bulge in that area and accumulating a droplet when the finger retracts.

In the same way that miniaturization changed computers from room-sized machines to pocket calculators, a similar change is coming to chemistry and the biological sciences. Familiar laboratory procedures are being automated and scaled down to the size of microchips. Some companies are even looking to such chips to manipulate and investigate individual cells, while others could benefit from a chip's ability to carry out possibly hundreds of tests on a new drug in just minutes. As the field expands, scientists are finding more uses for such micro-labs.

Eventually, other liquids will be able to be manipulated as well. Jones' team did some preliminary work on antifreeze and noted that while it stretched out similar fingers, the fingers always fully retracted to the mother drop. The team is now working on ways to control both water and other liquids with more finesse.

This research has received support from the National Science Foundation, the Japan Society for the Promotion of Science, the National Institutes of Health, the Infotonics Technology Center, and the Center for Future Health at the University of Rochester.