Big-Time Applications for Miniature Tests

If you think an iPod is the height of miniaturization, you haven’t met James Landers. Landers has reduced an entire laboratory for DNA analysis to a chip the size of a common, everyday microscopic slide. But the effect is the same in both cases: miniaturization completely redefines the category, liberates users from the constraints of the current technology, and makes previously unimagined applications possible.

With DNA analysis, miniaturization opens the way to vastly faster processing times because the forces used to manipulate the sample—changes in pressure and electrical field—have an outsized impact when applied at the microscale. Diagnostic tests that normally take as long as 48 hours can be done in 24 minutes. In addition, Landers’ microfluidic devices are much more sensitive than current techniques because they are designed for very small samples. And because the analytical process proceeds automatically, operator error—one of the principal causes of faulty results—is reduced significantly.

Of course, miniaturization also sets the stage for portability. Once the equipment used to manipulate the sample and manage its flow from one part of the chip to the other is similarly miniaturized, mass-produced and inexpensive lab-on-a-chip technology could become commonplace at doctors’ offices and pharmacies to diagnose disease, or at crime scenes to identify criminals.

Progress in microfluidics requires expertise in a dozen different fields. Landers is a professor of chemistry and mechanical engineering and an associate professor of pathology, but even this résumé, impressive as it is, is not sufficient to overcome the remaining obstacles to perfecting this technology. Today it is not only what you know but who you know that leads to advances in technology—and Landers has been able to tap a growing cadre of researchers at U.Va. who can help him move his microfluidic technology forward. “I find that researchers at U.Va. are extremely willing to collaborate,” he says.

For instance, Matthew Begley, a professor of mechanical engineering, has developed a novel system of valves, one of the core devices that make lab-on-a-chip technology possible. In DNA analysis, a sample passes through a series of discrete processes—nucleic acid purification, target-sequence amplification, and separation and detection. The ability to isolate each of these processes with valves is crucial, because they each require their own distinct—and often incompatible—reagents.

The valves currently used in microfluidic devices consist of a thin membrane controlled by a vacuum. Increase pressure and the valve closes; decrease pressure and it opens. Begley has devised a “valveless” system by incorporating a series of baffles in the channel below the junction with the previous process. Unless the fluid is pumped at the precise frequency dictated by the configuration of the baffles, it will not flow through the channel. Begley’s device opens up the possibility of differential flow to a series of channels, setting the stage for multiple analyses on a single chip. “One of the advantages of this new technology is that it will enable us to strip a 40-pound vacuum pump from the control unit, a significant step toward portability,” says Begley.

Landers also enlisted Dr. Sanford Feldman, director of the Center for Comparative Medicine; and infectious disease specialists Dr. Erik Hewlett and Dr. Molly Hughes for assistance in developing a prototype for identifying anthrax and whooping cough. Here serendipity played a role. As a member of the University’s Institutional Biosafety Committee, Feldman inspected Landers’ laboratory and was intrigued with what he saw. “We use molecular testing of the animals housed in the center for disease—and the assays we use are intricate and time-consuming,” Feldman says. “Microfluidic devices could revolutionize the way our laboratory operates.” Feldman contributed his expertise in polymerase chain reaction methodology, as well as a Sterne-strain anthrax specimen, the same strain that Hughes used to create an infected mouse.

Through colleagues, Landers learned that Hughes and Hewlett had clinical samples from infected animals that he could use to validate his tests. Like Feldman, Hughes and Hewlett were happy to help because they could envision their contribution making a real-world difference for their patients. “Rapid diagnosis is essential for successfully treating a disease like anthrax,” says Hughes. “We could use microfluidic devices like the one James is developing in the emergency room and save lives.”