Smaller. Faster. Better.

Chemistry professor James Landers is a master of compression. He has reduced an entire laboratory for DNA analysis to a chip the size of a common everyday microscope slide. Asked about the advantages of his Lilliputian laboratory, he’s appropriately succinct: “With a lab-on-a-chip, it takes just 30 minutes to do the work it would take three technicians and three instruments to complete in a week.”

The magnitude of Landers’ accomplishment, on the other hand, cannot be minimized. His paper announcing his lab-on-a-chip, published by the Proceedings of the National Academy of Sciences, was highlighted in Science and in the biotechnology edition of Nature, the two foremost scientific journals in the world. Landers demonstrated for the first time that it is possible to miniaturize and integrate a series of discrete analytic processes that require their own distinct — and often incompatible — reagents and to do so economically.

When it comes to analytic chemistry, small has many virtues. Landers’ lab-on-a-chip is relatively portable and will eventually require just a tabletop device to manipulate the sample, to manage its flow from one part of the chip to another and to analyze the results. It also requires just minute samples, making it appropriate for clinical and forensic analysis as well as biomedical research. Ultimately, though, miniaturization is just a means to an end. In Landers’ world, small is fast.

It’s really a matter of proportion. One segment of each chip is devoted to electrophoresis, a method of separating large molecules — such as DNA fragments or proteins — in a mixture of similar molecules by passing an electric current through the mixture. Each molecule travels through the medium at a different rate, depending on its electrical charge and size. The use of tiny troughs etched on the lab-on-a-chip allows Landers’ students to apply electric fields as high as 10,000 volts to drive these separations. This moves things along in a hurry.

Thanks to its vacuum-activated valves and laminar-flow properties, the microchip itself provides the ideal platform for integrating other technologies with electrophoresis. Landers’ lab-on-a-chip contains a section devoted to extracting DNA from a sample and an adjacent one supporting the polymerase chain reaction, a process used to replicate specific segments of DNA so that they can be easily identified. The ability to integrate distinct processes while isolating their reagents turns each chip into a miniature assembly line.

For instance, when an infant is suspected of having whooping cough, the normal procedure is to take a specimen and culture it for pertussis bacteria, a process that can take as long as 48 hours. Landers’ students simply insert the sample in the chip. In the first section of the chip, the DNA is automatically extracted.  It is then moved to a section of the chip where portions of DNA that would contain a telltale signature of the pertussis are amplified. They are then passed to a third area of the chip where they can be analyzed. “In this situation, the ability to perform this kind of analysis in less than an hour is critical,” Landers says.

The desire to increase the speed of medical diagnosis is a driving force behind Landers’ research. As a Canadian Medical Research Fellow at the Mayo Clinic, he was asked to investigate the potential of capillary electrophoresis for diagnosing illnesses more quickly. He went on to develop separation-based assays for multiple myeloma, multiple sclerosis and hypoglycemic drug abuse among other conditions. Landers, who holds a joint appointment in pathology, simply says that his primary motivation is to “give doctors the tools to improve quality of life.”

Landers also sees applications for his lab-on-a-chip technology to help process the tremendous backlog of rape case samples, estimated to be between 400,000 and 500,000. “It takes one tech one week to process a few samples,” he says. “As a result, many samples sit on the shelf for years.” The only alternative now is to hire more technicians, an approach cash-strapped localities are hesitant to take. Landers’ lab-on-a-chip would dramatically accelerate the process of analysis while providing a closed system that would limit the potential for contamination.

Moving analytic processes from macro- to micro-scale is not always straightforward. In some cases, it is simply a question of miniaturization. In others, it requires expertise from other fields. “Microminiaturization research is interdisciplinary and demands skills and knowledge beyond the traditional boundaries of chemistry,” says Landers, who has worked in recent years with engineering and medical faculty as well as his chemistry colleagues. “Connecting with people is easy here,” he says. “The way this institution is set up encourages collaboration.”

Oscar, 3/14/07