“Multiplexed capillary electrophoresis” may sound like a mouthful, but it is rapidly revolutionizing the field of chemical analysis.

Among those who track DNA sequences or develop new medicines, “high throughput”—sciencespeak for “more”—is a favorite term. Scientists want to test more chemicals faster to decode what makes a human a human or to identify the drugs that will improve or even save human lives.

Scientists at Ames National Laboratory in Ames, Iowa, developed technology to enable this express-lane molecule analysis. Led by senior chemist Ed Yeung, researchers bundled 96 separate experiments into one machine, complete with automation, so that the experiments can run at night and software can analyze the barrage of data when lab workers are sleeping. The technology netted Yeung an R & D 100 Award from R & D magazine as one of the top inventions of 2001.

Scientists often want to sort molecules, such as DNA, by size or electrical charge. In gel electrophoresis, an electrical current propels the molecules through a gelatin-like material. The smaller molecules zip through the gel, while larger chemicals take more time to navigate the matrix.

A standard gel ranges from dessert size to the size of a piece of paper, and holds a dozen or so samples. When scientists tackled the Human Genome Project, reading each of the three billion letters in a human DNA, they knew running every strand through the ordinary gels would take far too long. In 1990, Yeung developed a way to turn those gels into skinny capillary tubes—two feet long and the width of a human hair—and run 96 capillaries at the same time. Called multiplexed capillary electrophoresis, the technique is now standard for DNA sequencing. Couple the technology with robotics to control it, and the experiment practically runs itself.“The key point is to do it at high speed and high throughput,” Yeung said. “By doing it 96 at a time instead of one at a time, you immediately get that roughly hundredfold advantage.”

Capillary electrophoresis runs faster not only because many samples race through the strands at one time, but also because scientists can use much higher voltages to power the molecules’ travel. Standard gels run at around 100 volts, but capillaries can take as much as 20,000 volts. At that voltage, a regular gel “will basically start to boil,” Yeung said. Capillaries, in contrast, are exposed to cooling air on all sides, so the experiments are complete in minutes, instead of hours, without becoming overheated.

“One of the hallmarks of capillary electrophoresis is the exquisite level of separation that you can get,” said Steve Siembieda, chief operating officer at Advanced Analytical Technologies, Inc. in Ames, Iowa, which produces multiplexed capillary electrophoresis equipment. The technique can separate DNA strands that differ in length by a single base—that is, one of the three billion letters in the human genome. No other electrophoresis technique can match it, so it’s ideal for purifying compounds.

DNA sequencing depends on fluorescent tags glued to each molecule. A scanner reads the color to record when the molecules reach the end of their ride. But many molecules don’t fluoresce, and the colored tags can be expensive and toxic. In the late 1990s, Yeung realized that the technology could have more widespread application if it relied on ultraviolet (UV) light, instead of fluorescence, to detect the molecules whizzing through the tubes. Nearly all molecules absorb UV light.

In multiplexed capillary electrophoresis with UV absorption, the machine shines UV light on the samples as they reach the end of their journey. A scanner can detect the molecules based on how much light is absorbed. This kind of electrophoresis is “universal,” Yeung said. DNA, proteins and small molecules all show up.

The technology is now common lab equipment. Commercial machines run as many as 384 samples at a time. Researchers use it to sort proteins and carbohydrates and test how potential drugs interact with other compounds. Because the equipment processes multiple experiments simultaneously, costs are the same as or less than other techniques. For high-throughput work, the better, faster, cheaper capillaries have replaced the old-fashioned gel slabs for good.