R & D 100 Award is fourth for Ed Yeung and 15th for Ames Lab

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Ed Yeung, program director of Chemical and Biological Sciences, has won a 2001 R&D 100 Award for a remarkable advance in chemical separation technology called multiplexed capillary electrophoresis using absorption detection. R&D Magazine annually selects the top 100 products of technological significance that were marketed or licensed during the previous calendar year.

Yeung worked with former Ames Lab graduate student Xiaoyi Gong, now at Merck, Inc., in New Jersey, to develop the award-winning technology. Multiplexed capillary electrophoresis used in combination with absorption detection makes it possible to rapidly separate samples of complex chemical or biochemical mixtures and has the ability to decipher an individual's entire genetic code faster, more accurately and less expensively than conventional instrumentation – a feat that could potentially revolutionize the diagnosis of diseases and the development of treatments.

Yeung also helped launch a new company to turn the multi- plexed capillary electrophoresis technology into a commercial instrument – the MCE 2000. In an effort to accelerate the development process, he helped establish CombiSep Inc. in Ames (see Insider, February 2001). It took the startup company only nine months to design, develop, test and sell the first instrument. Yeung anticipates that the MCE 2000 will eventually replace high-performance liquid chromatography, one of the most successful commercial instruments for chemical separation used in both biology and chemistry laboratories.

"A head-to-head comparison indicates the MCE 2000 will do everything those standard commercial systems will do, except at 96 times higher speed," says Yeung, who is also an ISU distinguished professor of chemistry. "So, one of our instruments is equivalent to having 96 standard commercial HPLC systems all at once."

Yeung's award brings to 15 the number of R&D 100 Awards won by Ames Laboratory scientists since 1984. It is the fourth such award won by Yeung. Ames Laboratory Director Tom Barton, says, "This is an excellent example of extrapolating the results of DOE-funded fundamental research into breakthrough technology that definitely has the potential of improving people's lives."

Yeung says that any kind of chemical measurements that involve separation can, in principle, be fitted to use the MCE 2000 technology. "Multiplex" means the instrument runs several analyses at a time by using multiple capillaries – 96 in the case of Yeung's instrument. The end result is automated, high-throughput analysis, a technology in high demand in today's biotech industries. In addition to its usefulness in determining an individual's genotype, the MCE 2000 has fast-evolving applications in fields that include combinatorial chemistry, drug discovery and proteomics (the study of protein expression and function).

A look at the component technologies provides more insight on how the MCE 2000 operates. Capillary electrophoresis involves the use of an electrical current that causes the molecules in the sample under investigation to migrate at different speeds, according to size and charge. The capillaries are silica tubes about 2 feet long, with an inside diameter of 75 microns (about the diameter of a human hair). The capillaries disperse heat very well and so can withstand an electrical charge of up to 20,000 volts – and high voltage equals fast separations. The MCE 2000 can perform separations in as little as 15 minutes.

The instrument identifies molecules by means of absorbance detection. Ultraviolet light is focused through a tiny window to illuminate the capillaries. The migrating molecules within the capillaries absorb the light, which is then detected by an array of photodiodes. The resulting data, along with the time it takes the molecules to migrate, is sent to a standard personal computer, where specially designed software interprets it, revealing the type and quantity of the separated compounds.

The ability to detect molecules using ultraviolet light allows Yeung's instrument to handle a wider variety of compounds than other multiplexed capillary electrophoresis systems that rely on laser-excited fluorescence detection. Only about 10 percent of all compounds fluoresce naturally, so optical tags must be attached to those compounds that don't fluoresce. These tags are dyes that are expensive and may be toxic. The MCE 2000 eliminates the need for such costly and potentially dangerous markers.

Another plus for the MCE 2000 technology is that it uses 1,000 times less solvent than high-performance liquid chromatography, the widely recognized reigning method of separation technology. This means less threat to the environment and lower costs.

Perhaps best of all, the MCE 2000 technology allows future scale-up to 1,000 capillaries per instrument, with little modification or increase in cost. "The instrument has already generated real interest in the user community," says Yeung.

"Many of these companies are now negotiating to purchase an instrument. With the projected needs for a high level of sample throughput, we expect that a large fraction of the ten thousand or so DNA and protein analysis instruments presently in use worldwide will be replaced by our system."

Yeung's 2001 R&D 100 Award winning technology will be the subject of an article in the September issue of R&D Magazine. A banquet to honor R&D 100 Award winners will be held at Chicago's Museum of Science and Industry, October 4.

Research on multiplexed capillary electrophoresis using absorption detection was funded by the DOE Office of Basic Energy Sciences, Division of Chemical Sciences.

by Saren Johnston