Pharmaceutical companies will soon have a new tool to help them develop drugs.

Using technology refined at SIUC, two small Minnesota firms are devising an analytical instrument so sensitive that, in principle, it can detect just a few molecules of virtually any chemical compound.

Such sensitivity would prove useful to the drug industry in everything from pinpointing the components of newly discovered plants to checking the purity of a particular formula to monitoring the length of time a given drug stays in the bloodstream, says John Koropchak, SIUC vice chancellor for research and the chemist whose work underpins the new system.

His collaborators, David Blackford of Fluid Measurement Technologies Inc. and Fred Quant of Quant Technologies, are devising prototypes of the new system. The National Institutes of Health is funding the effort with $1.2 million through the federal Small Business Innovation Research program.

The system pairs two processes that have not previously been used together. It starts with something called high-performance liquid chromatography (HPLC), widely used for chemical analysis.

In HPLC, a liquid sample is injected into a column filled with an appropriate solid. Lipid-based samples, for example, require a column filled with silica gel. Different chemicals migrate down through the column at different rates and exit the column at different times.

A detector of some type is used to analyze those chemicals as they flow out. For example, certain chemicals can be identified by the UV light spectra that they absorb.

But existing detectors all have drawbacks. Some cannot detect small concentrations of substances. Others cannot detect certain classes of substances.

"The pharmaceutical industry, among others, has substantial needs for detection of every sample component," Koropchak says. "And the ability to analyze hard-to-detect substances such as lipids and carbohydrates could provide a powerful tool for drug discovery."

Koropchak's key idea was to realize that a type of instrument used for decades to count atmospheric particles might be adapted to serve as a more-sensitive, nearly universal chemical detector. The technology, called condensation nucleation light scattering, had not been used before for chemical analysis.

Just as tiny dust particles serve as "seeds" for raindrops, this technology condenses vapor on chemical particles from HPLC, creating droplets. The original particles may be just a few nanometers wide, too small for other detectors to pick up. But embedding each one in a droplet is, proportionately, like enlarging a grain of sand to the size of the Statue of Liberty. Light is then bounced off the droplets, allowing them to be detected and the amount of the chemical to be calculated.

With a less-sensitive detector, pharmaceutical chemists might conclude that a given drug hangs around in the bloodstream for eight days, when in fact it's 10. They might not realize that the drug sample they're testing has a trace contaminant. Or they might not be able to identify all the substances that a given drug breaks down into in the body.

In contrast, a condensation nucleation light scattering detector "can give you a response for virtually everything," Koropchak says, "and if it's an unknown substance, you can use other techniques to identify it."

Koropchak and postdoctoral fellows You Jing and Martin Waichigo are now testing second-generation prototypes of the new chemical analysis system on three different classes of compounds with which they have worked extensively.

"We know what their performance should be, so if there's a problem, we can quickly identify it," Koropchak says.

The new instrument should reach the market by 2008 and will probably cost less than current systems, even though it has broader detection capabilities.

—by K. C. Jaehnig, Media & Communication Resources, and Marilyn Davis, ed.