Cells as sensors.

When it comes to detecting tiny amounts of chemicals with great selectivity and sensitivity, nature sets the standard.

Cells usually win out as the best biosensors.

Yet when scientists try to detect small numbers of molecules in complex mixtures, using cells or other analytical techniques, they often run into trouble distinguishing one subtle reaction from another. To solve this problem, Richard N. Zare, a chemist at Stanford University, and his colleagues have devised a new biosensor that joins one living cell with an apparatus for chemical separation.

"People have made biosensors before and done chemical separations before," says Zare, "but this is the first time that a single cell and a separation system have been combined in one device. This system lets you work with very small volumes of material and achieve very high resolutions."

Through genetic engineering, scientists can breed cells with heightened sensitivities to specific chemicals. The sensing device separates a chemical mixture into its components, enabling researchers to see which molecules trigger a reaction, Zare and his colleagues report in the Jan. 6 SCIENCE.

Two biosensors successfully detected minuscule compounds. One sensed the binding of molecules to receptors on the surface of cultured rat cells. The other measured changes in plasma membrane ion permeability in a frog egg.

Zare sees many practical uses for such biosensors. "One goal is to detect neurotransmitters emitted from certain neurons, where the volumes and concentrations are very small," he says. "This will allow us to look for new neurotransmitters."

Another possible use is drug testing. "After giving someone a drug, you could test for metabolites and see what side effects they have [on cells]," Zare adds. "In medicine, you really want to know this kind of thing."