Biosensing Within the Cell

A microscopic sensor can size up the inner workings of a living cell. The sensor, unveiled last week in New Orleans at the Pittsburgh Conference on Analytical Chemistry and Applied Spectroscopy, could find wide use in the lab and may someday be able to detect signs of a person's exposure to biological or chemical weapons.

One sign of a living cell's health is the levels of certain ions inside it, which biologists usually measure by injecting dyes into a cell or poking the cells with electrodes. Raoul Kopelman and his colleagues at the University of Michigan, Ann Arbor, wanted to find a less invasive procedure.

The key turned out to be a molecule, called an ionophore, that specifically reacts with positively charged ions such as calcium, potassium, or magnesium to activate a fluorescent dye. Kopelman and his grad student Heather Clark packaged an ionophore-dye combo in microscopic particles made of a plasticlike polymer. Next, they injected the minisensors, dubbed PEBBLEs (Probes Encapsulated By BioListic Embedding), into brain cells or mouse eggs with a "gene gun," which normally shoots DNA into a cell with a burst of helium. The brightness of the PEBBLEs' glow revealed the concentration of different ions in the cells. Cells don't seem to mind the PEBBLEs, says Kopelman, probably because they take up little space--each occupies only a millionth of the average cell's volume.

Experts are impressed by the new sensor. "I think it's beautiful," says Stephen Weber, a chemist at the University of Pittsburgh. He notes that because PEBBLEs are used with a microscope, researchers can determine the exact three-dimensional position of the sensor as well as its readout. With the sensor, says Kopelman, "you can now follow changes in chemistry on a single-cell level and see how any change affects it within seconds, minutes, or hours." The PEBBLEs may one day be used to reveal the first signs of a cells reaction to a toxin.