Molecules get microscopic bar code labels.

Bar codes are everywhere. They're on cereal boxes, paint cans, and even lipsitck. If some researchers have their way, the microscopic equivalent of bar codes could infiltrate the molecular world just as widely.

By labeling molecules, the new bar codes could prove valuable for diagnosing diseases and tracking the success of treatments, says Michael J. Natan of SurroMed in Mountain View, Calif. He and his colleagues from SurroMed and Pennsylvania State University in State College report on the new tags in the Oct. 5 SCIENCE.

Nanoscale bar codes could also be applied far beyond biomedicine, suggests L. Andrew Lyon of the Georgia Institute of Technology in Atlanta. For instance, they could make it possible to unobtrusively identify and track ordinary materials or objects such as oil, money, or guns.

Although scientists have previously used the term bar coding to describe molecule labeling, the new tags are the first to actually look like miniature versions of grocery-store bar codes.

Many labeling techniques use tiny fluorescing particles that bond to the target molecule. Yet few varieties of molecules can be identified simultaneously in this way because generally only a couple of fluorescing colors can be viewed at the same time, says Natan.

Natan's bar codes circumvent this limitation. Typically, each tag is a metallic bar just 250 nanometers wide and 5 micrometers long, with alternating stripes of reflective metals, such as gold and silver. When viewed under an optical microscope, the stripes contrast in a way akin to the black-and-white bar code printed on a Coke can, says Natan. With variations in the color, number, width, and locations of the stripes, the number of potential combinations is limitless, he says.

To associate each bar code with a particular type of biological molecule, the researchers covalently bonded distinctively striped bars to an appropriate antibody. The antibodies carried the new tags along as they attached to their target molecules in test solutions.

Although the researchers could see the tags with an ordinary microscope, they couldn't immediately tell which of the bar coded antibodies had bonded to their targets, says study coauthor Christine D. Keating of Penn State. To determine this, the researchers fluorescently labeled the molecules. Whenever the researchers observed fluorescence at the locations of a microscopic bar code, they knew that the bar coded antibody had reached its goal.

Chad A. Mirkin of Northwestern University in Evanston, Ill., says that the tiny bar codes are "really ingenious" and could become the basis for new diagnostic and medical screening techniques. The bars are "certainly very exciting," adds Shuming Nie of Indiana University in Bloomington, who recently developed a technique for tagging molecules with small fluorescent balls (SN: 7/7/01, p. 7).

However, Mirkin and Nie say that challenges remain. For one thing, it's not easy to make big batches of identical microscopic bars. Also, to make the bar codes practical, researchers will have to make sure that the tags don't clump or break and that their affiliated antibodies bind only their target molecules. Nie notes also that the researchers have yet to determine how accurately they can read the bar codes, especially as the coding schemes get more complicated.