ENCODED Antibodies are bar coded with striped multimetal microrods. ILLUSTRATION BY MIRCHA PANDURU AND RON KRIETEMEYER

The bar-coded microrods, which comprise cylindrical segments of up to five different metals, are prepared by sequential electrochemical reduction of metal ions into the pores of an alumina membrane template with a silver film as its base. Each segment--or stripe--is between 50 nm and 5 µm long.

The work was carried out by Christine D. Keating, assistant professor of chemistry at Pennsylvania State University; Michael J. Natan, chief technology officer at SurroMed, a biotechnology company in Mountain View, Calif.; and their coworkers [Science, 294, 137 (2001)].

Different bar codes are produced by varying the sequence of metal electrodeposition. The lengths of the stripes in the code can also be varied by changing the amount of electrical charge passed through each metal ion solution. The bar-coded particles are released by dissolving the template and the silver film in nitric acid and sodium hydroxide solution, respectively.

The team uses conventional light microscopy to identify the bar codes. The method relies on the differences in optical reflectivity between adjacent metal stripes.

"We use the striping pattern of the particles as an identification tag, analogous to conventional bar coding encountered at the supermarket," Keating tells C&EN. "Because we have very good control over metal electroplating, and because several metals can be distinguished simultaneously based on their reflectivities, we expect to be able to synthesize incredible numbers of identifiable particles."

Microrods with different bar codes can, in principle, be coated with different reagents that capture a wide variety of biological molecules such as DNA sequences and proteins, the team points out. A mixture of bar-coded microrods could then be added to a solution--blood plasma, for example--and a standard technique such as fluorescence imaging used to detect and quantify analytes that bind to the bar-coded microrods. The identity of an analyte would be determined by the bar code reflectivity readout.

The team demonstrated the technique in a DNA hybridization experiment that used a single optically encoded microrod and also by using an immunoassay protocol to distinguish between human and rabbit antibodies.

SurroMed is aiming to develop the technique for a wide variety of bioanalytical applications in genomics, proteomics, and metabolite profiling, Natan says. "There is a great need to measure many thousands of species simultaneously in extremely small sample volumes, like a drop of blood or less, in solution," he adds.

According to D. Jed Harrison, chemistry professor at the University of Alberta, Edmonton, the technology is likely to play an important role in future designs of multiplexed biochemical assays.

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