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Unlike that of proteins and nucleic acids, the rapid detection of small-molecule targets remains a considerable challenge—particularly for work with biological samples. “If a doctor wants to look for a drug or drug metabolite in blood serum, it's got to be sent off to some lab where some tech does gas chromatography and mass spectrometry on it, and sends the results back days later,” says Kevin Plaxco, a chemist at the University of California at Santa Barbara.

Plaxco's team has amassed considerable experience in developing biological detection systems based on aptamers, small DNA molecules capable of binding to target molecules with high affinity and specificity. Last year, they described an electronic aptamer-based (E-AB) protein sensor, wherein a gold electrode was conjugated with thrombin-binding aptamers linked with methylene blue, a compound capable of mediating electron transfer to the electrode; the thrombin-aptamer complex assumes a conformation that inhibits electron transfer, and the resulting change in signal reveals the presence of thrombin in biological samples (Xiao et al., 2005).

In new work, they describe a similar system for the detection of a small-molecule target—cocaine. Their E-AB sensor proved capable of detecting micromolar quantities of cocaine diluted into complex biological fluids, like human saliva, and could even recognize the drug when it had been 'cut' with commonly used substances such as baking soda (Baker et al., 2006). Current detection limits are still an order of magnitude too poor to detect cocaine use in patients, but the level of sensitivity that Plaxco's team has obtained with other E-AB sensors—into the picomolar range—offers encouragement that sensitivity could be enhanced with the use of improved aptamers.

Combining simple construction—according to Plaxco, many of the sensors were assembled by high school students working in the lab—with broad flexibility, this system offers exciting possibilities for new diagnostic tools, and Plaxco's group is now looking to build E-AB sensors for the simultaneous detection of multiple compounds, and for the detection of disease biomarkers. “We've got a small molecule–sensing platform that's as generalizable as aptamers themselves are—and the literature suggests they're pretty generalizable,” he says. “Using these it should be easy to make a palm-top device that can detect a wide range of small molecules in seconds. That is really unprecedented; that's what I'm most excited about.”