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Biomedicine

DNA-Based Artificial Nose

Single-stranded DNA can be used to identify explosives and other airborne compounds.

Scientists have found a way to quickly identify which DNA sequences are ideal for detecting a particular odor and turn dried DNA into odor detectors. While many researchers are working on an electronic nose to detect toxins and explosives, this new platform could be used to create a wide array of sensors using existing high-throughput molecular-biology equipment.

Smart sniffer: Cogniscent’s electronic nose (above) now uses sensors made from short sequences of single-stranded DNA that can detect toxic and explosive chemicals in the air.

“Now what we can do is take a microarray of 20,000 sensors … and pick out those sensors that best respond to the odors of interest,” says lead researcher Joel White of Cogniscent, a company based in North Grafton, MA, that manufactures odor-detection devices.

Compared with man-made sensor technologies developed for vision and hearing, our ability to mimic the chemical senses–smell and taste–is relatively primitive. To detect explosive materials such as TNT, scientists typically design highly specific polymers that fluoresce when they come in contact with their target compounds. But building a more generalized electronic nose platform that could detect a wider range of chemicals hasn’t been possible.

Over the past decade, White and neuroscientist John Kauer of Tufts University have been working to improve their patented electronic nose, a handheld device that contains an array of 16 sensor types made of synthetic polymers. These polymers are cross-reactive, so that several sensor types may change shape in response to a single odor–a design analogous to the human nose. The polymers are dyed with a fluorescent marker, and their activation patterns can be monitored via optical electronic sensors and analyzed by an embedded microprocessor. But after 10 years of hard work, the pair had only been able to incorporate about 50 synthetic polymers–far less than the estimated 1,000 sensors in a human nose, which can respond to some 10,000 different odors.

Several years ago, the duo decided to test DNA–a natural polymer that is ubiquitous in the biological laboratories where the scientists spend most of their time. “When we first started talking about it with people, nobody imagined that dye-labeled DNA dried onto a substrate would respond to odors,” says White.

The scientists began their experiments haphazardly: by scavenging short pieces of single- and double-stranded DNA from neighboring labs at Tufts and looking at their responses to several standard compounds. Their first experiments with dye-labeled double-stranded DNA gave them a hint that the approach could work, but all the sequences they tried responded to odors in the same way.

Single-stranded DNA, on the other hand, provided repeatable responses to odors, and this response depended on the specific sequence of four nucleotide types that make up the genetic code. With a typical sequence about 20 nucleotides long, the team has the potential to create millions of sensor types. In the current issue of PLoS Biology, the researchers describe the response of just 30 sequences, but White says that now they have identified hundreds of useful DNA sequences, including one that responds to the vapor signature of TNT-containing land mines–an unusual finding indicating the versatility of the technique.

Alan Gelperin at Philadelphia’s Monell Chemical Senses Center hails the discovery as a major step. “The whole field has been hindered by a lack of diverse sensor technology,” he says. “This is the first demonstration that [DNA] could be used in this way.” Since first learning of the approach during a conference, Gelperin has collaborated with University of Pennsylvania physicist Charlie Johnson to take the concept one step further by incorporating an electronic readout made with carbon nanotube transistors.

For now, White says that his team has incorporated his DNA sensors alongside the synthetic polymers in targeted projects, including one device for detecting ammonia gas, which would be useful for warning emergency responders at toxic spills or for monitoring pollution from livestock operations. He says that there is even interest among vintners in developing a device that could help sniff out counterfeit wines. “This was news to me,” White says, laughing.

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