A More Sensitive Cancer Breathalyzer

Lung cancer is a brutal disease, often not caught until it's too late for treatment to do much good. Now researchers are building an electronic nose that could help physicians detect the disease during its initial stages. Using gold nanoparticles, scientists at the Israel Institute of Technology in Haifa have created sensors with an unprecedented sensitivity for sniffing out compounds present in the breath of lung-cancer patients.

Other attempts to do this have yielded promising results (see Lung-Cancer Breathalyzer and Cancer Breathalyzer), but those devices require a higher concentration of the telltale biomarker chemicals than the Israeli device. The chemicals, called volatile organic compounds (VOCs), are metabolic products present in the vapors that we breathe out, but they occur in such small amounts that researchers have had to find ways to increase their concentrations before testing. Now, Hossam Haick and his colleagues have built sensors using an array of gold nanoparticles that can detect these VOCs in their natural concentrations and under the humid conditions characteristic of human breath. Their research was recently published online in the journal Nature Nanotechnology.

Other devices used for the same kinds of tests depend on expensive means of VOC detection, such as optical sensors, mass spectrometry, and acoustic sensors. These systems aren't always portable, either. Gold-nanoparticle sensors, however, have the potential to be small and inexpensive--the only problem has been getting the VOCs to stick to the gold. "It was quite a lot of work to get them to stick," says Haick, a 2008 TR35 winner. "We're the first to do so, as far as I know." Because of an impending patent, Haick declined to explain how he achieved the desired stickiness.

Using breath samples from 40 healthy volunteers and 56 lung-cancer patients, the group used the sensors to identify which biomarkers would collectively act as an accurate sign of lung-cancer signature. After training the sensors to identify the signature and testing it again, Haick and his colleagues found that their device could reliably differentiate between cancerous and healthy breath. They're now testing the device on a larger group of people in various stages of the disease and believe they'll be ready to start clinical trials within two or three years.

"Any advance in the area of developing sensors for breath research is exciting to me, and I think this is certainly an advance," says Peter Mazzone, a lung cancer specialist and breath-analysis researcher at the Cleveland Clinic in Ohio. "This was a very well-done, very promising study. I don't know if it is accurate enough to use in clinical practice, yet it's very exciting to see another promising sensor system."

Small sensor: When exposed to particular gases, chemiresistors, such as the one shown above, change their resistance. Researchers are using an array of nine chemiresistors to detect lung cancer on the breath of human subjects.

Preliminary tests indicate that the gold-nanoparticle sensors can not only differentiate among stages of lung cancer, they can detect distinct signatures for other ailments, such as liver failure. Haick's group has even tested the electronic nose above colonies of cells grown in culture. This study found that while the sensor was able to sniff out compounds already known to be in breath, other lung-cancer-associated VOCs weren't detected. "Obviously, something is going on in the body to metabolize and create additional VOCs," Haick says. He's now working to figure out precisely what that is, in the hopes that it could provide new insight into lung cancer and how to treat it.



By Lauren Gravitz



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