Features
www.aftau.org

According to the U.S. Centers for Disease Control and Prevention, lung cancer is the leading cause of death in the US and the second most common cancer among men and women. The National Cancer Institute reports that lung and bronchus cancer causes more deaths in the US than the next three most common cancers combined (colon, breast, and pancreatic). This striking mortality rate is due largely to poor detection methods and uncontrollable metastasis.

Sniffing Out the Disease

Fig. 1 – (Left) A prototype of a hand-held device that collects exhaled breath from cancer patients. (Center) Exposure chamber with inlet for breath samples. (Right) Array of cross-reactive sensors based on different molecularly functionalized metal nanoparticles to diagnose breath samples. Inset showns a scanning electron microscopy image of the sensor’s template.
A new device developed by a team of Israeli, American, and British cancer researchers may, they say, help to accurately detect lung cancer and identifying its stage of progression. The breathalyzer test, which uses a Nano Artificial Nose (NA-NOSE) nanotech chip to literally “sniff out” cancer tumors, was invented by Dr. Hossam Haick of the Technion-Israel Institute of Technology, and developed by Haick along with Dr. Nir Peled of Tel Aviv University’s Sackler Faculty of Medicine, and Dr. Fred Hirsch of the University of Colorado (UC) School of Medicine in Denver.

“Lung cancer is a devastating disease, responsible for almost 2,000 deaths in Israel annually, a third of all cancer-related deaths,” said Dr. Peled. “Lung cancer diagnoses require invasive procedures such as bronchoscopies, computer-guided biopsies, or surgery. Our new device combines several novel technologies with a new concept—using exhaled breath as a medium of diagnosing cancer.” Diagnostic tests currently available are unsuitable for widespread screening because they are costly, occasionally miss tumors, and sometimes provide high rates of false positives, leading to unnecessary medical procedures.

How It Works

Since lung cancer tumors produce volatile organic compounds (VOCs), they easily evaporate into the air and produce a discernible scent profile. Haick harnessed nanotechnology to develop the highly sensitive NA-NOSE chip that can detect this unique signature of VOCs in collected exhaled breath. In four out of five cases, he said, the device was even able to differentiate between benign and malignant lung lesions and detect different cancer subtypes.

“In principle, the collected exhaled air is exposed to the nanoparticles, which are coated by unique polymers that produce a different resistance to different types of organic compounds,” Peled explained. “The device produces a unique signature for every condition, and the signature is kept in the memory of the device that is able to be reproduced. Our NA-NOSE was able to detect lung cancer with 90 percent accuracy even when the lung nodule was tiny and hard to sample. It was even able to discriminate between subtypes of cancer, which was unexpected,” said Peled. “The bigger the tumor, the more robust the signature.”

Fig. 2 – Illustration of the breath test concept with the NA-NOSE. The NA-NOSE identifies the unique breath code of each disease (or cancer) and converts it to an electrical or digital signal that can be understood by the user.
Peled went on to explain: “The exhaled breath represents the overall metabolic activity in the body. Moreover it is truly noninvasive, easy to sample, and takes no time. Therefore it is very convenient. For that reason, we are also able to detect other type of diseases like breast cancer (local disease), prostate cancer, and even renal failure. Nowdays we perform a combined signature to cross also other body fluids to evaluate if we can improve our performance.” (See Figure 2)

Their study, presented at a recent American Society of Clinical Oncology conference, was conducted on 358 patients either diagnosed with, or at risk for, lung cancer. The participants were enrolled at UC Denver, Tel Aviv University, University of Liverpool, and at a Jacksonville, FL, radiation center. Other researchers included Prof. Paul Bunn of UC Denver; Prof. Douglas Johnson, Dr. Stuart Milestone, and Dr. John Wells in Jacksonville; Prof. John Field of the University of Liverpool; and Dr. Maya Ilouze and Tali Feinberg of TAU.

The device and subsequent analysis accurately sorted healthy people from people with early-stage lung cancer 85 percent of the time, and healthy people from those with advanced lung cancer 82 percent of the time. The test also accurately distinguished between early and advanced lung cancer 79 percent of the time.

What’s Next

Alpha Szenszor, Inc., Boston, MA, a provider of advanced e-nose technology for a wide range of life science applications, has licensed the technology and hopes to introduce it to the market within the next few years. Meanwhile, a new, smaller version of the device has since been developed that can plug into a computer’s USB port.

Ongoing research into the device, called the LCAOS project, is an EUfunded collaborative seeking to enable the earliest possible detection of lung cancer (LC) using volatile biomarkers present in exhaled breath and/or headspace of LC tissues/cells by applying a novel, non-invasive, easy-to-use tool. For more information on the research, visit www.lcaos.eu. A video explaining the technology can be viewed at www.techbriefs.com/tv/NaNose.