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Volume:7, Number:44
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Sniffing Out Sickness

Scientists in a number of countries have been working for decades to figure out how to build an inexpensive odor sensor for quick, reliable, and non-invasive diagnoses

| Tanweer Hassan |

Ancient Greek and Chinese medical practitioners are said to have used a patient's scent to make diagnoses. Modern medical research, too, confirms the smell of someone's skin, breath, and bodily fluids can be suggestive of illness. The breath of diabetics sometimes smells of rotten apples, experts report; the skin of typhoid patients, like baking bread. But not every physician's nose is a precision instrument, and dogs, while adept at sniffing out cancer, get distracted. So researchers have been trying for decades to figure out how to build an inexpensive odor sensor for quick, reliable and noninvasive diagnoses. The field finally seems on the cusp of succeeding, says Billy Boyle, co-founder and president of operations at Owlstone, a manufacturer of chemical sensors in Cambridge, England.

Boyle, an electronics engineer, formed the company with two friends in 2004 to develop sensors to detect chemical weapons and explosives for customers, including the United States government. But when his girlfriend and eventual wife, Kate Gross, was diagnosed with colon cancer in 2012, his focus shifted to medical sensors, with an emphasis on cancer detection. Gross died at the end of 2014. That she might still be alive if her cancer had been detected earlier, continues to be a "big motivator" for Boyle. Owlstone has raised USD23.5 million to put its odor analysis technology into the hands of clinicians. Moreover, Britain's National Health Service is funding a 3,000-subject clinical trial to test Owlstone's sensor to diagnose lung cancer.

The sensor is a silicon chip stacked with various metal layers and tiny gold electrodes. While it looks like your mobile phone's SIM card, it works like a chemical filter. The molecules in an odor sample are first ionized - given a charge - and then an electric current is used to move only chemicals of diagnostic interest through the channels etched in the chip, where they can be detected. The company is also conducting a 1,400-subject trial, in collaboration with the University of Warwick, to detect colon cancer from urine samples, and is exploring whether its chips can help determine the best drugs for asthma patients by sorting through molecules in their breath. A similar diagnostic technology is being developed by Israeli chemical engineer Hossam Haick, who was also touched by cancer.

His smelling machine uses an array of sensors composed of gold nanoparticles or carbon nanotubes. They are coated with ligands, molecular receptors that have a high affinity for certain biomarkers of disease found in exhaled breath. Once these biomarkers latch onto the ligands, the nanoparticles and nanotubes swell or shrink, changing how long it takes for an electrical charge to pass between them. This gain or loss in conductivity is translated into a diagnosis. With artificial intelligence, professor Haick said, the machine becomes better at diagnosing with each exposure. Rather than detecting specific molecules that suggest disease, however, Haick's machine sniffs out the overall chemical stew that makes up an odor.

In the US, a team of researchers from the Monell Chemical Senses Center and the University of Pennsylvania received a USD815,000 grant in February from the Kleburg Foundation to advance work on a prototype odor sensor that detects ovarian cancer in samples of blood plasma. The team chose plasma because it is somewhat less likely than breath or urine to be corrupted by confounding factors like diet or environmental chemicals, including cleaning products or pollution. Instead of ligands, their sensors rely on snippets of single-strand DNA to do the work of latching onto odor particles. In addition to these groups, teams in Austria, Switzerland, and Japan are also developing odor sensors to diagnose disease.

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