New breathalyzer for disease can detect COVID in real time, can be used to detect cancer, lung diseases

With each breath, humans exhale more than 1,000 different molecules, producing a unique chemical fingerprint, or “breath” rich with clues about what’s going on inside the body.

For decades, scientists have tried to harness that information, turning to dogs, mice and bees to literally rule out cancer, diabetes, tuberculosis and more.

Scientists at CU Boulder and the National Institute of Standards and Technology (NIST) have made a major breakthrough in the quest to detect disease using exhaled breath, reporting that a new laser-based breathalyzer powered by artificial intelligence (AI) can detect COVID-19. 19 in real time with excellent accuracy.

The results were declared on April 5 Journal of Breath Research.

“Our results demonstrate the promise of breath analysis as an alternative, rapid, non-invasive test for COVID-19 and highlight its remarkable ability to diagnose diverse conditions and disease states,” said first author Qizong Liang, Ph.D. candidate in the Department of Physics at JILA and CU Boulder. JILA is a partnership between CU Boulder and NIST.

A multidisciplinary team of physicists, biochemists and biologists is now shifting its focus to a wide range of other diseases in hopes that the “frequency comb breathalyzer” born of Nobel Prize-winning technology from CU will revolutionize medical diagnosis.

“There is a real, foreseeable future in which you can go to a doctor and have your breath measured along with your height and weight … or you can blow into a mouthpiece integrated into your phone and get information about your health in real time,” said senior author Jun, a Zilla Fellow and associate professor of physics at CU Boulder. Yeh said. “The potential is endless.”

A COVID-Born Collaboration

As early as 2008, the Yeas lab reported that a technique called frequency comb spectroscopy—essentially using laser light to separate one molecule from another—could potentially identify biomarkers of disease in human breath.

The technology lacked sensitivity and, more importantly, the ability to link specific molecules to disease states, so they never tested it for diagnosing illness.

But Yeh’s team improved the sensitivity a thousandfold, allowing them to detect trace molecules at the parts-per-trillion level. They have also harnessed the power of AI.

“Molecules increase or decrease in concentrations when associated with specific health conditions,” Liang said. “Machine learning analyzes this information, identifies patterns, and develops criteria that we can use to predict diagnoses.”

As SARS-CoV-2 sweeps across the country and frustration grows over long response times for existing tests, it’s time to test the system on people. As a physicist, you’ve never worked with human subjects, so he enlisted the help of CU’s BioFrontiers Institute, an interdisciplinary center for biomedical research that heads the campus COVID testing program.

Non-invasive, fast, chemical free

Between May 2021 and January 2022, the research team collected breath samples from 170 CU Boulder students who, in the previous 48 hours, took a polymerase chain reaction (PCR) test by submitting a saliva or nasal sample.

Half of the tests are positive, half are negative. (For safety reasons, volunteer participants arrived in an outdoor campus parking lot, blew into a sample-collection bag, and left it for a lab tech waiting at a safe distance.)

Overall, the process took less than an hour from collection to result.

Compared to PCR, the gold standard COVID test, breathalyzer results match 85% of the time. For medical diagnosis, an accuracy of 80% or higher is considered “excellent”.

The researchers suspected that the accuracy would have been increased if the breath and saliva/nasal swab samples had been collected at the same time.

Unlike a nasal swab, a breathalyzer is non-invasive. And unlike a saliva sample, users are not asked to refrain from eating, drinking or smoking before using it. Expensive chemicals are not required to break down the sample. And the new test could, conceivably, be used on unconscious individuals.

But there is still a lot to learn, Yeh said.

“With one breath, we can collect several data points from you, but then what? We understand how certain molecules interact with certain conditions,” Ye said.

Building a small breathalyzer

Today, a “breathalyzer” consists of a complex array of lasers and mirrors the size of a dinner table.

A breath sample is piped through a tube as lasers fire invisible mid-infrared light at thousands of different frequencies. Dozens of tiny mirrors bounce the light back and forth through the molecules until, in the end, the light travels about 1.5 miles.

Because each type of molecule absorbs light differently, breathing patterns with different molecular makeup cast different shadows. The machine can distinguish between those different shadows or absorption patterns, boiling down millions of data—in the case of COVID—into a simple positive or negative, in seconds.

Efforts are already underway to miniaturize such systems to chip scale, allowing Liang to envision “real-time, on-the-go self-health monitoring.” The potential doesn’t end there.

“What if you could find a breath signature that detects pancreatic cancer before you have symptoms. That would be a home run,” said molecular biologist and co-author Leslie Leinwand, chief scientific officer of BioFrontiers and co-author of the study.

Elsewhere, scientists are working to develop the Human Breath Atlas, which will map every molecule in human breath and correlate it with health outcomes. Liang hopes to contribute to such efforts with a large-scale collection of breath samples.

Meanwhile, the team is collaborating with pediatric and respiratory experts at the CU Anschutz Medical Campus to explore how the breathalyzer not only detects diseases but also allows scientists to better understand them, providing clues about immune responses, nutritional deficiencies and other factors. Exacerbating or exacerbating illness.

“If you think about dogs, they’ve evolved over thousands of years to smell different things with remarkable sensitivity,” Yeh said. “We’re just at the beginning of training our laser-based nose. The more we teach it, the smarter it gets.”