New breathalyzer for COVID-sniffing disease in real-time, usable

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

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

For decades, scientists have attempted to exploit that information, turning to dogs, rats, and even bees to actually sniff out cancer, diabetes, tuberculosis, and more.

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

The results were published April 5 in Journal of Breath Research.

“Our results show the promise of breath analysis as an alternative, rapid, non-invasive test for COVID-19 and highlight its tremendous potential for diagnosing a variety of conditions and diseases,” said lead author Qizhong Liang, PhD candidate in JILA and the Department of Physics at CU Boulder. . JILA is a partnership between CU Boulder and NIST.

The multidisciplinary team of physicists, biochemists and biologists is now turning its focus to other diseases in the hope that the “frequency comb breathing analyzer”—born from CU’s Nobel Prize-winning technology—could revolutionize medical diagnostics.

“There is a real, predictable future where you can go to the doctor and take your breath along with your height and weight…Or you can blow a mouthpiece integrated into your phone and get information about your health in real-time, said senior author Jun Ye, a JILA fellow and assistant professor of physics at CU Boulder. “The potential is limitless.”

A collaboration born out of COVID

As far back as 2008, Ye’s lab reported that a technique called frequency comb spectroscopy—basically using laser light to distinguish one molecule from another—could potentially identify disease biomarkers in human breath.

The technology lacked the sensitivity and, more importantly, the ability to associate certain molecules with disease conditions, so they never tested them to diagnose disease.

But Ye’s team has since increased the sensitivity thousands of times, enabling the detection of trace molecules at the parts per trillion level. They also take advantage of the power of AI.

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

With the outbreak of SARS-CoV-2 across the country and growing frustration about the long response times for existing tests, the time had come to test the system on humans. As a physicist, Ye had never worked with human subjects, so he sought help from CU’s BioFrontiers Institute, an interdisciplinary center for biomedical research that leads the campus’ COVID testing program.

The National Science Foundation and the National Institutes of Health funded the research.

Non-invasive, fast, chemical free

Between May 2021 and January 2022, the research team collected breath samples from 170 CU Boulder students who, within the previous 48 hours, had undergone polymerase chain reaction (PCR) tests, either by submitting saliva or nasal samples.

Half tested positive, half negative. (For safety reasons, the volunteers came to the outdoor campus parking lot, blew into the sample collection bag and left it for the lab technicians to wait at a safe distance.)

Overall, the process takes less than an hour from collection to results.

When compared to PCR, the gold standard COVID test, breathalyzer results match 85% of the time. For medical diagnoses, an accuracy of 80% or more is considered “very good”.

The researchers suspect that accuracy would likely have been higher if breath and saliva/nasal swab samples were collected at the same time.

Unlike nasal swabs, breathalyzers are non-invasive. And unlike a saliva sample, users are not asked to refrain from eating, drinking, or smoking before using it. Does not require expensive chemicals to break down the sample. And this new test, conceivably, is used on unconscious individuals.

But there’s still a lot to learn, Ye said.

“With one breath, we can collect so many data points from you, but so what? We only understand how some molecules correlate with certain conditions,” said Ye.

Build a smaller breathalyzer

Today, the “breathalizer” consists of an elaborate array of lasers and mirrors the size of a banquet table.

The breath sample is passed through the tube as the laser fires invisible mid-infrared light at thousands of different frequencies. Dozens of tiny mirrors reflect light back and forth through the molecule so many times that in the end, the light travels about 1.5 miles.

Because each type of molecule absorbs light differently, breath samples with different molecular arrangements cast different images. Machines can distinguish between those different shadows or absorption patterns, boiling millions of data points down to—in the case of COVID—a simple positive or negative, within seconds.

Efforts are under way to shrink such systems down to the chip scale, enabling what Liang envisions as “real-time self-monitoring of health on the go”. The potential doesn’t end there.

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

Elsewhere, scientists are working to develop the Human Breath Atlas, which maps every molecule in human breath and links them to health outcomes. Liang hopes to contribute to the effort with larger-scale collection of breath samples.

Meanwhile, the team is working with pediatric and respiratory specialists at CU Anschutz Medical Campus to explore how breathalyzers can not only diagnose disease but also allow scientists to better understand it, offering clues about immune response, nutritional deficiencies, and other factors that may contribute. for or exacerbate the disease.

“If you think about dogs, they evolved over thousands of years to smell lots of different things with great sensitivity,” said Ye. “We recently started our laser-based nose training. The more we teach it, the smarter it will come.

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