Astronomers and physicists have long used laser-based sensors called “optical frequency combs” to study the composition of matter in the universe and measure time more accurately. But the COVID-19 pandemic has pushed this versatile tool out of space and physics and into healthcare.
An optical frequency comb is a laser that simultaneously emits pulses of light at multiple frequencies. These ultrafast pulses are so precisely positioned along the spectrum of light, from the infrared to the visible to the ultraviolet, that they form a series of comb-like peaks on the frequency graph. This “comb” can be used in many ways. For example, different types of molecules absorb different colors of light. By detecting which colors of light are absorbed near certain frequencies, combs can identify specific molecules in air samples. In a recent study, scientists have proven that the tool can detect COVID-19 in a breathalyzer-type test in which a subject simply blows into a tube, providing a rapid, non-invasive treatment for many diseases. It may pave the way for diagnostic testing.
Every time we exhale, we give off more than 1,000 trace molecules called volatile organic compounds (VOCs). “Changes in VOC profiles can be associated with specific health conditions,” says Christina Davis, vice president for interdisciplinary research and strategic initiatives at the University of California, Davis. Scientists have known for thousands of years that certain bad breaths are associated with clinical illnesses and disorders. Ancient Greek and Chinese medical texts show doctors using the nose as a diagnostic tool, Davis said. These days, dogs are being trained to identify some diseases in humans, and laser comb detectors need training, says physicist Jun Ye, co-author of the new study. “We are using machine learning to train the frequency comb nose. Once trained, it becomes an electronic dog with much better sensitivity,” says Ye.
This powerful artificial nose has the advantage of being able to sniff out disease in a rapid, non-invasive way, says Qizhong Liang, the study’s first author and a graduate student at the University of Colorado Boulder. For maximum accuracy, a positive result from the novel coronavirus test should be followed up with a more reliable PCR test, Liang added. However, rapid screening at airports, concert venues and hospitals could outperform other methods such as temperature scans used to assess potential COVID-19 infection without the need for invasive nasal swabs. have a nature.
Frequency combs can do more than identify molecules. These were originally developed in his 1990s to produce more accurate optical atomic clocks, and the inventors won his 2005 Nobel Prize in Physics. Combs can measure the natural vibrations of atoms with such precision that they have become an integral component of atomic clocks, which count these vibrations to keep time incredibly accurately. In astronomy, researchers use optical frequency combs to measure the frequencies of light coming from distant stars. The confusion could indicate that the star has exoplanets. In atmospheric science, it is used to study greenhouse gases. And in 2008, Ye and his colleagues at JILA (a joint research institute of the US National Institute of Standards and Technology and the University of Colorado, Boulder) were the first to demonstrate that this technology could be used as a breath test for disease biomarkers. They put this discovery aside, but global events suddenly became reason enough to revive the study in April 2020. “Using your breath as a diagnostic tool has been around for a while,” Davis said. To really advance research interest. “
Soon after the novel coronavirus pandemic began, Ye received a call from colleagues at the National Academy of Sciences, Engineering and Medicine and the Air Force Office of Scientific Research. They wanted to know if his early frequency comb “breath detector” work could help develop non-invasive COVID-19 tests.
Ye and his team started by refreshing the 2008 technology. The researchers extended the laser comb’s frequency range from the near-infrared region of the spectrum to the mid-infrared portion, where molecules absorb light two to three times more strongly. This signal enhancement allowed the researchers to improve the detection sensitivity of his tool by a factor of 1,000, allowing him to identify molecules at extremely low concentrations on the scale of hundreds of trillions.
Ye’s team then collected breath samples from 170 students and staff at the University of Colorado, Boulder, between May 2021 and January 2022. Each participant was tested for COVID-19 by conventional PCR nasal swab, and about half tested positive. The researchers then used a frequency comb to analyze the light absorption patterns between molecules in the participants’ breath. Applying machine learning to the frequency comb data and combining it with known PCR data about who is positive or negative, they found six “identifying molecules” of his that are indicative of COVID-19 infection. The study was described in a paper published in April. Respiratory Research Journal.
Liang said AI was key to the project’s success, thanks to the vast amount of information the frequency comb collects when analyzing respiration. “Machine learning can analyze all this data at the same time and automatically figure out the best way to use all the discriminating information to build a predictive model,” he says.
Frequency combs aren’t the only way to test human breath for COVID-19 and other diseases. Other methods include gas chromatography/mass spectrometry systems such as the InspectIR test, which received Emergency Use Authorization from the U.S. Food and Drug Administration in April 2022. In such chemical-based techniques, the gas molecules to be analyzed are separated by an inert gas. , broken down into pieces and measured. Davis calls this type of testing the “gold standard,” but it requires time, specialized training, and bulky equipment that limits lab use. Davis is working on the development of ion mobility spectrometers, a smaller, more portable type of test that identifies substances based on their molecular mobility in an electric field. In other options, he isolates and tests the VOCs using chemicals that bind to them. “There are more than 15 companies working on different tests of this kind,” says Davis.
Frequency comb technology differs from frequency comb technology because it uses laser spectroscopy to “detect molecules in the breath in a non-destructive manner,” Liang said. This means that the comb does not degrade the sample or create unwanted by-products, unlike breath tests that rely on chemical reactions. Frequency comb technology also has the potential to be very fast. Ultimately, results may be available in seconds, compared to minutes for other breath tests.
That said, you probably won’t be looking at a laser comb the next time you fly. “In general, we haven’t reached prime time for breath testing,” said Wilbur Lamb, a COVID-19 testing expert, pediatrician, and biomedical engineer at Emory University and Georgia Tech. Using the frequency comb method, “we get an optical signal, but we need to prove whether that optical signal really indicates COVID-19. At the moment, they show some degree of correlation.” But how does it correlate with other types of symptoms that can affect breathing?”
If the frequency comb “airway respirator” proves itself in further research, it could make a big difference in many clinical settings beyond rapid COVID-19 testing. Study co-author Kristen Björkmann, director of interdisciplinary research at the BioFrontier Institute, said the technology could one day detect chronic obstructive pulmonary disease, kidney failure, lung and pancreatic cancer, and even Alzheimer’s disease. suggests that it may be used for Several early studies have provided preliminary evidence that breath content can be used for these diagnoses.
Breathalyzer-style tests may also be ideal for diagnosing children, Ye said, and some pediatricians have already consulted him about frequency comb testing for asthma for children. Ye explained that when a child shows up in the emergency department unwell, many invasive tests are performed to determine if the symptoms are caused by a bacterial or viral illness or asthma. is required. He said a Denver-based pediatrician told him: Children don’t cry if they just donate their breath. “
