Imma Perfetto
Cosmos science journalist
Dr Sarah Scholten and Dr Chris Perrella, University of Adelaide researchers and COMBS Associate Investigators, describe the use of optical frequency combs for breath analysis. Credit: COMBS
Imagine standing in your kitchen at home, feeling a little off colour. You grab a handheld device from the medicine cabinet and breathe into it, looking for an instant diagnosis of whatever you’re coming down with.
Such a machine is being developed right now, using technology called optical frequency combs. Or just combs.
“You could imagine it in your phone,” suggests Dr Sarah Scholten, a researcher at the University of Adelaide’s Institute for Photonics and Advanced Sensing in Australia
“Maybe you’re having a phone call, or you’re scrolling through TikTok, you’re breathing on it, and it says, ‘hey, you’ve got the markers for the flu, you should go to the doctor.’”
Perhaps the device could be used by a doctor to track their patient’s health in remote areas that do not have access to state-of-the-art facilities, or without the need for invasive procedures.
In time-sensitive situations, it could reveal the identity of an infectious disease so it could be treated immediately, or whether a sportsperson has dabbled in doping.
Scholten and her colleagues are working to make these dreams a medical reality.
The technology would detect “volatile organic compounds” (VOCs) and other inorganic gases exhaled as we breathe, some of which have already been established as “biomarkers” of human health.
For example, exhaled nitric oxide is used to monitor asthma, while the amount of hydrogen can diagnose bacterial overgrowth in the small intestine.
But there are hundreds of VOCs in human breath, and they’re present at such low concentrations (down to the parts-per-trillion), that detecting them requires highly sensitive and selective instruments.
Dogs trained to detect changes in human physiology – such as cancer, infectious diseases, or medical episodes like seizures – are picking up on changes in the profile of these VOCs.
In the absence of a powerful canine olfactory system of their own, researchers have traditionally used expensive specialised equipment, technical know-how, and lots of time do the analysis in the laboratory.
But an affordable clinical instrument, sensitive enough to continuously monitor a range of these biomarkers and capable of doing so directly at the point-of-care, remains outside the scope of current technology.
Scholten, who is also an Associate Investigator at the Australian Research Council Centre of Excellence for Optical Microcombs for Breakthrough Science (COMBS), where believes that optical frequency combs might be the key to making it possible.
What is an optical frequency comb?
“An optical frequency comb is … the next generation of laser,” says Monash University Associate Professor and COMBS Chief Investigator, Bill Corcoran.
“We’ve had lasers since the 60s … they provide a really, really precise colour of light, be that … something we can see or [cannot] see.”
We usually think of light as the colours of the rainbow. But this is only a fraction of the entire electromagnetic spectrum, which spans from the highest frequency gamma radiation to the lowest frequency radio waves.
“What combs do is they not only create one precise colour of light, but they provide many, many different colours of light that are all spaced by a very precise amount,” says Corcoran.
“That’s why we call it a frequency comb – equally spaced teeth.”
Imagine a hair comb made of light, with many teeth spaced out in very precise, even intervals. If this was confined to visible light, the teeth would form a gradual rainbow from red to violet.
“That spacing between the lines is something we can measure relatively easily with electronics,” says Corcoran.
This property means optical frequency combs have a multitude of potential applications, from ultra-fast internet transmission to optical atomic clocks for GPS, and even astronomy.
Combs as molecular rulers
As COMBS Chief Investigator and University of South Australia Professor David Lancaster a explains, optical frequency combs can also be used as a ruler to look at molecules.
“Each of the molecules … absorb different colours [of light],” says Lancaster.
Each has its own structure and combination of atoms, which means it absorbs and re-emits light in a characteristic way.
When an optical frequency comb laser is passed through a sample of gas, certain absorbed wavelengths disappear from the comb spectrum. This leaves behind characteristic gaps, kind of like a comb with some of its teeth missing.
These gaps are unique, like a molecular fingerprint, and can be used to identify which molecules are present in the sample and at what concentration.
“The nice thing about this is it’s super stable, so potentially we can do spectroscopy at parts per billion level in the atmosphere,” says Lancaster. This could be used to measure the concentration of greenhouse gases or other pollutants more rapidly and accurately.
The dream is to use optical frequency combs to analyse breath samples.
“Combining that with machine learning … you [could see] whether somebody’s got diabetes from what’s coming out of their breath,” he speculates.
There’s still a way to go
In a paper published last year in Biomedical Optics Express, COMBS Associate Investigator Chris Perrella, Scholten, and collaborators at the University of Adelaide demonstrated their optical frequency comb prototype could observe the changing metabolism of a living organism by monitoring its carbon dioxide production in real-time.
Baker’s yeast (Saccharomyces cerevisiae) was chosen as simple analogue for human breath.
Like humans, baker’s yeast “exhales” carbon dioxide as it metabolises sugars.
It also does this in a moist environment (like human breath) which is important as water vapour contamination can make it hard to pick up gases present at much lower concentrations.
“The really cool thing about this is … you can even detect isotopologues,” says Scholten. Isotopologues of the same molecule have at least one atom, called an isotope, with a different number of neutrons.
Isotopologues are already used in medicine for diagnostic breath tests. For example, to diagnose the presence of Helicobacter pylori, a type of gut bacteria which can cause stomach ulcers, a person ingests urea containing carbon-13, which is converted by the bacteria into carbon-13 labelled CO2, which the person then exhales.
Scholten and the team fed the yeast mixtures of normal glucose and glucose labelled with carbon-13 and showed they could detect how much of the resulting carbon dioxide contained either carbon-13 or carbon-12.
While a clinical device still remains at least a decade away, the proof-of-concept study is an important first step towards increasing the capacity of the optical frequency comb spectrometer to detect biomarkers at much lower concentrations in human breath.
