NIST Scientists Enhance Frequency Comb Breathalyzer Enabling It to Detect Multiple Disease Biomarkers
Device could pave the way for real-time, noninvasive breath analysis to detect and monitor diseases and be a new service medical laboratories can offer
Breathalyzer technology is not new, but until now human breath detection devices have not been comparable to clinical laboratory blood testing for disease detection and monitoring. That may soon change and there are implications for clinical laboratories, partly because breath samples are considered to be non-invasive for patients.
Scientists with JILA, a research center jointly operated by the National Institutes of Standards and Technology (NIST) and the University of Colorado Boulder, recently increased the sensitivity of their laser frequency comb breathalyzer one thousand-fold. This created a device that can detect four disease biomarkers simultaneously, with the potential to identify six more, according to an NIST news release.
Medical laboratory scientists will understand the significance of this development. JILA’s enhanced breathalyzer device could pave the way for real-time, noninvasive breath analysis to detect and monitor diseases, and potentially eliminate the need for many blood-based clinical laboratory tests.
The JILA researchers published their findings in the journal Proceedings of the National Academy of Sciences (PNAS), titled, “Ultrasensitive Multispecies Spectroscopic Breath Analysis for Real-Time Health Monitoring and Diagnostics.”
Measuring Light to Spot Biomarkers of Disease
During their research, physicist Jun Ye, PhD, and David Nesbitt, PhD, both Fellows at JILA and professors at University of Colorado Boulder, detected and monitored four biomarkers in the breath of a volunteer:
- Methanol (CH3OH),
- Methane (CH4),
- Water (H2O), and
- Semiheavy water (HDO).
These chemicals can be indicators of various health conditions. Methane in the breath, for example, can indicate intestinal problems.
The researchers say the JILA breathalyzer also could detect six additional biomarkers of disease without any further modifications to the device. They would include:
- Formaldehyde (H2CO),
- Ethane (C2H6),
- Carbonyl sulfide (OCS),
- Ethylene (C2H4),
- Carbon disulfide (CS2), and
- Ammonia (NH3).
“Determining the identity and concentration of the molecules present in breath is a powerful tool to assess the overall health of a person, analogous to blood testing in clinical medicine, but in a faster and less invasive manner,” the researchers wrote in PNAS.
“The presence of a particular molecule (or combination of molecules) can indicate the presence of a certain health condition or infection, facilitating a diagnosis. Monitoring the concentration of the molecules of interest over time can help track the development (or recurrence) of a condition, as well as the effectiveness of the administered treatment,” they added.
How the JILA Breathalyzer Detects Biomarkers
According to a 2008 NIST news release, JILA researchers had developed a prototype comb breathalyzer in that year. However, the research did not continue. But then the COVID-19 pandemic brought the JILA/NIST laboratories focus back to the breathalyzer with hopes that new research could lead to a breath test for detecting the SARS-CoV-2 coronavirus and other conditions.
“We are really quite optimistic and committed to pushing this technology to real medical applications,” Ye said in the 2021 NIST news release.
Analytical Scientist explained that JILA’s new and improved breathalyzer system “fingerprints” chemicals by measuring the amount of light absorbed as a laser frequency comb passes back and forth through breath samples loaded into a mirrored glass tube.
JILA’s original 13-year-old prototype comb analyzed colors and amounts of light in the near-infrared band. However, JILA’s recent improvements include advances in optical coatings and a shift to analyzing mid-infrared band light, allowing detection sensitivity up to parts-per-trillion level, a thousand-fold improvement over the prototype.
Corresponding study author Jutta Toscano, PhD, postdoctoral researcher at the University of Basel in Switzerland and previously Lindemann fellow at JILA, told Physics World the new frequency comb can “probe the molecular fingerprint region where fundamental, and more intense, spectroscopic transitions are found.
“By matching the frequency of the comb teeth with the cavity modes—the ‘standing modes’ of the cavity—we can increase the interaction path length between molecules inside the cavity and laser light by a factor of around 4000, equivalent to an effective path length of a few kilometers,” she added. “We then probe the light that leaks out of the cavity by sending it into an FTIR [Fourier-transform infrared] spectrometer to find out which exact comb teeth have been absorbed and by how much. In turn, this tells us which molecules are present in the breath sample and their concentration.”
Even Hippocrates Studied Breath
Ye noted in the NIST statement that JILA is the only institution that has published research on comb breathalyzers.
In their PNAS paper, the researchers wrote, “Breath analysis is an exceptionally promising and rapidly developing field of research, which examines the molecular composition of exhaled breath. … Despite its distinctive advantages of being a rapid, noninvasive technique and its long history dating back to Hippocrates, breath analysis has not yet been as widely deployed for routine diagnostics and monitoring as other methods, such as blood-based analysis.
“We have shown that this technique offers unique advantages and opportunities for the detection of light biomarkers in breath,” the researchers noted, “and it is poised to facilitate real-time, noninvasive monitoring of breath for clinical studies, as well as for early detection and long-term monitoring of temporary and permanent health conditions.”
Validation of these findings and further design research to make the system portable are required before JILA’s frequency comb breathalyzer can become a competitor to clinical laboratory blood tests for disease identification and monitoring. Nevertheless, JILA’s research brings breathalyzer technology a step closer to offering real-time, non-invasive analysis of human biomarkers for disease.
—Andrea Downing Peck