Frequency comb spectroscopy detects disease via breath analysis
February 20, 2008, Boulder, CO--A team of scientists at JILA, a joint institute of the National Institute of Standards and Technology (NIST) and the University of Colorado (CU) at Boulder, has shown that by sampling a person's breath with laser light they can detect molecules in the breath that may be markers for diseases like asthma or cancer.
While many studies have been done to showcase the potential of optical technologies for breath analysis, the JILA approach takes an important step toward demonstrating the full power of optics for this prospective medical application. Their findings are published in the latest issue of Optics Express (www.opticsinfobase.org).
The technique, called cavity-enhanced direct optical frequency comb spectroscopy, may one day allow doctors to screen people for certain diseases simply by sampling their breath. "This technique can give a broad picture of many different molecules in the breath all at once," says Jun Ye, who led the research. He is a fellow of JILA, a fellow of NIST and a professor adjoint at CU-Boulder's Department of Physics.
Optical frequency comb spectroscopy was developed in the 1990s by Ye's JILA colleague John L. Hall and Theodor W. Hänsch of Germany's Max-Planck Institute (they shared the 2005 Nobel Prize in Physics with Roy J. Glauber for their invention). In the paper, Michael Thorpe, a graduate research assistant, Ye, and their colleagues describe the novel application of this technique to breath analysis. Optical comb spectroscopy is powerful enough to sort through all the molecules in human breath, Ye says, but it is also sensitive enough to find those rarest molecules that may be markers of specific diseases.
Every time we breathe in, we inhale a complex mixture of gasses--mostly nitrogen, oxygen, carbon dioxide, and water vapor, but also traces of other gasses, such as carbon monoxide, nitrous oxide, and methane. Each time we exhale, we blow out a slightly different mixture with less oxygen, more carbon dioxide, and a rich collection of more than a thousand types of other molecules--most of which are present only in trace amounts.
Some of these tracer breath molecules are biomarkers of disease. Just as bad breath may indicate dental problems, excess methylamine can be used to detect liver and kidney disease, ammonia on the breath may be a sign of renal failure, elevated acetone levels in the breath can indicate diabetes, and nitric oxide levels can be used to diagnose asthma. When many breath molecules are detected simultaneously, highly reliable and disease-specific information can be collected. For instance, asthma can be detected much more reliably when carbonyl sulfide, carbon monoxide, and hydrogen peroxide are all detected in parallel with nitric oxide. The reported approach offers exactly this kind of potential.
In the experiments performed by Ye and his colleagues, optical frequency comb spectroscopy was used to analyze the breath of several student volunteers. They showed that they could detect trace signatures of gasses like ammonia, carbon monoxide, and methane on their breath. In one of these measurements, they detected carbon monoxide in a student smoker and found that it was five times higher when compared to a non-smoking student.
The researchers had the students breathe into an optical cavity designed so that when they aimed a pulsed laser light into it, the light bounced back and forth so many times that it covered a distance of several kilometers by the time it exited the cavity. This essentially allowed the light to sample the entire volume of the cavity, striking all the molecules therein. In addition, this lengthens the light-molecule interaction time thereby increasing the sensitivity. By comparing the light coming out of the cavity to the light that went in, Ye and his colleagues could determine which frequencies of light were absorbed and by how much. This information told them which molecules were present in the breath from the start. The remarkable combination of a broad spectral coverage of the entire comb and a sharp spectral resolution of individual comb lines allows them to sensitively identify many different molecules, as they show in their paper.
While the efficacy of this technique has yet to be evaluated in clinical trials, monitoring the breath for such biomarkers is an attractive approach to medicine because breath analysis is the ultimate non-invasive and low-cost procedure. Existing approaches to breath analysis are limited, because the equipment is either not selective enough to detect a diverse set of rare biomarkers, or it is not sensitive enough to detect trace amounts of the molecules exhaled in human breath. The biggest shortcoming of existing approaches is their inability to provide rapid and reliable breath measurements for many biomarkers. The new technique addresses these problems with its capability to rapidly, simultaneously, sensitively, and accurately detect many breath biomarkers. The results can qualitatively change the field of breath analysis, realizing its real potential as a low-cost, rapid, robust, and non-invasive method for health screening.
Funding for this work was provided by the Air Force Office of Scientific Research, Agilent Technologies Foundation, the Defense Advanced Research Projects Agency, NIST, the National Science Foundation, and a University of Colorado proof of concept grant.