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Optical frequency comb spectroscopy checks breath for disease

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In the future, instead of having blood drawn at your doctor’s office, you may simply breathe into a bag, and an optical system would analyze your breath for a host of common ailments, including asthma, cystic fibrosis, diabetes, pneumonia, liver or kidney failure as well as cancer. A proof-of-concept system for this purpose was used recently to analyze the breath of volunteers.

For years, medical researchers have known that disease markers in the breath could be used as a potential diagnostic tool. Instruments such as single-frequency laser systems and mass spectrometers have been used for such detection. However, researchers at the National Institute of Standards and Technology and at the University of Colorado at Boulder used optical frequency comb spectroscopy.

According to lead author Michael J. Thorpe, “The improvement offered by the optical frequency comb is the ability to choose a spectral region that contains absorption features for many interesting compounds and detect them all simultaneously in real time. Other laser systems can detect one or a few compounds, but they can’t detect 10 to 100 such compounds.” Mass spectrometers can detect hundreds of compounds but take long periods to perform detections, he added.

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Researchers hope to develop a system based on optical comb spectroscopy that can rapidly analyze a person’s breath for markers of a variety of diseases, including asthma, cystic fibrosis, diabetes, pneumonia, liver or kidney failure, and cancer. Reprinted with permission of Optics Express.

Thorpe and fellow researchers used an optical comb spectrometer operating from 1.5 to 1.7 μm. The system was built around a custom-made erbium-ion fiber laser. For 1.5 to 1.6 μm, they used the output of the laser directly and coupled it into a 1 l/min gas flow optical enhancement cavity, through which the breath passed for analysis. A Raman amplifier shifted the spectrum to get the 1.6- to 1.7-μm range, and the output of the enhancement cavity was passed through a virtually imaged phased array spectrometer, which created vertical diffraction. From there, the light reflected off a horizontal diffraction grating and passed through the imaging lens to a Xenics XEVA InGaAs camera.

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For its trial run, the researchers focused on measuring CO2, CO and ammonia; however, additional analytes, such as H2O and CH4, appeared in the spectralregion. In addition, they tested two volunteers — a smoker who had smoked 15 minutes before testing and a nonsmoker. The nonsmoker showed a 1.3-ppm CO level. The smoker’s CO level was 6.5 ppm — five times that of the nonsmoker — a rate that the authors note caused them to check their instruments. The researchers also tested concentrations of ammonia, a marker for renal failure. They determined that the optical comb system would be sensitive enough to detect ammonia in the breath of people in the early stages of renal failure.

Thorpe said that several conditions appear to be well-suited for detection via breath analysis, especially lung disorders and Helicobacter pylori, the bacteria that cause stomach ulcers. Although the system is still too untried and expensive to compete with blood testing, Thorpe said that they hope to provide devices that will enable medical researchers to advance the field of breath analysis. Eventually, the system could be used as part of a routine check-up.

Besides looking for partners for medical research, the investigators want to expand the laser system. “We are currently working on a laser system that will provide a frequency comb from 2.8 to 5.0 mm,” Thorpe said. “This system will be able to detect hundreds of compounds found in human breath at concentrations below one part per billion.”
Kevin Robinson

Optics Express, Feb. 18, 2008, pp. 2387-2397.

Published: April 2008
Glossary
optical system
A group of lenses, or any combination of lenses, mirrors and prisms, so constructed as to refract or reflect light to perform some definite optical function.
Biophotonicsmedical researchersNews & Featuresoptical systemsingle-frequency laser systemsspectroscopy

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