A new approach to detecting a weak photoacoustic signal in a gas medium is described. Instead of a gas-filled resonant acoustic cavity, the sound energy is accumulated in a high- Q crystal element. Feasibility experiments utilizing a quartz-watch tuning fork demonstrate a sensitivity of 1.2x10(-7) cm(-1) W/ radicalHz . Potential further developments and applications of this technique are discussed.

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Laser absorption spectroscopy (LAS) in the mid-infrared region offers a promising new effective technique for the quantitative analysis of trace gases in human breath. LAS enables sensitive, selective detection, quantification and monitoring in real time, of gases present in breath. This review summarizes some of the recent advances in LAS based on semiconductor lasers and optical detection techniques for clinically relevant exhaled gas analysis in breath, specifically such molecular biomarkers as nitric oxide, ammonia, carbon monoxide, ethane, carbonyl sulfide, formaldehyde and acetone.

Tunable-laser absorption spectroscopy in the mid-IR spectral region is a sensitive analytical technique for trace-gas quantification. The detection of nitric oxide (NO) in exhaled breath is of particular interest in the diagnosis of lower-airway inflammation associated with a number of lung diseases and illnesses. A gas analyzer based on a continuous-wave mid-IR quantum cascade laser operating at approximately 5.2 microm and on off-axis integrated cavity output spectroscopy (ICOS) has been developed to measure NO concentrations in human breath. A compact sample cell, 5.3 cm in length and with a volume of < 80 cm3, that is suitable for on-line and off-line measurements during a single breath cycle, has been designed and tested. A noise-equivalent (signal-to-noise ratio of 1) sensitivity of 10 parts in 10(9) by volume (ppbv) of NO was achieved. The combination of ICOS with wavelength modulation resulted in a 2-ppbv noise-equivalent sensitivity. The total data acquisition and averaging time was 15 s in both cases. The feasibility of detecting NO in expired human breath as a potential noninvasive medical diagnostic tool is discussed.

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Exhaled nitric oxide (NO) is an important biomarker in asthma and other respiratory disorders. The optical performance of a NOCO(2) sensor employing integrated cavity output spectroscopy (ICOS) with a quantum cascade laser operating at 5.22 microm capable of real-time NO and CO(2) measurements in a single breath cycle is reported. A NO noise-equivalent concentration of 0.4 ppb within a 1-sec integration time is achieved. The off-axis ICOS sensor performance is compared to a chemiluminescent NO analyzer and a nondispersive infrared (NDIR) CO(2) absorption capnograph. Differences between the gas analyzers are assessed by the Bland-Altman method to estimate the expected variability between the gas sensors. The off-axis ICOS sensor measurements are in good agreement with the data acquired with the two commercial gas analyzers. This work demonstrates the performance characteristics and merits of mid-infrared spectroscopy for exhaled breath analysis.

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