Laser spectroscopy for breath analysis : towards clinical implementation

Detection and analysis of volatile compounds in exhaled breath represents an attractive tool for monitoring the metabolic status of a patient and disease diagnosis, since it is non-invasive and fast. Numerous studies have already demonstrated the benefit of breath analysis in clinical settings/applications and encouraged multidisciplinary research to reveal new insights regarding the origins, pathways, and pathophysiological roles of breath components. Many breath analysis methods are currently available to help explore these directions, ranging from mass spectrometry to laser-based spectroscopy and sensor arrays. This review presents an update of the current status of optical methods, using near and mid-infrared sources, for clinical breath gas analysis over the last decade and describes recent technological developments and their applications. The review includes: tunable diode laser absorption spectroscopy, cavity ring-down spectroscopy, integrated cavity output spectroscopy, cavity-enhanced absorption spectroscopy, photoacoustic spectroscopy, quartz-enhanced photoacoustic spectroscopy, and optical frequency comb spectroscopy. A SWOT analysis (strengths, weaknesses, opportunities, and threats) is presented that describes the laser-based techniques within the clinical framework of breath research and their appealing features for clinical use.Peer reviewe

CEAS with any light source

International audienceOptical cavities have proven to be powerful objects, giving rise to kilometric absorption pathlength from meter sized sample cells, at the expense of a reduced average broadband light transmission. Through trace detection examples, we will show and illustrate how to couple continuous or pulsed broadband sources, continuous lasers but also mode-locked lasers to such "absorption amplifiers". We will then debate on the reached and/or expected performances for various experimental setups

Accurate measurements and temperature dependence of the water vapor self-continuum absorption in the 2.1 μm atmospheric window

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NO2_2 TRACE MEASUREMENTS BY OPTICAL-FEEDBACK CAVITY-ENHANCED ABSORPTION SPECTROSCOPY

Author Institution: Laboratoire de Spectrometrie Physique, CNRS UMR5588, Univ. J. Fourier de Grenoble, St Martin d'Heres, FranceIn order to reach the sub-ppb NO$_2$ detection level required for environmental applications in remote areas, we develop a spectrometer based on a technique introduced a few years ago, named Optical-Feedback Cavity-Enhanced Absorption Spectroscopy (OF-CEAS) [1]. It allows very sensitive and selective measurements, together with the realization of compact and robust set-ups as was subsequently demonstrated during measurements campaigns in harsh environments [2]. OF-CEAS benefits from the optical feedback to efficiently inject a cw-laser in a V-shaped high finesse cavity (typically 10 000). Cavity-enhanced absorption spectra are acquired on a small spectral region ($\sim$1\,cm$^{-1}$) that enables selective and quantitative measurements at a fast acquisition rate with a detection limit of several 10$^{-10}$\,cm$^{-1}$ as reported in this work. Spectra are obtained with high spectral definition (150\,MHz highly precisely spaced data points) and are self calibrated by cavity rind-down measurements regularly performed (typically every second). NO$_2$ measurements are performed with a commercial extended cavity diode laser around 411\,nm, spectral region where intense electronic transitions occur. We will describe the set-up developed for in-situ measurements allowing real time concentration measurements at typically 5\,Hz; and then report on the measurements performed with calibrated NO$_2$ reference samples to evaluate the linearity of the apparatus. The minimum detectable absorption loss is estimated by considering the standard deviation of the residual of one spectrum. We achieved 2x10$^{-10}$\,cm$^{-1}$ for a single spectrum recorded in less than 100\,ms at 100\,mbar. It leads to a potential detection limit of 3x10$^8$ molecules/cm$^3$, corresponding to about 150\,pptv at this pressure. \\ [1] J. Morville, S. Kassi, M. Chenevier, and D. Romanini, Appl. Phys. B, 80, 1027 (2005). [2] D. Romanini, M. Chenevrier, S. Kassi, M. Schmidt, C. Valant, M. Ramonet, J. Lopez, and H.-J. Jost, Appl. Phys. B, 83, 659 (2006)

Cavity Enhanced Absorption Spectroscopy with a red LED source for NOx trace analysis

International audienceThis study presents a high sensitivity absorption system using a red LED source emitting at 625 nm and a small CCD spectrometer as detector [1]. This system is based on IBB-CEAS (Incoherent Broad Band Cavity Enhanced Absorption Spectroscopy). The expected application is the measurement of NO2 and NO3 in urban concentration (ppbv and ppmv levels). The IBB-CEAS was firstly developed with arc lamps and then with LED. Systems based on this technique are easy to use, highly sensitive, compact and robust. They also are inexpensive. Existent techniques to measure NO2 and NO3 are generally slow or not sensitive enough and need frequently calibrations (chemical luminescent) or are characterized by a low spatial resolution (Long Path Differential Optical Absorption Spectroscopy). Previous works based on diodes lasers emitting around 410 nm and coupled with High Finess Cavity proved a highest sensibility than ppbv and a time measurement of 0.1 s [2]. This sensibility is necessary for measurements in unpolluted environment but a more expensive and more complex system is needed. NO2 is chosen for testing as it is stable and available in calibrated diluted samples. An excellent agreement in the range from 610 nm to 630 nm was gotten between an absorption spectrum obtained by IBB-CEAS and a spectrum calculated using a reference NO2 absorption cross section by Voigt et al [3] (after convolution with a 2.05-nm FWHM Gaussian simulating our spectrometer response function). The reflectivity of the mirrors was determined with a commercial spectrophotometer and was used to deduce the absorption spectrum of NO2 from the transmission spectrum of the cavity. We obtained by estimating the sensitivity of our setup from the noise in a baseline measurement of absorption, (standard deviation = 2E-10 cm-1). This corresponds (under atmospheric conditions) to a sensitivity about 0.5 ppbv. NO3 cross-section absorption is 600 times higher than the NO2 (at 623 nm), so a detection limit of 1 pptv is expected for NO3. Thus the developed system is suitable for atmospheric urban concentration of NO2 and NO3. [1] M. triki, P. Cermak, G. Méjean, and D. Romanini, Appl. Phys. B 91, 195 (2008). [2] I. Courtillot, J. Morville, V. Motto-Ros and D. Romanini, Appl. Phys. B 85, 407 (2006) [3] S. Voigt, J. Orphal, and J. Burrows, J. Photochem. Photobiol. A 149, 1( 2002)

Water vapor self-continuum absorption measurements in the 4.0 and 2.1 µm transparency windows

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Collision-induced absorption and electric quadrupole transitions of N2 by OF-CEAS near 4.0 µm and CRDS near 2.1 µm

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Incoherent broad-band cavity-enhanced absorption spectroscopy for simultaneous trace measurements of NO2 and NO3 with a LED source

International audienceIn the past decade, due to a growing awareness of the importance of air quality and air pollution control, many diagnostic tools and techniques have been developed to detect and quantify the concentration of pollutants such as NO x , SO x , CO, and CO2. We present here an Incoherent Broad-Band Cavity-Enhanced Spectroscopy (IBB-CEAS) set-up which uses a LED emitting around 625 nm for the simultaneous detection of NO2 and NO3. The LED light transmitted through a high-finesse optical cavity filled with a gas sample is detected by a low resolution spectrometer. After calibration of the spectrometer with a NO2 reference sample, a linear multicomponent fit analysis of the absorption spectra allows for simultaneous measurements of NO2 and NO3 concentrations in a flow of ambient air. The optimal averaging time is found to be on the order of 400 s and appears to be limited by the drift of the spectrometer. At this averaging time the smallest detectable absorption is 2×10-10 cm-1, which corresponds to detection limits of 600 pptv for NO2 and 2 pptv for NO3. This compact and low cost instrument is a promising diagnostic tool for air quality control in urban environments

Optical-feedback cavity-enhanced absorption spectroscopy with a quantum-cascade laser yields the lowest formaldehyde detection limit

International audienceWe report on the first application of Optical Feedback-Cavity Enhanced Absorption Spectroscopy to formaldehyde trace gas analysis at mid-infrared wavelengths. A continuous-wave room-temperature, distributed-feedback quantum cascade laser emitting around 1,769 cm-1 has been successfully coupled to an optical cavity with finesse 10,000 in an OF-CEAS spectrometer operating on the ν2 fundamental absorption band of formaldehyde. This compact setup (easily transportable) is able to monitor H2CO at ambient concentrations within few seconds, presently limited by the sample exchange rate. The minimum detectable absorption is 1.6 × 10-9 cm-1 for a single laser scan (100 ms, 100 data points), with a detectable H2CO mixing ratio of 60 pptv at 10 Hz. The corresponding detection limit at 1 Hz is 5 × 10-10 cm-1, with a normalized figure of merit of 5 × 10-11cm^{-1}/sqrtHz (100 data points recorded in each spectrum taken at 10 Hz rate). A preliminary Allan variance analysis shows white noise averaging down to a minimum detection limit of 5 pptv at an optimal integration time of 10 s, which is significantly better than previous results based on multi-pass or cavity-enhanced tunable QCL absorption spectroscopy

Cavity-enhanced multiplexed comb spectroscopy down to the photon shot noise

International audienceWe demonstrate quantum-noise-limited frequency-comb cavity-enhanced absorption spectroscopy with spectrally multiplexed detection for acquisition times ranging from 10 ms up to 10 min, where a record absorption sensitivity of 7×10-13 cm-1 per spectral element is attained with nW power levels. For this, a widely tuneable frequency-doubled free-running fs Ti:sapphire laser oscillator is coupled to a cavity of extreme finesse (32 000) whose length is modulated and whose output is spectrally dispersed over a linear charge coupled device array. This scheme is robust, as it does not require tight frequency locking or controlling the comb frequency offset, and works with spectrally broad combs, as it is not limited by cavity dispersion