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Title: Applications of infrared laser spectroscopy to breath analysis
Author: Cummings, Beth L.
ISNI:       0000 0004 2722 0118
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2011
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The work presented in this thesis is concerned with development of spectroscopic detection methods based on absorption spectroscopy using semiconductor lasers, with particular ref- erence to the field of medical diagnostics through breath analysis. The first part of this thesis deals with the design and testing of a prototype analyser for simultaneous monitoring of the exchange gases O2 , CO2 and H2O in breath. The aim of this analyser is to provide information required to monitor respiration, with potential use in intensive care monitoring or during anaesthesia. The relatively high concentrations of these gases in breath and read- ily available diode laser sources make detection in the near-infrared (NIR) ideal. However, the relatively weakly absorbing A-band O2 transitions at 760 nm require the application of a sensitive spectroscopic method, cavity enhanced absorption spectroscopy (CEAS). In contrast, CO2 and H2O are monitored using direct single pass absorption spectroscopy, with transitions arising from the 2ν1 + ν3 band at 2 μm and ν1 + ν3 band at 1.3 μm, respectively. It has been demonstrated that these gases can be detected simultaneously over a short pathlength (2.74 - 4 cm) in the respiratory flow by combining various spectroscopic methodologies and real-time data analysis. This analyser is shown to offer a viable alter- native for monitoring respiration, exhibiting absolute detection limits of changes of 0.26 % O2 , 0.02 % CO2 and 0.003 % H2O with a 10 ms time resolution, which are comparable to current mass spectrometry based methods, but without their inherent delays. Following this, investigations into the detection of the main gas constituents in breath in the NIR employing noise-reduction modulation based spectroscopic techniques, namely wavelength and frequency modulation (WMS and FMS respectively) are also reported. The described WMS studies on water at 1.37 μm provide a demonstration of conventional WMS detection, as well as a “proof-of-principle” example of a relatively new approach to calibrating the non-absolute information obtained from a WMS absorption signal. Typically WMS spectra are calibrated using mixtures of known gas concentrations or an absolute direct absorption spectrum where possible. In this work however, a self-calibrating method, the phasor decomposition method (PDM), is employed and the returned concentration from this calibration is compared to direct absorption measurement. From this, the calculated concentration using the PDM is found to differ by 9 % from the concentration value obtained by direct absorption, providing an alternative method of calibration for when direct absorption measurements are not possible. The use of FMS in the NIR is also demonstrated as a potential alternative to CEAS for monitoring O2 at 760 nm. FMS detection is performed on atmospherically broadened O2 and a time-normalised αmin(t) of 2.45 ×10−6 cm−1 s1/2 is obtained, which is two orders of magnitude less sensitive than the value of αmin(t) = 2.35 ×10−8 cm−1 s1/2 obtained with CEAS. This combined with the experimental requirements of an FMS system, make its use for detection of O2 a less practicable option compared to CEAS for real-time breath analysis. The latter work in this thesis involves a change in focus to detection of trace gases in breath in the mid-infrared (MIR). The move of spectroscopic detection to the MIR exploits the larger absorption cross-sections available in this region, and to achieve this, a relatively new form of semiconductor laser, the quantum cascade laser (QCL) is used. The design of a continuous wave QCL spectrometer at 8 μm and its operating characteristics are demon- strated and improvements in its performances are also discussed. This QCL system is then utilised to demonstrate the potential of monitoring species in breath, namely the narrow- band absorber methane and the broadband absorber acetone, taking into consideration the potential interference from other absorbing species in breath and the different spectroscopic characteristics exhibited by these molecules. Finally, the potential to further improve the sensitive detection of trace gases in breath in the MIR is also investigated with studies on the use of CEAS and multipass cells. In this work, the molecule of interest is the biomarker OCS, using transitions of the 2ν2 band at 1031 cm−1 , that are probed using a 10 μm QCL. The application of CEAS in the MIR is not as well developed as in the NIR, and the experimental consequences of using optical cavities at these wavelengths, where equipment tends to be more limited, are investigated and sensitivities discussed in the context of other literature. The experimental procedure of optimising a cavity for CEAS using the off-axis alignment method is also studied in detail, as well as the addition of WMS to further improve the signal quality. An effective absorption pathlength of ∼ 100 m was achieved in the cavity, with a bandwidth reduced αmin(BW) of 1.7 ×10−7 cm−1 Hz−1/2 using WMS CEAS achieved. With the poorer quality optics and limitations in equipment in the MIR for CEAS experiments, the use of a multipass cell, a 238 m Herriott cell, is also investigated as an alternative to the use of an optical cavity at 10 μm. Detection of OCS using direct absorption and WMS is demonstrated in the Herriott cell, achieving αmin(BW) = 2.03×10−8 cm−1 Hz−1/2 using WMS. This shows an improvement in sensitivity compared to WMS CEAS, and also shows the potential for future work on biomarker detection, as it approaches the ∼ ppb levels required for breath analysis.
Supervisor: Hancock, Gus Sponsor: Engineering and Physical Sciences Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Chemistry & allied sciences ; Laser Absorption Spectroscopy ; mid-infrared detection ; sensitive spectroscopic absorption methods ; diode lasers ; semiconductor lasers ; breath analysis ; biomarkers ; respiration