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Technological Advancements in Breath Analysisde Silva, Geethanga January 2016 (has links)
No description available.
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Exhaled breath analysis for diagnosis and phenotyping in obstructive lung diseasesIbrahim, Baharudin January 2011 (has links)
Introduction: Asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous diseases with a wide range of clinical manifestations not adequately described within the current diagnostic criteria. Exhaled breath analysis may provide a novel method for diagnosing and phenotyping these diseases. Our aim was to ascertain patterns of breath volatile organic compounds (VOCs) and nuclear magnetic resonance (NMR) spectral regions identifying diseased patients and subgroups determined by treatment requirement, asthma control, exacerbation frequency and inflammatory phenotypes. The validity and reproducibility of the methodology and the outcome were also investigated. Methods: Three separate clinical studies (two involving exhaled gas and one involving breath condensate) were conducted, as well as validation studies. In exhaled gas analysis, the adaptive breath sampler developed by Basanta et al was modified; efficiency of air supply and air filter and the reproducibility and stability of VOCs in storage were determined by comparing breath chromatograms. Concentrated late-expiratory breath samples were collected from asthmatics, COPD subjects and healthy controls. In the asthmatic group, sputum induction with hypertonic saline, fraction exhaled nitric oxide (FeNO) measurement and asthma control questionnaire (ACQ) were performed. In COPD subjects, sputum induction and exacerbation frequency were collected. In the exhaled breath condensate (EBC) study, similar data were collected in asthmatics and healthy controls. Breath samples were analysed using gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) while EBC was analysed using NMR spectroscopy. Discriminatory compounds or NMR spectral regions were identified by univariate logistic regression, followed by multivariate analysis: 1. principal component analysis (PCA); 2. multivariate logistic regression; 3. receiver operating characteristic (ROC) analysis. The reproducibility was assessed using intraclass correlation coefficient (ICC).Results: In the COPD exhaled breath study, 11 VOCs significantly discriminated the COPD and healthy controls with AUROC of 0.74. The AUROC for phenotype discrimination was 0.83, 0.90, 0.94, 0.96 and 0.97 for inhaled corticosteroid (ICS) use, sputum eosinophilia (1% and 2% cut-off), neutrophilia (median cut-off) and exacerbation frequency respectively. In the asthma study, 15 VOCs significantly discriminated the two groups with AUROC of 0.93. The AUROC for phenotype discrimination was 0.96, 0.98, 0.90 and 0.97 for ICS use, eosinophils (2% cut-off), neutrophils (40% cut-off) and asthma control respectively. In EBC analysis, AUROC for asthmatics vs controls comparison was 0.96. Phenotyping results in this study were less good: only ICS use and sputum neutrophilia (65% cut-off) were clearly classified with AUROC of 0.89 and 0.88 while eosinophilia (3% cut-off) and asthma control had poor discrimination; 0.69 and 0.62 respectively. Breath VOC reproducibility varied greatly depending on the class of compounds studied, while for the EBC analysis, reproducibility was moderate to very good (ICCs in the range of 0.42-0.99).Conclusions: We have demonstrated the ability of breath analysis in discriminating asthmatics and COPD subjects from controls. Exhaled breath analysis was also able to phenotype these patients based on steroid treatment, sputum inflammatory cells, exacerbation frequency and asthma control. This metabolomic approach could provide a novel, non-invasive method of diagnosing and phenotyping obstructive lung diseases in the future.
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Applications of Membrane Extraction with a Sorbent InterfaceMorley, Melissa January 2009 (has links)
Membrane extraction with a sorbent interface (MESI) is a sample preparation technique with a rugged and simple design allowing for solvent-free, on-line performance. When coupled to gas chromatography (GC), MESI is an extremely promising tool for the analysis of volatile organic compounds (VOCs), as it is selective and sensitive for detecting trace levels of analytes. A new calibration method to be used with the MESI technique is presented herein. The aim of this project was to characterize and quantify the biomarker ethylene in human breath and plant emissions. The MESI-GC system was optimized, and an external calibration curve for ethylene standard was obtained. Qualitative measures were obtained from emissions of the higher plant Arabidopsis thaliana. The dominant calibration method was validated by examining changes in mass transfer trends when flow and temperature conditions were altered. Finally, the dominant calibration method was used to quantify ethylene in real human breath samples from non-smoking and smoking volunteers. Results were consistent with those reported in literature. These findings suggest that the dominant calibration technique is a useful tool for monitoring ethylene in human breath and Arabidopsis.
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Applications of Membrane Extraction with a Sorbent InterfaceMorley, Melissa January 2009 (has links)
Membrane extraction with a sorbent interface (MESI) is a sample preparation technique with a rugged and simple design allowing for solvent-free, on-line performance. When coupled to gas chromatography (GC), MESI is an extremely promising tool for the analysis of volatile organic compounds (VOCs), as it is selective and sensitive for detecting trace levels of analytes. A new calibration method to be used with the MESI technique is presented herein. The aim of this project was to characterize and quantify the biomarker ethylene in human breath and plant emissions. The MESI-GC system was optimized, and an external calibration curve for ethylene standard was obtained. Qualitative measures were obtained from emissions of the higher plant Arabidopsis thaliana. The dominant calibration method was validated by examining changes in mass transfer trends when flow and temperature conditions were altered. Finally, the dominant calibration method was used to quantify ethylene in real human breath samples from non-smoking and smoking volunteers. Results were consistent with those reported in literature. These findings suggest that the dominant calibration technique is a useful tool for monitoring ethylene in human breath and Arabidopsis.
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Využití chemirezistorů pro zlepšené snímání látek při analýze dechu / Usage of electric noise in chemiresistors for improved sensing of substances for breath analysisKřivský, Josef January 2019 (has links)
The master's thesis deals with the question of breath analysis using chemiresistors as detection elements for exhaled air analysis. Emphasis is placed on the application of fluctuation-enhanced sensing for chemiresistors for breath analysis, construction design of usable measurement system, and its calibration. Compared to the usual concept, which includes various methods ranging from DC processing in time to controlled impedance measurement, this method of signal analysis focuses on the evaluation of fluctuations and determination of indicators of its change in dependence of change in detected substance concentration.
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Development and application of spectroscopic techniques in the mid-infraredWhittaker, Kimberley Elaine January 2014 (has links)
Applications of laser absorption spectroscopy for trace gas detection are many and diverse, ranging from the environmental and atmospheric to the medical and industrial. The aim of creating a spectrometer which combines high sensitivities and selectivities (in order to measure small amounts of absorbers or species that are only weakly absorbing, in a complex background matrix) with a wide spectral coverage (to allow broadband absorbers or multi-component samples to be studied) can be realised by implementing three separate concepts: the exploitation of the strong, fundamental transitions of the mid-infrared; the use of sensitive spectroscopic techniques; and the selection of a widely tunable laser source. In this thesis, these ideas are investigated individually and in combination in order to achieve such a goal. Laser spectroscopic techniques based on optical cavities are used to build a high resolution spectrometer covering a large spectral range capable of selectively detecting low levels of gaseous compounds of interest, especially those of medical or environmental significance. Work in both the near- and mid-infrared is presented, including much of the initial, developmental work which was conducted in the former region. The thesis begins with an overview of both narrowband and broadband near-infrared radiation sources, with a particular emphasis on commonly available diode lasers (DLs). A novel laser source, the digital supermode distributed Bragg reector (DS-DBR) laser, is introduced as a useful laser source for spectroscopy, combining the usual benefits of telecom DLs with a wide tunability (1563 – 1613 nm). The laser can be operated in an internal or external ramping mode, allowing the output wavelength to be scanned or stepped across a desired region. The observation of mode-hopping during the application of the scanning methodology is examined and rationalised. The ability of the DS-DBR laser to perform high resolution spectroscopy over its entire spectral coverage is demonstrated by recording spectra of carbon dioxide (CO<sub>2</sub>) over this range, covering transitions from two of the four Fermi resonance components of the 3ν<sub>1</sub> + ν<sub>3</sub> combination band. The results of conducting wavelength modulation spectroscopy on CO<sub>2</sub> are also reported. A system developed for performing cavity ring-down spectroscopy (CRDS), capable of the real-time retrieval of ring-down times (RDTs), is presented and discussed. The outcomes of initial tests performed with a conventional DL at 1557 nm, to study a calibrated mixture of CO<sub>2</sub> in air at various pressures, are given. In addition, the results of combining this system with the DS-DBR laser are discussed. The bandwidth of the DS-DBR laser was found to be larger than that of a standard DFB DL, resulting in the presence of noisy cavity modes. Despite this, the acquisition of reproducible RDTs is demonstrated, with single wavelength studies of an evacuated cavity at 1605.5 nm yielding a RDT of 24.54 ± 0.04 µs and Allan variance calculations signalling an attainable minimum detectable absorption coefficient, α<sub>min</sub>, of 2.8 x 10<sup>-10</sup> cm<sup>-1</sup> over 20 s. The ability to perform CRDS across the whole DSDBR laser wavelength range without the need for cavity re-alignment is illustrated, and studies conducted on CO<sub>2</sub> in air, calibrated mixtures and breath are reported. Investigations are also described into the accurate determination of the <sup>13</sup>C/<sup>12</sup>C ratio in exhaled CO<sub>2</sub> undertaken using CRDS and cavity enhanced absorption spectroscopy (CEAS) on CO<sub>2</sub> isotopologues, an approach which can be utilised as a diagnostic aid in determining Helicobacter pylori infection. The focus of the thesis then moves to the mid-infrared, to describe quasi phase matching difference frequency generation (QPM-DFG) and its use to generate laser light at 3 µm by optically mixing near-infrared DLs. The theory behind this non-linear optical interaction is outlined, and the construction of a free-space QPM-DFG system using periodically poled lithium niobate is detailed and characterised. This DL-based QPM-DFG arrangement has been coupled with the CRDS system developed to create a mid-infrared CRD spectrometer. The results of single wavelength studies indicate RDTs of ~ 6 µs and an achievable αmin of 2.9 x 10<sup>-9</sup> cm<sup>-1</sup> over 44 s for an evacuated cavity. Spectroscopic investigations carried out on methane (CH<sub>4</sub>), acetone and deuterium are documented; for the latter species, Dicke narrowing of the electric quadrupole ν(1←0) Q(2) transition at 2987.29 cm<sup>-1</sup> is observed and the integrated absorption cross-section for the same transition measured as 2.29 ± 0.03 x 10<sup>-27</sup> cm<sup>2</sup>cm<sup>-1</sup>molec<sup>-1</sup>. The results of modifications made to the system, namely the use of a more powerful Nd:YAG laser as the pump radiation source, as well as a faster detector combined with a variable amplifier, are presented; these include the observation of an improved optimal α<sub>min</sub> of 6.4 x 10<sup>-10</sup> cm<sup>-1</sup> over 151 s for an empty cavity. Finally, work utilising the DS-DBR laser as one of the near-infrared sources for the QPM-DFG set-up is presented. This configuration generates radiation covering a wide mid-infrared range (3130 – 3330 nm) and has been used to perform direct absorption and wavelength modulation spectroscopy on ro-vibrational transitions within the fundamental ν<sub>3</sub> (F<sub>2</sub>) band of CH<sub>4</sub>. The spectrum of methanethiol (CH<sub>3</sub>SH) over this region has also been investigated, with preliminary studies identifying a feature at 3040 cm<sup>-1</sup> as a potential indicator for monitoring this biomarker in breath. The results of coupling this mid-infrared radiation with an optical cavity to perform CEAS combined with phase sensitive detection are subsequently reported. Studies were conducted on calibrated CH<sub>4</sub> mixtures and ambient air to examine two transitions of the fundamental ν<sub>3</sub> (F<sub>2</sub>) band of CH<sub>4</sub> in order to characterise the system: effective path lengths of ~ 700 m and α<sub>min</sub> of 6.2 x 10<sup>-8</sup> cm<sup>-1</sup> over 8 s were found. The <sup>R</sup>Q<sub>4</sub> CH<sub>3</sub>SH absorption feature at 3040 cm<sup>-1</sup> was also further studied with this system using prepared samples of CH<sub>3</sub>SH in N<sub>2</sub> at different concentrations, yielding a CH<sub>3</sub>SH detection limit of 2.4 ppm at 19 Torr. The potential of such a cavity-based, DS-DBR sourced, QPM-DFG mid-infrared spectrometer for trace gas sensing having thus been demonstrated, possible improvements that could be implemented to increase the sensitivity of the system are then discussed.
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Development of techniques for trace gas detection in breathLangley, Cathryn Elinor January 2012 (has links)
This thesis aims to investigate the possibility of developing spectroscopic techniques for trace gas detection, with particular emphasis on their applicability to breath analysis and medical diagnostics. Whilst key breath molecules such as methane and carbon dioxide will feature throughout this work, the focus of the research is on the detection of breath acetone, a molecule strongly linked with the diabetic condition. Preliminary studies into the suitability of cavity enhanced absorption spectroscopy (CEAS) for the analysis of breath are carried out on methane, a molecule found in varying quantities in breath depending on whether the subject is a methane-producer or not. A telecommunications near-infrared semiconductor diode laser (1.6 µm) is used with an optical cavity based detection system to probe transitions within the vibrational overtone of methane. Achieving a minimum detectable sensitivity of 600 ppb, the device is used to analyse the breath of 48 volunteers, identifying approximately one in three as methane producers. Following this, a second type of laser source, the novel and widely tunable Digital Supermode Distributed Bragg Reflector (DS-DBR) laser, is characterised and the first demonstration of its use in spectroscopy documented. Particular emphasis is given to its application to CEAS and to probing the transitions of the two Fermi resonance components of the CO_2 3ν_1 + ν_3 combination bands found within the spectral range (1.56 - 1.61 µm) of the laser, providing the means to determine accurate ^{13}CO_2/^{12}CO_2 ratios for use in the urea breath test. Not all molecules exhibit narrow, well-resolved ro-vibrational transitions and the next section of the thesis focuses on the detection of molecules, such as acetone, with broad, congested absorption features which are not readily discernible using narrowband laser sources. To provide the necessary specificity for these molecules, two types of broadband source, a Superluminescent Light Emitting Diode (SLED) and a Supercontinuum source (SC), both emitting over the 1.6 - 1.7 µm region, are used in the development of a series of broadband cavity enhanced absorption (BB-CEAS) spectrometers. The three broadband absorbers investigated here, butadiene, acetone and isoprene, all exhibit overtone and combination bands in this spectral region and direct absorption measurements are taken to determine absorption cross-sections for all three molecules. The first BB-CEAS spectrometer couples the SLED device with a dispersive monochromator, attaining a minimum detectable sensitivity of 6 x 10^{-8} cm^{-1}, which is further enhanced to 1.5 x 10^{-8} cm^{-1} on replacing the monochromator with a Fourier Transform interferometer. The spectral coverage is then extended to 1.5 - 1.7 µm by coupling the first SLED with a second device, providing a demonstration of simultaneous multiple species detection. Finally, a SC source is used to provide greater power and uniform spectral intensity, resulting in an improved minimum detectable sensitivity of 5 x 10^{-9} cm^{-1}, or 200 ppb, 400 ppb and 200 ppb for butadiene, acetone and isoprene respectively. This device is then applied to acetone-enriched breath samples; the resulting spectra are fitted with a simulation to return the acetone levels present in the breath-matrix. Following this, the development of a prototype breath acetone analyser, carried out at Oxford Medical Diagnostics Ltd. (OMD), is described. To fulfill the requirements of a compact and commercially-viable device, a diode laser-based system is used, which necessitates a thorough investigation into all possible sources of absorption level change. Most notably, this includes a study into the removal and negating of interfering species, such as water vapour, and to a lesser extent, methane. A novel solution is presented, utilising a water-removal device in conjunction with molecular sieve so that each breath sample generates its own background, which has allowed breath acetone levels to be measured within an uncertainty of 200 ppb. Spectroscopic detection then moves to the mid-infrared with the demonstration of a continuous wave 8 µm quantum cascade laser, which allows the larger absorption cross-sections associated with fundamental vibrational modes to be probed. Following the laser's characterisation using methane, including a wavelength modulation spectroscopy study, the low effective laser linewidth is utilised to resolve rotational structure in low pressure samples of pure acetone. Absorption cross-sections are determined before the sensitivity of the system is enhanced for the detection of dilute concentrations of acetone using two types of multipass cells, firstly a White cell and secondly a home-built Herriott cell. This allows an acetone minimum detectable absorption of 350 ppb and 20 ppb to be attained, respectively. Following this, an optical cavity is constructed and, on treating breath samples in a water-removal device prior to analysis, breath acetone levels determined and corroborated with a mass spectrometer. Finally, a preliminary study probing acetone in the ultraviolet is presented. Utilising an LED centred at 280 nm with a low finesse optical cavity and an imaging spectrograph, detection of 25 ppm of acetone is demonstrated and possible vibronic structure resolved. Combining large absorption cross-sections with the potential to be compact and commercially viable, further development of this arrangement could ultimately represent the optimum solution for breath acetone detection.
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Boundaries in volatile organic compounds in human breathTurner, Matthew A. January 2016 (has links)
Exhaled breath is a rich and complex matrix containing many hundreds of compounds. Every breath offers the potential of a non-invasive measurement of the biochemical processes occurring in the human body and it is this notion that has led to the application of breath analysis for the detection of disease. With the majority of research in the field being focused on the detection of biomarkers, little has been presented on how the seemingly homeostatic matrix of breath varies during the course of normal life events. The research in this thesis describes how a subject's emotional state, physical state, and daily activities can alter the composition of exhaled breath.
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Noninvasive Metabolic Monitoring: An Assessment of Thermoelectric Gas Adsorption Biosensors for Acetone and Ethanol Detection in Breath AnalysisJanuary 2011 (has links)
abstract: In the search for chemical biosensors designed for patient-based physiological applications, non-invasive diagnostic approaches continue to have value. The work described in this thesis builds upon previous breath analysis studies. In particular, it seeks to assess the adsorptive mechanisms active in both acetone and ethanol biosensors designed for breath analysis. The thermoelectric biosensors under investigation were constructed using a thermopile for transduction and four different materials for biorecognition. The analytes, acetone and ethanol, were evaluated under dry-air and humidified-air conditions. The biosensor response to acetone concentration was found to be both repeatable and linear, while the sensor response to ethanol presence was also found to be repeatable. The different biorecognition materials produced discernible thermoelectric responses that were characteristic for each analyte. The sensor output data is presented in this report. Additionally, the results were evaluated against a mathematical model for further analysis. Ultimately, a thermoelectric biosensor based upon adsorption chemistry was developed and characterized. Additional work is needed to characterize the physicochemical action mechanism. / Dissertation/Thesis / M.S. Bioengineering 2011
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Portable Sensors for Breath AnalysisJanuary 2013 (has links)
abstract: Human breath is a concoction of thousands of compounds having in it a breath-print of physiological processes in the body. Though breath provides a non-invasive and easy to handle biological fluid, its analysis for clinical diagnosis is not very common. Partly the reason for this absence is unavailability of cost effective and convenient tools for such analysis. Scientific literature is full of novel sensor ideas but it is challenging to develop a working device, which are few. These challenges include trace level detection, presence of hundreds of interfering compounds, excessive humidity, different sampling regulations and personal variability. To meet these challenges as well as deliver a low cost solution, optical sensors based on specific colorimetric chemical reactions on mesoporous membranes have been developed. Sensor hardware utilizing cost effective and ubiquitously available light source (LED) and detector (webcam/photo diodes) has been developed and optimized for sensitive detection. Sample conditioning mouthpiece suitable for portable sensors is developed and integrated. The sensors are capable of communication with mobile phones realizing the idea of m-health for easy personal health monitoring in free living conditions. Nitric oxide and Acetone are chosen as analytes of interest. Nitric oxide levels in the breath correlate with lung inflammation which makes it useful for asthma management. Acetone levels increase during ketosis resulting from fat metabolism in the body. Monitoring breath acetone thus provides useful information to people with type1 diabetes, epileptic children on ketogenic diets and people following fitness plans for weight loss. / Dissertation/Thesis / Ph.D. Chemistry 2013
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