Application Of Breath Analysis Research Articles

Nano-Optomechanical Systems for Gas Chromatography

Microgas chromatography (GC) is promising for portable chemical analysis. We demonstrate a nano-optomechanical system (NOMS) as an ultrasensitive mass detector in gas chromatography. Bare, native oxide, silicon surfaces are sensitive enough to monitor volatile organic compounds at ppm levels, while simultaneously demonstrating chemical selectivity. The NOMS is able to sense GC peaks from derivatized metabolites at physiological concentrations. This is an important milestone for small-molecule quantitation assays in next generation metabolite analyses for applications such as disease diagnosis and personalized medicine. The optical microring, which plays an important role in the nanomechanical signal transduction mechanism, can also be used as an analyte concentration sensor. Different adsorption kinetics regimes are realized at different temperatures allowing temporary condensation of the analyte onto the sensor surfaces. This effect amplifies the signal, resulting in a 1 ppb level limit of detection, without partition enhancement from absorbing media. This sensitivity bodes well for NOMS as universal, ultrasensitive detectors in micro-GC, breath analysis, and other chemical-sensing applications.

Enhanced non-invasive respiratory sampling from bottlenose dolphins for breath metabolomics measurements

Chemical analysis of exhaled breath metabolites is an emerging alternative to traditional clinical testing for many physiological conditions. The main advantage of breath analysis is its inherent non-invasive nature and ease of sample collection. Therefore, there exists a great interest in further development of this method for both humans and animals. The physiology of cetaceans is exceptionally well suited for breath analysis due to their explosive breathing behavior and respiratory tract morphology. At the present time, breath analysis in cetaceans has very limited practical applications, in large part due to lack of widely adopted sampling device(s) and methodologies that are well-standardized. Here, we present an optimized design and the operating principles of a portable apparatus for reproducible collection of exhaled breath condensate from small cetaceans, such as bottlenose dolphins (Tursiops truncatus). The device design is optimized to meet two criteria: standardized collection and preservation of information-rich metabolomic content of the biological sample, and animal comfort and ease of breath sample collection. The intent is to furnish a fully-benchmarked technology that can be widely adopted by researchers and conservationists to spur further developments of breath analysis applications for marine mammal health assessments.

Volatile organic compounds in breath as markers for irritable bowel syndrome: a metabolomic approach.

The diagnosis of irritable bowel syndrome (IBS) is challenging because of its heterogeneity and multifactorial pathophysiology. No reliable biomarkers of IBS have been identified so far. In a case-control study, using a novel application of breath analysis to distinguish IBS patients from healthy controls based on the analysis of volatile organic compounds (VOCs). Subsequently, the diagnostic VOC-biomarker set was correlated with self-reported gastrointestinal (GI) symptoms of subjects of the Maastricht IBS clinical cohort and of a general population cohort, LifeLines DEEP. Breath samples were collected from 170 IBS patients and 153 healthy controls in the clinical cohort and from 1307 participants in general population cohort. Multivariate statistics were used to identify the most discriminatory set of VOCs in the clinical cohort, and to find associations between VOCs and GI symptoms in both cohorts. A set of 16 VOCs correctly predicted 89.4% of the IBS patients and 73.3% of the healthy controls (AUC = 0.83). The VOC-biomarker set correlated moderately with a set of GI symptoms in the clinical (r = 0.55, P = 0.0003) and general population cohorts (r = 0.54, P = 0.0004). A Kruskal-Wallis test showed no influence from possible confounding factors in distinguishing IBS patients from healthy controls. A set of 16 breath-based biomarkers that distinguishes IBS patients from healthy controls was identified. The VOC-biomarker set correlated significantly with GI symptoms in two independent cohorts. We demonstrate the potential use of breath analysis in the diagnosis and monitoring of IBS, and a possible application of VOC analyses in a general population cohort.

Low-temperature-sensitive relative humidity sensor based on tapered square no-core fiber coated with SiO 2 nanoparticles

Abstract A low-temperature-sensitive relative humidity (RH) sensor based on multimode interference effects has been proposed. The sensor consists of a section of tapered square no-core fiber (TSNCF) coated with SiO2 nanoparticles which is fabricated by splicing the TSNCF with two single-mode fibers (SMFs). The refractive index of SiO2 nanoparticles changes with the variation of environmental humidity levels. Characteristics of the transmission spectral have been investigated under different humidity levels. The wavelength shifts up to 10.2 nm at 1410 nm and 11.5 nm at 1610 nm for a RH range of 43.6–98.6% have been experimentally achieved, and the corresponding sensitivities reach 456.21 pm/%RH and 584.2 pm/%RH for a RH range of 83–96.6%, respectively. The temperature response of the proposed sensor has also been experimentally investigated. Due to the fact that the sensing head is made of a pure silica rod with a low thermal expansion coefficient and the thermo-optic coefficient, the transmission spectrum shows a low temperature sensitivity of about 6 pm/°C for an environmental temperature of 20.9–80 °C, which is a desirable merit to resolve the temperature cross sensitivity. Therefore, the proposed sensor could be applied to breath analysis applications with low temperature fluctuations.

Exhaled nitric oxide and carbon monoxide in mechanically ventilated brain-injured patients

The inflammatory influence and biological markers of prolonged mechanical-ventilation in uninjured human lungs remains controversial. We investigated exhaled nitric oxide (NO) and carbon monoxide (CO) in mechanically-ventilated, brain-injured patients in the absence of lung injury or sepsis at two different levels of positive end-expiratory pressure (PEEP).Exhaled NO and CO were assessed in 27 patients, without lung injury or sepsis, who were ventilated with 8ml kg−1 tidal volumes under zero end-expiratory pressure (ZEEP group, n = 12) or 8 cm H2O PEEP (PEEP group, n = 15). Exhaled NO and CO was analysed on days 1, 3 and 5 of mechanical ventilation and correlated with previously reported markers of inflammation and gas exchange.Exhaled NO was higher on day 3 and 5 in both patient groups compared to day 1: (PEEP group: 5.8 (4.4–9.7) versus 11.7 (6.9–13.9) versus 10.7 (5.6–16.6) ppb (p < 0.05); ZEEP group: 5.3 (3.8–8.8) versus 9.8 (5.3–12.4) versus 9.6 (6.2–13.5) ppb NO peak levels for days 1, 3 and 5, respectively, p < 0.05). Exhaled CO remained stable on day 3 but significantly decreased by day 5 in the ZEEP group only (6.3 (4.3–9.0) versus 8.1 (5.8–12.1) ppm CO peak levels for day 5 versus 1, p < 0.05). The change scores for peak exhaled CO over day 1 and 5 showed significant correlations with arterial blood pH and plasma TNF levels (rs = 0.49, p = 0.02 and rs = −0.51 p = 0.02, respectively). Exhaled NO correlated with blood pH in the ZEEP group and with plasma levels of IL-6 in the PEEP group.We observed differential changes in exhaled NO and CO in mechanically-ventilated patients even in the absence of manifest lung injury or sepsis. These may suggest subtle pulmonary inflammation and support application of real time breath analysis for molecular monitoring in critically ill patients.

Ultrapure Organically Modified Gold Nanoparticles for Breath Analysis

In this study we present a new technological approach for the fabrication of ultrapure organically modified gold nanoparticles (AuNPs) for chemical sensing applied to exhaled breath analysis. To achieve a high purity level of the sensing films, we combined Advanced Gas Deposition (AGD) technique to deposit ultrapure monodispersed AuNPs, and dip coating process for functionalization of the AuNPs with thiolated organic ligands. Morphology and surface analysis revealed the deposition of ultrapure isolated AuNPs after the first processing step, and a network of nanoparticle–ligand nanoassemblies after the second processing step. Gas sensing measurements were performed with exhaled breath samples collected from a group of smokers, a group of non-smokers, and ambient air. Sensors responses towards these samples demonstrated characteristic responses for each study group. PCA analysis further revealed samples classification in three distinct characteristic clusters, which indicates the suitability of the molecularly modified AuNPs presented in this communication for breath analysis applications.

Selective detection of part per billion concentrations of ammonia using a p–n semiconducting oxide heterostructure

Detection of low levels of ammonia is relevant for environmental, combustion and health-related applications. Resistive semiconducting metal oxide sensing platforms are extensively studied for ammonia and other gas detection. Two important aspects of gas sensing are enhancing sensitivity and selectivity. In this paper, we present a sensor platform with n-type In2O3 and p-type NiO placed side by side with a shared 30μm interface. The substrate on which these metal oxides are placed allows for measuring the resistance change across In2O3, NiO or any combination of both oxides. Our focus was to develop an ammonia sensor with ppb sensitivity, with possible application in breath analysis. With low concentrations of NH3 (<100 ppb), the change in resistance with NiO was anomalous at 300°C, the resistance decreased and then gradually increased over tens of minutes before decreasing again to reach the baseline. In situ diffuse reflectance infrared spectroscopy exhibited a band at 1267cm−1, which was assigned to O2− and the change in intensity of this band with time mirrored the transient change in resistance with 1ppm NH3 at 300°C, indicating that NH3 chemisorption was correlated with the O2− species. Taking advantage of the transient resistance decrease of NiO with NH3, and combining the In2O3 and NiO allowed selectivity enhancement towards NH3 at concentrations as low as 100 ppb. Interference to CO, NOx and humidity were studied. By selecting a suitable combination of both oxides, the response to CO at <10ppm could be negated. Similarly, with NO at <10 ppb, there was minimal sensor response. The sensor was used to analyze NH3 mixed into human breath at 10–1000 ppb concentrations. Water had to be completely removed from the breath via a moisture trap, since water interfered with the NH3 chemisorption chemistry. Potential applications of this sensor platform in breath analysis are discussed.

Catalyst-decorated hollow WO3 nanotubes using layer-by-layer self-assembly on polymeric nanofiber templates and their application in exhaled breath sensor

In this work, highly porous WO3 nanotubes (NTs) were synthesized by facile layer-by-layer (LbL) self-assembly on polymeric nanofiber (NF) templates followed by calcination. Polymeric NFs using poly(methyl methacrylate) (PMMA) were prepared by electrospinning as sacrificial templates. Then, ionic polymers were coated on PMMA to modify the surface charge of PMMA NFs. Catalyst-loaded WO3 NTs were synthesized by self-assembly of tungsten precursor and catalytic precursor on the surface of the polymeric PMMA NFs followed by calcination at 500°C for 1h. Gas sensing performances were evaluated in highly humid atmosphere (90% RH) using pristine WO3 NTs, Pt-loaded WO3 NTs (Pt-WO3 NTs), and Pd-loaded WO3 NTs (Pd-WO3 NTs). Pristine WO3 NTs exhibited a high NO response (Rgas/Rair=63.59 at 5ppm) at 350°C and cross-selectivity toward toluene (Rair/Rgas=1.05 at 5ppm). On the other hand, Pt-WO3 NTs and Pd-WO3 NTs exhibited a high toluene response (Rair/Rgas=2.24 for the Pt-WO3 NTs and Rair/Rgas=2.35 for the Pd-WO3 NTs at 5ppm) at 400°C and a negligible NO response (Rgas/Rair=1.25 for the Pt-WO3 NTs and Rgas/Rair=1.04 for the Pd-WO3 NTs at 5ppm) at 400°C. These results demonstrated that LbL synthesis is a highly promising method for producing hollow semiconductor metal oxide NTs functionalized with various catalysts, which leads to potential application in exhaled breath analysis for asthma and lung cancer diagnosis.

Breath analysis: technical developments and challenges in the monitoring of human exposure to volatile organic compounds.

At present, there is a growing concern about human quality of life. In particular, there is an awareness of the impact of volatile organic compounds (VOCs) on the environment and human health, so the monitoring of human exposure to VOCs is an increasingly urgent need. Biomonitoring is theoretically more accurate compared with traditional ambient air monitoring, and it plays an essential role in human environmental exposure assessment. Breath analysis is a biomonitoring method with many advantages, which is applicable to assessments of human exposure to a large number of VOCs. Techniques are being developed to improve the sensitivity and precision of breath analysis based on in-direct and direct measurements which will be reviewed in this paper. This paper briefly reviews the frequently used methods in both of these categories, specifically highlighting some promising new techniques. Furthermore, this review also provides theoretical background knowledge about the use of breath analysis as a biomonitoring tool for human exposure assessment. A review of the application of breath analysis to human exposure monitoring during last two decades is also provided according to occupational/non-occupational exposure. Obstacles and potential challenges in this field are also summarized. Based on the gradual improvements in the theoretical basis and technology reviewed in this paper, breath analysis is an enormous potential approach for the monitoring of human exposure to VOCs.

Simultaneous atmospheric nitrous oxide, methane and water vapor detection with a single continuous wave quantum cascade laser.

A continuous wave (CW) quantum cascade laser (QCL) based absorption sensor system was demonstrated and developed for simultaneous detection of atmospheric nitrous oxide (N(2)O), methane (CH(4)), and water vapor (H(2)O). A 7.73-µm CW QCL with its wavelength scanned over a spectral range of 1296.9-1297.6 cm(-1) was used to simultaneously target three neighboring strong absorption lines, N(2)O at 1297.05 cm(-1), CH(4) at 1297.486 cm(-1), and H(2)O at 1297.184 cm(-1). An astigmatic multipass Herriott cell with a 76-m path length was utilized for laser based gas absorption spectroscopy at an optimum pressure of 100 Torr. Wavelength modulation and second harmonic detection was employed for data processing. Minimum detection limits (MDLs) of 1.7 ppb for N(2)O, 8.5 ppb for CH(4), and 11 ppm for H(2)O were achieved with a 2-s integration time for individual gas detection. This single QCL based multi-gas detection system possesses applications in environmental monitoring and breath analysis.

Micropreconcentrator in LTCC Technology with Mass Spectrometry for the Detection of Acetone in Healthy and Type-1 Diabetes Mellitus Patient Breath.

Breath analysis has long been recognized as a potentially attractive method for the diagnosis of several diseases. The main advantage over other diagnostic methods such as blood or urine analysis is that breath analysis is fully non-invasive, comfortable for patients and breath samples can be easily obtained. One possible future application of breath analysis may be the diagnosing and monitoring of diabetes. It is, therefore, essential, to firstly determine a relationship between exhaled biomarker concentration and glucose in blood as well as to compare the results with the results obtained from non-diabetic subjects. Concentrations of molecules which are biomarkers of diseases’ states, or early indicators of disease should be well documented, i.e., the variations of abnormal concentrations of breath biomarkers with age, gender and ethnic issues need to be verified. Furthermore, based on performed measurements it is rather obvious that analysis of exhaled acetone as a single biomarker of diabetes is unrealistic. In this paper, the author presents results of his research conducted on samples of breath gas from eleven healthy volunteers (HV) and fourteen type-1 diabetic patients (T1DM) which were collected in 1-l SKC breath bags. The exhaled acetone concentration was measured using mass spectrometry (HPR-20 QIC, Hiden Analytical, Warrington, UK) coupled with a micropreconcentrator in LTCC (Low Temperature Cofired Ceramic). However, as according to recent studies the level of acetone varies to a significant extent for each blood glucose concentration of single individuals, a direct and absolute relationship between blood glucose and acetone has not been proved. Nevertheless, basing on the research results acetone in diabetic breath was found to be higher than 1.11 ppmv, while its average concentration in normal breath was lower than 0.83 ppmv.

Non-labeling multiplex surface enhanced Raman scattering (SERS) detection of volatile organic compounds (VOCs)

In this paper, we report multiplex SERS based VOCs detection with a leaning nano-pillar substrate. The VOCs analyte molecules adsorbed at the tips of the nano-pillars produced SERS signal due to the field enhancement occurring at the localized surface plasmon hot spots between adjacent leaning nano-pillars. In this experiment, detections of acetone and ethanol vapor at different concentrations were demonstrated. The detection limits were found to be 0.0017ng and 0.0037ng for ethanol and acetone vapor molecules respectively. Our approach is a non-labeling method such that it does not require the incorporation of any chemical sensing layer for the enrichment of gas molecules on sensor surface. The leaning nano-pillar substrate also showed highly reproducible SERS signal in cyclic VOCs detection, which can reduce the detection cost in practical applications. Further, multiplex SERS detection on different combination of acetone and ethanol vapor was also successfully demonstrated. The vibrational fingerprints of molecular structures provide specific Raman peaks for different VOCs contents. To the best of our knowledge, this is the first multiplex VOCs detection using SERS. We believe that this work may lead to a portable device for multiplex, specific and highly sensitive detection of complex VOCs samples that can find potential applications in exhaled breath analysis, hazardous gas analysis, homeland security and environmental monitoring.

Suppressing the influence of optical fringes in dispersion spectroscopy

In this letter we show that in chirped laser dispersion spectroscopy (CLaDS) a significant reduction of parasitic optical fringes can be achieved. Good agreement between theoretical model and experimental data is demonstrated. Such a fringe reduction capability makes CLaDS technique a good candidate for field applications in which long-term accuracy is critical. Full Text: PDF References A. Cygan et al., High-signal-to-noise-ratio laser technique for accurate measurements of spectral line parameters, Phys. Rev. A 85, 022508 (2012) CrossRef B. Tuzson et al., Continuous isotopic composition measurements of tropospheric CO2 at Jungfraujoch (3580 m a.s.l.), Switzerland: real-time observation of regional pollution events, Atmos. Chem. Phys. 11 1685 (2011) CrossRef M. Nikodem, G. Wysocki, Chirped Laser Dispersion Spectroscopy for Remote Open-Path Trace-Gas Sensing, Sensors 12, 16466 (2012) CrossRef B. Brumfield, et al., Direct In Situ Quantification of HO2 from a Flow Reactor, J. Phys. Chem. Lett. 4, 872 (2013) CrossRef P. Kluczynski et al., Detection of acetylene impurities in ethylene and polyethylene manufacturing processes using tunable diode laser spectroscopy in the 3-?m range, Appl. Phys. B 105, 427 (2011) CrossRef M. R. McCurdy et al., Recent advances of laser-spectroscopy-based techniques for applications in breath analysis, J. Breath Res. 1, 014001 (2007) CrossRef K. Krzempek et al., CW DFB RT diode laser-based sensor for trace-gas detection of ethane using a novel compact multipass gas absorption cell, Appl. Phys. B 112, 461 (2013) CrossRef R. W. Wood, The Anomalous Dispersion of Sodium Vapour, Proc. of the Royal Society of London 69, 157 (1902) CrossRef G. C. Bjorklund, Frequency-modulation spectroscopy: a new method for measuring weak absorptions and dispersions, Opt. Lett. 5, 15 (1980) CrossRef S. Marchett, R. Simili, Measurement of the refractive index dispersion around an absorbing line, Opt. Comm. 249, 37 (2005) CrossRef R. Lewicki et al., Ultrasensitive detection of nitric oxide at 5.33 ?m by using external cavity quantum cascade laser-based Faraday rotation spectroscopy, Proc. Natl. Acad. Sci. U. S. A. 106, 12587 (2009) CrossRef P. Ehlers et al., Fiber-laser-based noise-immune cavity-enhanced optical heterodyne molecular spectrometry instrumentation for Doppler-broadened detection in the 10?12??cm?1?Hz?1/2 region, J. Opt. Soc. Am. B 29, 1305 (2012) CrossRef G. Wysocki, D. Weidmann, Molecular dispersion spectroscopy for chemical sensing using chirped mid-infrared quantum cascade laser, Opt. Exp. 18, 26123 (2010) CrossRef M. Nikodem, G. Wysocki, Molecular dispersion spectroscopy ? new capabilities in laser chemical sensing, Ann. NY Acad.Sci. 1260, 101 (2012) CrossRef M. Nikodem, G. Wysocki, Measuring optically thick molecular samples using chirped laser dispersion spectroscopy, Opt. Lett. 38, 3834 (2013) CrossRef N.-Y. Chou et al., Optical fringe reduction technique for FM laser spectroscopy, Appl. Opt. 28, 4973 (1989) CrossRef M. Nikodem et al., Signal-to-noise ratio in chirped laser dispersion spectroscopy, Opt. Expr. 20, 644 (2012) CrossRef A. Fried et al., Reduction of interference fringes in small multipass absorption cells by pressure modulation, Appl. Opt. 29, 900 (1990) CrossRef

Exhaled breath analysis by electronic nose in airways disease. Established issues and key questions

Exhaled air contains many volatile organic compounds (VOCs) that are the result of normal and disease-associated metabolic processes anywhere in the body. Different omics techniques can assess the pattern of these VOCs. One such omics technique suitable for breath analysis is represented by electronic noses (eNoses), providing fingerprints of the exhaled VOCs, called breathprints. Breathprints have been shown to be altered in different disease states, including in asthma and COPD. This review describes the current status on clinical validation and application of breath analysis by electronic noses in the diagnosis and monitoring of chronic airways diseases. Furthermore, important methodological issues including breath sampling, modulating factors and incompatibility between eNoses are raised and discussed. Next steps towards clinical application of electronic noses are provided, including further validation in suspected disease, assessment of the influence of different comorbidities, the value in longitudinal monitoring of patients with asthma and COPD and the possibility to predict treatment responses. Eventually, a Breath Cloud may be constructed, a large database containing disease-specific breathprints. When collaborative efforts are put into optimization of this technique, it can provide a rapid and non-invasive first line diagnostic test.

The application of exhaled breath analysis in racing Thoroughbreds and the influence of high intensity exercise and ambient temperature on the concentration of carbon monoxide and pH in exhaled breath

Analyses of exhaled breath (EB) and exhaled breath condensate (EBC) are non-invasive modalities for assessing the lower airways but these methods have not been applied to Thoroughbred racehorses in training. The aims of this study were to determine whether EB and EBC could be obtained from Thoroughbred racehorses in the field and to investigate the effects of exercise per se and during different ambient temperatures and humidity on exhaled concentrations of nitric oxide (eNO), carbon monoxide (eCO) and EBC pH. EB and EBC samples were obtained from 28 Thoroughbred racehorses pre- and post-exercise during warm (n=23) and/or cold (n=19) ambient temperatures.eNO was detected in 19/84 EB samples. eCO was measured in 39/42 EB samples pre-exercise (median 1.3ppm) and concentrations decreased significantly post-exercise (median 0.8ppm, P<0.005) and were associated with ambient temperature. EBC pH was 4.51±0.23 pre-exercise and increased significantly post-exercise (4.79±0.59, P=0.003). The study documented the collection of EB and EBC from Thoroughbred racehorses in a field setting. Alterations in concentrations of volatile gases and EBC pH occurred in response to exercise, and were likely to have been influenced by environmental factors.

Exertion in Kangoo Jumps Aerobic: Evaluation and Interpretation Using Spectroscopic Technique Determinations

Laser photoacoustic spectroscopy (LPAS) is growing quickly in its applications to real world problems—one of the problems is to prevent obesity—being a candidate technology for breath analysis applications. The ongoing paper is aiming to investigate the evaluation of oxidative stress in womens practicing Kangoo Jumps (KJ) aerobics. Because it is not possible to directly measure free radicals in the body, we approach that by measuring the by-products (breath ethylene) that result from free radical reactions. We found out that the mixture of exhaled breath in women's after the KJ exercises contains low concentration of ethylene compared to the exhaled breath of the women before the start of exercise program. This result can add valuable information to the contribution to reduce the generation of prooxidants during and after KJ aerobics.

A comparison of spectroscopic techniques for human breath analysis

The analysis of human breath has been driven to new heights and has great potential to impact our society in the area of medical science. Breath analysis is promising as non-invasive, simple and point-of-care clinical measurements to reduce the medical burden caused by invasive, time-consuming and expensive clinical devices. Spectroscopic techniques for breath analysis can offer information to correlate its signals to exhaled substances for molecular identification and quantification to provide the pathophysiological status of the body. In this review paper, techniques such as mass spectrometry-based (gas chromatography-mass spectrometry, proton transfer reaction-mass spectrometry, selected ion flow tube-mass spectrometry), laser absorption spectroscopy-based (cavity ring down spectroscopy and tunable diode laser absorption spectroscopy) and other spectroscopic techniques for breath analysis applications are compared in terms of its advantages/disadvantages, versatilities and plausibility to be transformed in clinical applications.

Can volatile compounds in exhaled breath be used to monitor control in diabetes mellitus?

Although it has been known for centuries that there are compounds in exhaled breath that are altered in disease, it is only in the last few decades that it has been possible to measure them with sufficient accuracy and precision to make them clinically useful. The clinical utility of breath analysis has also been limited by the practical difficulties of collecting representative breath samples, free from contaminants. More recent methods of breath analysis have allowed real-time analysis of breath, eliminating the need for sample collection, and therefore potentially allowing the rapid feedback of results to patient and clinician. One possible future application of breath analysis may be the monitoring of metabolic control in patients with diabetes mellitus. This perspective article provides an overview of the studies of breath analysis in diabetes, focusing on the breath metabolites; acetone, isoprene and also methyl nitrate that have previously been reported to be altered in diabetes, highlighting the factors that may potentially confound their interpretation. Specific attention is given to selected ion flow tube mass spectrometry (SIFT-MS) and proton transfer reaction mass spectrometry (PTR-MS), because they are techniques that have been developed specifically for the absolute quantification of breath metabolites in real time, although reference is made to some of the alternative techniques, including sensors and optical devices. Whilst breath analysis, using SIFT-MS, PTR-MS and other sensitive techniques, can potentially be used for the non-invasive monitoring of metabolic conditions that may include diabetes mellitus, further work is required in terms of the clinical and analytical validation. Furthermore, it is unclear at present what breath metabolites should be monitored and what factors may confound their interpretation. Although a non-invasive method of monitoring glycaemic control is clearly desirable, it will be important to demonstrate its analytical comparability with the well-established and validated methods for blood glucose measurement.

An LDA based sensor selection approach used in breath analysis system

Abstract In the application of breath analysis, the redundant specificities of a sensor array often exceed the needs of the discrimination application. When recognizing types of diseases, not all sensors are required. However, it is difficult to decide which sensor is more useful for an unknown sample because some sensors are cross-sensitive to the biomarkers of the diseases. In this paper, we propose a linear discriminant analysis (LDA) based sensor selection technique (LDASS) which chooses an optimal configuration of sensors for a particular application from a whole set of available sensors. The proposed method finds the direction w via the LDA such that when data are projected onto this direction, the samples from two classes are as separate as possible. It is found that after projection, the difference of means of the two distinct sample classes can be expressed as the linear combination of the responses of all the sensors in the system, and w can be regarded as the weight vectors for these sensors which indicate the contribution weight of each sensor. Accordingly, it is possible to determine which sensor has a greater contribution in classifying the two classes. A series of experiments on different databases show that the proposed method outperforms other sensor selection techniques, such as the sequential forward selection (SFS) and genetic algorithm (GA) in recognition accuracy and processing time. This technique is not only applicable for breath analysis, but also useful in the general applications of e-noses.

Progress in SIFT‐MS: Breath analysis and other applications

The development of selected ion flow tube mass spectrometry, SIFT-MS, is described from its inception as the modified very large SIFT instruments used to demonstrate the feasibility of SIFT-MS as an analytical technique, towards the smaller but bulky transportable instruments and finally to the current smallest Profile 3 instruments that have been located in various places, including hospitals and schools to obtain on-line breath analyses. The essential physics and engineering principles are discussed, which must be appreciated to design and construct a SIFT-MS instrument. The versatility and sensitivity of the Profile 3 instrument is illustrated by typical mass spectra obtained using the three precursor ions H(3)O(+), NO(+) and O(2)(+)·, and the need to account for differential ionic diffusion and mass discrimination in the analytical algorithms is emphasized to obtain accurate trace gas analyses. The performance of the Profile 3 instrument is illustrated by the results of several pilot studies, including (i) on-line real time quantification of several breath metabolites for cohorts of healthy adults and children, which have provided representative concentration/population distributions, and the comparative analyses of breath exhaled via the mouth and nose that identify systemic and orally-generated compounds, (ii) the enhancement of breath metabolites by drug ingestion, (iii) the identification of HCN as a marker of Pseudomonas colonization of the airways and (iv) emission of volatile compounds from urine, especially ketone bodies, and from skin. Some very recent developments are discussed, including the quantification of carbon dioxide in breath and the combination of SIFT-MS with GC and ATD, and their significance. Finally, prospects for future SIFT-MS developments are alluded to.