Detection of volatile organic compounds as biomarkers in breath analysis by different analytical techniques.

Breath is a rich mixture containing numerous volatile organic compounds at trace amounts (ppbv-pptv level) such as: hydrocarbons, alcohols, ketones, aldehydes, esters or heterocycles. The presence of some of them depends on health status. Therefore, breath analysis might be useful for clinical diagnostics, therapy monitoring and control of metabolic or biochemical cell cycle products. This Review presents an update on the latest developments in breath analysis applied to diagnosing different diseases with the help of high-quality equipment. Efforts were made to fully and accurately describe traditional and modern techniques used to determine the components of breath. The techniques were compared in terms of design, function and also detection limit of different volatile organic compounds. GC with different detectors, MS, optical sensor and laser spectroscopic detection techniques are also discussed.

[1]  Tarek Mekhail,et al.  Exhaled Breath Analysis with a Colorimetric Sensor Array for the Identification and Characterization of Lung Cancer , 2012, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[2]  Giorgio Pennazza,et al.  Application of a quartz microbalance based gas sensor array for the study of halitosis , 2008, Journal of breath research.

[3]  P. Hering,et al.  Isotopic ratio measurement of methane in ambient air using mid-infrared cavity leak-out spectroscopy , 2001 .

[4]  B. Buszewski,et al.  Analytical and unconventional methods of cancer detection using odor , 2012 .

[5]  David Smith,et al.  Progress in SIFT-MS: breath analysis and other applications. , 2011, Mass spectrometry reviews.

[6]  T. Ligor.  Analytical Methods for Breath Investigation , 2009 .

[7]  J. Shaji,et al.  Breath biomarker for clinical diagnosis and different analysis technique , 2010 .

[8]  David Smith,et al.  Can volatile compounds in exhaled breath be used to monitor control in diabetes mellitus? , 2011, Journal of breath research.

[9]  S. Herndon,et al.  A practical alternative to chemiluminescence-based detection of nitrogen dioxide: cavity attenuated phase shift spectroscopy. , 2008, Environmental science & technology.

[10]  Kenneth W. Busch,et al.  Cavity-ringdown spectroscopy : an ultratrace-absorption measurement technique , 1999 .

[11]  A. O’Keefe,et al.  Cavity ring‐down optical spectrometer for absorption measurements using pulsed laser sources , 1988 .

[12]  Marc Quirynen,et al.  Breath biomarkers of liver cirrhosis. , 2012, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[13]  C. Hoeschen,et al.  Effects of carbon dioxide in breath gas on proton transfer reaction-mass spectrometry (PTR-MS) measurements , 2008 .

[14]  Zbigniew Bielecki,et al.  Applying CEAS method to UV, VIS, and IR spectroscopy sensors , 2011 .

[15]  John Tulip,et al.  Pulsed quantum cascade laser-based cavity ring-down spectroscopy for ammonia detection in breath. , 2006, Applied optics.

[16]  W. Miekisch,et al.  Breath biomarkers for lung cancer detection and assessment of smoking related effects--confounding variables, influence of normalization and statistical algorithms. , 2010, Clinica chimica acta; international journal of clinical chemistry.

[17]  I. Horváth,et al.  Exhaled biomarkers in lung cancer , 2009, European Respiratory Journal.

[18]  P. Thomas,et al.  Exhaled breath analysis: novel approach for early detection of lung cancer. , 2009, Lung cancer.

[19]  M. Fiegl,et al.  Noninvasive detection of lung cancer by analysis of exhaled breath , 2009, BMC Cancer.

[20]  Giorgio Pennazza,et al.  Diagnostic performance of an electronic nose, fractional exhaled nitric oxide, and lung function testing in asthma. , 2010, Chest.

[21]  Jin Luo,et al.  Nanoparticle-structured thin film sensor arrays for breath sensing , 2012 .

[22]  P. Španěl,et al.  The challenge of breath analysis for clinical diagnosis and therapeutic monitoring. , 2007, The Analyst.

[23]  L R Narasimhan,et al.  Correlation of breath ammonia with blood urea nitrogen and creatinine during hemodialysis , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[24]  Sandeep Kumar Vashist,et al.  Recent Advances in Quartz Crystal Microbalance-Based Sensors , 2011, J. Sensors.

[25]  Bogusław Buszewski,et al.  Human exhaled air analytics: biomarkers of diseases. , 2007, Biomedical chromatography : BMC.

[26]  A. Buettner,et al.  Real-time breath gas analysis for pharmacokinetics: monitoring exhaled breath by on-line proton-transfer-reaction mass spectrometry after ingestion of eucalyptol-containing capsules , 2010, Journal of breath research.

[27]  M. Epton,et al.  Measurement of breath acetone concentrations by selected ion flow tube mass spectrometry in type 2 Diabetes , 2011, Journal of breath research.

[28]  Š. Matejčík,et al.  Corona discharge ion mobility spectrometry with orthogonal acceleration time of flight mass spectrometry for monitoring of volatile organic compounds. , 2012, Analytical chemistry.

[29]  Bogusław Buszewski,et al.  Chemotherapy control by breath profile with application of SPME-GC/MS method. , 2012, Journal of separation science.

[30]  Michael Schivo,et al.  Chemically Polymerized Polypyrrole for On-Chip Concentration of Volatile Breath Metabolites. , 2010, Sensors and actuators. B, Chemical.

[31]  Jun Ye,et al.  Cavity-enhanced optical frequency comb spectroscopy: application to human breath analysis. , 2008, Optics express.

[32]  Peter J Sterk,et al.  An electronic nose in the discrimination of patients with asthma and controls. , 2007, The Journal of allergy and clinical immunology.

[33]  T. Rocha-Santos,et al.  Comparison of a gas chromatography-optical fibre (GC-OF) detector with a gas chromatography-flame ionization detector (GC-FID) for determination of alcoholic compounds in industrial atmospheres. , 2008, Talanta.

[34]  G. Berden,et al.  Cavity ring-down spectroscopy: Experimental schemes and applications , 2000 .

[35]  R. Dweik,et al.  Cardiovascular biomarkers in exhaled breath. , 2012, Progress in cardiovascular diseases.

[36]  G. Sun,et al.  Quantitative breath analysis of volatile organic compounds of lung cancer patients. , 2010, Lung cancer.

[37]  M. Evans,et al.  An exploratory comparative study of volatile compounds in exhaled breath and emitted by skin using selected ion flow tube mass spectrometry. , 2008, Rapid communications in mass spectrometry : RCM.

[38]  A C Duarte,et al.  Optical fiber biosensor coupled to chromatographic separation for screening of dopamine, norepinephrine and epinephrine in human urine and plasma. , 2009, Talanta.

[39]  Sotiris E Pratsinis,et al.  Si:WO(3) Sensors for highly selective detection of acetone for easy diagnosis of diabetes by breath analysis. , 2010, Analytical chemistry.

[40]  C. Baumgartner,et al.  Non-invasive diagnosis of liver diseases by breath analysis using an optimized ion–molecule reaction-mass spectrometry approach: a pilot study , 2010, Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals.

[41]  Julian King,et al.  Physiological modeling of isoprene dynamics in exhaled breath. , 2010, Journal of theoretical biology.

[42]  Miles J Padgett,et al.  Dynamic study of oxidative stress in renal dialysis patients based on breath ethane measured by optical spectroscopy , 2007, Journal of breath research.

[43]  U. Weimar,et al.  Detection of volatile compounds correlated to human diseases through breath analysis with chemical sensors , 2002 .

[44]  A. L. Kukla,et al.  Application of sensor arrays based on thin films of conducting polymers for chemical recognition of volatile organic solvents , 2009 .

[45]  Russell Binions,et al.  Metal Oxide Semi-Conductor Gas Sensors in Environmental Monitoring , 2010, Sensors.

[46]  R. Peverall,et al.  3.5-μm high-resolution gas sensing employing a LiNbO3 QPM-DFG waveguide module , 2009 .

[47]  P. Španěl,et al.  Selected ion flow tube mass spectrometry of exhaled breath condensate headspace. , 2008, Rapid communications in mass spectrometry : RCM.

[48]  T. Rocha-Santos,et al.  Breath analysis by optical fiber sensor for the determination of exhaled organic compounds with a view to diagnostics. , 2011, Talanta.

[49]  K. Unterkofler,et al.  Breath acetone—aspects of normal physiology related to age and gender as determined in a PTR-MS study , 2009, Journal of breath research.

[50]  E. Woltering,et al.  Optical parametric oscillator-based photoacoustic detection of CO2 at 4.23 μm allows real-time monitoring of the respiration of small insects , 2006 .

[51]  H. Haick,et al.  Effect of humidity on nanoparticle-based chemiresistors: a comparison between synthetic and real-world samples. , 2012, ACS applied materials & interfaces.

[52]  CCD based fiber-optic spectrometer detection. , 2009, Methods in molecular biology.

[53]  Haiyang Li,et al.  Quartz crystal microbalance sensor array for the detection of volatile organic compounds. , 2009, Talanta.

[54]  G. Hanna,et al.  On-line, real time monitoring of exhaled trace gases by SIFT-MS in the perioperative setting: a feasibility study. , 2011, The Analyst.

[55]  T. Rocha-Santos,et al.  Microscale optical fibre sensor for monitoring in landfill leachate. , 2009, Analytical methods : advancing methods and applications.

[56]  N. Bârsan,et al.  Electronic nose: current status and future trends. , 2008, Chemical reviews.

[57]  Kyung Soo Park,et al.  Gas sensing properties of defect-controlled ZnO-nanowire gas sensor , 2008 .

[58]  A. B. Robinson,et al.  Quantitative analysis of urine vapor and breath by gas-liquid partition chromatography. , 1971, Proceedings of the National Academy of Sciences of the United States of America.

[59]  Armando C. Duarte,et al.  Development of a fluorosiloxane polymer-coated optical fibre sensor for detection of organic volatile compounds , 2008 .

[60]  Tianshu Wang,et al.  Analysis of breath, exhaled via the mouth and nose, and the air in the oral cavity , 2008, Journal of breath research.

[61]  Richard N Zare,et al.  Stable isotope ratios using cavity ring-down spectroscopy: determination of 13C/12C for carbon dioxide in human breath. , 2002, Analytical chemistry.

[62]  M. Shepherd,et al.  A Study on Breath Acetone in Diabetic Patients Using a Cavity Ringdown Breath Analyzer: Exploring Correlations of Breath Acetone With Blood Glucose and Glycohemoglobin A1C , 2010, IEEE Sensors Journal.

[63]  Gerard Wysocki,et al.  Pulsed quantum-cascade laser-based sensor for trace-gas detection of carbonyl sulfide. , 2004, Applied optics.

[64]  K. Namjou,et al.  Determination of exhaled nitric oxide distributions in a diverse sample population using tunable diode laser absorption spectroscopy , 2006 .

[65]  Malina K. Storer,et al.  Accurate, reproducible measurement of acetone concentration in breath using selected ion flow tube-mass spectrometry , 2010, Journal of breath research.

[66]  T. Fritsch,et al.  Infrared laser-spectroscopic analysis of 14NO and 15NO in human breath , 2009 .

[67]  Graham Bothamley,et al.  Breath biomarkers of active pulmonary tuberculosis. , 2010, Tuberculosis.

[68]  B. Vidakovic,et al.  Breath Analysis by Mass Spectrometry: A New Tool for Breast Cancer Detection? , 2011, The American surgeon.

[69]  E. M. Gaspar,et al.  Organic metabolites in exhaled human breath--a multivariate approach for identification of biomarkers in lung disorders. , 2009, Journal of chromatography. A.

[70]  António S. Barros,et al.  Allergic asthma exhaled breath metabolome: a challenge for comprehensive two-dimensional gas chromatography. , 2012, Journal of chromatography. A.

[71]  T. Stacewicz,et al.  Cavity ring down spectroscopy: detection of trace amounts of substance , 2012 .

[72]  Frank K Tittel,et al.  Mid-infrared quantum cascade laser based off-axis integrated cavity output spectroscopy for biogenic nitric oxide detection. , 2004, Applied optics.

[73]  H. Gietema,et al.  Screening for emphysema via exhaled volatile organic compounds , 2011, Journal of breath research.

[74]  H. Byun,et al.  Analysis of diabetic patient's breath with conducting polymer sensor array , 2005 .

[75]  P. Mazzone,et al.  Exhaled breath volatile organic compound biomarkers in lung cancer , 2012, Journal of breath research.

[76]  W. Miekisch,et al.  Breath gas aldehydes as biomarkers of lung cancer , 2009, International journal of cancer.

[77]  B. Buszewski,et al.  Preliminary study of volatile organic compounds from breath and stomach tissue by means of solid phase microextraction and gas chromatography–mass spectrometry , 2007, Journal of breath research.

[78]  A C Duarte,et al.  Remote optical fibre microsensor for monitoring BTEX in confined industrial atmospheres. , 2009, Talanta.

[79]  Graham Bothamley,et al.  Point-of-care breath test for biomarkers of active pulmonary tuberculosis. , 2012, Tuberculosis.

[80]  P Hering,et al.  Mid-infrared cavity leak-out spectroscopy for ultrasensitive detection of carbonyl sulfide. , 2005, Optics letters.

[81]  Lav R. Khot,et al.  Development and evaluation of piezoelectric-polymer thin film sensors for low concentration detection of volatile organic compounds related to food safety applications , 2011 .

[82]  M P van der Schee,et al.  External validation of exhaled breath profiling using an electronic nose in the discrimination of asthma with fixed airways obstruction and chronic obstructive pulmonary disease , 2011, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[83]  S. Semancik,et al.  Machine learning applied to chemical analysis: sensing multiple biomarkers in simulated breath using a temperature-pulsed electronic-nose. , 2012, Analytical chemistry.

[84]  D. Smith,et al.  Selected Ion Flow Tube Mass Spectrometry for On-Line Trace Gas Analysis in Biology and Medicine , 2007, European journal of mass spectrometry.

[85]  K. Schwarz,et al.  Determining concentration patterns of volatile compounds in exhaled breath by PTR-MS , 2009, Journal of breath research.

[86]  M. Angelmahr,et al.  Photoacoustic spectroscopy of formaldehyde with tunable laser radiation at the parts per billion level , 2006 .

[87]  Yuyuan Tian,et al.  Online sample conditioning for portable breath analyzers. , 2012, Analytical chemistry.

[88]  David Smith,et al.  Selected ion flow tube mass spectrometry (SIFT-MS) for on-line trace gas analysis. , 2005, Mass spectrometry reviews.

[89]  O. Wolfbeis.  Fiber-optic chemical sensors and biosensors. , 2000, Analytical chemistry.

[90]  Dong Xiang,et al.  Metal Oxide Gas Sensors: Sensitivity and Influencing Factors , 2010, Sensors.

[91]  David Smith,et al.  An investigation of suitable bag materials for the collection and storage of breath samples containing hydrogen cyanide , 2012, Journal of breath research.

[92]  David Smith,et al.  Hydrogen cyanide as a biomarker for Pseudomonas aeruginosa in the breath of children with cystic fibrosis , 2009, Pediatric pulmonology.

[93]  Douglas A Christensen,et al.  Optical system design for biosensors based on CCD detection. , 2009, Methods in molecular biology.

[94]  Bogusław Buszewski,et al.  Investigation of lung cancer biomarkers by hyphenated separation techniques and chemometrics , 2012, Clinical chemistry and laboratory medicine.

[95]  T. Rocha-Santos,et al.  High performance liquid chromatography coupled to an optical fiber detector coated with laccase for screening catecholamines in plasma and urine. , 2009, Journal of chromatography. A.

[96]  P. Mazzone,et al.  Detection of lung cancer by sensor array analyses of exhaled breath. , 2005, American journal of respiratory and critical care medicine.

[97]  Khosrow Namjou,et al.  Measurement of acetaldehyde in exhaled breath using a laser absorption spectrometer. , 2007, Applied optics.

[98]  D. Romanini,et al.  CW cavity ring down spectroscopy , 1997 .

[99]  Jeffrey K. Hollingsworth,et al.  Instrumentation and Measurement , 1998, 2022 International Symposium on Electronics and Telecommunications (ISETC).

[100]  A. Cho,et al.  Spectroscopic detection of biological NO with a quantum cascade laser , 2001, Applied physics. B, Lasers and optics.

[101]  K. Unterkofler,et al.  Breath isoprene – aspects of normal physiology related to age, gender and cholesterol profile as determined in a proton transfer reaction mass spectrometry study , 2008, Clinical chemistry and laboratory medicine.

[102]  G. Hanna,et al.  Selected ion flow tube-MS analysis of headspace vapor from gastric content for the diagnosis of gastro-esophageal cancer. , 2012, Analytical chemistry.

[103]  Hsin-Hsien Lu,et al.  Direct characterization and quantification of volatile organic compounds by piezoelectric module chips sensor , 2009 .

[104]  Anton Amann,et al.  Lung cancer detection by proton transfer reaction mass-spectrometric analysis of human breath gas , 2007 .

[105]  V. Shestivska,et al.  Quantification of methyl thiocyanate in the headspace of Pseudomonas aeruginosa cultures and in the breath of cystic fibrosis patients by selected ion flow tube mass spectrometry. , 2011, Rapid communications in mass spectrometry : RCM.

[106]  P. Hering,et al.  Online monitoring of ethane traces in exhaled breath with a difference frequency generation spectrometer , 2006 .

[107]  N. Saito,et al.  High sensitive detection of volatile organic compounds using superhydrophobic quartz crystal microbalance , 2012 .

[108]  C W Li,et al.  The Research on Artificial Olfaction System-Electronic Nose , 2006 .

[109]  John Mortensen,et al.  Polymer coated quartz crystal microbalance sensors for detection of volatile organic compounds in gas mixtures. , 2007, Analytica chimica acta.

[110]  P. Hering,et al.  Rapid formaldehyde monitoring in ambient air by means of mid-infrared cavity leak-out spectroscopy , 2002 .

[111]  M. Syu,et al.  Preparation and identification of β-cyclodextrin polymer thin film for quartz crystal microbalance sensing of benzene, toluene, and p-xylene , 2008 .

[112]  Nicolae Barsan,et al.  CO sensing mechanism with WO3 based gas sensors , 2010 .

[113]  F. V. van Schooten,et al.  The versatile use of exhaled volatile organic compounds in human health and disease , 2012, Journal of breath research.

[114]  B. Buszewski,et al.  Identification of volatile lung cancer markers by gas chromatography–mass spectrometry: comparison with discrimination by canines , 2012, Analytical and Bioanalytical Chemistry.

[115]  Masanobu Matsuguchi,et al.  Molecular imprinting strategy for solvent molecules and its application for QCM-based VOC vapor sensing , 2006 .

[116]  P. Sterk,et al.  An electronic nose distinguishes exhaled breath of patients with Malignant Pleural Mesothelioma from controls. , 2012, Lung cancer.

[117]  Hua Bai,et al.  Gas Sensors Based on Conducting Polymers , 2007, Sensors (Basel, Switzerland).

[118]  M. Sigrist,et al.  Spectroscopic investigation of methylated amines by a cavity-ringdown-based spectrometer. , 2007, Applied Optics.

[119]  Wolfram Miekisch,et al.  Data interpretation in breath biomarker research: pitfalls and directions , 2012, Journal of breath research.

[120]  Nicola Donato,et al.  Real-time monitoring of breath ammonia during haemodialysis: use of ion mobility spectrometry (IMS) and cavity ring-down spectroscopy (CRDS) techniques. , 2012, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[121]  Tianshu Wang,et al.  A selected ion flow tube mass spectrometry study of ammonia in mouth- and nose-exhaled breath and in the oral cavity. , 2008, Rapid communications in mass spectrometry : RCM.

[122]  John Tulip,et al.  Sensitive detection of ammonia and ethylene with a pulsed quantum cascade laser using intra and interpulse spectroscopic techniques , 2009 .

[123]  Tai Hyun Park,et al.  Recent advances in electronic and bioelectronic noses and their biomedical applications. , 2011, Enzyme and microbial technology.

[124]  L. Trizio,et al.  Chemical characterization of exhaled breath to differentiate between patients with malignant plueral mesothelioma from subjects with similar professional asbestos exposure , 2010, Analytical and bioanalytical chemistry.

[125]  Alphus D. Wilson,et al.  Advances in Electronic-Nose Technologies Developed for Biomedical Applications , 2011, Sensors.

[126]  F. Capasso,et al.  Cavity ringdown spectroscopic detection of nitric oxide with a continuous-wave quantum-cascade laser. , 2001, Applied optics.

[127]  M. Quirynen,et al.  GC-MS analysis of breath odor compounds in liver patients. , 2008, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[128]  Nagy L. Torad,et al.  Alcohol vapours sensor based on thin polyaniline salt film and quartz crystal microbalance. , 2009, Talanta.

[129]  Olaf Tietje,et al.  Volatile biomarkers of pulmonary tuberculosis in the breath. , 2007, Tuberculosis.

[130]  Onofrio Resta,et al.  An electronic nose in the discrimination of patients with non-small cell lung cancer and COPD. , 2009, Lung cancer.

[131]  T. Rocha-Santos,et al.  Optical fibre-based micro-analyser for indirect measurements of volatile amines levels in fish , 2010 .

[132]  Gerard Wysocki,et al.  Performance of an exhaled nitric oxide and carbon dioxide sensor using quantum cascade laser-based integrated cavity output spectroscopy. , 2007, Journal of biomedical optics.