Detecting cancer by breath volatile organic compound analysis: a review of array-based sensors

Cancer diagnosis is typically delayed to the late stages of disease due to the asymptomatic nature of cancer in its early stages. Cancer screening offers the promise of early cancer detection, but most conventional diagnostic methods are invasive and remain ineffective at early detection. Breath analysis is, however, non-invasive and has the potential to detect cancer at an earlier stage by analyzing volatile biomarkers in exhaled breath. This paper summarizes breath sampling techniques and recent developments of various array-based sensor technologies for breath analysis. Significant advancements were made by a number of different research groups in the development of nanomaterial-based sensor arrays, and the ability to accurately distinguish cancer patients from healthy controls based on the volatile organic compounds (VOCs) in exhaled breath has been demonstrated. Optical sensors based on colorimetric sensor array technology are also discussed, where preliminary clinical studies suggest that metabolic VOC profiles could be used to accurately diagnose various forms of lung cancer. Recent studies have demonstrated the potential of using metabolic VOCs for cancer detection, but further standardization and validation is needed before breath analysis can be widely adopted as a clinically useful tool.

[1]  H. J. O’neill,et al.  Volatile organic compounds in exhaled air from patients with lung cancer. , 1985, Clinical chemistry.

[2]  G. Preti,et al.  Analysis of lung air from patients with bronchogenic carcinoma and controls using gas chromatography-mass spectrometry. , 1988, Journal of chromatography.

[3]  K. Kanazawa,et al.  Physical description of a viscoelastically loaded AT‐cut quartz resonator , 1990 .

[4]  M. Phillips,et al.  Alveolar gradient of pentane in normal human breath. , 1994, Free radical research.

[5]  R. W. Marshall,et al.  Detection and simultaneous identification of microorganisms from headspace samples using an electronic nose. , 1997 .

[6]  Giuseppe Ferri,et al.  An electronic nose for food analysis , 1997 .

[7]  R. Lucklum,et al.  Response of quartz-crystal resonators to gas and liquid analyte exposure , 1998 .

[8]  Michael P. Craven,et al.  The prediction of bacteria type and culture growth phase by an electronic nose with a multi-layer perceptron network , 1998 .

[9]  Charles M. Lieber,et al.  Covalently functionalized nanotubes as nanometre- sized probes in chemistry and biology , 1998, Nature.

[10]  Lennart Ljung,et al.  Bacteria classification based on feature extraction from sensor data , 1998 .

[11]  R. Cataneo,et al.  Volatile organic compounds in breath as markers of lung cancer: a cross-sectional study , 1999, The Lancet.

[12]  A Macagnano,et al.  Biomedical application of an electronic nose. , 2000, Critical reviews in biomedical engineering.

[13]  Josef Guttmann,et al.  CO2-controlled sampling of alveolar gas in mechanically ventilated patients , 2001 .

[14]  Kevin Gleeson,et al.  Detection of lung cancer with volatile markers in the breath. , 2003, Chest.

[15]  M. Shim,et al.  Noncovalent functionalization of carbon nanotubes for highly specific electronic biosensors , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[16]  E. Martinelli,et al.  Lung cancer identification by the analysis of breath by means of an array of non-selective gas sensors. , 2003, Biosensors & bioelectronics.

[17]  J. Crowley,et al.  Prevalence of prostate cancer among men with a prostate-specific antigen level < or =4.0 ng per milliliter. , 2004, The New England journal of medicine.

[18]  W. Miekisch,et al.  Diagnostic potential of breath analysis--focus on volatile organic compounds. , 2004, Clinica chimica acta; international journal of clinical chemistry.

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

[20]  L. Bianchi,et al.  Exhaled volatile organic compounds in patients with non-small cell lung cancer: cross sectional and nested short-term follow-up study , 2005, Respiratory research.

[21]  M. Mcculloch,et al.  Diagnostic Accuracy of Canine Scent Detection in Early- and Late-Stage Lung and Breast Cancers , 2006, Integrative cancer therapies.

[22]  Ting Zhang,et al.  Electrochemically Functionalized Single‐Walled Carbon Nanotube Gas Sensor , 2006 .

[23]  Olaf Tietje,et al.  Prediction of breast cancer using volatile biomarkers in the breath , 2006, Breast Cancer Research and Treatment.

[24]  N. Arber,et al.  Screening techniques for prevention and early detection of colorectal cancer in the average-risk population. , 2007, Gastrointestinal cancer research : GCR.

[25]  J. Austin,et al.  Prediction of lung cancer using volatile biomarkers in breath. , 2007, Cancer biomarkers : section A of Disease markers.

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

[27]  Min Wu,et al.  Multiparameter metabolic analysis reveals a close link between attenuated mitochondrial bioenergetic function and enhanced glycolysis dependency in human tumor cells. , 2007, American journal of physiology. Cell physiology.

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

[29]  Ying-Sheng Huang,et al.  Quartz crystal microbalance sensor based on nanostructured IrO2 , 2007 .

[30]  Michele Penza,et al.  The effect of purification of single-walled carbon nanotube bundles on the alcohol sensitivity of nanocomposite Langmuir–Blodgett films for SAW sensing applications , 2007 .

[31]  Tarek Mekhail,et al.  Diagnosis of lung cancer by the analysis of exhaled breath with a colorimetric sensor array , 2007, Thorax.

[32]  Sabine Kischkel,et al.  Impact of sampling procedures on the results of breath analysis , 2008, Journal of breath research.

[33]  H. Haick,et al.  Detecting simulated patterns of lung cancer biomarkers by random network of single-walled carbon nanotubes coated with nonpolymeric organic materials. , 2008, Nano letters.

[34]  J. Beauchamp,et al.  On the use of Tedlar® bags for breath-gas sampling and analysis , 2008, Journal of breath research.

[35]  J. Austin,et al.  Detection of lung cancer using weighted digital analysis of breath biomarkers. , 2008, Clinica chimica acta; international journal of clinical chemistry.

[36]  Masanobu Matsuguchi,et al.  Chemically modified copolymer coatings for mass-sensitive toluene vapor sensors , 2008 .

[37]  Jens Herbig,et al.  Buffered end-tidal (BET) sampling—a novel method for real-time breath-gas analysis , 2008, Journal of breath research.

[38]  A. Karellas,et al.  Breast cancer imaging: a perspective for the next decade. , 2008, Medical physics.

[39]  M. O’Hara,et al.  Development of a protocol to measure volatile organic compounds in human breath: a comparison of rebreathing and on-line single exhalations using proton transfer reaction mass spectrometry , 2008, Physiological measurement.

[40]  H. Haick,et al.  Sniffing chronic renal failure in rat model by an array of random networks of single-walled carbon nanotubes. , 2009, ACS nano.

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

[42]  Magdalena Ligor,et al.  Determination of volatile organic compounds in exhaled breath of patients with lung cancer using solid phase microextraction and gas chromatography mass spectrometry , 2009, Clinical chemistry and laboratory medicine.

[43]  Qing Wang,et al.  Gas Sensors Based on Semiconducting Metal Oxide One-Dimensional Nanostructures , 2009, Sensors.

[44]  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.

[45]  H. Haick,et al.  Diagnosing lung cancer in exhaled breath using gold nanoparticles. , 2009, Nature nanotechnology.

[46]  Liang Feng,et al.  An Optoelectronic Nose for Detection of Toxic Gases , 2009, Nature chemistry.

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

[48]  Hossam Haick,et al.  Sniffing the unique "odor print" of non-small-cell lung cancer with gold nanoparticles. , 2009, Small.

[49]  Angela Mariotto,et al.  Lead time and overdiagnosis in prostate-specific antigen screening: importance of methods and context. , 2009, Journal of the National Cancer Institute.

[50]  Alphus D. Wilson,et al.  Applications and Advances in Electronic-Nose Technologies , 2009, Sensors.

[51]  Anton Amann,et al.  Improved pre-concentration and detection methods for volatile sulphur breath constituents. , 2009, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[52]  Je Hoon Oh,et al.  Evaluation of the limit-of-detection capability of carbon black-polymer composite sensors for volatile breath biomarkers , 2010 .

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

[54]  Ulrike Tisch,et al.  Classification of breast cancer precursors through exhaled breath , 2011, Breast Cancer Research and Treatment.

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

[56]  Liang Feng,et al.  A simple and highly sensitive colorimetric detection method for gaseous formaldehyde. , 2010, Journal of the American Chemical Society.

[57]  Massimo Corradi,et al.  Determination of aldehydes in exhaled breath of patients with lung cancer by means of on-fiber-derivatisation SPME-GC/MS. , 2010, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[58]  Liang Feng,et al.  Colorimetric sensor array for determination and identification of toxic industrial chemicals. , 2010, Analytical chemistry.

[59]  M. Phillips,et al.  Volatile biomarkers in the breath of women with breast cancer , 2010, Journal of breath research.

[60]  A. Amann,et al.  Application of GC-MS with a SPME and thermal desorption technique for determination of dimethylamine and trimethylamine in gaseous samples for medical diagnostic purposes , 2010, Journal of breath research.

[61]  Liang Feng,et al.  Discrimination of complex mixtures by a colorimetric sensor array: coffee aromas. , 2010, Analytical chemistry.

[62]  H. Haick,et al.  Detection of lung, breast, colorectal, and prostate cancers from exhaled breath using a single array of nanosensors , 2010, British Journal of Cancer.

[63]  Giorgio Pennazza,et al.  An investigation on electronic nose diagnosis of lung cancer. , 2010, Lung cancer.

[64]  K. Suslick,et al.  A colorimetric sensor array for identification of toxic gases below permissible exposure limits. , 2010, Chemical communications.

[65]  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.

[66]  M. Plescia,et al.  Vital signs: colorectal cancer screening among adults aged 50-75 years - United States, 2008. , 2010, MMWR. Morbidity and mortality weekly report.

[67]  B. Buszewski,et al.  Determination of volatile organic compounds as biomarkers of lung cancer by SPME-GC-TOF/MS and chemometrics. , 2011, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[68]  C Hoeschen,et al.  Influences of mixed expiratory sampling parameters on exhaled volatile organic compound concentrations , 2011, Journal of breath research.

[69]  Avijit Sen,et al.  Rapid identification of bacteria with a disposable colorimetric sensing array. , 2011, Journal of the American Chemical Society.

[70]  Hengwei Lin,et al.  Preoxidation for colorimetric sensor array detection of VOCs. , 2011, Journal of the American Chemical Society.

[71]  C. Gatsonis,et al.  Reduced Lung-Cancer Mortality with Low-Dose Computed Tomographic Screening , 2012 .

[72]  E. Llobet,et al.  Gas sensing properties of multiwall carbon nanotubes decorated with rhodium nanoparticles , 2011, 1605.08079.

[73]  Oliver F Bathe,et al.  Metabolomics and surgical oncology: Potential role for small molecule biomarkers , 2011, Journal of surgical oncology.

[74]  B. Buszewski,et al.  The application of statistical methods using VOCs to identify patients with lung cancer , 2011, Journal of breath research.

[75]  Jing Li,et al.  A carbon-nanotube-based sensor array for formaldehyde detection. , 2011, Nanotechnology.

[76]  John Kurhanewicz,et al.  Analysis of cancer metabolism by imaging hyperpolarized nuclei: prospects for translation to clinical research. , 2011, Neoplasia.

[77]  H. Haick,et al.  Diagnosis of head-and-neck cancer from exhaled breath , 2011, British Journal of Cancer.

[78]  Massimo Corradi,et al.  Lung cancer biomarkers in exhaled breath , 2011, Expert review of molecular diagnostics.

[79]  Yoshihiro Kakeji,et al.  Colorectal cancer screening with odour material by canine scent detection , 2011, Gut.

[80]  Deborah H Yates,et al.  A breath test for malignant mesothelioma using an electronic nose , 2011, European Respiratory Journal.

[81]  T. Walles,et al.  Canine scent detection in the diagnosis of lung cancer: revisiting a puzzling phenomenon , 2011, European Respiratory Journal.

[82]  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.

[83]  D. Berry,et al.  Benefits and harms of CT screening for lung cancer: a systematic review. , 2012, JAMA.

[84]  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.

[85]  Arnaldo D'Amico,et al.  Electronic noses calibration procedure in the context of a multicentre medical study , 2012 .

[86]  Koffi Badjagbo Exhaled breath analysis for early cancer detection: principle and progress in direct mass spectrometry techniques , 2012, Clinical chemistry and laboratory medicine.

[87]  Q. Jöbsis,et al.  Clinical use of exhaled volatile organic compounds in pulmonary diseases: a systematic review , 2012, Respiratory Research.

[88]  Paolo Montuschi,et al.  The Electronic Nose in Respiratory Medicine , 2012, Respiration.

[89]  Ping Wang,et al.  The analysis of volatile organic compounds biomarkers for lung cancer in exhaled breath, tissues and cell lines. , 2012, Cancer biomarkers : section A of Disease markers.

[90]  R. Deberardinis,et al.  Cellular Metabolism and Disease: What Do Metabolic Outliers Teach Us? , 2012, Cell.

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

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

[93]  G. Hanna,et al.  Selected ion flow tube mass spectrometry analysis of exhaled breath for volatile organic compound profiling of esophago-gastric cancer. , 2013, Analytical chemistry.

[94]  H. Haick,et al.  A nanomaterial-based breath test for distinguishing gastric cancer from benign gastric conditions , 2013, British Journal of Cancer.

[95]  Brian Taba,et al.  Colorimetric Sensor Array Allows Fast Detection and Simultaneous Identification of Sepsis-Causing Bacteria in Spiked Blood Culture , 2013, Journal of Clinical Microbiology.

[96]  Rongwei Fu,et al.  Screening for Lung Cancer With Low-Dose Computed Tomography: A Systematic Review to Update the U.S. Preventive Services Task Force Recommendation , 2013, Annals of Internal Medicine.

[97]  Brian Taba,et al.  The Use of Colorimetric Sensor Arrays to Discriminate between Pathogenic Bacteria , 2013, PloS one.

[98]  Morteza Mahmoudi,et al.  Themed Issue: Chemical and Biological Detection Chemical Society Reviews Optical Sensor Arrays for Chemical Sensing: the Optoelectronic Nose , 2022 .

[99]  Michelle Gallagher,et al.  Volatile biomarkers from human melanoma cells. , 2013, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[100]  A. Jemal,et al.  Cancer statistics, 2013 , 2013, CA: a cancer journal for clinicians.

[101]  J. Feller,et al.  An e-nose made of carbon nanotube based quantum resistive sensors for the detection of eighteen polar/nonpolar VOC biomarkers of lung cancer. , 2013, Journal of materials chemistry. B.

[102]  J. Jett,et al.  The Analysis of Volatile Organic Compound Profiles in the Breath as a Biomarker of Lung Cancer , 2013 .

[103]  Joachim D Pleil,et al.  Clinical breath analysis: discriminating between human endogenous compounds and exogenous (environmental) chemical confounders , 2013, Journal of breath research.

[104]  H. Haick,et al.  Sensors for breath testing: from nanomaterials to comprehensive disease detection. , 2014, Accounts of chemical research.

[105]  G. Morell,et al.  Room temperature gas sensor based on tin dioxide-carbon nanotubes composite films , 2014 .

[106]  B. Kramer,et al.  Overdiagnosis in low-dose computed tomography screening for lung cancer. , 2014, JAMA internal medicine.

[107]  Begoña Garcia-Zapirain,et al.  EEG artifact removal—state-of-the-art and guidelines , 2015, Journal of neural engineering.