ENose: a new frontier for non-invasive cancer detection and monitoring

Abstract

Electronic Nose (ENose) technology has emerged as a transformative tool in medical diagnostics, leveraging sensor arrays that mimic the human olfactory system to detect odors and volatile organic compounds (VOCs) in various biological samples. ENose systems utilize a range of sensor types, such as metal oxide semiconductors and conducting polymers, to generate unique “smell fingerprints” through pattern recognition algorithms. These systems have shown promise in diagnosing various medical conditions, including respiratory diseases, infectious diseases, metabolic disorders, and neurological conditions. Notably, ENose technology holds significant promise in cancer diagnostics, offering a non-invasive, cost-effective, and rapid approach to early detection and monitoring. It has demonstrated impressive accuracy (85%-95%) in detecting cancers and monitoring complications. However, challenges remain, including issues with standardization, sensor sensitivity, and data interpretation. Despite these hurdles, ENose technology’s market growth is fueled by the increasing prevalence of chronic diseases. Recent developments in Artificial Intelligence (AI), particularly machine learning techniques like deep learning, have enhanced the diagnostic accuracy and robustness of ENose devices. This paper explores the evolution, core principles, applications, challenges, and future potential of ENose technology, with particular emphasis on integrating recent advancements in AI for enhanced detection and interpretation. Future research and collaboration across sectors are essential to overcome existing challenges and integrate ENose into mainstream healthcare.

Keywords

Electronic nose / volatile organic compound / ENose in healthcare / pattern recognition algorithms / cancer / diagnosis

References

[1] Aly MT,Najjaran H,Hoorfar M.Pattern recognition system for rapid detection of gases using microfluidic olfaction detector: a case study using methane and ethane.Sens Actuators B Chem2024;403:135201

[2] Shigaki S,Kurabayashi D.Robust moth-inspired algorithm for odor source localization using multimodal information.Sensors2023;23:1475 PMCID:PMC9921094

[3] Li H,Yuan H.An active olfaction approach using deep reinforcement Learning for Indoor Attenuation Odor Source Localization.IEEE Sensors J2024;24:14561-72

[4] Jabeen M,Jing T.Robot odor source localization in indoor environments based on gradient adaptive extremum seeking search.Build Environ2023;229:109983

[5] Qu X,Xu C.Optical sensors of volatile organic compounds for non-invasive diagnosis of diseases.Chem Eng J2024;485:149804

[6] Javed R,Khan AH,Bukhari A.Deep learning for lungs cancer detection: a review.Artif Intell Rev2024;57:197

[7] Wijbenga N,Mathot BJ.The potential of electronic nose technology in lung transplantation: a proof of principle.ERJ Open Res2022;8:00048-2022 PMCID:PMC9271757

[8] van Geffen WH,Costantini A.The electronic nose: emerging biomarkers in lung cancer diagnostics.Breathe2019;15:e135-41 PMCID:PMC7121878

[9] Kokocińska-Kusiak A,Zybala M,Barłowska K.Canine olfaction: physiology, behavior, and possibilities for practical applications.Animals2021;11:2463 PMCID:PMC8388720

[10] van de Goor R, van Hooren M, Dingemans AM, Kremer B, Kross K. Training and validating a portable electronic nose for lung cancer screening.J Thorac Oncol2018;13:676-81

[11] Zakari S,Olagunju GV.Emerging biomarkers for non-invasive diagnosis and treatment of cancer: a systematic review.Front Oncol2024;14:1405267

[12] Scheepers MHMC,Brandts L,van Grinsven B.Diagnostic performance of electronic noses in cancer diagnoses using exhaled breath: a systematic review and meta-analysis.JAMA Netw Open2022;5:e2219372 PMCID:PMC9244610

[13] Lupan I,Stroe C.The importance of genetic screening on the syndromes of colorectal cancer and gastric cancer: a 2024 update.Biomedicines2024;12:2655 PMCID:PMC11674014

[14] Tyagi H,Bannaga AS,Covington JA.Non-invasive detection and staging of colorectal cancer using a portable electronic nose.Sensors2021;21:5440 PMCID:PMC8398649

[15] Borowik P,Tarakowski R,Grzywacz T.Odor detection using an E-Nose with a reduced sensor array.Sensors2020;20:3542 PMCID:PMC7349593

[16] Yan J,Ge X,Peng X.A novel bionic olfactory network combined with an electronic nose for identification of industrial exhaust.Microchem J2024;200:110287

[17] Lucchi G,Chambaron S.Effects of psychological stress on the emission of volatile organic compounds from the skin.Sci Rep2024;14:7238 PMCID:PMC10973438

[18] Teodoro-Morrison T,Rifai N.Animal olfactory detection of disease: promises and pitfalls.Clin Chem2014;60:1473-9

[19] Sakr R,Rbeiz C.COVID-19 detection by dogs: from physiology to field application-a review article.Postgrad Med J2022;98:212-8

[20] Červený K,Vaněčková K.Olfactory evaluation in clinical medical practice.J Clin Med2022;11:6628 PMCID:PMC9698169

[21] Katotomichelakis M,Tripsianis G.Improvement of olfactory function for quality of life recovery.Laryngoscope2013;123:E10-6

[22] Maniaci A,Vaira LA.Taste and smell disorders: a critical look at olfactory and gustatory dysfunction.Life2024;14:301 PMCID:PMC10970991

[23] Toussaint N,van Campen JP,Boesveldt S.Loss of olfactory function and nutritional status in vital older adults and geriatric patients.Chem Senses2015;40:197-203

[24] Oleszkiewicz A,Larsson M.Consequences of undetected olfactory loss for human chemosensory communication and well-being.Philos Trans R Soc Lond B2020;375:20190265 PMCID:PMC7209944

[25] Oleszkiewicz A,Resler K.Quality of life in patients with olfactory loss is better predicted by flavor identification than by orthonasal olfactory function.Chem Senses2019;44:371-7

[26] Fatuzzo I,Zoccali F.Neurons, nose, and neurodegenerative diseases: olfactory function and cognitive impairment.Int J Mol Sci2023;24:2117 PMCID:PMC9916823

[27] Baldini C,Sansone F,Domenici C.Electronic nose as a novel method for diagnosing cancer: a systematic review.Biosensors2020;10:84 PMCID:PMC7459473

[28] Scheepers MHMC,Brandts L,van Grinsven B.Diagnostic performance of electronic noses in cancer diagnoses using exhaled breath: a systematic review and meta-analysis.JAMA Netw Open2022;5:e2219372 PMCID:PMC9244610

[29] Li W,Xie D,Cui J.Recognizing lung cancer using a homemade e-nose: a comprehensive study.Comput Biol Med2020;120:103706

[30] Verschakelen JA,De Wever W.Computed tomography in staging for lung cancer.Eur Respir J Suppl2002;19:40s-8s

[31] Rocco G,Tan KS.A real-world assessment of stage I lung cancer through electronic nose technology.J Thorac Oncol2024;19:1272-83

[32] Lee MR,Hsieh YC.Cross-site validation of lung cancer diagnosis by electronic nose with deep learning: a multicenter prospective study.Respir Res2024;25:203 PMCID:PMC11084132

[33] Vadala R,Bangaru S.A review on electronic nose for diagnosis and monitoring treatment response in lung cancer.J Breath Res2023;17:024002

[34] Machado RF,Deffenderfer O.Detection of lung cancer by sensor array analyses of exhaled breath.Am J Respir Crit Care Med2005;171:1286-91 PMCID:PMC2718462

[35] Di Natale C,Martinelli E.Lung cancer identification by the analysis of breath by means of an array of non-selective gas sensors.Biosens Bioelectron2003;18:1209-18

[36] D’Amico A,Santonico M.An investigation on electronic nose diagnosis of lung cancer.Lung Cancer2010;68:170-6

[37] Tran VH,Thurston M.Breath analysis of lung cancer patients using an electronic nose detection system.IEEE Sensors J2010;10:1514-8

[38] Peng G,Broza YY.Detection of lung, breast, colorectal, and prostate cancers from exhaled breath using a single array of nanosensors.Br J Cancer2010;103:542-51 PMCID:PMC2939793

[39] Bikov A,Korosi BZ.Expiratory flow rate, breath hold and anatomic dead space influence electronic nose ability to detect lung cancer.BMC Pulm Med2014;14:202 PMCID:PMC4289562

[40] Hubers AJ,Boksem RJ.Combined sputum hypermethylation and eNose analysis for lung cancer diagnosis.J Clin Pathol2014;67:707-11

[41] Tirzīte M,Strazda G,Taivans I.Detection of lung cancer in exhaled breath with an electronic nose using support vector machine analysis.J Breath Res2017;11:036009

[42] Tirzïte M,Strazda G,Taivans I.Detection of lung cancer with electronic nose and logistic regression analysis.J Breath Res2018;13:016006

[43] Huang CH,Wang YC.A study of diagnostic accuracy using a chemical sensor array and a machine learning technique to detect lung cancer.Sensors2018;18:2845 PMCID:PMC6164114

[44] Berna A.Metal oxide sensors for electronic noses and their application to food analysis.Sensors10;10:3882-910 PMCID:PMC3274253

[45] Benet J, Seo M, Khine M, Gumà Padró J, Pardo Martnez A, Kurdahi F. Breast cancer detection by analyzing the volatile organic compound (VOC) signature in human urine.Sci Rep2022;12:14873 PMCID:PMC9435419

[46] Ramírez W,Ramírez E,Meza D.Exploring components, sensors, and techniques for cancer detection via eNose technology: a systematic review.Sensors2024;24:7868 PMCID:PMC11645018

[47] Tyagi H,Bannaga AS,Covington JA.Development of electronic nose as a complementary screening tool for breath testing in colorectal cancer.Biosensors2025;15:82

[48] Zheng W,Min Y.Prospect and challenges of volatile organic compound breath testing in non-cancer gastrointestinal disorders.Biomedicines2024;12:1815 PMCID:PMC11351786

[49] Schuermans VNE,Jongen ACHM.Pilot study: detection of gastric cancer from exhaled air analyzed with an electronic nose in chinese patients.Surg Innov2018;25:429-34 PMCID:PMC6166235

[50] Capelli L,Grizzi F.Optimization of training and measurement protocol for eNose analysis of urine headspace aimed at prostate cancer diagnosis.Sci Rep2021;11:20898 PMCID:PMC8536694

[51] Taverna G,Bax C.Prostate cancer risk stratification via eNose urine odor analysis: a preliminary report.Front Oncol2024;14:1339796 PMCID:PMC10948417

[52] Tagar MR,Mastafa M.Investigating the potential of non-invasive breath test analysis for early detection of oral cancer: a systematic review: non-invasive breath test for early oral cancer detection.PJHS2024;5:229-36

[53] Hooren MR, Leunis N, Brandsma DS, Dingemans AC, Kremer B, Kross KW. Differentiating head and neck carcinoma from lung carcinoma with an electronic nose: a proof of concept study.Eur Arch Otorhinolaryngol2016;273:3897-903 PMCID:PMC5052311

[54] Hakim M,Tisch U.Diagnosis of head-and-neck cancer from exhaled breath.Br J Cancer2011;104:1649-55 PMCID:PMC3101906

[55] Gruber M,Jeries R.Analysis of exhaled breath for diagnosing head and neck squamous cell carcinoma: a feasibility study.Br J Cancer2014;111:790-8 PMCID:PMC4134502

[56] Goertzen A,Ahmed N.Potential urinary volatile organic compounds as screening markers in cancer - a review.Front Oncol2024;14:1448760

[57] Tyagi H,Bannaga AS,Covington JA.Electronic nose for bladder cancer detection^†.Chem Proc2021;5:22.

[58] Anzivino R,Dragonieri S.The role of a polymer-based E-Nose in the detection of head and neck cancer from exhaled breath.Sensors2022;22:6485 PMCID:PMC9460264

[59] Blanchet L,Baranska A.Factors that influence the volatile organic compound content in human breath.J Breath Res2017;11:016013

[60] Berkhout DJC,de Boer NKH.Revival of an ancient greek art: scent detection as diagnostic tool for tuberculosis.Pediatr Res2018;84:4-5

[61] Ahmad B,Ashfaq UA,Nahid N.Smart E-noses for medical and clinical applications. In: Advanced Sensors for Smart Healthcare. Elsevier; 2025. pp. 231-42.

[62] Selvaraj R,Nagendra SMS.Advances in mid-infrared spectroscopy-based sensing techniques for exhaled breath diagnostics.Molecules2020;25:2227 PMCID:PMC7249025

[63] Pleil JD,Sobus JR,Madden MC.Observing the human exposome as reflected in breath biomarkers: heat map data interpretation for environmental and intelligence research.J Breath Res2011;5:037104

[64] Sundar KM,Morris MJ.Laryngeal dysfunction manifesting as chronic refractory cough and dyspnea: laryngeal physiology in respiratory health and disease.Chest2024;166:171-86

[65] Moshayedi AJ,Shuxin Y.E-Nose design and structures from statistical analysis to application in robotic: a compressive review.EAI Endorsed Trans AI Robotics2023;2:e1

[66] Albastaki Y.Clustering algorithms as a tool for odour classifications in enose developments. In: Musleh Al-sartawi AM, Razzaque A, Kamal MM, editors. Artificial intelligence systems and the internet of things in the digital era. Cham: Springer International Publishing; 2021. pp. 46-56.

[67] Teixeira GG,Estevinho L.Enose lab made with vacuum sampling: quantitative applications.Chemosensors2022;10:261

[68] Moshayedi AJ.Evaluation of bio inspired Mokhtar: odor localization system. In: 2017 18th International Carpathian Control Conference (ICCC), Sinaia, Romania, 2017, pp. 527-32.

[69] Liu X,Liu H,Zhang D.A survey on gas sensing technology.Sensors2012;12:9635-65 PMCID:PMC3444121

[70] Oates MJ,Ruiz-abellon MC,Ramos JA.Using a low-cost components e-Nose for basic detection of different foodstuffs.IEEE Sensors J2022;22:13872-81

[71] Bosch S,Pees S.Electronic nose sensor drift affects diagnostic reliability and accuracy of disease-specific algorithms.Sensors2022;22:9246 PMCID:PMC9740993

[72] Buma AIG,de Vries R.eNose analysis for early immunotherapy response monitoring in non-small cell lung cancer.Lung Cancer2021;160:36-43

[73] Binson VA,Mathew L.Prediction of lung cancer with a sensor array based e-nose system using machine learning methods.Microsyst Technol2024;30:1421-34

[74] Vries R, Sterk PJ. eNose breathprints as composite biomarker for real-time phenotyping of complex respiratory diseases.J Allergy Clin Immunol2020;146:995-6

[75] Wilson AD.Noninvasive early disease diagnosis by electronic-nose and related VOC-detection devices.Biosensors2020;10:73 PMCID:PMC7400621

[76] Wilson AD.Recent applications of electronic-nose technologies for the noninvasive early diagnosis of gastrointestinal diseases^†.Proceedings2018;2:147

[77] Behera B,Anil Vishnu GK,Pandya HJ.Electronic nose: a non-invasive technology for breath analysis of diabetes and lung cancer patients.J Breath Res2019;13:024001

[78] Wasilewski T,Gębicki J.Critical review of electronic nose and tongue instruments prospects in pharmaceutical analysis.Anal Chim Acta2019;1077:14-29

[79] Alfieri G,Riggi R.Recent advances and future perspectives in the E-nose technologies addressed to the wine industry.Sensors2024;24:2293 PMCID:PMC11014050

[80] Wilson AD.Applications and advances in electronic-nose technologies.Sensors2009;9:5099-148 PMCID:PMC3274163

[81] Ahmad B,Mahmood-ur-rahman .E-nose-based technology for healthcare. In: Nanotechnology-Based E-noses. Elsevier; 2023. pp. 241-56.

[82] Goyal D.Smart electronic noses for biomedical application. In: Advanced Sensors for Smart Healthcare. Elsevier; 2025. pp. 313-27.