{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T08:45:50Z","timestamp":1778575550529,"version":"3.51.4"},"reference-count":47,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,4,23]],"date-time":"2021-04-23T00:00:00Z","timestamp":1619136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003715","name":"Korea Research Institute of Bioscience and Biotechnology","doi-asserted-by":"publisher","award":["KGM9952011"],"award-info":[{"award-number":["KGM9952011"]}],"id":[{"id":"10.13039\/501100003715","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sensors"],"abstract":"<jats:p>Early detection is critical to successfully eradicating a variety of cancers, so the development of a new cancer primary screening system is essential. Herein, we report an animal nose sensor system for the potential primary screening of lung cancer. To establish this, we developed an odor discrimination training device based on operant conditioning paradigms for detection of toluene, an odor indicator component of lung cancer. The rats (N = 15) were trained to jump onto a floating ledge in response to toluene-spiked breath samples. Twelve rats among 15 trained rats reached performance criterion in 12 consecutive successful tests within a given set, or over 12 sets, with a success rate of over 90%. Through a total of 1934 tests, the trained rats (N = 3) showed excellent performance for toluene detection with 82% accuracy, 83% sensitivity, 81% specificity, 80% positive predictive value (PPV) and 83% negative predictive value (NPV). The animals also acquired considerable performance for odor discrimination even in rigorous tests, validating odor specificity. Since environmental and long-term stability are important factors that can influence the sensing results, the performance of the trained rats was studied under specified temperature (20, 25, and 30 \u00b0C) and humidity (30%, 45%, and 60% RH) conditions, and monitored over a period of 45 days. At given conditions of temperature and humidity, the animal sensors showed an average accuracy within a deviation range of \u00b110%, indicating the excellent environmental stability of the detection rats. Surprisingly, the trained rats did not differ in retention of last odor discrimination when tested 45 days after training, denoting that the rats\u2019 memory for trained odor is still available over a long period of time. When taken together, these results indicate that our odor discrimination training system can be useful for non-invasive breath testing and potential primary screening of lung cancer.<\/jats:p>","DOI":"10.3390\/s21092967","type":"journal-article","created":{"date-parts":[[2021,4,25]],"date-time":"2021-04-25T02:12:57Z","timestamp":1619316777000},"page":"2967","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Olfactory Detection of Toluene by Detection Rats for Potential Screening of Lung Cancer"],"prefix":"10.3390","volume":"21","author":[{"given":"Yunkwang","family":"Oh","sequence":"first","affiliation":[{"name":"Bionanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahang-ro, Yuseong-gu, Daejeon 34141, Korea"},{"name":"Department of Chemical and Biological Engineering, Korea University, 145 Anam-ro, Sungbuk-gu, Seoul 02841, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oh-Seok","family":"Kwon","sequence":"additional","affiliation":[{"name":"Infectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahang-ro, Yuseong-gu, Daejeon 34141, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sun-Seek","family":"Min","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Eulji University School of Medicine, 77 Gyeryong-ro, Jung-gu, Daejeon 34824, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong-Beom","family":"Shin","sequence":"additional","affiliation":[{"name":"Bionanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahang-ro, Yuseong-gu, Daejeon 34141, Korea"},{"name":"KRIBB School, Korea University of Science and Technology (UST), 217 Gajeong-ro, Yuseong-gu, Daejeon 34113, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6406-3930","authenticated-orcid":false,"given":"Min-Kyu","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biological Engineering, Korea University, 145 Anam-ro, Sungbuk-gu, Seoul 02841, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moonil","family":"Kim","sequence":"additional","affiliation":[{"name":"Bionanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahang-ro, Yuseong-gu, Daejeon 34141, Korea"},{"name":"KRIBB School, Korea University of Science and Technology (UST), 217 Gajeong-ro, Yuseong-gu, Daejeon 34113, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1109\/JSEN.2014.2358261","article-title":"Applications of animal biosensors: A review","volume":"15","author":"Oh","year":"2015","journal-title":"IEEE Sens. J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.neuron.2005.10.022","article-title":"Olfaction: Diverse species, conserved principles","volume":"48","author":"Ache","year":"2005","journal-title":"Neuron"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.forsciint.2014.01.013","article-title":"Efficacy of drug detection by fully-trained police dogs varies by breed, training level, type of drug and search environment","volume":"237","author":"Jezierski","year":"2014","journal-title":"Forensic Sci. Int."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1007\/s00216-003-2018-7","article-title":"Laboratory and field experiments used to identify Canis lupus var. familiaris active odor signature chemicals from drugs, explosives, and humans","volume":"376","author":"Lorenzo","year":"2003","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1901\/jaba.2011.44-351","article-title":"Using trained pouched rats to detect land mines: Another victory for operant conditioning","volume":"44","author":"Poling","year":"2011","journal-title":"J. Appl. Behav. Anal."},{"key":"ref_6","first-page":"22","article-title":"Mine detection rats: Effects of repeated extinction on detection accuracy","volume":"16","author":"Mahoney","year":"2015","journal-title":"J. CWD"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.applanim.2013.11.010","article-title":"Explosives detection by military working dogs: Olfactory generalization from components to mixtures","volume":"151","author":"Lazarowski","year":"2014","journal-title":"Appl. Anim. Behav. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1136\/bmj.329.7468.712","article-title":"Olfactory detection of human bladder cancer by dogs: Proof of principle study","volume":"329","author":"Willis","year":"2004","journal-title":"BMJ"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1177\/1534735405285096","article-title":"Diagnostic accuracy of canine scent detection in early- and late-stage lung and breast cancers","volume":"5","author":"McCulloch","year":"2006","journal-title":"Integr. Cancer Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1186\/1471-2407-10-643","article-title":"Characteristic odour in the blood reveals ovarian carcinoma","volume":"10","author":"Horvath","year":"2010","journal-title":"BMC Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.tube.2012.07.006","article-title":"Mycobacterium tuberculosis volatiles for diagnosis of tuberculosis by Cricetomys rats","volume":"92","author":"Mgode","year":"2012","journal-title":"Tuberculosis"},{"key":"ref_12","first-page":"737","article-title":"African pouched rats for the detection of pulmonary tuberculosis in sputum samples","volume":"13","author":"Weetjens","year":"2009","journal-title":"Int. J. Tuberc. Lung Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1016\/j.snb.2013.07.078","article-title":"Biomarkers and biosensors for the early diagnosis of lung cancer","volume":"188","author":"Altintas","year":"2013","journal-title":"Sens. Actuators B Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"76","DOI":"10.3389\/fmolb.2018.00076","article-title":"Molecular diagnostics in clinical oncology","volume":"5","author":"Sokolenko","year":"2018","journal-title":"Front. Mol. Biosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5416","DOI":"10.1158\/1078-0432.CCR-16-3155","article-title":"Early evaluation of circulating tumor DNA as marker of therapeutic efficacy in metastatic colorectal cancer patients (PLACOL Study)","volume":"23","author":"Garlan","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1682382","DOI":"10.1080\/2162402X.2019.1682382","article-title":"Establishment and validation of an immunodiagnostic model for prediction of breast cancer","volume":"9","author":"Qiu","year":"2019","journal-title":"Oncoimmunology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.ejca.2017.12.025","article-title":"The future of blood-based biomarkers for the early detection of breast cancer","volume":"92","author":"Loke","year":"2018","journal-title":"Eur. J. Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Kato, S., and Honda, K. (2020). Use of biomarkers and imaging for early detection of pancreatic cancer. Cancers, 12.","DOI":"10.3390\/cancers12071965"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"35","DOI":"10.21037\/tgh.2019.05.04","article-title":"Pancreatic cancer detection and characterization-state of the art cross-sectional imaging and imaging data analysis","volume":"4","author":"Kaissis","year":"2019","journal-title":"Transl. Gastroenterol. Hepatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2759","DOI":"10.1007\/s00216-015-9200-6","article-title":"Detection of volatile organic compounds (VOCs) from exhaled breath as noninvasive methods for cancer diagnosis","volume":"408","author":"Sun","year":"2016","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e182815","DOI":"10.1001\/jamaoncol.2018.2815","article-title":"Accuracy and methodologic challenges of volatile organic compound-based exhaled breath tests for cancer diagnosis: A systematic review and meta-analysis","volume":"5","author":"Hanna","year":"2019","journal-title":"JAMA Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"96","DOI":"10.3389\/fvets.2016.00096","article-title":"Using scent detection dogs in conservation settings: A review of scientific literature regarding their selection","volume":"3","author":"Beebe","year":"2016","journal-title":"Front. Vet. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1093\/jb\/mvr090","article-title":"The scent of disease: Volatile organic compounds of the human body related to disease and disorder","volume":"150","author":"Shirasu","year":"2011","journal-title":"J. Biochem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1016\/S0140-6736(89)92257-5","article-title":"Sniffer dogs in the melanoma clinic?","volume":"1","author":"Williams","year":"1989","journal-title":"Lancet"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.eururo.2010.10.006","article-title":"Olfactory detection of prostate cancer by dogs sniffing urine: A step forward in early diagnosis","volume":"59","author":"Cornua","year":"2011","journal-title":"Eur. Urol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1136\/gut.2010.218305","article-title":"Colorectal cancer screening with odour material by canine scent detection","volume":"60","author":"Sonoda","year":"2011","journal-title":"Gut"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e7396","DOI":"10.1136\/bmj.e7396","article-title":"Using a dog\u2019s superior olfactory sensitivity to identify Clostridium difficile in stools and patients: Proof of principle study","volume":"345","author":"Bomers","year":"2012","journal-title":"Br. Med. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.applanim.2006.05.004","article-title":"The quality of the relation between handler and military dogs influences efficiency and welfare of dogs","volume":"104","author":"Lefebvre","year":"2007","journal-title":"Appl. Anim. Behav. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1007\/s10071-010-0373-2","article-title":"Handler beliefs affect scent detection dog outcomes","volume":"14","author":"Lit","year":"2011","journal-title":"Anim. Cogn."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/S0168-1591(02)00274-5","article-title":"Explosives detection by sniffer dogs following strenuous physical activity","volume":"81","author":"Gazit","year":"2003","journal-title":"Appl. Anim. Behav. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/S0039-9140(00)00546-4","article-title":"The scientific foundation and efficacy of the use of canines as chemical detectors for explosives","volume":"54","author":"Furton","year":"2001","journal-title":"Talanta"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.bbr.2017.11.031","article-title":"Automated center-out rodent behavioral trainer (ACRoBaT), an automated device for training rats to perform a modified center out task","volume":"346","author":"Bjanes","year":"2018","journal-title":"Behav. Brain Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"10019","DOI":"10.1038\/srep10019","article-title":"An odor detection system based on automatically trained mice by relative go no-go olfactory operant conditioning","volume":"5","author":"He","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Li, W., Dai, W., Liu, M., Long, Y., Wang, C., Xie, S., Liu, Y., Zhang, Y., Shi, Q., and Peng, X. (2019). VOC biomarkers identification and predictive model construction for lung cancer based on exhaled breath analysis: Research protocol for an exploratory study. BMJ Open, 9.","DOI":"10.1136\/bmjopen-2018-028448"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1038\/nnano.2009.235","article-title":"Diagnosing lung cancer in exhaled breath using gold nanoparticles","volume":"4","author":"Peng","year":"2009","journal-title":"Nat. Nanotechnol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Dung, T.T., Oh, Y., Choi, S.J., Kim, I.D., Oh, M.K., and Kim, M. (2018). Applications and advances in bioelectronic noses for odour sensing. Sensors, 18.","DOI":"10.3390\/s18010103"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1016\/j.trac.2011.03.011","article-title":"Analysis of biogenic volatile organic compounds in human health and disease","volume":"30","author":"Dummer","year":"2011","journal-title":"Trends Analyt. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1016\/j.snb.2019.03.045","article-title":"Sensitivity enhancement in photoionization detector using microelectrodes with integrated 1D nanostructures","volume":"288","author":"Pyo","year":"2019","journal-title":"Sens. Actuators B Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"13431","DOI":"10.1021\/jacs.6b09167","article-title":"Heterogeneous sensitization of metal\u2014Organic framework driven metal@metal oxide complex catalysts on an oxide nanofiber scaffold toward superior gas sensors","volume":"138","author":"Koo","year":"2016","journal-title":"J. Am. Chem. Soc."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1186\/1556-276X-9-576","article-title":"Detection biomarkers of lung cancer using mini-GC-PID system integrated with micro GC column and micro pre-concentrator","volume":"9","author":"Sun","year":"2014","journal-title":"Nanoscale Res. Lett."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1016\/j.snb.2013.12.011","article-title":"Highly sensitive and selective hydrogen sulfide and toluene sensors using Pd functionalized WO3 nanofibers for potential diagnosis of halitosis and lung cancer","volume":"193","author":"Kim","year":"2014","journal-title":"Sens. Actuators B Chem."},{"key":"ref_42","first-page":"R191","article-title":"Effects of temperature on nervous-system implications for behavioral performance","volume":"259","author":"Montgomery","year":"1990","journal-title":"Am. J. Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1016\/j.jinsphys.2009.06.009","article-title":"The effect of environmental temperature on olfactory perception in Drosophila melanogaster","volume":"55","author":"Riveron","year":"2009","journal-title":"J. Insect Physiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1016\/j.jinsphys.2011.08.016","article-title":"Environmental temperature modulates olfactory reception in Drosophila melanogaster","volume":"57","author":"Martin","year":"2011","journal-title":"J. Insect Physiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1002\/cne.22084","article-title":"Long-term survival of olfactory sensory neurons after target depletion","volume":"515","author":"Toledo","year":"2009","journal-title":"J. Comp. Neurol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2679","DOI":"10.1523\/JNEUROSCI.22-07-02679.2002","article-title":"Enriched odor exposure increases the mber of newborn neurons in the adult olfactory bulb and improves odor memory","volume":"22","author":"Rochefort","year":"2002","journal-title":"J. Neurosci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.bios.2017.08.055","article-title":"In vivo bioelectronic nose using transgenic mice for specific odor detection","volume":"102","author":"Gao","year":"2018","journal-title":"Biosens. Bioelectron."}],"container-title":["Sensors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8220\/21\/9\/2967\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:52:02Z","timestamp":1760161922000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8220\/21\/9\/2967"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,23]]},"references-count":47,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["s21092967"],"URL":"https:\/\/doi.org\/10.3390\/s21092967","relation":{},"ISSN":["1424-8220"],"issn-type":[{"value":"1424-8220","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,23]]}}}