{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T15:27:58Z","timestamp":1788362878131,"version":"build-2803163510"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,6,10]],"date-time":"2021-06-10T00:00:00Z","timestamp":1623283200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,6,10]],"date-time":"2021-06-10T00:00:00Z","timestamp":1623283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004014","name":"Japan IDDM network","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004014","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Volatile organic compounds (VOCs) released through skin (transcutaneous gas) has been increasing in importance for the continuous and real-time assessment of diseases or metabolisms. For stable monitoring of transcutaneous gas, finding a body part with little interference on the measurement is essential. In this study, we have investigated the possibility of external ears for stable and real-time measurement of ethanol vapour by developing a monitoring system that consisted with an over-ear gas collection cell and a biochemical gas sensor (bio-sniffer). The high sensitivity with the broad dynamic range (26\u00a0ppb\u2013554\u00a0ppm), the high selectivity to ethanol, and the capability of the continuous measurement of the monitoring system uncovered three important characteristics of external ear-derived ethanol with alcohol intake for the first time: there is little interference from sweat glands to a sensor signal at the external ear; similar temporal change in ethanol concentration to that of breath with delayed peak time (avg. 13\u00a0min); relatively high concentration of ethanol relative to other parts of a body (external ear-derived ethanol:breath ethanol\u2009=\u20091:590). These features indicated the suitability of external ears for non-invasive monitoring of blood VOCs.<\/jats:p>","DOI":"10.1038\/s41598-021-90146-1","type":"journal-article","created":{"date-parts":[[2021,6,10]],"date-time":"2021-06-10T16:04:25Z","timestamp":1623341065000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["External ears for non-invasive and stable monitoring of volatile organic compounds in human blood"],"prefix":"10.1038","volume":"11","author":[{"given":"Koji","family":"Toma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shota","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Arakawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiko","family":"Iwasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohji","family":"Mitsubayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,6,10]]},"reference":[{"key":"90146_CR1","doi-asserted-by":"publisher","first-page":"034001","DOI":"10.1088\/1752-7155\/8\/3\/034001","volume":"8","author":"A Amann","year":"2014","unstructured":"Amann, A. et al. The human volatilome: volatile organic compounds (VOCs) in exhaled breath, skin emanations, urine, feces and saliva. J. Breath Res. 8, 034001 (2014).","journal-title":"J. Breath Res."},{"key":"90146_CR2","doi-asserted-by":"publisher","first-page":"2287","DOI":"10.4155\/bio.13.183","volume":"5","author":"B Buszewski","year":"2013","unstructured":"Buszewski, B. et al. Detection of volatile organic compounds as biomarkers in breath analysis by different analytical techniques. Bioanalysis 5, 2287\u20132306 (2013).","journal-title":"Bioanalysis"},{"key":"90146_CR3","doi-asserted-by":"publisher","first-page":"1246","DOI":"10.1021\/acssensors.8b00400","volume":"3","author":"AH Jalal","year":"2018","unstructured":"Jalal, A. H. et al. Prospects and challenges of volatile organic compound sensors in human healthcare. ACS Sensors 3, 1246\u20131263 (2018).","journal-title":"ACS Sensors"},{"key":"90146_CR4","doi-asserted-by":"publisher","first-page":"N23","DOI":"10.1088\/0967-3334\/32\/8\/N01","volume":"32","author":"P \u0160pan\u011bl","year":"2011","unstructured":"\u0160pan\u011bl, P., Dryahina, K., Rej\u0161kov\u00e1, A., Chippendale, T. W. E. & Smith, D. Breath acetone concentration; biological variability and the influence of diet. Physiol. Meas. 32, N23\u2013N31 (2011).","journal-title":"Physiol. Meas."},{"key":"90146_CR5","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/S0021-9673(03)01103-8","volume":"1011","author":"C Prado","year":"2003","unstructured":"Prado, C., Mar\u00edn, P. & Periago, J. F. Application of solid-phase microextraction and gas chromatography-mass spectrometry to the determination of volatile organic compounds in end-exhaled breath samples. J. Chromatogr. A 1011, 125\u2013134 (2003).","journal-title":"J. Chromatogr. A"},{"key":"90146_CR6","doi-asserted-by":"publisher","first-page":"1471","DOI":"10.2116\/analsci.21.1471","volume":"21","author":"K Nose","year":"2005","unstructured":"Nose, K. et al. Identification of ammonia in gas emanated from human skin and its correlation with that in blood. Anal. Sci. 21, 1471\u20131474 (2005).","journal-title":"Anal. Sci."},{"key":"90146_CR7","doi-asserted-by":"publisher","unstructured":"Tsuda, T., Ohkuwa, T. & Itoh, H. Findings of skin gases and their possibilities in healthcare monitoring. in Gas Biology Research in Clinical Practice 125\u2013132 (KARGER, 2011). doi:https:\/\/doi.org\/10.1159\/000321953.","DOI":"10.1159\/000321953"},{"key":"90146_CR8","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1186\/1471-2407-9-348","volume":"9","author":"A Bajtarevic","year":"2009","unstructured":"Bajtarevic, A. et al. Noninvasive detection of lung cancer by analysis of exhaled breath. BMC Cancer 9, 348 (2009).","journal-title":"BMC Cancer"},{"key":"90146_CR9","doi-asserted-by":"publisher","first-page":"027004","DOI":"10.1088\/1752-7155\/3\/2\/027004","volume":"3","author":"J Herbig","year":"2009","unstructured":"Herbig, J. et al. On-line breath analysis with PTR-TOF. J. Breath Res. 3, 027004 (2009).","journal-title":"J. Breath Res."},{"key":"90146_CR10","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1088\/0967-3334\/27\/7\/007","volume":"27","author":"C Turner","year":"2006","unstructured":"Turner, C., \u0160pan\u011bl, P. & Smith, D. A longitudinal study of methanol in the exhaled breath of 30 healthy volunteers using selected ion flow tube mass spectrometry, SIFT-MS.  Physiol. Meas. 27, 637\u2013648 (2006).","journal-title":"Physiol. Meas."},{"key":"90146_CR11","doi-asserted-by":"publisher","first-page":"2380","DOI":"10.3390\/s19102380","volume":"19","author":"B Lansdorp","year":"2019","unstructured":"Lansdorp, B., Ramsay, W., Hamid, R. & Strenk, E. Wearable enzymatic alcohol biosensor.  Sensors (Switzerland) 19, 2380 (2019).","journal-title":"Sensors (Switzerland)"},{"key":"90146_CR12","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1021\/acssensors.6b00356","volume":"1","author":"J Kim","year":"2016","unstructured":"Kim, J. et al. Noninvasive alcohol monitoring using a wearable tattoo-based iontophoretic-biosensing system. ACS Sens. 1, 1011\u20131019 (2016).","journal-title":"ACS Sens."},{"key":"90146_CR13","unstructured":"Yamada, Y., Hiyama, S., Toyooka, T., Onoe, H. & Takeuchi, S. Skin-emitted acetone detection toward self-monitoring of fat metabolisms. in 17th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2013 vol. 3 1842\u20131844 (2013)."},{"key":"90146_CR14","doi-asserted-by":"publisher","first-page":"7588","DOI":"10.1021\/acs.analchem.5b00296","volume":"87","author":"Y Yamada","year":"2015","unstructured":"Yamada, Y. et al. Ultratrace measurement of acetone from skin using zeolite: toward development of a wearable monitor of fat metabolism. Anal. Chem. 87, 7588\u20137594 (2015).","journal-title":"Anal. Chem."},{"key":"90146_CR15","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.jchromb.2014.04.006","volume":"959","author":"P Mochalski","year":"2014","unstructured":"Mochalski, P., King, J., Unterkofler, K., Hinterhuber, H. & Amann, A. Emission rates of selected volatile organic compounds from skin of healthy volunteers . J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 959, 62\u201370 (2014).","journal-title":"J. Chromatogr. B Anal. Technol. Biomed. Life Sci."},{"key":"90146_CR16","doi-asserted-by":"publisher","first-page":"594","DOI":"10.1080\/10473289.1999.10463831","volume":"49","author":"JD Fenske","year":"1999","unstructured":"Fenske, J. D. & Paulson, S. E. Human breath emissions of VOCs. J. Air Waste Manag. Assoc. 49, 594\u2013598 (1999).","journal-title":"J. Air Waste Manag. Assoc."},{"key":"90146_CR17","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.bios.2018.09.070","volume":"129","author":"T Arakawa","year":"2019","unstructured":"Arakawa, T. et al. Real-time monitoring of skin ethanol gas by a high-sensitivity gas phase biosensor (bio-sniffer) for the non-invasive evaluation of volatile blood compounds. Biosens. Bioelectron. 129, 245\u2013253 (2019).","journal-title":"Biosens. Bioelectron."},{"key":"90146_CR18","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1111\/j.1467-2494.2007.00387.x","volume":"29","author":"K Wilke","year":"2007","unstructured":"Wilke, K., Martin, A., Terstegen, L. & Biel, S. S. A short history of sweat gland biology. Int. J. Cosmet. Sci. 29, 169\u2013179 (2007).","journal-title":"Int. J. Cosmet. Sci."},{"key":"90146_CR19","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/2046-7648-2-4","volume":"2","author":"NASA Taylor","year":"2013","unstructured":"Taylor, N. A. S. A. & Machado-Moreira, C. A. Regional variations in transepidermal water loss, eccrine sweat gland density, sweat secretion rates and electrolyte composition in resting and exercising humans. Extreme Physiol. Med. 2, 4 (2013).","journal-title":"Extreme Physiol. Med."},{"key":"90146_CR20","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1038\/jid.1952.77","volume":"19","author":"WC Lobitz","year":"1952","unstructured":"Lobitz, W. C. & Campbell, C. J. Physiology of the glands of the human ear canal: preliminary report. J. Investig. Dermatol. 19, 125\u2013135 (1952).","journal-title":"J. Investig. Dermatol."},{"key":"90146_CR21","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1111\/joa.12344","volume":"228","author":"N Anthwal","year":"2016","unstructured":"Anthwal, N. & Thompson, H. The development of the mammalian outer and middle ear. J. Anat. 228, 217\u2013232 (2016).","journal-title":"J. Anat."},{"key":"90146_CR22","doi-asserted-by":"publisher","first-page":"92","DOI":"10.3109\/00016489009122520","volume":"110","author":"L Hergils","year":"1990","unstructured":"Hergils, L. & Magnuson, B. Human middle ear gas composition studied by mass spectrometry. Acta Otolaryngol. 110, 92\u201399 (1990).","journal-title":"Acta Otolaryngol."},{"key":"90146_CR23","doi-asserted-by":"publisher","first-page":"643","DOI":"10.3109\/00016489409126119","volume":"114","author":"H Takahashi","year":"1994","unstructured":"Takahashi, H. et al. Assessment of the gas exchange function of the middle ear using nitrous oxide a preliminary study. Acta Otolaryngol. 114, 643\u2013646 (1994).","journal-title":"Acta Otolaryngol."},{"key":"90146_CR24","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1080\/00016480802360657","volume":"129","author":"S Yuksel","year":"2009","unstructured":"Yuksel, S., Swarts, J. D., Banks, J., Seroky, J. T. & Doyle, W. J. In vivo measurement of O2 and CO2 gas exchange across the human tympanic membrane. Acta Otolaryngol. 129, 716\u2013725 (2009).","journal-title":"Acta Otolaryngol."},{"key":"90146_CR25","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1016\/j.jchromb.2008.08.031","volume":"875","author":"S Van den Velde","year":"2008","unstructured":"Van den Velde, S., Nevens, F., Van Hee, P., Van Steenberghe, D. & Quirynen, M. GC-MS analysis of breath odor compounds in liver patients . J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 875, 344\u2013348 (2008).","journal-title":"J. Chromatogr. B Anal. Technol. Biomed. Life Sci."},{"key":"90146_CR26","first-page":"132","volume":"3","author":"D Modun","year":"2010","unstructured":"Modun, D., Vukovi\u0107, J., Sutlovi\u0107, D., Budimir, D. & Boban, M. Comparison of breath and blood alcohol concentrations in a controlled drinking study. Period. Biol. 3, 132 (2010).","journal-title":"Period. Biol."},{"key":"90146_CR27","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/j.forsciint.2006.07.018","volume":"168","author":"L Lindberg","year":"2007","unstructured":"Lindberg, L. et al. Breath alcohol concentration determined with a new analyzer using free exhalation predicts almost precisely the arterial blood alcohol concentration. Forensic Sci. Int. 168, 200\u2013207 (2007).","journal-title":"Forensic Sci. Int."},{"key":"90146_CR28","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/S0379-0738(02)00417-6","volume":"132","author":"AW Jones","year":"2003","unstructured":"Jones, A. W. & Andersson, L. Comparison of ethanol concentrations in venous blood and end-expired breath during a controlled drinking study. Forensic Sci. Int. 132, 18\u201325 (2003).","journal-title":"Forensic Sci. Int."},{"key":"90146_CR29","doi-asserted-by":"publisher","first-page":"593","DOI":"10.2114\/ahs1983.11.593","volume":"11","author":"SJ Park","year":"1992","unstructured":"Park, S. J. & Tamura, T. Distribution of evaporation rate on human body surface. Ann. Physiol. Anthropol. 11, 593\u2013609 (1992).","journal-title":"Ann. Physiol. Anthropol."},{"key":"90146_CR30","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1097\/00000478-200403000-00003","volume":"28","author":"LDR Thompson","year":"2004","unstructured":"Thompson, L. D. R., Nelson, B. L. & Barnes, E. L. Ceruminous adenomas. Am. J. Surg. Pathol. 28, 308\u2013318 (2004).","journal-title":"Am. J. Surg. Pathol."},{"key":"90146_CR31","doi-asserted-by":"publisher","first-page":"2915","DOI":"10.1039\/C9AN02089F","volume":"145","author":"K Iitani","year":"2020","unstructured":"Iitani, K., Naisierding, M., Toma, K., Arakawa, T. & Mitsubayashi, K. Evaluation for regional difference of skin-gas ethanol and sweat rate using alcohol dehydrogenase-mediated fluorometric gas-imaging system (sniff-cam). Analyst 145, 2915\u20132924 (2020).","journal-title":"Analyst"},{"key":"90146_CR32","doi-asserted-by":"publisher","first-page":"431","DOI":"10.3390\/proceedings1040431","volume":"1","author":"B Lawson","year":"2017","unstructured":"Lawson, B. et al. Transdermal alcohol measurements using MOX sensors in clinical trials. Proceedings 1, 431 (2017).","journal-title":"Proceedings"},{"key":"90146_CR33","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/0034-5687(78)90104-4","volume":"32","author":"P Gehr","year":"1978","unstructured":"Gehr, P., Bachofen, M. & Weibel, E. R. The normal human lung: ultrastructure and morphometric estimation of diffusion capacity. Respir. Physiol. 32, 121\u2013140 (1978).","journal-title":"Respir. Physiol."},{"key":"90146_CR34","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1007\/s00276-002-0034-5","volume":"24","author":"Y Lee","year":"2002","unstructured":"Lee, Y. & Hwang, K. Skin thickness of Korean adults. Surg. Radiol. Anat. 24, 183\u2013189 (2002).","journal-title":"Surg. Radiol. Anat."},{"key":"90146_CR35","doi-asserted-by":"publisher","unstructured":"Dasgupta, A. Measurement of alcohol levels in body fluids and transdermal alcohol sensors. in Alcohol and its Biomarkers 65\u201390 (Elsevier, 2015). doi:https:\/\/doi.org\/10.1016\/B978-0-12-800339-8.00003-1.","DOI":"10.1016\/B978-0-12-800339-8.00003-1"},{"key":"90146_CR36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1520\/JFS2003101","volume":"49","author":"O Laakso","year":"2004","unstructured":"Laakso, O., Pennanen, T., Himberg, K., Kuitunen, T. & Himberg, J.-J. Effect of eight solvents on ethanol analysis by Dr\u00e4ger 7110 evidential breath analyzer. J. Forensic Sci. 49, 1\u20134 (2004).","journal-title":"J. Forensic Sci."},{"key":"90146_CR37","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1007\/s00216-007-1824-8","volume":"391","author":"H Kudo","year":"2008","unstructured":"Kudo, H. et al. Glucose sensor using a phospholipid polymer-based enzyme immobilization method. Anal. Bioanal. Chem. 391, 1269\u20131274 (2008).","journal-title":"Anal. Bioanal. Chem."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-90146-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-90146-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-90146-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T08:25:59Z","timestamp":1670055959000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-90146-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,10]]},"references-count":37,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["90146"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-90146-1","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,10]]},"assertion":[{"value":"11 December 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 April 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 June 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"10415"}}