{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T18:24:44Z","timestamp":1787423084393,"version":"build-2736575974"},"reference-count":60,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,11,30]],"date-time":"2024-11-30T00:00:00Z","timestamp":1732924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Sciences and Engineering Research Council (NSERC) of Canada"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biosensors"],"abstract":"<jats:p>Hypoxia, characterized by inadequate tissue oxygenation, may result in tissue damage and organ failure if not addressed. Current detection approaches frequently prove insufficient, depending on symptoms and rudimentary metrics such as tissue oxygenation, which fail to comprehensively identify the onset of hypoxia. The European Pressure Ulcer Advisory Panel (EPUAP) has recognized sweat lactate as a possible marker for the early identification of decubitus ulcers, nevertheless, neither sweat lactate nor oxygenation independently provides an appropriate diagnosis of hypoxia. We have fabricated a wearable device that non-invasively and concurrently monitors sweat lactate and tissue oxygenation to fill this gap. The apparatus comprises three essential components: (i) a hydrogel-based colorimetric lactate biosensor, (ii) a near-infrared (NIR) sensor for assessing tissue oxygenation, and (iii) an integrated form factor for enhanced wearability. The lactate sensor alters its hue upon interaction with lactate in sweat, whereas the NIR sensor monitors tissue oxygenation levels in real-time. The device underwent testing on phantom exhibiting tissue-mimicking characteristics and on human sweat post aerobic and anaerobic activities. Moreover, the device was demonstrated to be capable of real-time \u201con-body\u201d simultaneous monitoring of sweat lactate spikes and tissue oxygenation (StO2) drops, which showed strong correlation during a hypoxia protocol. This innovative technology has a wide range of potential applications, such as post-operative care, sepsis detection, and athletic performance monitoring, and may provide economical healthcare solutions in resource-limited regions.<\/jats:p>","DOI":"10.3390\/bios14120584","type":"journal-article","created":{"date-parts":[[2024,12,3]],"date-time":"2024-12-03T10:52:30Z","timestamp":1733223150000},"page":"584","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Detecting Hypoxia Through the Non-Invasive and Simultaneous Monitoring of Sweat Lactate and Tissue Oxygenation"],"prefix":"10.3390","volume":"14","author":[{"given":"Cindy","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Chemistry, University of Waterloo, 200 University Ave West, Waterloo, ON N2L 3G1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7846-6677","authenticated-orcid":false,"given":"Sayan","family":"Ganguly","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Waterloo, 200 University Ave West, Waterloo, ON N2L 3G1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Waterloo, 200 University Ave West, Waterloo, ON N2L 3G1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9734-4365","authenticated-orcid":false,"given":"Xiaowu","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Waterloo, 200 University Ave West, Waterloo, ON N2L 3G1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1800444","DOI":"10.1002\/admt.201800444","article-title":"Recent advances in smart wearable sensing systems","volume":"3","author":"Lou","year":"2018","journal-title":"Adv. Mater. Technol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1016\/j.measurement.2009.02.002","article-title":"Development of a wearable sensor system for quantitative gait analysis","volume":"42","author":"Liu","year":"2009","journal-title":"Measurement"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1038\/s41578-022-00460-x","article-title":"End-to-end design of wearable sensors","volume":"7","author":"Ates","year":"2022","journal-title":"Nat. Rev. Mater."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1109\/JSEN.2020.3019016","article-title":"Wearable sensors for real-time kinematics analysis in sports: A review","volume":"21","author":"Rana","year":"2020","journal-title":"IEEE Sens. J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2113012","DOI":"10.1002\/adfm.202113012","article-title":"Gold nanomaterials-implemented wearable sensors for healthcare applications","volume":"32","author":"Yi","year":"2022","journal-title":"Adv. Funct. Mater."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"112105","DOI":"10.1016\/j.sna.2020.112105","article-title":"Progress and challenges in fabrication of wearable sensors for health monitoring","volume":"312","author":"Nasiri","year":"2020","journal-title":"Sens. Actuators A Phys."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2106475","DOI":"10.1002\/adfm.202106475","article-title":"Emerging wearable sensors for plant health monitoring","volume":"31","author":"Lee","year":"2021","journal-title":"Adv. Funct. Mater."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2100116","DOI":"10.1002\/adhm.202100116","article-title":"Flexible wearable sensors for cardiovascular health monitoring","volume":"10","author":"Chen","year":"2021","journal-title":"Adv. Healthc. Mater."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Xu, J., Fang, Y., and Chen, J. (2021). Wearable biosensors for non-invasive sweat diagnostics. Biosensors, 11.","DOI":"10.3390\/bios11080245"},{"key":"ref_10","first-page":"36","article-title":"Review of Recent Advances in Non-invasive, Flexible, Wearable Sweat Monitoring Sensors","volume":"7","author":"Medagedara","year":"2020","journal-title":"Instrumentation"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2206064","DOI":"10.1002\/smll.202206064","article-title":"Access and management of sweat for non-invasive biomarker monitoring: A comprehensive review","volume":"19","author":"Saha","year":"2023","journal-title":"Small"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Pour, S.R.S., Calabria, D., Emamiamin, A., Lazzarini, E., Pace, A., Guardigli, M., Zangheri, M., and Mirasoli, M. (2024). Microfluidic-Based Non-Invasive Wearable Biosensors for Real-Time Monitoring of Sweat Biomarkers. Biosensors, 14.","DOI":"10.3390\/bios14010029"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Thaveesangsakulthai, I., Chatdarong, K., Somboonna, N., Pombubpa, N., Palaga, T., Makmuang, S., Wongravee, K., Hoven, V., Somboon, P., and Torvorapanit, P. (2024). A large scale study of portable sweat test sensor for accurate, non-invasive and rapid COVID-19 screening based on volatile compound marker detection. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-68250-9"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2787","DOI":"10.1021\/acssensors.1c01133","article-title":"State of sweat: Emerging wearable systems for real-time, noninvasive sweat sensing and analytics","volume":"6","author":"Ghaffari","year":"2021","journal-title":"ACS Sens."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"342988","DOI":"10.1016\/j.aca.2024.342988","article-title":"A physiological perspective of the relevance of sweat biomarkers and their detection by wearable microfluidic technology: A Review","volume":"1327","author":"Morros","year":"2024","journal-title":"Anal. Chim. Acta"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Qiao, Y., Qiao, L., Chen, Z., Liu, B., Gao, L., and Zhang, L. (2022). Wearable sensor for continuous sweat biomarker monitoring. Chemosensors, 10.","DOI":"10.3390\/chemosensors10070273"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Ibrahim, N.F.A., Sabani, N., Johari, S., Manaf, A.A., Wahab, A.A., Zakaria, Z., and Noor, A.M. (2022). A comprehensive review of the recent developments in wearable sweat-sensing devices. Sensors, 22.","DOI":"10.3390\/s22197670"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s12576-021-00811-3","article-title":"Monitor for lactate in perspiration","volume":"71","author":"Luo","year":"2021","journal-title":"J. Physiol. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1016\/j.talanta.2018.09.086","article-title":"Non-invasive textile based colorimetric sensor for the simultaneous detection of sweat pH and lactate","volume":"192","author":"Promphet","year":"2019","journal-title":"Talanta"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"6295","DOI":"10.1039\/C9SC01937E","article-title":"Construction of a flexible electrochemiluminescence platform for sweat detection","volume":"10","author":"Chen","year":"2019","journal-title":"Chem. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1007\/s12200-009-0050-8","article-title":"Portable muscle oxygenation monitor based on near infrared spectroscopy","volume":"2","author":"Zhang","year":"2009","journal-title":"Front. Optoelectron. China"},{"key":"ref_22","first-page":"916","article-title":"High lactate levels predict likelihood of metastases, tumor recurrence, and restricted patient survival in human cervical cancers","volume":"60","author":"Walenta","year":"2000","journal-title":"Cancer Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/j.jss.2009.04.020","article-title":"A different view of lactate in trauma patients: Protecting the injured brain","volume":"159","author":"Cureton","year":"2010","journal-title":"J. Surg. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1007\/s12576-012-0213-z","article-title":"Lactate in human sweat: A critical review of research to the present day","volume":"62","author":"Derbyshire","year":"2012","journal-title":"J. Physiol. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s12576-009-0073-3","article-title":"The relationship between exercise intensity and the sweat lactate excretion rate","volume":"60","author":"Buono","year":"2010","journal-title":"J. Physiol. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.bios.2016.09.038","article-title":"A wearable multisensing patch for continuous sweat monitoring","volume":"93","author":"Anastasova","year":"2017","journal-title":"Biosens. Bioelectron."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/0003-2670(94)80004-9","article-title":"Analysis of metabolites in sweat as a measure of physical condition","volume":"289","author":"Mitsubayashi","year":"1994","journal-title":"Anal. Chim. Acta"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"8071","DOI":"10.1021\/acsami.0c22730","article-title":"Wearable osmotic-capillary patch for prolonged sweat harvesting and sensing","volume":"13","author":"Saha","year":"2021","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Ohkuwa, T., Tsukamoto, K., Yamai, K., Itoh, H., Yamazaki, Y., and Tsuda, T. (2009). The relationship between exercise intensity and lactate concentration on the skin surface. Int. J. Biomed. Sci. IJBS, 5.","DOI":"10.59566\/IJBS.2009.5023"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1590\/S0100-879X2007000100017","article-title":"Effect of age and gender on sweat lactate and ammonia concentrations during exercise in the heat","volume":"40","author":"Meyer","year":"2007","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1007\/s004210050676","article-title":"Gender differences in sweat lactate","volume":"82","author":"Green","year":"2000","journal-title":"Eur. J. Appl. Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1111\/j.1469-445X.2000.02058.x","article-title":"Variations in regional sweat composition in normal human males","volume":"85","author":"Patterson","year":"2000","journal-title":"Exp. Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1177\/193229680700100414","article-title":"Blood lactate measurements and analysis during exercise: A guide for clinicians","volume":"1","author":"Goodwin","year":"2007","journal-title":"J. Diabetes Sci. Technol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1016\/j.bios.2018.06.054","article-title":"Lactate biosensing: The emerging point-of-care and personal health monitoring","volume":"117","author":"Alam","year":"2018","journal-title":"Biosens. Bioelectron."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Sakharov, D., Shkurnikov, M., Vagin, M.Y., Yashina, E., Karyakin, A., and Tonevitsky, A. (2010). Relationship between lactate concentrations in active muscle sweat and whole blood. Bull. Exp. Biol. Med., 150.","DOI":"10.1007\/s10517-010-1075-0"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1002\/celc.201901703","article-title":"Relationship between sweat and blood lactate levels during exhaustive physical exercise","volume":"7","author":"Karpova","year":"2020","journal-title":"ChemElectroChem"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1021\/acssensors.8b01218","article-title":"Soft, skin-integrated multifunctional microfluidic systems for accurate colorimetric analysis of sweat biomarkers and temperature","volume":"4","author":"Choi","year":"2019","journal-title":"ACS Sens."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1601355","DOI":"10.1002\/adhm.201601355","article-title":"Thin, soft, skin-mounted microfluidic networks with capillary bursting valves for chrono-sampling of sweat","volume":"6","author":"Choi","year":"2017","journal-title":"Adv. Healthc. Mater."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1177\/0040517514528565","article-title":"Microfluidic device on a nonwoven fabric: A potential biosensor for lactate detection","volume":"84","author":"Baysal","year":"2014","journal-title":"Text. Res. J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"366ra165","DOI":"10.1126\/scitranslmed.aaf2593","article-title":"A soft, wearable microfluidic device for the capture, storage, and colorimetric sensing of sweat","volume":"8","author":"Koh","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bprint.2017.12.001","article-title":"3D bioprinting of liver-mimetic construct with alginate\/cellulose nanocrystal hybrid bioink","volume":"9","author":"Wu","year":"2018","journal-title":"Bioprinting"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"25390","DOI":"10.1039\/D0TA09315G","article-title":"Role of a high calcium ion content in extending the properties of alginate dual-crosslinked hydrogels","volume":"8","author":"Zhang","year":"2020","journal-title":"J. Mater. Chem. A"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.jmbbm.2014.05.004","article-title":"Effects of alginate hydrogel cross-linking density on mechanical and biological behaviors for tissue engineering","volume":"37","author":"Jang","year":"2014","journal-title":"J. Mech. Behav. Biomed. Mater."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"15105","DOI":"10.1021\/acs.analchem.1c03387","article-title":"Integration and quantitative visualization of 3,3\u2032,5,5\u2032-tetramethylbenzidine-probed enzyme-linked immunosorbent assay-like signals in a photothermal bar-chart microfluidic chip for multiplexed immunosensing","volume":"93","author":"Fu","year":"2021","journal-title":"Anal. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1021\/acssensors.0c01980","article-title":"Wearable analytical platform with enzyme-modulated dynamic range for the simultaneous colorimetric detection of sweat volume and sweat biomarkers","volume":"6","author":"Vaquer","year":"2020","journal-title":"ACS Sens."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"342453","DOI":"10.1016\/j.aca.2024.342453","article-title":"Flexible microfluidic colorimetric detection chip integrated with ABTS\u00b7+ and Co@ MnO2 nanozyme catalyzed TMB reaction systems for bio-enzyme free detection of sweat uric acid","volume":"1299","author":"Li","year":"2024","journal-title":"Anal. Chim. Acta"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Lee, H.K., Yang, Y.J., Koirala, G.R., Oh, S., and Kim, T.-i. (2024). From Lab to Wearables: Innovations in Multifunctional Hydrogel Chemistry for Next-Generation Bioelectronic Devices. Biomaterials, 310.","DOI":"10.1016\/j.biomaterials.2024.122632"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"i3","DOI":"10.1093\/bja\/aep299","article-title":"Near-infrared spectroscopy as an index of brain and tissue oxygenation","volume":"103","author":"Murkin","year":"2009","journal-title":"Br. J. Anaesth."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1007\/s10877-012-9348-y","article-title":"Monitoring tissue oxygenation by near infrared spectroscopy (NIRS): Background and current applications","volume":"26","author":"Scheeren","year":"2012","journal-title":"J. Clin. Monit. Comput."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Jamnick, N.A., Botella, J., Pyne, D.B., and Bishop, D.J. (2018). Manipulating graded exercise test variables affects the validity of the lactate threshold and V\u02d9 O 2 peak. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0199794"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Wernbom, M., Schoenfeld, B.J., Paulsen, G., Bj\u00f8rnsen, T., Cumming, K.T., Aagaard, P., Clark, B.C., and Raastad, T. (2020). Commentary: Can blood flow restricted exercise cause muscle damage? Commentary on blood flow restriction exercise: Considerations of methodology, application, and safety. Front. Physiol., 11.","DOI":"10.3389\/fphys.2020.00243"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"211043","DOI":"10.20964\/2021.10.54","article-title":"Molecularly Imprinted Sensor based on Ag-Au NPs\/SPCE for Lactate Determination in Sweat for Healthcare and Sport Monitoring","volume":"16","author":"Zhou","year":"2021","journal-title":"Int. J. Electrochem. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Regiart, M., Ledo, A., Fernandes, E., Messina, G.A., Brett, C.M., Bertotti, M., and Barbosa, R.M. (2022). Highly sensitive and selective nanostructured microbiosensors for glucose and lactate simultaneous measurements in blood serum and in vivo in brain tissue. Biosens. Bioelectron., 199.","DOI":"10.1016\/j.bios.2021.113874"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Currano, L.J., Sage, F.C., Hagedon, M., Hamilton, L., Patrone, J., and Gerasopoulos, K. (2018). Wearable Sensor System for Detection of Lactate in Sweat. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-33565-x"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3389","DOI":"10.1007\/s00604-017-2345-6","article-title":"Molecularly imprinted polymers for selective solid-phase extraction of phospholipids from human milk samples","volume":"184","year":"2017","journal-title":"Microchim. Acta"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"8732","DOI":"10.1021\/acsomega.2c08127","article-title":"Fabrication of a Lactate-Specific Molecularly Imprinted Polymer toward Disease Detection","volume":"8","author":"Mustafa","year":"2023","journal-title":"ACS Omega"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"6646","DOI":"10.1021\/acs.analchem.0c05108","article-title":"Fiber-based electrochemical biosensors for monitoring pH and transient neurometabolic lactate","volume":"93","author":"Booth","year":"2021","journal-title":"Anal. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"126456","DOI":"10.1016\/j.matchemphys.2022.126456","article-title":"Green one-step reduction approach to prepare rGO@ AgNPs coupled with molecularly imprinted polymer for selective electrochemical detection of lactic acid as a cancer biomarker","volume":"289","author":"Moussa","year":"2022","journal-title":"Mater. Chem. Phys."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2763","DOI":"10.1021\/acssensors.1c01009","article-title":"Lactate biosensing for reliable on-body sweat analysis","volume":"6","author":"Xuan","year":"2021","journal-title":"ACS Sens."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Joly, K., Gurarie, E., Sorum, M.S., Kaczensky, P., Cameron, M.D., Jakes, A.F., Borg, B.L., Nandintsetseg, D., Hopcraft, J.G.C., and Buuveibaatar, B. (2019). Longest terrestrial migrations and movements around the world. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-51884-5"}],"container-title":["Biosensors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6374\/14\/12\/584\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:43:27Z","timestamp":1760114607000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6374\/14\/12\/584"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,30]]},"references-count":60,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["bios14120584"],"URL":"https:\/\/doi.org\/10.3390\/bios14120584","relation":{},"ISSN":["2079-6374"],"issn-type":[{"value":"2079-6374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,30]]}}}