{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T23:18:32Z","timestamp":1788218312188,"version":"build-2803163510"},"reference-count":38,"publisher":"American Chemical Society (ACS)","issue":"33","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Urea is a clinically important biomarker for monitoring chronic kidney disease (CKD). Saliva provides a noninvasive alternative to blood for urea measurements, making it attractive for routine disease monitoring. Urease-based pH sensing has been extensively investigated for urea diagnostics due to its transduction simplicity and clinical relevance. However, this approach has two key challenges that are critical for quantitative accuracy but remain unexplored in existing literature. First, significant variations in salivary pH and buffering capacity across populations and within the same person lead to sample-dependent pH-urea calibration curves, thereby compromising quantitative accuracy. Second, pH sensor responses saturate at elevated urea concentrations, thus limiting quantitative detection across the full clinically relevant range (2\u201345 mM). To address these challenges, a saliva dilution strategy was investigated using bipolar junction transistor (BJT)-based sensors with enhanced pH sensitivity. The optimal conditions, comprising a 60-fold dilution of saliva in 4 mM MES buffer (pH 5.88), produced a saliva-independent linear pH\u2013urea calibration curve spanning the entire clinically relevant urea concentration range. The BJT sensor-based urea measurements were validated against a commercial gold-standard colorimetric assay, with Bland\u2013Altman analysis showing a mean difference of \u22120.858 mM. In summary, this work provides a pathway toward robust, scalable, and miniaturized urea sensors for portable CKD diagnostics.<\/jats:p>","DOI":"10.1021\/acsomega.6c05076","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T06:02:16Z","timestamp":1786341736000},"page":"50156-50167","source":"Crossref","is-referenced-by-count":0,"title":["Sample-Invariant\nSalivary Urea Quantification across the Clinically Relevant Range\nUsing a Silicon Device-Based pH Sensor"],"prefix":"10.1021","volume":"11","author":[{"given":"Kuan Yu","family":"Hsieh","sequence":"first","affiliation":[{"name":"IBM T. J. Watson Research Center , 1101 Kitchawan Road , , ,","place":["Yorktown Heights, New York, United States, 10598"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sufi","family":"Zafar","sequence":"additional","affiliation":[{"name":"IBM T. J. Watson Research Center , 1101 Kitchawan Road , , ,","place":["Yorktown Heights, New York, United States, 10598"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"issue":"10","key":"2026083119114643300_cit1","doi-asserted-by":"publisher","first-page":"ZC58","DOI":"10.7860\/JCDR\/2016\/20294.8651","article-title":"Assessment and Correlation of Urea\nand Creatinine Levels in Saliva and Serum of Patients with Chronic\nKidney Disease, Diabetes and Hypertension- A Research Study","volume":"10","author":"Pandya","year":"2016","journal-title":"J. Clin. Diagn. Res."},{"issue":"7","key":"2026083119114643300_cit2","doi-asserted-by":"publisher","first-page":"ZC18","DOI":"10.7860\/JCDR\/2014\/8081.4553","article-title":"Analysis of\nBlood and Salivary Urea Levels in Patients Undergoing Haemodialysis\nand Kidney Transplant","volume":"8","author":"Suresh","year":"2014","journal-title":"J. Clin. Diagn. Res."},{"issue":"1","key":"2026083119114643300_cit3","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/j.jobcr.2015.08.006","article-title":"Saliva as a Diagnostic Tool for Oral and Systemic Diseases","volume":"6","author":"Javaid","year":"2016","journal-title":"J. Oral Biol. Craniofac. Res."},{"key":"2026083119114643300_cit4","doi-asserted-by":"crossref","unstructured":"Namavar-Kordshouli, M.; Vaziri-Amjad, S.; Khazaei, S.; Ahmadi-Motamayel, F.\n          Evaluation\nof Salivary Biomarkers in Chronic Kidney Disease: A Systematic Review\nand Meta-Analysis\n          J. Craniomaxillofac. Surg.\n          2026\n          104564\n          10.1016\/j.jcms.2026.104564.","DOI":"10.1016\/j.jcms.2026.104564"},{"key":"2026083119114643300_cit5","doi-asserted-by":"publisher","DOI":"10.1186\/s12882-016-0222-x","article-title":"Salivary\nCreatinine and Urea Analysis in Patients with Chronic Kidney Disease:\nA Case Control Study","volume":"17","author":"Lasisi","year":"2016","journal-title":"BMC Nephrol."},{"issue":"8","key":"2026083119114643300_cit6","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1080\/00016357.2017.1356467","article-title":"Validation of the Salivary Urea and\nCreatinine Tests as Screening Methods of Chronic Kidney Disease in\nVietnamese Patients","volume":"75","author":"Pham","year":"2017","journal-title":"Acta Odontol. Scand."},{"issue":"6","key":"2026083119114643300_cit7","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.1515\/cclm-2023-1285","article-title":"The Correlation of Urea and Creatinine\nConcentrations in Sweat and Saliva with Plasma during Hemodialysis:\nAn Observational Cohort Study","volume":"62","author":"Adelaars","year":"2024","journal-title":"Clin. Chem. Lab.\nMed."},{"key":"2026083119114643300_cit8","unstructured":"Jyoti, P.; Chand, G.; Mahajan, M.; Neki, N. S.; Stage, C.\n          Correlation of Salivary Urea and Salivary\nCreatinine with Blood Urea and Serum Creatinine in Patients with Chronic\nKidney Disease\n          Int. J. Curr. Med. Pharm. Res.\n          2018\n          10.24327\/23956429.ijcmpr20170362."},{"issue":"11","key":"2026083119114643300_cit9","doi-asserted-by":"publisher","first-page":"1789","DOI":"10.1039\/D4SD00241E","article-title":"Point-of-Care\nBiosensors and Devices for Diagnostics of Chronic Kidney Disease","volume":"3","author":"Liu","year":"2024","journal-title":"Sens. Diagn."},{"key":"2026083119114643300_cit10","doi-asserted-by":"publisher","DOI":"10.1016\/j.trac.2022.116570","article-title":"Recent Advances in Wearable Biosensors for Non-Invasive\nMonitoring of Specific Metabolites and Electrolytes Associated with\nChronic Kidney Disease: Performance Evaluation and Future Challenges","volume":"150","author":"Kukkar","year":"2022","journal-title":"Trends Analyt. Chem."},{"issue":"1","key":"2026083119114643300_cit11","doi-asserted-by":"publisher","DOI":"10.1002\/adsr.202500117","article-title":"Advances in\nElectrochemical Urea Biosensors: Trends and Future Prospects","volume":"5","author":"Shurbaji","year":"2026","journal-title":"Adv. Sens. Res."},{"issue":"1\u20133","key":"2026083119114643300_cit12","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.molcatb.2009.01.003","article-title":"Ureases I. Functional, Catalytic\nand Kinetic Properties: A Review","volume":"59","author":"Krajewska","year":"2009","journal-title":"J. Mol. Catal.\nB:Enzym."},{"issue":"23","key":"2026083119114643300_cit13","doi-asserted-by":"publisher","DOI":"10.3390\/ijms262311604","article-title":"Small-Molecule Detection in Biological\nFluids: The Emerging Role of Potentiometric Biosensors","volume":"26","author":"Lenar","year":"2025","journal-title":"Int. J. Mol. Sci."},{"issue":"4","key":"2026083119114643300_cit14","doi-asserted-by":"publisher","DOI":"10.1002\/elsa.202100207","article-title":"ISFET-based Sensors for (Bio)Chemical Applications:\nA Review","volume":"3","author":"Cao","year":"2023","journal-title":"Electrochem. Sci. Adv."},{"issue":"14","key":"2026083119114643300_cit15","doi-asserted-by":"publisher","first-page":"26300","DOI":"10.1109\/JSEN.2025.3570755","article-title":"A Disposable Solid-State EGFET Chip\nIntegrated with a Mini-Readout System for Multi-Ion and Urea Detection","volume":"25","author":"Yang","year":"2025","journal-title":"IEEE Sens. J."},{"issue":"8","key":"2026083119114643300_cit16","doi-asserted-by":"publisher","DOI":"10.35848\/1347-4065\/adf382","article-title":"Extended-Gate\nField-Effect Transistor-Based Biosensors for the Detection of Urea\nas an Indicator of Renal Function","volume":"64","author":"Koike","year":"2025","journal-title":"Jpn. J. Appl.\nPhys."},{"issue":"5","key":"2026083119114643300_cit17","doi-asserted-by":"publisher","DOI":"10.3390\/bios13050565","article-title":"Highly Sensitive\nDetection of Urea Using Si Electrolyte-Gated Transistor with Low Power\nConsumption","volume":"13","author":"Choi","year":"2023","journal-title":"Biosensors (Basel)"},{"key":"2026083119114643300_cit18","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1016\/j.bios.2016.10.035","article-title":"Enzyme-Polyelectrolyte\nMultilayer Assemblies on Reduced Graphene Oxide Field-Effect Transistors\nfor Biosensing Applications","volume":"92","author":"Piccinini","year":"2017","journal-title":"Biosens. Bioelectron."},{"issue":"26","key":"2026083119114643300_cit19","doi-asserted-by":"publisher","first-page":"4381","DOI":"10.1039\/D4AY00551A","article-title":"A Salivary Urea Sensor Based on a Microsieve Disposable\nGate AlGaN\/GaN High Electron Mobility Transistor","volume":"16","author":"Yang","year":"2024","journal-title":"Anal. 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Commun.\n(Camb.)"},{"key":"2026083119114643300_cit22","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.bios.2016.04.077","article-title":"Enzyme Assays Using\nSensor Arrays Based on Ion-Selective Carbon Nanotube Field-Effect\nTransistors","volume":"84","author":"Melzer","year":"2016","journal-title":"Biosens. Bioelectron."},{"issue":"9","key":"2026083119114643300_cit23","doi-asserted-by":"publisher","first-page":"5315","DOI":"10.1021\/nl502366e","article-title":"Direct, Rapid, and\nLabel-Free Detection of Enzyme-Substrate Interactions in Physiological\nBuffers Using CMOS-Compatible Nanoribbon Sensors","volume":"14","author":"Mu","year":"2014","journal-title":"Nano Lett."},{"issue":"2","key":"2026083119114643300_cit24","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/S0003-9969(98)00108-3","article-title":"Individual Variations\nof pH, Buffer Capacity, and Concentrations of Calcium and Phosphate\nin Unstimulated Whole Saliva","volume":"44","author":"Larsen","year":"1999","journal-title":"Arch. Oral Biol."},{"issue":"4","key":"2026083119114643300_cit25","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1016\/S0003-9969(03)00007-4","article-title":"Saturation of Human Saliva with Respect to Calcium\nSalts","volume":"48","author":"Larsen","year":"2003","journal-title":"Arch. Oral Biol."},{"issue":"1","key":"2026083119114643300_cit26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0003-9969(99)00119-3","article-title":"The Buffer Capacity and Buffer Systems of Human Whole\nSaliva Measured without Loss of CO2","volume":"45","author":"Bardow","year":"2000","journal-title":"Arch. Oral\nBiol."},{"issue":"6","key":"2026083119114643300_cit27","doi-asserted-by":"publisher","DOI":"10.1063\/1.4907611","article-title":"A Comparison\nbetween Bipolar Transistor and Nanowire Field Effect Transistor Biosensors","volume":"106","author":"Zafar","year":"2015","journal-title":"Appl. Phys. Lett."},{"key":"2026083119114643300_cit28","doi-asserted-by":"publisher","DOI":"10.1038\/srep41430","article-title":"Comparison\nbetween Field Effect Transistors and Bipolar Junction Transistors\nas Transducers in Electrochemical Sensors","volume":"7","author":"Zafar","year":"2017","journal-title":"Sci.\nRep."},{"key":"2026083119114643300_cit29","doi-asserted-by":"crossref","unstructured":"Zafar, S.; Picunko, T.; Cabral, C.; Hopstaken, M.; Solomon, P.; Hamann, H. F.\n          Silicon\nDevice-Based Sensing for Sustainability, 2023 International\nElectron Devices Meeting (IEDM); 2023; pp 1\u2013410.1109\/iedm45741.2023.10413816.","DOI":"10.1109\/IEDM45741.2023.10413816"},{"key":"2026083119114643300_cit30","unstructured":"Urease, type IX from Canavalia ensiformis\n(Jack Bean). https:\/\/www.sigmaaldrich.com\/deepweb\/assets\/sigmaaldrich\/product\/documents\/278\/195\/u4002dat.pdf."},{"key":"2026083119114643300_cit31","unstructured":"Life Technologies Corporation. Urea nitrogen\n(BUN) colorimetric detection kit. https:\/\/documents.thermofisher.com\/TFS-Assets\/LSG\/manuals\/MAN0025406_EIABUN_BUN_color_detection_PI.pdf."},{"issue":"11","key":"2026083119114643300_cit32","doi-asserted-by":"publisher","first-page":"14646","DOI":"10.1021\/acsnano.0c03962","article-title":"Local Environment Affects the Activity\nof Enzymes on a 3D Molecular Scaffold","volume":"14","author":"Xiong","year":"2020","journal-title":"ACS Nano"},{"issue":"2","key":"2026083119114643300_cit33","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1067\/mpr.2001.113778","article-title":"A Review of Saliva: Normal Composition, Flow, and Function","volume":"85","author":"Humphrey","year":"2001","journal-title":"J. Prosthet. Dent."},{"issue":"1","key":"2026083119114643300_cit34","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1039\/C7EW00271H","article-title":"Characterization\nof Urea Hydrolysis in Fresh Human Urine and Inhibition by Chemical\nAddition","volume":"4","author":"Ray","year":"2018","journal-title":"Environ. Sci. (Camb."},{"issue":"1","key":"2026083119114643300_cit35","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1111\/j.1574-6968.1992.tb05535.x","article-title":"Kinetic Properties\nof Helicobacter Pyloriurease Compared with Jack Bean Urease","volume":"99","author":"Cesareo","year":"1992","journal-title":"FEMS Microbiol. Lett."},{"issue":"1\u20132","key":"2026083119114643300_cit36","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/S1381-1177(98)00129-5","article-title":"The Effect of Phosphate\nBuffer in the Range of pH 5.80\u20138.07 on Jack Bean Urease Activity","volume":"6","author":"Krajewska","year":"1999","journal-title":"J. Mol. Catal. B Enzym."},{"issue":"3","key":"2026083119114643300_cit37","doi-asserted-by":"publisher","first-page":"2427","DOI":"10.1007\/s10973-015-5145-4","article-title":"Thermodynamic Study\nof Competitive Inhibitors\u2019 Binding to Urease","volume":"123","author":"Krajewska","year":"2016","journal-title":"J. Therm. Anal. Calorim."},{"issue":"8476","key":"2026083119114643300_cit38","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1016\/S0140-6736(86)90837-8","article-title":"Statistical Methods\nfor Assessing Agreement between Two Methods of Clinical Measurement","volume":"327","author":"Martin Bland","year":"1986","journal-title":"Lancet"}],"container-title":["ACS Omega"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsomega.6c05076","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/11\/33\/50156\/66467943\/acsomega.6c05076.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/11\/33\/50156\/66467943\/acsomega.6c05076.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T23:11:52Z","timestamp":1788217912000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/acsodf\/article\/11\/33\/50156\/5250885\/Sample-Invariant-Salivary-Urea-Quantification"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,10]]},"references-count":38,"journal-issue":{"issue":"33","published-online":{"date-parts":[[2026,8,10]]},"published-print":{"date-parts":[[2026,8,25]]}},"URL":"https:\/\/doi.org\/10.1021\/acsomega.6c05076","relation":{},"ISSN":["2470-1343"],"issn-type":[{"value":"2470-1343","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,10]]}}}