{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:07:46Z","timestamp":1787029666467,"version":"build-2736575974"},"reference-count":40,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,2,23]],"date-time":"2023-02-23T00:00:00Z","timestamp":1677110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sensors"],"abstract":"<jats:p>The ion-sensitive field-effect transistor is a well-established electronic device typically used for pH sensing. The usability of the device for detecting other biomarkers in easily accessible biologic fluids, with dynamic range and resolution compliant with high-impact medical applications, is still an open research topic. Here, we report on an ion-sensitive field-effect transistor that is able to detect the presence of chloride ions in sweat with a limit-of-detection of 0.004 mol\/m3. The device is intended for supporting the diagnosis of cystic fibrosis, and it has been designed considering two adjacent domains, namely the semiconductor and the electrolyte containing the ions of interest, by using the finite element method, which models the experimental reality with great accuracy. According to the literature explaining the chemical reactions that take place between the gate oxide and the electrolytic solution, we have concluded that anions directly interact with the hydroxyl surface groups and replace protons previously adsorbed from the surface. The achieved results confirm that such a device can be used to replace the traditional sweat test in the diagnosis and management of cystic fibrosis. In fact, the reported technology is easy-to-use, cost-effective, and non-invasive, leading to earlier and more accurate diagnoses.<\/jats:p>","DOI":"10.3390\/s23052491","type":"journal-article","created":{"date-parts":[[2023,2,24]],"date-time":"2023-02-24T02:03:26Z","timestamp":1677204206000},"page":"2491","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Potentiometric Chloride Ion Biosensor for Cystic Fibrosis Diagnosis and Management: Modeling and Design"],"prefix":"10.3390","volume":"23","author":[{"given":"Annabella","family":"la Grasta","sequence":"first","affiliation":[{"name":"Department of Electrical and Information Engineering, Polytechnic University of Bari, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0612-7742","authenticated-orcid":false,"given":"Martino","family":"De Carlo","sequence":"additional","affiliation":[{"name":"Department of Electrical and Information Engineering, Polytechnic University of Bari, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4166-7755","authenticated-orcid":false,"given":"Attilio","family":"Di Nisio","sequence":"additional","affiliation":[{"name":"Department of Electrical and Information Engineering, Polytechnic University of Bari, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9874-5008","authenticated-orcid":false,"given":"Francesco","family":"Dell\u2019Olio","sequence":"additional","affiliation":[{"name":"Department of Electrical and Information Engineering, Polytechnic University of Bari, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0802-4464","authenticated-orcid":false,"given":"Vittorio M. 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Biotechnol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1016\/j.matt.2021.03.005","article-title":"All-in-One Conformal Epidermal Patch for Multimodal Biosensing","volume":"4","author":"Fang","year":"2021","journal-title":"Matter"},{"key":"ref_3","first-page":"100135","article-title":"Learning from Nature for Healthcare, Energy, and Environment","volume":"2","author":"Xiao","year":"2021","journal-title":"Innovation"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2007502","DOI":"10.1002\/adma.202007502","article-title":"Triboelectric Nanogenerators for Therapeutic Electrical Stimulation","volume":"33","author":"Conta","year":"2021","journal-title":"Adv. Mater."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1016\/j.trechm.2021.04.009","article-title":"Triboelectric Nanogenerators for Self-Powered Drug Delivery","volume":"3","author":"Li","year":"2021","journal-title":"Trends Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1016\/j.matt.2020.01.022","article-title":"Photo-Rechargeable Fabrics as Sustainable and Robust Power Sources for Wearable Bioelectronics","volume":"2","author":"Zhang","year":"2020","journal-title":"Matter"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"112078","DOI":"10.1016\/j.bios.2020.112078","article-title":"Highly Fluorescent Copper Nanoclusters for Sensing and Bioimaging","volume":"154","author":"An","year":"2020","journal-title":"Biosens. Bioelectron."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Naresh, V., and Lee, N. (2021). A Review on Biosensors and Recent Development of Nanostructured Materials-Enabled Biosensors. Sensors, 21.","DOI":"10.3390\/s21041109"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Singh, A., Sharma, A., Ahmed, A., Sundramoorthy, A.K., Furukawa, H., Arya, S., and Khosla, A. (2021). Recent Advances in Electrochemical Biosensors: Applications, Challenges, and Future Scope. Biosensors, 11.","DOI":"10.3390\/bios11090336"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"22404","DOI":"10.1109\/JSEN.2022.3216682","article-title":"Platinum Nanostructured Needle-Shaped Sensors for Ion Detection in Biomedical Applications","volume":"22","author":"Giaquinto","year":"2022","journal-title":"IEEE Sens. J."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Parizi, K.B., Yeh, A.J., Poon, A.S.Y., and Wong, H.S.P. (2012, January 10\u201313). Exceeding Nernst Limit (59mV\/PH): CMOS-Based PH Sensor for Autonomous Applications. Proceedings of the 2012 International Electron Devices Meeting, San Francisco, CA, USA.","DOI":"10.1109\/IEDM.2012.6479098"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4872","DOI":"10.1021\/nn5064216","article-title":"Sensing with Advanced Computing Technology: Fin Field-Effect Transistors with High-k Gate Stack on Bulk Silicon","volume":"9","author":"Rigante","year":"2015","journal-title":"ACS Nano"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.snb.2004.03.004","article-title":"The Development of Scalable Sensor Arrays Using Standard CMOS Technology","volume":"103","author":"Milgrew","year":"2004","journal-title":"Sens. Actuators B Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4173","DOI":"10.1039\/C7AN00455A","article-title":"Field-Effect Sensors\u2014From PH Sensing to Biosensing: Sensitivity Enhancement Using Streptavidin\u2013Biotin as a Model System","volume":"142","author":"Lowe","year":"2017","journal-title":"Analyst"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.bios.2017.09.005","article-title":"Preparation, Characterization and Application of Urease Nanoparticles for Construction of an Improved Potentiometric Urea Biosensor","volume":"100","author":"Jakhar","year":"2018","journal-title":"Biosens. Bioelectron."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"112302","DOI":"10.1016\/j.bios.2020.112302","article-title":"Modulating the Mixed Potential for Developing Biosensors: Direct Potentiometric Determination of Glucose in Whole, Undiluted Blood","volume":"163","author":"Blondeau","year":"2020","journal-title":"Biosens. Bioelectron."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1016\/j.snb.2018.07.001","article-title":"Wearable Potentiometric Tattoo Biosensor for On-Body Detection of G-Type Nerve Agents Simulants","volume":"273","author":"Mishra","year":"2018","journal-title":"Sens. Actuators B Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/j.bios.2013.11.039","article-title":"Epidermal Tattoo Potentiometric Sodium Sensors with Wireless Signal Transduction for Continuous Non-Invasive Sweat Monitoring","volume":"54","author":"Bandodkar","year":"2014","journal-title":"Biosens. Bioelectron."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"9111","DOI":"10.1021\/acs.analchem.9b01587","article-title":"Potential Reproducibility of Potassium-Selective Electrodes Having Perfluorinated Alkanoate Side Chain Functionalized Poly(3,4-Ethylenedioxytiophene) as a Hydrophobic Solid Contact","volume":"91","author":"Papp","year":"2019","journal-title":"Anal. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1109\/TBME.1970.4502688","article-title":"Development of an Ion-Sensitive Solid-State Device for Neurophysiological Measurements","volume":"BME\u201317","author":"Bergveld","year":"1970","journal-title":"IEEE Trans. Biomed. Eng."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Ma, X., Peng, R., Mao, W., Lin, Y., and Yu, H. (Electrochem. Sci. Adv., 2022). Recent Advances in Ion-sensitive Field-effect Transistors for Biosensing Applications, Electrochem. Sci. Adv., accepted.","DOI":"10.1002\/elsa.202100163"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Cao, S., Sun, P., Xiao, G., Tang, Q., Sun, X., Zhao, H., Zhao, S., Lu, H., and Yue, Z. (Electrochem. Sci. Adv, 2022). ISFET-based Sensors for (Bio)Chemical Applications: A Review, Electrochem. Sci. Adv, accepted.","DOI":"10.1002\/elsa.202100207"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1016\/j.jpeds.2008.05.005","article-title":"Guidelines for Diagnosis of Cystic Fibrosis in Newborns through Older Adults: Cystic Fibrosis Foundation Consensus Report","volume":"153","author":"Farrell","year":"2008","journal-title":"J. Pediatr."},{"key":"ref_24","unstructured":"Madou, M.J., and Morrison, S.R. (1989). Chemical Sensing with Solid State Devices, Academic Press."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e2100147","DOI":"10.1002\/elsa.202100147","article-title":"A Comprehensive Review of FET-based PH Sensors: Materials, Fabrication Technologies, and Modeling","volume":"2","author":"Sinha","year":"2022","journal-title":"Electrochem. Sci. Adv."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Vinoy, K.J., Ananthasuresh, G.K., Pratap, R., and Krupanidhi, S.B. (2014). Micro and Smart Devices and Systems, Springer. Springer Tracts in Mechanical Engineering.","DOI":"10.1007\/978-81-322-1913-2"},{"key":"ref_27","unstructured":"Kharbanda, D.K., and Khanna, P.K. (2015, January 24\u201325). Optimization of Dam-and-Fill Technique for Sensor Packaging Applications. Proceedings of the 2nd International Conference On Emerging Technologies: Micro To Nano 2015 (ETMN-2015), Rajasthan, India."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1109\/TED.2020.2964062","article-title":"General Approach to Model the Surface Charge Induced by Multiple Surface Chemical Reactions in Potentiometric FET Sensors","volume":"67","author":"Mele","year":"2020","journal-title":"IEEE Trans. Electron Devices"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S0001-8686(96)00307-7","article-title":"A General Model to Describe the Electrostatic Potential at Electrolyte Oxide Interfaces","volume":"69","author":"Eijkel","year":"1996","journal-title":"Adv. Colloid Interface Sci."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Wrege, R., Schneider, M.C., Goncalves Guimaraes, J., and Galup-Montoro, C. (2019, January 24\u201329). ISFETs: Theory, Modeling and Chip for Characterization. Proceedings of the 2019 IEEE 10th Latin American Symposium on Circuits & Systems (LASCAS), Armenia, Colombia.","DOI":"10.1109\/LASCAS.2019.8667572"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2025","DOI":"10.1016\/j.microrel.2006.10.003","article-title":"Study of the Electrolyte-Insulator-Semiconductor Field-Effect Transistor (EISFET) with Applications in Biosensor Design","volume":"47","author":"Landheer","year":"2007","journal-title":"Microelectron. Reliab."},{"key":"ref_32","unstructured":"Sze, S.M., Li, Y., and Ng, K.K. (2021). Physics of Semiconductor Devices, Wiley. [4th ed.]."},{"key":"ref_33","unstructured":"Newman, J., and Balsara, N.P. (2021). Electrochemical Systems; The Electrochemical Society Series, Wiley. [4th ed.]."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"9291","DOI":"10.1021\/nn303795r","article-title":"Understanding the Electrolyte Background for Biochemical Sensing with Ion-Sensitive Field-Effect Transistors","volume":"6","author":"Tarasov","year":"2012","journal-title":"ACS Nano"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3379","DOI":"10.1109\/TED.2015.2464251","article-title":"A TCAD-Based Methodology to Model the Site-Binding Charge at ISFET\/Electrolyte Interfaces","volume":"62","author":"Bandiziol","year":"2015","journal-title":"IEEE Trans. Electron Devices"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"197","DOI":"10.13031\/2013.2694","article-title":"Membrane selection and isfet configuration evaluation for soil nitrate sensing","volume":"43","author":"Birrell","year":"2000","journal-title":"Trans. ASAE"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Mele, L.J., Palestri, P., and Selmi, L. (2020, January 1). Modeling Selectivity and Cross-Sensitivity in Membrane-Based Potentiometric Sensors. Proceedings of the 2020 Joint International EUROSOI Workshop and International Conference on Ultimate Integration on Silicon (EUROSOI-ULIS), Caen, France.","DOI":"10.1109\/EUROSOI-ULIS49407.2020.9365285"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"B\u0103nic\u0103, F. (2012). Chemical Sensors and Biosensors: Fundamentals and Applications, Wiley. [1st ed.].","DOI":"10.1002\/9781118354162"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"12987","DOI":"10.1109\/JSEN.2022.3178297","article-title":"Modeling Non-Equilibrium Ion-Transport in Ion-Selective-Membrane\/Electrolyte Interfaces for Electrochemical Potentiometric Sensors","volume":"22","author":"Mele","year":"2022","journal-title":"IEEE Sens. J."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Ghoreishizadeh, S.S., Georgiou, P., Carrara, S., and De Micheli, G. (2016, January 22\u201325). An Integrated Platform for Differential Electrochemical and ISFET Sensing. Proceedings of the 2016 IEEE International Symposium on Circuits and Systems (ISCAS), Montr\u00e9al, QC, Canada.","DOI":"10.1109\/ISCAS.2016.7539193"}],"container-title":["Sensors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8220\/23\/5\/2491\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:40:42Z","timestamp":1760121642000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8220\/23\/5\/2491"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,23]]},"references-count":40,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["s23052491"],"URL":"https:\/\/doi.org\/10.3390\/s23052491","relation":{},"ISSN":["1424-8220"],"issn-type":[{"value":"1424-8220","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,23]]}}}