{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T02:53:10Z","timestamp":1790563990320,"version":"4.1.0"},"reference-count":42,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T00:00:00Z","timestamp":1739923200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"KMITL","award":["RE-KRIS\/FF67\/025"],"award-info":[{"award-number":["RE-KRIS\/FF67\/025"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Polymers"],"abstract":"<jats:p>Depression and anxiety are two common mental health issues that require serious attention, as they have significant impacts on human well-being, with both being emotionally and physically reflected in the increasing number of suicide cases globally. The World Health Organization (WHO) estimated that about 322 million people around the world experienced mental illnesses in 2017, and this number continues to increase. Cortisol is a major stress-controlled hormone that is regulated by the hypothalamic\u2013pituitary\u2013adrenal (HPA) axis. The HPA axis has three main components, including the hypothalamus, pituitary gland, and adrenal gland, where cortisol, the primary stress hormone, is released. It plays crucial roles in responding to stress, energy balance, and the immune system. The cortisol level in the bloodstream usually increases when stress develops. Molecularly imprinted polymers (MIPs) have been highlighted in terms of creating artificial bioreceptors by mimicking the shape of detected biomolecules, making natural bioreceptor molecules no longer required. MIPs can overcome the limitations of chemicals and physical properties reducing over time and the short-time shelf life of natural bioreceptors. MIPs\u2019 benefits are reflected in their ease of use, high sensitivity, high specificity, reusability, durability, and the lack of requirement for complicated sample preparation before use. Moreover, MIPs incur low costs in manufacturing, giving them a favorable budget for the market with simple utilization. MIPs can be formulated by only three key steps, including formation, the polymerization of functional monomers, and the creation of three-dimensional cavities mimicking the shape and size of targeting molecules. MIPs have a high potential as biosensors, especially working as bioanalytics for protein, anti-body, antigen, or bacteria detection. Herein, this research proposes an MIP-based cortisol biosensor in which cortisol is imprinted on methyl methacrylate (MMA) and methacrylic acid (MAA) produced by UV polymerization. This MIP-based biosensor may be an alternative method with which to detect and monitor the levels of hormones in biological samples such as serum, saliva, or urine due to its rapid detection ability, which would be of benefit for diagnosing depression and anxiety and prescribing treatment. In this study, quantitative detection was performed using an electrochemical technique to measure the changes in electrical signals in different concentrations of a cortisol solution ranging from 0.1 to 1000 pg\/mL. The MIP-based biosensor, as derived by calculation, achieved its best detection limit of 1.035 pg\/mL with a gold electrode. Tests were also performed on molecules with a similar molecular structure, including Medroxyprogesterone acetate and drospirenone, to ensure the sensitivity and accuracy of the sensors, demonstrating a low sensitivity and low linear response.<\/jats:p>","DOI":"10.3390\/polym17040545","type":"journal-article","created":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T08:36:46Z","timestamp":1739954206000},"page":"545","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Electrochemical Biosensors by Means of Molecularly Imprinted Polymers (MIPs) Cortisol Recognition"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5669-0823","authenticated-orcid":false,"given":"Jindapa","family":"Nampeng","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, School of Engineering, King Mongkut\u2019s Institute of Technology Ladkrabang, Bangkok 10520, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5036-226X","authenticated-orcid":false,"given":"Naphatsawan","family":"Vongmanee","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, School of Engineering, King Mongkut\u2019s Institute of Technology Ladkrabang, Bangkok 10520, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuchart","family":"Pintavirooj","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, School of Engineering, King Mongkut\u2019s Institute of Technology Ladkrabang, Bangkok 10520, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0310-0675","authenticated-orcid":false,"given":"Wen-Tai","family":"Chiu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, National Cheng Kung University, Tainan City 701401, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarinporn","family":"Visitsattapongse","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, School of Engineering, King Mongkut\u2019s Institute of Technology Ladkrabang, Bangkok 10520, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,19]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2017). Depression and Other Common Mental Disorders: Global Health Estimates, World Health Organization."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/nrn2639","article-title":"Effects of stress throughout the lifespan on the brain, behaviour and cognition","volume":"10","author":"Lupien","year":"2009","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Urizar, G.G., Hernandez, H.S., Rayo, J., and Bhansali, S. (2020). Validation of an Electrochemical Sensor to Detect Cortisol Responses to the Trier Social Stress Test. Neurobiol. Stress, 13.","DOI":"10.1016\/j.ynstr.2020.100263"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.mce.2010.04.005","article-title":"The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights","volume":"335","author":"Coutinho","year":"2011","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1113\/expphysiol.2008.045484","article-title":"Adrenal corticosteroid effects in the central nervous system on long-term control of blood pressure","volume":"95","author":"Scheuer","year":"2010","journal-title":"Exp. Physiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.biopsycho.2004.11.009","article-title":"Sex differences in HPA axis responses to stress: A review","volume":"69","author":"Kudielka","year":"2005","journal-title":"Biol. Psychol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1097\/FTD.0b013e31829daa0a","article-title":"The detection of cortisol in human sweat: Implications for measurement of cortisol in hair","volume":"36","author":"Russell","year":"2014","journal-title":"Ther. Drug Monit."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"110","DOI":"10.17305\/bjbms.2008.2962","article-title":"Daily fluctuation of cortisol in the saliva and serum of healthy persons","volume":"8","author":"Sapcanin","year":"2008","journal-title":"Bosn. J. Basic Med. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1515\/cclm-2014-0912","article-title":"Different methods to estimate serum free cortisol: A comparison during cortisol tetracosactide testing","volume":"53","author":"Brossaud","year":"2015","journal-title":"Clin. Chem. Lab. Med. (CCLM)"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1007\/s10815-014-0359-0","article-title":"Urine cortisol concentration as a biomarker of stress is unrelated to IVF outcomes in women and men","volume":"31","author":"Butts","year":"2014","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"S140","DOI":"10.1093\/geront\/gnu174","article-title":"Hair Cortisol Analysis: A Promising Biomarker of HPA Activation in Older Adults","volume":"55","author":"Wright","year":"2015","journal-title":"Gerontologist"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"8211","DOI":"10.1021\/acsomega.0c00498","article-title":"Comparison of Colorimetric Analyses to Determine Cortisol in Human Sweat","volume":"5","author":"Tu","year":"2020","journal-title":"ACS Omega"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.clinthera.2015.02.014","article-title":"Salivary cortisol results obtainable within minutes of sample collection correspond with traditional immunoassays","volume":"37","author":"Shirtcliff","year":"2015","journal-title":"Clin. Ther."},{"key":"ref_14","first-page":"72","article-title":"Molecular imprinting: A useful approach for drug delivery","volume":"3","author":"Zaidi","year":"2020","journal-title":"Mater. Sci. Energy Technol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2330","DOI":"10.1016\/j.chempr.2022.05.021","article-title":"Applications of molecularly imprinted polymers and perspectives for their use as food quality trackers","volume":"8","author":"Carballido","year":"2022","journal-title":"Chem"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Liu, R., and Poma, A.A.-O. (2021). Advances in Molecularly Imprinted Polymers as Drug Delivery Systems. Molecules, 26.","DOI":"10.3390\/molecules26123589"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"100153","DOI":"10.1016\/j.snr.2023.100153","article-title":"Molecularly imprinted polymer (MIP) based electrochemical sensors and their recent advances in health applications","volume":"5","author":"Wang","year":"2023","journal-title":"Sens. Actuators Rep."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Pintavirooj, C., Vongmanee, N., Sukjee, W., Sangma, C., and Visitsattapongse, S. (2022). Biosensors for Klebsiella pneumoniae with Molecularly Imprinted Polymer (MIP) Technique. Sensors, 22.","DOI":"10.3390\/s22124638"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"107820","DOI":"10.1016\/j.microc.2022.107820","article-title":"Electrochemical chiral sensor based on molecularly imprinted polymer for determination of (1S,2S)-pseudoephedrine in dosage forms and biological sample","volume":"181","author":"Karadurmus","year":"2022","journal-title":"Microchem. J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/s00604-022-05321-6","article-title":"Enantioselective recognition of esomeprazole with a molecularly imprinted sol-gel-based electrochemical sensor","volume":"189","author":"Karadurmus","year":"2022","journal-title":"Microchim. Acta"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2190","DOI":"10.1039\/c3tb00027c","article-title":"Influenza A virus molecularly imprinted polymers and their application in virus sub-type classification","volume":"1","author":"Wangchareansak","year":"2013","journal-title":"J. Mater. Chem. B"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.1080\/09205063.2017.1338503","article-title":"An influenza A virus agglutination test using antibody-like polymers","volume":"28","author":"Sukjee","year":"2017","journal-title":"J. Biomater. Sci. Polym. Ed."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"131973","DOI":"10.1016\/j.matlet.2022.131973","article-title":"Virus MIP-composites for SARS-CoV-2 detection in the aquatic environment","volume":"315","author":"Sukjee","year":"2022","journal-title":"Mater. Lett."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"127708","DOI":"10.1016\/j.snb.2020.127708","article-title":"Molecularly imprinted polymer-based SAW sensor for label-free detection of cerebral dopamine neurotrophic factor protein","volume":"308","author":"Kidakova","year":"2020","journal-title":"Sens. Actuators B Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"130556","DOI":"10.1016\/j.snb.2021.130556","article-title":"Laser-scribed graphene sensor based on gold nanostructures and molecularly imprinted polymers: Application for Her-2 cancer biomarker detection","volume":"347","author":"Lahcen","year":"2021","journal-title":"Sens. Actuators B Chem."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Kinnamon, D., Ghanta, R., Lin, K.A.-O., Muthukumar, S., and Prasad, S. (2017). Portable biosensor for monitoring cortisol in low-volume perspired human sweat. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-13684-7"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1186\/s11671-019-3012-0","article-title":"Salivary Electrochemical Cortisol Biosensor Based on Tin Disulfide Nanoflakes","volume":"14","author":"Liu","year":"2019","journal-title":"Nanoscale Res. Lett."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Halima, H.B., Zine, N., Gallardo-Gonz\u00e1lez, J., Aissari, A.E., Sigaud, M., Alcacer, A., Bausells, J., and Errachid, A. (2019, January 23\u201327). A Novel Cortisol Biosensor Based on the Capacitive Structure of Hafnium Oxide: Application for Heart Failure Monitoring. Proceedings of the 2019 20th International Conference on Solid-State Sensors, Actuators and Microsystems & Eurosensors XXXIII (TRANSDUCERS & EUROSENSORS XXXIII), Berlin, Germany.","DOI":"10.1109\/TRANSDUCERS.2019.8808561"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"32890","DOI":"10.1021\/acsomega.0c03223","article-title":"Aptamer-Based Lateral Flow Biosensor for Rapid Detection of Salivary Cortisol","volume":"5","author":"Dalirirad","year":"2020","journal-title":"ACS Omega"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.1007\/s00216-020-02430-0","article-title":"Flexible molecularly imprinted electrochemical sensor for cortisol monitoring in sweat","volume":"412","author":"Mugo","year":"2020","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"170300","DOI":"10.1098\/rsos.170300","article-title":"Oriented, molecularly imprinted cavities with dual binding sites for highly sensitive and selective recognition of cortisol","volume":"4","author":"Suda","year":"2017","journal-title":"R. Soc. Open Sci."},{"key":"ref_32","unstructured":"Poudyal, S.S. (2017). Screen Printed Carbon Electrode Based Microfluidic Biosensor for Sweat Cortisol Detection. [Master\u2019s Thesis, South Dakota State University]."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"115898","DOI":"10.1016\/j.trac.2020.115898","article-title":"Screen-printed carbon based biosensors and their applications in agri-food safety","volume":"127","author":"Smart","year":"2020","journal-title":"TrAC Trends Anal. Chem."},{"key":"ref_34","first-page":"13117","article-title":"POF-based biosensors for cortisol detection in seawater as a tool for aquaculture systems","volume":"14","author":"Arcadio","year":"2024","journal-title":"Sci. Rep. (Nat. Publ. Group)"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3863","DOI":"10.1007\/s00216-023-04577-y","article-title":"Advances in wearable electrochemical antibody-based sensors for cortisol sensing","volume":"415","author":"Khumngern","year":"2023","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_36","unstructured":"Duke, K. (2024). Laser Induced Graphene-Gold Nanoparticle Hybrid Composite Electrode Towards Point-of-Care Diagnostics. [Master\u2019s Thesis, Youngstown State University]."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/s00216-023-05047-1","article-title":"Advances in electrochemical biosensor design for the detection of the stress biomarker cortisol","volume":"416","author":"Weber","year":"2024","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_38","unstructured":"Dalirirad, S. (2016). Developing Aptamer-Based Biosensor for Onsite Detection of Stress Biomarkers in Noninvasive Biofluids. [Ph.D. Thesis, University of Cincinnati]."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1007\/s00216-022-04487-5","article-title":"Fabrication of a novel electrochemical biosensor based on a molecular imprinted polymer-aptamer hybrid receptor for lysozyme determination","volume":"415","author":"Beiki","year":"2023","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"120225","DOI":"10.1016\/j.talanta.2019.120225","article-title":"Non-invasive cortisol detection in saliva by using molecularly cortisol imprinted fullerene-acrylamide modified screen printed electrodes","volume":"206","author":"Uygun","year":"2020","journal-title":"Talanta"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"B54","DOI":"10.1149\/2.0781702jes","article-title":"A Reusable Electrochemical Biosensor for Monitoring of Small Molecules (Cortisol) Using Molecularly Imprinted Polymers","volume":"164","author":"Manickam","year":"2017","journal-title":"J. Electrochem. Soc."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.snb.2013.02.096","article-title":"An LTCC-based microfluidic system for label-free, electrochemical detection of cortisol","volume":"182","author":"Vasudev","year":"2013","journal-title":"Sens. Actuators B Chem."}],"container-title":["Polymers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4360\/17\/4\/545\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:37:54Z","timestamp":1760027874000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4360\/17\/4\/545"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,19]]},"references-count":42,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["polym17040545"],"URL":"https:\/\/doi.org\/10.3390\/polym17040545","relation":{},"ISSN":["2073-4360"],"issn-type":[{"value":"2073-4360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,19]]}}}