{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T18:38:30Z","timestamp":1775932710999,"version":"3.50.1"},"reference-count":48,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,3,5]],"date-time":"2020-03-05T00:00:00Z","timestamp":1583366400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31871882"],"award-info":[{"award-number":["31871882"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31772059"],"award-info":[{"award-number":["31772059"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2018M642440"],"award-info":[{"award-number":["2018M642440"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sensors"],"abstract":"<jats:p>Cortisol is commonly used as a significant biomarker of psychological or physical stress. With the accelerated pace of life, non-invasive cortisol detection at the point of care (POC) is in high demand for personal health monitoring. In this paper, an ultrasensitive immunosensor using gold nanoparticles\/molybdenum disulfide\/gold nanoparticles (AuNPs\/MoS2\/AuNPs) as transducer was explored for non-invasive salivary cortisol monitoring at POC with the miniaturized differential pulse voltammetry (DPV) system based on a smartphone. Covalent binding of cortisol antibody (CORT-Ab) onto the AuNPs\/MoS2\/AuNPs transducer was achieved through the self-assembled monolayer of specially designed polyethylene glycol (PEG, SH-PEG-COOH). Non-specific binding was avoided by passivating the surface with ethanolamine. The miniaturized portable DPV system was utilized for human salivary cortisol detection. A series current response of different cortisol concentrations decreased and exhibited a linear range of 0.5\u2013200 nM, the detection limit of 0.11 nM, and high sensitivity of 30 \u03bcA M\u22121 with a regression coefficient of 0.9947. Cortisol was also distinguished successfully from the other substances in saliva. The recovery ratio of spiked human salivary cortisol and the variation of salivary cortisol level during one day indicated the practicability of the immunosensor based on the portable system. The results demonstrated the excellent performance of the smartphone-based immunosensor system and its great potential application for non-invasive human salivary cortisol detection at POC.<\/jats:p>","DOI":"10.3390\/s20051422","type":"journal-article","created":{"date-parts":[[2020,3,6]],"date-time":"2020-03-06T07:33:46Z","timestamp":1583480026000},"page":"1422","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["Salivary Cortisol Determination on Smartphone-Based Differential Pulse Voltammetry System"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9602-8918","authenticated-orcid":false,"given":"Jingjing","family":"Liu","sequence":"first","affiliation":[{"name":"Biosensor National Special Laboratory, Key Laboratory for Biomedical Engineering of Education Ministry, Department of Biomedical Engineering, Zhejiang University, Hangzhou 310027, China"},{"name":"College of Automation Engineering, Northeast Electric Power University, Jilin 132012, China"},{"name":"Department of Computer Science and Bioimaging Research Center, University of Georgia, Athens, GA 30602, USA"}]},{"given":"Ning","family":"Xu","sequence":"additional","affiliation":[{"name":"College of Automation Engineering, Northeast Electric Power University, Jilin 132012, China"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0215-4399","authenticated-orcid":false,"given":"Hong","family":"Men","sequence":"additional","affiliation":[{"name":"College of Automation Engineering, Northeast Electric Power University, Jilin 132012, China"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3483-5087","authenticated-orcid":false,"given":"Shuang","family":"Li","sequence":"additional","affiliation":[{"name":"Biosensor National Special Laboratory, Key Laboratory for Biomedical Engineering of Education Ministry, Department of Biomedical Engineering, Zhejiang University, Hangzhou 310027, China"}]},{"given":"Yanli","family":"Lu","sequence":"additional","affiliation":[{"name":"Biosensor National Special Laboratory, Key Laboratory for Biomedical Engineering of Education Ministry, Department of Biomedical Engineering, Zhejiang University, Hangzhou 310027, China"}]},{"given":"Sze Shin","family":"Low","sequence":"additional","affiliation":[{"name":"Biosensor National Special Laboratory, Key Laboratory for Biomedical Engineering of Education Ministry, Department of Biomedical Engineering, Zhejiang University, Hangzhou 310027, China"}]},{"given":"Xin","family":"Li","sequence":"additional","affiliation":[{"name":"Biosensor National Special Laboratory, Key Laboratory for Biomedical Engineering of Education Ministry, Department of Biomedical Engineering, Zhejiang University, Hangzhou 310027, China"}]},{"given":"Lihang","family":"Zhu","sequence":"additional","affiliation":[{"name":"Biosensor National Special Laboratory, Key Laboratory for Biomedical Engineering of Education Ministry, Department of Biomedical Engineering, Zhejiang University, Hangzhou 310027, China"}]},{"given":"Chen","family":"Cheng","sequence":"additional","affiliation":[{"name":"Biosensor National Special Laboratory, Key Laboratory for Biomedical Engineering of Education Ministry, Department of Biomedical Engineering, Zhejiang University, Hangzhou 310027, China"}]},{"given":"Gang","family":"Xu","sequence":"additional","affiliation":[{"name":"Biosensor National Special Laboratory, Key Laboratory for Biomedical Engineering of Education Ministry, Department of Biomedical Engineering, Zhejiang University, Hangzhou 310027, China"}]},{"given":"Qingjun","family":"Liu","sequence":"additional","affiliation":[{"name":"Biosensor National Special Laboratory, Key Laboratory for Biomedical Engineering of Education Ministry, Department of Biomedical Engineering, Zhejiang University, Hangzhou 310027, China"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1161\/CIR.0000000000000157","article-title":"Executive summary: Heart disease and stroke statistics\u20142015 update: A report from the American Heart Association","volume":"131","author":"Mozaffarian","year":"2015","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/nri.2015.5","article-title":"The role of inflammation in depression: From evolutionary imperative to modern treatment target","volume":"16","author":"Miller","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.psyneuen.2015.05.007","article-title":"Hair cortisol concentrations and cortisol stress reactivity predict PTSD symptom increase after trauma exposure during military deployment","volume":"59","author":"Stalder","year":"2015","journal-title":"Psychoneuroendocrinology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.tins.2015.02.001","article-title":"Epigenetic mechanisms of chronic pain","volume":"38","author":"Descalzi","year":"2015","journal-title":"Trends Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/nrn1683","article-title":"Stress and the brain: From adaptation to disease","volume":"6","author":"Holsboer","year":"2005","journal-title":"Nat. Rev. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1037\/0033-2909.133.1.25","article-title":"If it goes up, must it come down? Chronic stress and the hypothalamic-pituitary-adrenocortical axis in humans","volume":"133","author":"Miller","year":"2007","journal-title":"Psychol Bull."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1161\/CIRCULATIONAHA.104.489088","article-title":"Cortisol, testosterone, and coronary heart disease: Prospective evidence from the Caerphilly study","volume":"112","author":"Smith","year":"2005","journal-title":"Circulation"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0006-3223(03)00473-6","article-title":"Association of depression with medical illness: Does cortisol play a role?","volume":"55","author":"Brown","year":"2004","journal-title":"Biol. Psychiatry"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1016\/S0006-3223(99)00203-6","article-title":"Decrease in cortisol reverses human hippocampal atrophy following treatment of Cushing\u2019s disease","volume":"46","author":"Starkman","year":"1999","journal-title":"Biol. Psychiatry"},{"key":"ref_10","first-page":"109","article-title":"Continuous subcutaneous hydrocortisone infusion in Addison\u2019s disease","volume":"157","author":"Husebye","year":"2007","journal-title":"J. Endocrinol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1093\/jnci\/92.12.994","article-title":"Diurnal cortisol rhythm as a predictor of breast cancer survival","volume":"92","author":"Sephton","year":"2000","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.physbeh.2012.06.005","article-title":"Daily profile in two circadian markers \u201cmelatonin and cortisol\u201d and associations with metabolic syndrome components","volume":"123","author":"Madrid","year":"2014","journal-title":"Physiol. Behav."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.bios.2018.07.074","article-title":"Smartphone-based integrated voltammetry system for simultaneous detection of ascorbic acid, dopamine, and uric acid with graphene and gold nanoparticles modified screen-printed electrodes","volume":"119","author":"Ji","year":"2018","journal-title":"Biosens. Bioelectron."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.bios.2018.09.082","article-title":"Smartphone-based differential pulse amperometry system for real-time monitoring of levodopa with carbon nanotubes and gold nanoparticles modified screen-printing electrodes","volume":"129","author":"Ji","year":"2019","journal-title":"Biosens. Bioelectron."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1016\/j.snb.2017.02.149","article-title":"Passive and wireless near field communication tag sensors for biochemical sensing with smartphone","volume":"246","author":"Xu","year":"2017","journal-title":"Sens. Actuators B Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.bios.2015.08.037","article-title":"Biosensors and bioelectronics on smartphone for portable biochemical detection","volume":"75","author":"Zhang","year":"2016","journal-title":"Biosens. Bioelectron."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.bios.2016.09.084","article-title":"Smartphone-based sensing system using ZnO and graphene modified electrodes for VOCs detection","volume":"93","author":"Liu","year":"2017","journal-title":"Biosens. Bioelectron."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"13312","DOI":"10.1038\/s41598-017-13684-7","article-title":"Portable biosensor for monitoring cortisol in low-volume perspired human sweat","volume":"7","author":"Kinnamon","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/j.bios.2013.09.060","article-title":"Recent advances in cortisol sensing technologies for point-of-care application","volume":"53","author":"Kaushik","year":"2014","journal-title":"Biosens. Bioelectron."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.bios.2016.11.067","article-title":"Microfluidic immunosensor for rapid and highly-sensitive salivary cortisol quantification","volume":"90","author":"Pinto","year":"2017","journal-title":"Biosens. Bioelectron."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.bios.2012.08.016","article-title":"Immunosensor with fluid control mechanism for salivary cortisol analysis","volume":"41","author":"Yamaguchi","year":"2013","journal-title":"Biosens. Bioelectron."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1080\/00032717208069558","article-title":"Radioimmunoassay of plasma cortisol","volume":"5","author":"Abraham","year":"1972","journal-title":"Anal. Lett."},{"key":"ref_23","first-page":"844","article-title":"Determination of cortisol and cortisone in human saliva by a liquid chromatography-tandem mass spectrometry method","volume":"58","author":"Vieira","year":"2014","journal-title":"Arch. Endocrinol. Metab."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1039\/C5TB02069G","article-title":"A molecularly imprinted nanocavity-based fluorescence polarization assay platform for cortisol sensing","volume":"4","author":"Murase","year":"2016","journal-title":"J. Mater. Chem. B"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.bios.2017.07.017","article-title":"Direct immune-detection of cortisol by chemiresistor graphene oxide sensor","volume":"98","author":"Kim","year":"2017","journal-title":"Biosens. Bioelectron."},{"key":"ref_26","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."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.bios.2011.07.015","article-title":"Polyaniline protected gold nanoparticles based mediator and label free electrochemical cortisol biosensor","volume":"28","author":"Arya","year":"2011","journal-title":"Biosens. Bioelectron."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4382","DOI":"10.1016\/j.bios.2011.04.045","article-title":"Label-free, chemiresistor immunosensor for stress biomarker cortisol in saliva","volume":"26","author":"Tlili","year":"2011","journal-title":"Biosens. Bioelectron."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2296","DOI":"10.1016\/j.bios.2010.03.016","article-title":"Dithiobis (succinimidyl propionate) modified gold microarray electrode based electrochemical immunosensor for ultrasensitive detection of cortisol","volume":"25","author":"Arya","year":"2010","journal-title":"Biosens. Bioelectron."},{"key":"ref_30","first-page":"41","article-title":"Noninvasive label-free detection of cortisol and lactate using graphene embedded screen-printed electrode","volume":"10","author":"Tuteja","year":"2018","journal-title":"Nanomicro Lett."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.bios.2015.11.044","article-title":"Aptamer-functionalized nanoparticles for surface immobilization-free electrochemical detection of cortisol in a microfluidic device","volume":"78","author":"Sanghavi","year":"2016","journal-title":"Biosens. Bioelectron."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"14586","DOI":"10.1038\/srep14586","article-title":"Flexible nanoporous tunable electrical double layer biosensors for sweat diagnostics","volume":"5","author":"Munje","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1021\/nn901660v","article-title":"Two-dimensional graphene bridges enhanced photoinduced charge transport in dye-sensitized solar cells","volume":"4","author":"Yang","year":"2010","journal-title":"ACS Nano"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1038\/nmat4170","article-title":"The role of graphene for electrochemical energy storage","volume":"14","author":"Raccichini","year":"2015","journal-title":"Nat. Mater."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"6225","DOI":"10.1021\/acs.chemrev.6b00558","article-title":"Recent advances in ultrathin two-dimensional nanomaterials","volume":"117","author":"Tan","year":"2017","journal-title":"Chem. Rev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4074","DOI":"10.1021\/nn405938z","article-title":"Few-layer MoS2: A promising layered semiconductor","volume":"8","author":"Ganatra","year":"2014","journal-title":"ACS Nano"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"136805","DOI":"10.1103\/PhysRevLett.105.136805","article-title":"Atomically thin MoS2: A new direct-gap semiconductor","volume":"105","author":"Mak","year":"2010","journal-title":"Phys. Rev. Lett."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.snb.2018.01.166","article-title":"Two-dimensional molybdenum disulfide (MoS2) with gold nanoparticles for biosensing of explosives by optical spectroscopy","volume":"261","author":"Wu","year":"2018","journal-title":"Sens. Actuators B Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3766","DOI":"10.1021\/cr300263a","article-title":"Graphene-like two-dimensional materials","volume":"113","author":"Xu","year":"2013","journal-title":"Chem. Rev."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Shavanova, K., Bakakina, Y., and Burkova, I. (2016). Application of 2D non-graphene materials and 2D oxide nanostructures for biosensing technology. Sensors, 16.","DOI":"10.3390\/s16020223"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4434","DOI":"10.1021\/nl402278y","article-title":"Controlled, defect-guided, metal-nanoparticle incorporation onto MoS2 via chemical and microwave routes: Electrical, thermal, and structural properties","volume":"13","author":"Sreeprasad","year":"2013","journal-title":"Nano Lett."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"6826","DOI":"10.1021\/acsami.5b12833","article-title":"Dual-target electrochemical biosensing based on DNA structural switching on gold nanoparticle-decorated MoS2 nanosheets","volume":"8","author":"Su","year":"2016","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1038\/nature16521","article-title":"Fully integrated wearable sensor arrays for multiplexed in situ perspiration analysis","volume":"529","author":"Gao","year":"2016","journal-title":"Nature"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1016\/j.bios.2014.09.098","article-title":"Olfactory biosensor for insect semiochemicals analysis by impedance sensing of odorant-binding proteins on interdigitated electrodes","volume":"67","author":"Lu","year":"2015","journal-title":"Biosens. Bioelectron."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1880","DOI":"10.1021\/la026327q","article-title":"Covalent coupling of antibodies to self-assembled monolayers of carboxy-functionalized poly (ethylene glycol): Protein resistance and specific binding of biomolecules","volume":"19","author":"Herrwerth","year":"2003","journal-title":"Langmuir"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"5578","DOI":"10.1021\/ma020071d","article-title":"Terminal attachment of polyethylene glycol (PEG) chains to a gold electrode surface. Cyclic voltammetry applied to the quantitative characterization of the flexibility of the attached PEG chains and of their penetration by mobile PEG chains","volume":"35","author":"Anne","year":"2002","journal-title":"Macromolecules"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.snb.2018.03.154","article-title":"Ultrasensitive enzyme-free electrochemical immunosensor for microcystin-LR using molybdenum disulfide\/gold nanoclusters nanocomposites as platform and Au@Pt core-shell nanoparticles as signal enhancer","volume":"266","author":"Pang","year":"2018","journal-title":"Sens. Actuators B Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.bios.2013.06.012","article-title":"Mediator and label free estimation of stress biomarker using electrophoretically deposited Ag@AgO\u2013polyaniline hybrid nanocomposite","volume":"50","author":"Kaushik","year":"2013","journal-title":"Biosens. Bioelectron."}],"container-title":["Sensors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8220\/20\/5\/1422\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:04:22Z","timestamp":1760173462000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8220\/20\/5\/1422"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,5]]},"references-count":48,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2020,3]]}},"alternative-id":["s20051422"],"URL":"https:\/\/doi.org\/10.3390\/s20051422","relation":{},"ISSN":["1424-8220"],"issn-type":[{"value":"1424-8220","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,5]]}}}