{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,14]],"date-time":"2026-11-14T14:48:06Z","timestamp":1794667686433,"version":"4.9.1"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,6,30]],"date-time":"2020-06-30T00:00:00Z","timestamp":1593475200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,6,30]],"date-time":"2020-06-30T00:00:00Z","timestamp":1593475200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A uric acid (UA) electrochemical biosensor was constructed using ferrocene (Fc) decorated cuprous oxide (Cu<jats:sub>2<\/jats:sub>O) enhanced electro-active characteristics and covalently immobilized with uricase (UOx) on glassy carbon electrode (GCE). The electrochemical characteristics of the fabricated electrode was analysed by cyclic voltammetry, electrochemical impedance spectroscopy and differential pulse voltammetry (DPV). DPV studies revealed rapid response of fabricated electrode UOx\/Fc\/Cu<jats:sub>2<\/jats:sub>O\/GCE towards UA in a wide concentration range of 0.1\u20131,000\u00a0\u03bcM with a sensitivity of 1.900\u00a0\u03bcA\u00a0mM<jats:sup>\u22121<\/jats:sup>\u00a0cm<jats:sup>\u22122<\/jats:sup>and very low detection limit of 0.0596\u00a0\u03bcM. A very low magnitude Michaelis\u2013Menten constant (Km) value was evaluated as 34.7351\u00a0\u03bcM which indicated the chemical attraction of the enzyme towards the UA was much higher. The developed biosensor was successfully applied to detect UA in human urine samples. Moreover, reproducibility and stability studies demonstrated the fabricated UOx\/Fc\/Cu<jats:sub>2<\/jats:sub>O\/GCE biosensor had high reproducibility with a RSD of 2.8% and good reusability with a RSD of 3.2%. Specificity studies results showed the fabricated biosensor had\u00a0strong anti-interference ability. The improved sensor performance was attributed to the synergistic electronic properties of Cu<jats:sub>2<\/jats:sub>O and Fc that provided enhances delectrocatalytic activity and electron transfer. The present biosensor can be extended for use in clinical settings.<\/jats:p>","DOI":"10.1038\/s41598-020-67394-8","type":"journal-article","created":{"date-parts":[[2020,6,30]],"date-time":"2020-06-30T10:03:57Z","timestamp":1593511437000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":147,"title":["A highly sensitive uric acid electrochemical biosensor based on a nano-cube cuprous oxide\/ferrocene\/uricase modified glassy carbon electrode"],"prefix":"10.1038","volume":"10","author":[{"given":"Qinghua","family":"Yan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Zhi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangri","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qigao","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiqing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shujuan","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,6,30]]},"reference":[{"key":"67394_CR1","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.bios.2011.09.026","volume":"30","author":"K Arora","year":"2011","unstructured":"Arora, K., Tomar, M. & Gupta, V. Highly sensitive and selective uric acid biosensor based on RF sputtered NiO thin film. Biosens. Bioelectron. 30, 333\u2013336 (2011).","journal-title":"Biosens. Bioelectron."},{"key":"67394_CR2","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.bios.2018.12.008","volume":"127","author":"S Jain","year":"2019","unstructured":"Jain, S., Verma, S., Singh, S. P. & Sharma, S. N. An electrochemical biosensor based on novel butylamine capped CZTS nanoparticles immobilized by uricase for uric acid detection. Biosens. Bioelectron. 127, 135\u2013141 (2019).","journal-title":"Biosens. Bioelectron."},{"key":"67394_CR3","unstructured":"Nery, E. W. Analysis of Glucose, Cholesterol and uric acid. In Analysis of samples of clinical and alimentary interest with paper-based devices. Springer theses (recognizing outstanding Ph.D. research) (Springer, Cham, 2016)."},{"key":"67394_CR4","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1038\/nrrheum.2012.143","volume":"9","author":"KL Rock","year":"2013","unstructured":"Rock, K. L., Kataoka, H. & Lai, J. J. Uric acid as a danger signal in gout and its comorbidities. Nat. Rev. Rheumatol. 9, 13\u201323 (2013).","journal-title":"Nat. Rev. Rheumatol."},{"key":"67394_CR5","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1023\/A:1005348504512","volume":"20","author":"WL Nyhan","year":"1997","unstructured":"Nyhan, W. L. The recognition of Lesch\u2013Nyhan syndrome as an inborn error of purine metabolism. J. Inherit. Metab. Dis. 20, 171\u2013178 (1997).","journal-title":"J. Inherit. Metab. Dis."},{"key":"67394_CR6","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1002\/oa.1009","volume":"20","author":"D Swinson","year":"2010","unstructured":"Swinson, D., Snaith, J., Buckberryc, J. & Brickley, M. High performance liquid chromatography (HPLC) in the investigation of gout in palaeopathology. Int. J. Osteoarchaeol. 20, 135\u2013143 (2010).","journal-title":"Int. J. Osteoarchaeol."},{"key":"67394_CR7","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.microc.2009.08.010","volume":"94","author":"DL Rocha","year":"2010","unstructured":"Rocha, D. L. & Rocha, F. R. P. A flow-based procedure with solenoid micro-pumps for the spectrophotometric determination of uric acid in urine. Microchem. J. 94, 53\u201359 (2010).","journal-title":"Microchem. J."},{"key":"67394_CR8","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1016\/j.bios.2015.09.057","volume":"77","author":"D Jin","year":"2016","unstructured":"Jin, D. et al. Quantitative determination of uric acid using CdTe nanoparticles as fluorescence probes. Biosens. Bioelectron. 77, 359\u2013365 (2016).","journal-title":"Biosens. Bioelectron."},{"key":"67394_CR9","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.jchromb.2015.11.015","volume":"1026","author":"Y Zhang","year":"2016","unstructured":"Zhang, Y. et al. Separation and characterization of bufadienolides in toad skin using two-dimensional normal-phase liquid chromatography \u00d7 reversed-phase liquid chromatography coupled with mass spectrometry. J. Chromatogr. B 1026, 67\u201374 (2016).","journal-title":"J. Chromatogr. B"},{"key":"67394_CR10","doi-asserted-by":"publisher","first-page":"3053","DOI":"10.1007\/s00604-016-1953-x","volume":"183","author":"H Dai","year":"2016","unstructured":"Dai, H. et al. Voltammetric uric acid sensor based on a glassy carbon electrode modified with a nanocomposite consisting of polytetraphenylporphyrin, polypyrrole, and graphene oxide. Microchim. Acta. 183, 3053\u20133059 (2016).","journal-title":"Microchim. Acta."},{"key":"67394_CR11","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/j.jallcom.2016.01.092","volume":"666","author":"C Hou","year":"2016","unstructured":"Hou, C., Liu, H., Zhang, D. & Zhang, M. Synthesis of ZnO nanorods-Au nanoparticles hybrids via in-situ plasma sputtering-assisted method for simultaneous electrochemical sensing of ascorbic acid and uric acid. J. Alloys Compd. 666, 178\u2013184 (2016).","journal-title":"J. Alloys Compd."},{"key":"67394_CR12","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1016\/j.matchemphys.2015.09.044","volume":"166","author":"J Zhao","year":"2015","unstructured":"Zhao, J., Mu, F., Qin, L., Jia, X. & Yang, C. Synthesis and characterization of MgO\/ZnO composite nanosheets for biosensor. Mater. Chem. Phys. 166, 176\u2013181 (2015).","journal-title":"Mater. Chem. Phys."},{"key":"67394_CR13","doi-asserted-by":"publisher","first-page":"780","DOI":"10.3390\/s16060780","volume":"16","author":"R Gaia","year":"2016","unstructured":"Gaia, R. et al. Enzyme biosensors for biomedical applications: strategies for safeguarding analytical performances in biological fluids. Sensors 16, 780\u2013801 (2016).","journal-title":"Sensors"},{"key":"67394_CR14","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/0003-2670(96)00093-1","volume":"327","author":"AR Vijayakumar","year":"1996","unstructured":"Vijayakumar, A. R., Csoregi, E., Heller, A. & Gorton, L. Alcohol biosensors based on coupled oxidase-peroxidase systems. Anal. Chim. Acta. 327, 223\u2013234 (1996).","journal-title":"Anal. Chim. Acta."},{"key":"67394_CR15","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/0956-5663(92)87018-K","volume":"7","author":"S Dong","year":"1992","unstructured":"Dong, S., Wang, B. & Liu, B. Amperometric glucose sensor with ferrocene as an electron transfer mediator. Biosens. Bioelectron. 7, 215\u2013222 (1992).","journal-title":"Biosens. Bioelectron."},{"key":"67394_CR16","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1016\/j.talanta.2013.01.043","volume":"107C","author":"PE Erden","year":"2013","unstructured":"Erden, P. E. & K\u0131l\u0131\u00e7, E. A review of enzymatic uric acid biosensors based on a mperometric detection. Talanta 107C, 312\u2013323 (2013).","journal-title":"Talanta"},{"key":"67394_CR17","doi-asserted-by":"publisher","first-page":"1240","DOI":"10.1016\/S1872-2040(14)60764-7","volume":"42","author":"Y Hu","year":"2014","unstructured":"Hu, Y., Du, W. & Chen, C. Fabrication of flower-shaped Pt-Au-graphene nanostructure and its application in electrochemical detection of glucose. Chin. J. Anal. Chem. 42, 1240\u20131244 (2014).","journal-title":"Chin. J. Anal. Chem."},{"key":"67394_CR18","doi-asserted-by":"publisher","first-page":"7239","DOI":"10.1021\/nn502259g","volume":"8","author":"BT Sneed","year":"2014","unstructured":"Sneed, B. T. et al. Shaped Pd-Ni-Pt Core-sandwich-shell nanoparticles: influence of Ni sandwich layers on catalytic electrooxidations. ACS Nano 8, 7239\u20137250 (2014).","journal-title":"ACS Nano"},{"key":"67394_CR19","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1016\/j.electacta.2014.11.171","volume":"152","author":"K Wang","year":"2015","unstructured":"Wang, K., Dong, X., Zhao, C., Qian, X. & Xu, Y. Facile synthesis of Cu2O\/CuO\/RGO nanocomposite and its superior cyclability in supercapacitor. Electrochim. Acta. 152, 433\u2013442 (2015).","journal-title":"Electrochim. Acta."},{"key":"67394_CR20","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1016\/j.snb.2014.06.128","volume":"203","author":"R Khan","year":"2014","unstructured":"Khan, R. et al. Glucose-assisted synthesis of Cu2O shuriken-like nanostructures and their application as nonenzymatic glucose biosensors. Sens. Actuat. B Chem. 203, 471\u2013476 (2014).","journal-title":"Sens. Actuat. B Chem."},{"key":"67394_CR21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.bioelechem.2014.11.001","volume":"102","author":"T Ghosh","year":"2015","unstructured":"Ghosh, T., Sarkar, P. & Turner, A. P. F. A novel third generation uric acid biosensor using uricase electro-activated with ferrocene on a Nafion coated glassy carbon electrode. Bioelectrochemistry 102, 1\u20139 (2015).","journal-title":"Bioelectrochemistry"},{"key":"67394_CR22","doi-asserted-by":"publisher","first-page":"5289","DOI":"10.1016\/0040-4039(96)01094-5","volume":"37","author":"RS Herrick","year":"1996","unstructured":"Herrick, R. S. et al. Ordered conformations in bis(amino acid) derivatives of 1,1\u2032-ferrocenedicarboxylic acid. Tetrahedron Lett. 37, 5289\u20135292 (1996).","journal-title":"Tetrahedron Lett."},{"key":"67394_CR23","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.jelechem.2018.12.053","volume":"834","author":"M Zhao","year":"2019","unstructured":"Zhao, M., Zhao, J., Qin, L., Jia, H. & Liu, S. Synthesis of Ta\/Ni microcavity array film for highly sensitive uric acid detection. J. Electroanal. Chem. 834, 86\u201393 (2019).","journal-title":"J. Electroanal. Chem."},{"key":"67394_CR24","doi-asserted-by":"publisher","first-page":"1271","DOI":"10.1016\/j.msec.2011.04.002","volume":"31","author":"M Chen","year":"2011","unstructured":"Chen, M., Wei, X., Qian, H. & Diao, G. Fabrication of GNPs\/CDSH-Fc\/nafion modified electrode for the detection of dopamine in the presence of ascorbic acid. Mater. Sci. Eng. C Mater. 31, 1271\u20131277 (2011).","journal-title":"Mater. Sci. Eng. C Mater."},{"key":"67394_CR25","doi-asserted-by":"publisher","first-page":"1771","DOI":"10.1002\/smll.201303005","volume":"10","author":"SR Ye","year":"2014","unstructured":"Ye, S. R., Rathmell, A. R., Wilson, A. R. & Wiley, B. J. Copper nanowires: the role of cuprous oxide seeds in the one-pot and seeded syntheses of copper nanowires. Small 10, 1771\u20131778 (2014).","journal-title":"Small"},{"key":"67394_CR26","doi-asserted-by":"publisher","first-page":"17301","DOI":"10.1021\/acsomega.9b02031","volume":"4","author":"GR Surikanti","year":"2019","unstructured":"Surikanti, G. R., Bajaj, P. & Sunkara, M. V. g-C3N4-mediated synthesis of Cu2O To obtain porous composites with improved visible light photocatalytic degradation of organic dyes. ACS Omega 4, 17301\u201317316 (2019).","journal-title":"ACS Omega"},{"key":"67394_CR27","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1016\/j.jcis.2019.11.031","volume":"561","author":"FX Li","year":"2020","unstructured":"Li, F. X. et al. Promoting the spatial charge separation by building porous ZrO2@TiO2 heterostructure toward photocatalytic hydrogen evolution. J. Colloid Interface Sci. 561, 568\u2013575 (2020).","journal-title":"J. Colloid Interface Sci."},{"key":"67394_CR28","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/j.jcis.2020.02.110","volume":"570","author":"Y Fu","year":"2020","unstructured":"Fu, Y. et al. In-situ chemical vapor deposition to fabricate cuprous oxide\/copper sulfide core\u2013shell flowers with boosted and stable wide-spectral region photocatalytic performance. J. Colloid Interf. Sci. 570, 143\u2013152 (2020).","journal-title":"J. Colloid Interf. Sci."},{"key":"67394_CR29","doi-asserted-by":"publisher","first-page":"8631","DOI":"10.1021\/acsami.5b00822","volume":"7","author":"JC Wang","year":"2015","unstructured":"Wang, J. C. et al. Enhanced photoreduction CO2 activity over direct Z-scheme alpha-Fe2O3\/Cu2O heterostructures under visible light irradiation. ACS Appl. Mater. Interface 7, 8631\u20138639 (2015).","journal-title":"ACS Appl. Mater. Interface"},{"key":"67394_CR30","doi-asserted-by":"publisher","first-page":"4774","DOI":"10.1021\/nl202587b","volume":"11","author":"J Zhang","year":"2011","unstructured":"Zhang, J., Yu, J. G., Zhang, Y. M., Li, Q. & Gong, J. R. Visible light photocatalytic H2-production activity of CuS\/ZnS porous nanosheets based on photoinduced interfacial charge transfer. Nano. Lett. 11, 4774\u20134779 (2011).","journal-title":"Nano. Lett."},{"key":"67394_CR31","volume-title":"Electrochemical Methods Fundamentals and Applications","author":"JB Allen","year":"2001","unstructured":"Allen, J. B. & Larry, R. F. Electrochemical Methods Fundamentals and Applications (Wiley, New York, 2001)."},{"key":"67394_CR32","doi-asserted-by":"publisher","first-page":"4353","DOI":"10.1039\/c3an36695b","volume":"138","author":"K Jindal","year":"2013","unstructured":"Jindal, K., Tomar, M. & Gupta, V. Nitrogen-doped zinc oxide thin films biosensor for determination of uric acid. Analyst 138, 4353\u20134362 (2013).","journal-title":"Analyst"},{"key":"67394_CR33","doi-asserted-by":"publisher","first-page":"27462","DOI":"10.1021\/acsami.7b06839","volume":"9","author":"S Verma","year":"2017","unstructured":"Verma, S. et al. Anti-IL8\/AuNPs-rGO\/ITO as an immunosensing platform for noninvasive electrochemical detection of oral cancer. ACS Appl. Mater. Interfaces 9, 27462\u201327474 (2017).","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"67394_CR34","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1016\/j.ijbiomac.2019.02.121","volume":"130","author":"S Verma","year":"2019","unstructured":"Verma, S., Choudhary, J., Singh, K. P., Chandra, P. & Singh, S. P. Uricase grafted nanoconducting matrix based electrochemical biosensor for ultrafast uric acid detection in human serum samples. Int. J. Biol. Macromol. 130, 333\u2013341 (2019).","journal-title":"Int. J. Biol. Macromol."},{"key":"67394_CR35","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.ab.2011.02.007","volume":"413","author":"N Chauhan","year":"2011","unstructured":"Chauhan, N. & Pundir, C. S. An amperometric uric acid biosensor based on multiwalled carbon nanotube-gold nanoparticle composite. Anal. Biochem. 413, 97\u2013103 (2011).","journal-title":"Anal. Biochem."},{"key":"67394_CR36","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.bios.2012.03.043","volume":"38","author":"K Jindal","year":"2012","unstructured":"Jindal, K., Tomar, M. & Gupta, V. CuO thin film based uric acid biosensor with enhanced response characteristics. Biosens. Bioelectron. 38, 11\u201318 (2012).","journal-title":"Biosens. Bioelectron."},{"key":"67394_CR37","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1007\/s00604-013-0981-z","volume":"180","author":"Y Zhao","year":"2013","unstructured":"Zhao, Y., Yan, X., Kang, Z., Lin, P. & Fang, X. Highly sensitive uric acid biosensor based on individual zinc oxide micro\/nanowires. Microchim. Acta. 180, 759\u2013766 (2013).","journal-title":"Microchim. Acta."},{"key":"67394_CR38","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1016\/j.snb.2012.10.090","volume":"179","author":"S Piermarini","year":"2013","unstructured":"Piermarini, S., Migliorelli, D., Volpe, G., Massoud, R. & Palleschi, G. Uricase biosensor based on a screen-printed electrode modified with Prussian blue for detection of uric acid in human blood serum. Sens. Actuat. B Chem. 179, 170\u2013174 (2013).","journal-title":"Sens. Actuat. B Chem."},{"key":"67394_CR39","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1002\/elan.201500539","volume":"28","author":"C Cheng","year":"2016","unstructured":"Cheng, C. & Kao, C. An electrochemical biosensor with uricase immobilized on functionalized gold coated copper wire electrode for urinary uric acid assay. Electroanal. 28, 695\u2013703 (2016).","journal-title":"Electroanal."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-67394-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-67394-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-67394-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T05:49:40Z","timestamp":1696312180000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-67394-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,30]]},"references-count":39,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["67394"],"URL":"https:\/\/doi.org\/10.1038\/s41598-020-67394-8","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,30]]},"assertion":[{"value":"20 February 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 June 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 June 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors decalre no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"10607"}}