{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T19:28:30Z","timestamp":1791314910353,"version":"4.3.1"},"reference-count":42,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,2,7]],"date-time":"2022-02-07T00:00:00Z","timestamp":1644192000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004731","name":"Zhejiang Provincial Natural Science Foundation","doi-asserted-by":"publisher","award":["LQ20F010011, LY18H180006"],"award-info":[{"award-number":["LQ20F010011, LY18H180006"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["61501400, 81501555"],"award-info":[{"award-number":["61501400, 81501555"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biosensors"],"abstract":"<jats:p>Levodopa (L-Dopa) is considered to be one of the most effective therapies available for Parkinson\u2019s disease (PD) treatment. The therapeutic window of L-Dopa is narrow due to its short half-life, and long-time L-Dopa treatment will cause some side effects such as dyskinesias, psychosis, and orthostatic hypotension. Therefore, it is of great significance to monitor the dynamic concentration of L-Dopa for PD patients with wearable biosensors to reduce the risk of complications. However, the high concentration of interferents in the body brings great challenges to the in vivo monitoring of L-Dopa. To address this issue, we proposed a minimal-invasive L-Dopa biosensor based on a flexible differential microneedle array (FDMA). One working electrode responded to L-Dopa and interfering substances, while the other working electrode only responded to electroactive interferences. The differential current response of these two electrodes was related to the concentration of L-Dopa by eliminating the common mode interference. The differential structure provided the sensor with excellent anti-interference performance and improved the sensor\u2019s accuracy. This novel flexible microneedle sensor exhibited favorable analytical performance of a wide linear dynamic range (0\u201320 \u03bcM), high sensitivity (12.618 nA \u03bcM\u22121 cm\u22122) as well as long-term stability (two weeks). Ultimately, the L-Dopa sensor displayed a fast response to in vivo L-Dopa dynamically with considerable anti-interference ability. All these attractive performances indicated the feasibility of this FDMA for minimal invasive and continuous monitoring of L-Dopa dynamic concentration for Parkinson\u2019s disease.<\/jats:p>","DOI":"10.3390\/bios12020102","type":"journal-article","created":{"date-parts":[[2022,2,7]],"date-time":"2022-02-07T20:36:42Z","timestamp":1644266202000},"page":"102","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Differential Amperometric Microneedle Biosensor for Wearable Levodopa Monitoring of Parkinson\u2019s Disease"],"prefix":"10.3390","volume":"12","author":[{"given":"Lu","family":"Fang","sequence":"first","affiliation":[{"name":"Department of Automation, Hangzhou Dianzi University, Hangzhou 310018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hangxu","family":"Ren","sequence":"additional","affiliation":[{"name":"Biosensor National Special Laboratory, Key Laboratory of Biomedical Engineering of Ministry of Education, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiyu","family":"Mao","sequence":"additional","affiliation":[{"name":"Biosensor National Special Laboratory, Key Laboratory of Biomedical Engineering of Ministry of Education, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Biosensor National Special Laboratory, Key Laboratory of Biomedical Engineering of Ministry of Education, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Cai","sequence":"additional","affiliation":[{"name":"Biosensor National Special Laboratory, Key Laboratory of Biomedical Engineering of Ministry of Education, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyi","family":"Xu","sequence":"additional","affiliation":[{"name":"Biosensor National Special Laboratory, Key Laboratory of Biomedical Engineering of Ministry of Education, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Automation, Hangzhou Dianzi University, Hangzhou 310018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihua","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Automation, Hangzhou Dianzi University, Hangzhou 310018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuesong","family":"Ye","sequence":"additional","affiliation":[{"name":"Biosensor National Special Laboratory, Key Laboratory of Biomedical Engineering of Ministry of Education, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3670-2296","authenticated-orcid":false,"given":"Bo","family":"Liang","sequence":"additional","affiliation":[{"name":"Biosensor National Special Laboratory, Key Laboratory of Biomedical Engineering of Ministry of Education, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1002\/mds.25945","article-title":"The prevalence of Parkinson\u2019s disease: A systematic review and meta-analysis","volume":"29","author":"Pringsheim","year":"2014","journal-title":"Mov. Disord."},{"key":"ref_2","first-page":"353","article-title":"MDS Research Criteria for Prodromal Pakrinson\u2019s Disease (P5. 353)","volume":"86","author":"Postuma","year":"2016","journal-title":"Neurology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1016\/S1474-4422(18)30295-3","article-title":"Global, regional, and national burden of Parkinson\u2019s disease, 1990\u20132016: A systematic analysis for the Global Burden of Disease Study 2016","volume":"17","author":"Dorsey","year":"2018","journal-title":"Lancet Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1038\/nrn983","article-title":"Pathogenesis of Parkinson\u2019s disease: Dopamine, vesicles and \u03b1-synuclein","volume":"3","author":"Lotharius","year":"2002","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.expneurol.2005.04.008","article-title":"An active transport system in the blood\u2013brain barrier may reduce levodopa availability","volume":"195","author":"Hawkins","year":"2005","journal-title":"Exp. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2468","DOI":"10.1056\/NEJMct0800326","article-title":"Levodopa for the treatment of Parkinson\u2019s disease","volume":"359","author":"LeWitt","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1111\/j.1468-1331.2009.02697.x","article-title":"Levodopa in the treatment of Parkinson\u2019s disease","volume":"16","author":"Schapira","year":"2009","journal-title":"Eur. J. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1002\/mds.20243","article-title":"Levodopa in the treatment of Parkinson\u2019s disease: Current controversies","volume":"19","author":"Olanow","year":"2004","journal-title":"Mov. Disord."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1002\/mds.26424","article-title":"MDS clinical diagnostic criteria for Parkinson\u2019s disease","volume":"30","author":"Postuma","year":"2015","journal-title":"Mov. Disord."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"677","DOI":"10.2165\/00023210-200721080-00005","article-title":"Medical Management of Levodopa-Associated Motor Complications in Patients with Parkinson\u2019s Disease","volume":"21","author":"Jankovic","year":"2007","journal-title":"CNS Drugs"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.1001\/jama.2014.3654","article-title":"Pharmacological treatment of Parkinson disease: A review","volume":"311","author":"Connolly","year":"2014","journal-title":"JAMA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.aca.2007.09.006","article-title":"Simultaneous kinetic-spectrophotometric determination of carbidopa, levodopa and methyldopa in the presence of citrate with the aid of multivariate calibration and artificial neural networks","volume":"603","author":"Chamsaz","year":"2007","journal-title":"Anal. Chim. Acta"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/S0003-2670(00)01327-1","article-title":"Separation and determination of levodopa and carbidopa in composite tablets by ca-pillary zone electrophoresis with amperometric detection","volume":"431","author":"Zhang","year":"2001","journal-title":"Anal. Chim. Acta"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1016\/j.talanta.2009.01.001","article-title":"Simultaneous spectrofluorimetric determination of levodopa and pro-pranolol in urine using feed-forward neural networks assisted by principal component analysis","volume":"78","author":"Madrakian","year":"2009","journal-title":"Talanta"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1097\/00002826-200203000-00006","article-title":"Levodopa pharmacokinetics and motor performance during activities of daily living in patients with Parkinson\u2019s disease on individual drug combinations","volume":"25","author":"Nyholm","year":"2002","journal-title":"Clin. Neuropharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1016\/j.snb.2011.02.006","article-title":"Amperometric determination of l-dopa by nickel hexacyanoferrate film modified gold nanoparticle graphite composite electrode","volume":"156","author":"Prabhu","year":"2011","journal-title":"Sens. Actuators B Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.tibtech.2014.04.005","article-title":"Non-invasive wearable electrochemical sensors: A review","volume":"32","author":"Bandodkar","year":"2014","journal-title":"Trends Biotechnol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1021\/acs.analchem.6b04308","article-title":"In Vivo Analysis with Electrochemical Sensors and Biosensors","volume":"89","author":"Xiao","year":"2016","journal-title":"Anal. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"113760","DOI":"10.1016\/j.bios.2021.113760","article-title":"Fully integrated flexible biosensor for wearable continuous glucose monitoring","volume":"196","author":"Jin","year":"2021","journal-title":"Biosens. Bioelectron."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/s41551-019-0462-8","article-title":"Functionalized helical fibre bundles of carbon nanotubes as electrochemical sensors for long-term in vivo monitoring of multiple disease biomarkers","volume":"4","author":"Wang","year":"2019","journal-title":"Nat. Biomed. Eng."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"7671","DOI":"10.1039\/D0CS00304B","article-title":"Electrochemical glucose sensors in diabetes management: An updated review (2010\u20132020)","volume":"49","author":"Teymourian","year":"2020","journal-title":"Chem. Soc. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3895","DOI":"10.1021\/ac4042087","article-title":"Continuous and Simultaneous Electrochemical Measurements of Glucose, Lactate, and Ascorbate in Rat Brain Following Brain Ischemia","volume":"86","author":"Lin","year":"2014","journal-title":"Anal. Chem."},{"key":"ref_23","first-page":"35","article-title":"Biosensors based on electrochemical lactate detection: A comprehensive review","volume":"5","author":"Rathee","year":"2015","journal-title":"Biochem. Biophys. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1016\/j.electacta.2017.05.183","article-title":"Electrochemical Analysis of Dopamine: Perspectives of Specific In Vivo Detection","volume":"245","author":"Ferapontova","year":"2017","journal-title":"Electrochim. Acta"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1021\/acssensors.0c00563","article-title":"Integrated Smart Janus Textile Bands for Self-Pumping Sweat Sampling and Analysis","volume":"5","author":"He","year":"2020","journal-title":"ACS Sens."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"8880","DOI":"10.1021\/acs.nanolett.1c03426","article-title":"Biospired Janus Silk E-Textiles with Wet\u2013Thermal Comfort for Highly Efficient Biofluid Monitoring","volume":"21","author":"He","year":"2021","journal-title":"Nano Lett."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Erdem, \u00d6., E\u015f, I., Akceoglu, G.A., Saylan, Y., and Inci, F. (2021). Recent Advances in Microneedle-Based Sensors for Sampling, Diagnosis and Monitoring of Chronic Diseases. Biosensors, 11.","DOI":"10.3390\/bios11090296"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jpha.2020.08.001","article-title":"Towards wearable and implantable continuous drug monitoring: A review","volume":"11","author":"Bian","year":"2020","journal-title":"J. Pharm. Anal."},{"key":"ref_29","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":"2018","journal-title":"Biosens. Bioelectron."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2196","DOI":"10.1021\/acssensors.9b01127","article-title":"Wearable Electrochemical Microneedle Sensor for Continuous Monitoring of Levodopa: Toward Parkinson Management","volume":"4","author":"Goud","year":"2019","journal-title":"ACS Sens."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"6346","DOI":"10.1021\/acs.nanolett.9b02478","article-title":"Wearable Sweat Band for Noninvasive Levodopa Monitoring","volume":"19","author":"Tai","year":"2019","journal-title":"Nano Lett."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Oung, Q.W., Hariharan, M., Lee, H.L., Basah, S.N., Sarillee, M., and Lee, C.H. (2015, January 27\u201329). Wearable multimodal sensors for evaluation of patients with Parkinson disease. Proceedings of the 2015 IEEE International Conference on Control System, Computing and Engineering (ICCSCE), Penang, Malaysia.","DOI":"10.1109\/ICCSCE.2015.7482196"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.ensci.2018.09.003","article-title":"Pharmacokinetics and safety\/efficacy of levodopa pro-drug ONO-2160\/carbidopa for Parkinson\u2019s disease","volume":"13","author":"Nomoto","year":"2018","journal-title":"Eneurologicalsci"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1097\/01.wnf.0000144041.28224.b7","article-title":"Levodopa infusion therapy in Parkinson disease: State of the art in 2004","volume":"27","author":"Nyholm","year":"2004","journal-title":"Clin. Neuropharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2566","DOI":"10.1021\/ac00197a022","article-title":"Pulsed amperometric detection of glucose in biological fluids at a surface-modified gold electrode","volume":"61","author":"Bindra","year":"1989","journal-title":"Anal. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2481","DOI":"10.1007\/s00216-010-4158-x","article-title":"Molecularly imprinted polymers: Synthetic receptors in bioanalysis","volume":"398","author":"Bui","year":"2010","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/S1367-5931(02)00371-X","article-title":"Implantable chemical sensors for real-time clinical monitoring: Progress and challenges","volume":"6","author":"Frost","year":"2002","journal-title":"Curr. Opin. Chem. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1021\/ac00079a038","article-title":"Elimination of the Acetaminophen Interference in an Implantable Glucose Sensor","volume":"66","author":"Zhang","year":"1994","journal-title":"Anal. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1021\/nl0347233","article-title":"Glucose Biosensors Based on Carbon Nanotube Nanoelectrode Ensembles","volume":"4","author":"Lin","year":"2003","journal-title":"Nano Lett."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1900041","DOI":"10.1002\/gch2.201900041","article-title":"Nanomaterial-Modified Conducting Paper: Fabrication, Properties, and Emerging Biomedical Applications","volume":"3","author":"Kumar","year":"2019","journal-title":"Glob. Chall."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.bios.2017.04.043","article-title":"A needle-type glucose biosensor based on PANI nanofibers and PU\/E-PU membrane for long-term invasive continuous monitoring","volume":"97","author":"Fang","year":"2017","journal-title":"Biosens. Bioelectron."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1056\/NEJMoa033447","article-title":"Levodopa and the progression of Parkinson\u2019s disease","volume":"351","author":"Group","year":"2004","journal-title":"N. Engl. J. Med."}],"container-title":["Biosensors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6374\/12\/2\/102\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:15:40Z","timestamp":1760134540000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6374\/12\/2\/102"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,7]]},"references-count":42,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["bios12020102"],"URL":"https:\/\/doi.org\/10.3390\/bios12020102","relation":{},"ISSN":["2079-6374"],"issn-type":[{"value":"2079-6374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,7]]}}}