{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T17:42:29Z","timestamp":1772905349388,"version":"3.50.1"},"reference-count":26,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,10,27]],"date-time":"2023-10-27T00:00:00Z","timestamp":1698364800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto de Innovaci\u00f3n, Ciencia y Emprendimiento para la Competitividad para el Estado de Guanajuato (IDEA GTO)","award":["SOL-392"],"award-info":[{"award-number":["SOL-392"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Micromachines"],"abstract":"<jats:p>The electric stimulation (ES) of the cornea is a novel therapeutic approach to the treatment of degenerative visual diseases. Currently, ES is delivered by placing a mono-element electrode on the surface of the cornea that uniformly stimulates the eye along the electrode site. It has been reported that a certain degree of correlation exists between the location of the stimulated retinal area and the position of the electrode. Therefore, in this study, we present the development of a sectioned surface electrode for selective electric stimulation of the human cornea. The proposed device consists of 16 independent microelectrodes, a reference electrode, and 18 contact pads. The microelectrodes have a size of 200 \u00b5m \u00d7 200 \u00b5m, are arranged in a 4 \u00d7 4 matrix, and cover a total stimulation area of 16 mm2. The proposed fabrication process, based on surface micromachining technology and flexible electronics, uses only three materials: polyimide, aluminum, and titanium, which allow us to obtain a simplified, ergonomic, and reproducible fabrication process. The fabricated prototype was validated to laboratory level by electrical and electrochemical tests, showing a relatively high electrical conductivity and average impedance from 712 k\u2126 to 1.4 M\u2126 at the clinically relevant frequency range (from 11 Hz to 30 Hz). Additionally, the biocompatibility of the electrode prototype was demonstrated by performing in vivo tests and by analyzing the polyimide films using Fourier transform infrared spectroscopy (FTIR). The resulting electrode prototype is robust, mechanically flexible, and biocompatible, with a high potential to be used for selective ES of the cornea.<\/jats:p>","DOI":"10.3390\/mi14111999","type":"journal-article","created":{"date-parts":[[2023,10,27]],"date-time":"2023-10-27T11:57:56Z","timestamp":1698407876000},"page":"1999","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Fabrication and Characterization of a Flexible Thin-Film-Based Array of Microelectrodes for Corneal Electrical Stimulation"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3800-9003","authenticated-orcid":false,"given":"Natiely","family":"Hern\u00e1ndez-Sebasti\u00e1n","sequence":"first","affiliation":[{"name":"Centro de Investigaciones en \u00d3ptica, A.C. Loma del Bosque 115, Le\u00f3n 37150, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V\u00edctor Manuel","family":"Carpio-Verd\u00edn","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones en \u00d3ptica, A.C. Loma del Bosque 115, Le\u00f3n 37150, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabi\u00e1n","family":"Ambriz-Vargas","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones en \u00d3ptica, A.C. Loma del Bosque 115, Le\u00f3n 37150, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisco","family":"Morales-Morales","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones en \u00d3ptica, A.C. Loma del Bosque 115, Le\u00f3n 37150, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfredo","family":"Ben\u00edtez-Lara","sequence":"additional","affiliation":[{"name":"CONAHCYT, Centro de Investigaciones en \u00d3ptica, A.C. Loma del Bosque 115, Le\u00f3n 37150, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8332-2704","authenticated-orcid":false,"given":"Mario Humberto","family":"Buenrostro-J\u00e1uregui","sequence":"additional","affiliation":[{"name":"Laboratorio de Neurociencias, Departamento de Psicolog\u00eda, Universidad Iberoamericana Ciudad de M\u00e9xico, Ciudad de M\u00e9xico 01219, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9986-0611","authenticated-orcid":false,"given":"Erik","family":"Bojorges-Valdez","sequence":"additional","affiliation":[{"name":"Departamento de Estudios en Ingenier\u00eda para la Innovaci\u00f3n, Universidad Iberoamericana Ciudad de M\u00e9xico, Ciudad de M\u00e9xico 01219, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernardino","family":"Barrientos-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones en \u00d3ptica, A.C. Loma del Bosque 115, Le\u00f3n 37150, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,27]]},"reference":[{"key":"ref_1","first-page":"2667","article-title":"Mechanisms of electrical stimulation in eye diseases: A narrative review","volume":"2","author":"Liu","year":"2022","journal-title":"Adv. Ophthalmol. Pract. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1007\/s00417-014-2889-7","article-title":"The role of electrical stimulation therapy in ophthalmic diseases","volume":"253","author":"Fu","year":"2015","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1007\/s00586-008-0729-3","article-title":"Role of electrical stimulation for rehabilitation and regeneration after spinal cord injury: An overview","volume":"17","author":"Hamid","year":"2008","journal-title":"Eur. Spine J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"9745","DOI":"10.1038\/s41598-021-89243-y","article-title":"Multi-channel transorbital electrical stimulation for effective stimulation of posterior retina","volume":"11","author":"Lee","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.exer.2016.06.010","article-title":"Whole-eye electrical stimulation therapy preserves visual function and structure in P23H-1 rats","volume":"149","author":"Adam","year":"2016","journal-title":"Exp. Eye Res."},{"key":"ref_6","first-page":"914","article-title":"The transcorneal electrical stimulation as a novel therapeutic strategy against retinal and optic neuropathy: A review of experimental and clinical trials","volume":"9","author":"Tao","year":"2016","journal-title":"Int. J. Ophthalmol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Fernandez, E. (2018). Development of visual Neuroprostheses: Trends and challenges. Bioelectron. Med., 4.","DOI":"10.1186\/s42234-018-0013-8"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1113\/jphysiol.1974.sp010766","article-title":"Phosphenes produced by electrical stimulation of human occipital cortex, and their application to the development of a prosthesis for the blind","volume":"243","author":"Dobelle","year":"1974","journal-title":"J. Physiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1001\/archopht.122.4.460","article-title":"The artificial silicon retina microchip for the treatment of vision loss from retinitis pigmentosa","volume":"122","author":"Chow","year":"2004","journal-title":"Arch. Ophthalmol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Stett, A., Schatz, A., Franklin, J., and Gekeler, F. (2022). Transcorneal electrical stimulation reduces the annual rate of visual field decline in retinitis pigmentosa. Acta Ophthalmol., 100.","DOI":"10.1111\/j.1755-3768.2022.228"},{"key":"ref_11","first-page":"239","article-title":"Non-invasive current stimulation in vision recovery: A review of the literature","volume":"38","author":"Perin","year":"2020","journal-title":"Rest. Neuro. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Cui, H., Xie, X., Xu, S., Chan, L.L., and Hu, Y. (2019). Electrochemical characteristics of microelectrode designed for electrical stimulation. BioMed. Eng. OnLine, 18.","DOI":"10.1186\/s12938-019-0704-8"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/j.survophthal.2021.08.008","article-title":"Electrical devices for visual restoration","volume":"67","author":"Sharf","year":"2022","journal-title":"Surv. Ophthalmol."},{"key":"ref_14","first-page":"1558","article-title":"Non-invasive electrical stimulation as a potential treatment for retinal degenerative diseases","volume":"8","author":"Chang","year":"2021","journal-title":"Neural Regen. Res."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Enayati, S., Chang, K., Achour, H., Cho, K.S., Xu, F., Guo, S., Enayati, K.Z., Xie, J., Zhao, E., and Turunen, T. (2020). Electrical stimulation induces retinal M\u00fcller cell proliferation and their progenitor cell potential. Cells, 9.","DOI":"10.3390\/cells9030781"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1177\/1535370219900495","article-title":"Retinal neurovascular responses to transcorneal electrical stimulation measured with optical coherence tomography","volume":"245","author":"Su","year":"2020","journal-title":"Exp. Biol. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2783","DOI":"10.1016\/j.ajpath.2016.07.017","article-title":"Electrical stimulation as a means for improving vision","volume":"186","author":"Sehic","year":"2016","journal-title":"Am. J. Pathol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1080\/17469899.2016.1221761","article-title":"Non-invasive electrical stimulation for vision restoration: Dream or reality?","volume":"11","author":"Rahmatnejad","year":"2016","journal-title":"Expert Rev. Ophthalmol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4725","DOI":"10.1167\/iovs.06-1404","article-title":"Transcorneal electrical stimulation promotes the survival of photoreceptors and preserves retinal function in royal college of surgeons rats","volume":"48","author":"Morimoto","year":"2007","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1932","DOI":"10.1109\/TBME.2010.2087378","article-title":"Modeling and percept of transcorneal electrical stimulation in humans","volume":"58","author":"Xie","year":"2011","journal-title":"IEEE Transact. Biomed. Eng."},{"key":"ref_21","first-page":"e61494","article-title":"Simultaneous monitoring of wireless electrophysiology and memory behavioral test as a tool to study hippocampal neurogenesis","volume":"162","author":"Buenrostro","year":"2020","journal-title":"J. Vis. Exp."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Choi, B.J., Kim, J.H., Yang, W.J., Han, D.J., Park, J., and Park, D.W. (2020). Parylene-Based flexible microelectrode arrays for the electrical recording of muscles and the effect of electrode size. Appl. Sci., 10.","DOI":"10.3390\/app10207364"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"125010","DOI":"10.1088\/0960-1317\/23\/12\/125010","article-title":"Fabrication of a flexible penetrating microelectrode array for use on curved surfaces of neural tissues","volume":"23","author":"Byun","year":"2013","journal-title":"J. Micromech. Microeng."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1109\/JMEMS.2009.2039773","article-title":"Fabrication and Characterization of a Parylene-Based three-dimensional microelectrode array for use in retinal prosthesis","volume":"19","author":"Wang","year":"2010","journal-title":"J. Micromech. Microeng."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1109\/JMEMS.2008.2011122","article-title":"Integration of Au nanorods with flexible thin-film microelectrode arrays for improved neural interfaces","volume":"18","author":"Zhou","year":"2009","journal-title":"J. Microelectromechanical Syst."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/1743-0003-10-48","article-title":"In vitro and in vivo evaluation of a photosensitive polyimide thin-film microelectrode array suitable for epiretinal stimulation","volume":"10","author":"Jiang","year":"2013","journal-title":"J. Neuroeng. Rehabil."}],"container-title":["Micromachines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-666X\/14\/11\/1999\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:13:12Z","timestamp":1760130792000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-666X\/14\/11\/1999"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,27]]},"references-count":26,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2023,11]]}},"alternative-id":["mi14111999"],"URL":"https:\/\/doi.org\/10.3390\/mi14111999","relation":{},"ISSN":["2072-666X"],"issn-type":[{"value":"2072-666X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,27]]}}}