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Optimizing the fabrication of a 3D high-resolution implant for neural stimulation

BACKGROUND: Tissue-integrated micro-electronic devices for neural stimulation hold great potential in restoring the functionality of degenerated organs, specifically, retinal prostheses, which are aimed at vision restoration. The fabrication process of 3D polymer-metal devices with high resolution a...

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Autores principales: Shpun, Gal, Farah, Nairouz, Chemla, Yoav, Markus, Amos, Leibovitch, Tamar Azrad, Lasnoy, Erel, Gerber, Doron, Zalevsky, Zeev, Mandel, Yossi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10463680/
https://www.ncbi.nlm.nih.gov/pubmed/37620951
http://dx.doi.org/10.1186/s13036-023-00370-8
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author Shpun, Gal
Farah, Nairouz
Chemla, Yoav
Markus, Amos
Leibovitch, Tamar Azrad
Lasnoy, Erel
Gerber, Doron
Zalevsky, Zeev
Mandel, Yossi
author_facet Shpun, Gal
Farah, Nairouz
Chemla, Yoav
Markus, Amos
Leibovitch, Tamar Azrad
Lasnoy, Erel
Gerber, Doron
Zalevsky, Zeev
Mandel, Yossi
author_sort Shpun, Gal
collection PubMed
description BACKGROUND: Tissue-integrated micro-electronic devices for neural stimulation hold great potential in restoring the functionality of degenerated organs, specifically, retinal prostheses, which are aimed at vision restoration. The fabrication process of 3D polymer-metal devices with high resolution and a high aspect-ratio (AR) is very complex and faces many challenges that impair its functionality. APPROACH: Here we describe the optimization of the fabrication process of a bio-functionalized 3D high-resolution 1mm circular subretinal implant composed of SU-8 polymer integrated with dense gold microelectrodes (23μm pitch) passivated with 3D micro-well-like structures (20μm diameter, 3μm resolution). The main challenges were overcome by step-by-step planning and optimization while utilizing a two-step bi-layer lift-off process; bio-functionalization was carried out by N(2) plasma treatment and the addition of a bio-adhesion molecule. MAIN RESULTS: In-vitro and in-vivo investigations, including SEM and FIB cross section examinations, revealed a good structural design, as well as a good long-term integration of the device in the rat sub-retinal space and cell migration into the wells. Moreover, the feasibility of subretinal neural stimulation using the fabricated device was demonstrated in-vitro by electrical activation of rat’s retina. CONCLUSIONS: The reported process and optimization steps described here in detail can aid in designing and fabricating retinal prosthetic devices or similar neural implants. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13036-023-00370-8.
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spelling pubmed-104636802023-08-30 Optimizing the fabrication of a 3D high-resolution implant for neural stimulation Shpun, Gal Farah, Nairouz Chemla, Yoav Markus, Amos Leibovitch, Tamar Azrad Lasnoy, Erel Gerber, Doron Zalevsky, Zeev Mandel, Yossi J Biol Eng Methodology BACKGROUND: Tissue-integrated micro-electronic devices for neural stimulation hold great potential in restoring the functionality of degenerated organs, specifically, retinal prostheses, which are aimed at vision restoration. The fabrication process of 3D polymer-metal devices with high resolution and a high aspect-ratio (AR) is very complex and faces many challenges that impair its functionality. APPROACH: Here we describe the optimization of the fabrication process of a bio-functionalized 3D high-resolution 1mm circular subretinal implant composed of SU-8 polymer integrated with dense gold microelectrodes (23μm pitch) passivated with 3D micro-well-like structures (20μm diameter, 3μm resolution). The main challenges were overcome by step-by-step planning and optimization while utilizing a two-step bi-layer lift-off process; bio-functionalization was carried out by N(2) plasma treatment and the addition of a bio-adhesion molecule. MAIN RESULTS: In-vitro and in-vivo investigations, including SEM and FIB cross section examinations, revealed a good structural design, as well as a good long-term integration of the device in the rat sub-retinal space and cell migration into the wells. Moreover, the feasibility of subretinal neural stimulation using the fabricated device was demonstrated in-vitro by electrical activation of rat’s retina. CONCLUSIONS: The reported process and optimization steps described here in detail can aid in designing and fabricating retinal prosthetic devices or similar neural implants. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13036-023-00370-8. BioMed Central 2023-08-24 /pmc/articles/PMC10463680/ /pubmed/37620951 http://dx.doi.org/10.1186/s13036-023-00370-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Methodology
Shpun, Gal
Farah, Nairouz
Chemla, Yoav
Markus, Amos
Leibovitch, Tamar Azrad
Lasnoy, Erel
Gerber, Doron
Zalevsky, Zeev
Mandel, Yossi
Optimizing the fabrication of a 3D high-resolution implant for neural stimulation
title Optimizing the fabrication of a 3D high-resolution implant for neural stimulation
title_full Optimizing the fabrication of a 3D high-resolution implant for neural stimulation
title_fullStr Optimizing the fabrication of a 3D high-resolution implant for neural stimulation
title_full_unstemmed Optimizing the fabrication of a 3D high-resolution implant for neural stimulation
title_short Optimizing the fabrication of a 3D high-resolution implant for neural stimulation
title_sort optimizing the fabrication of a 3d high-resolution implant for neural stimulation
topic Methodology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10463680/
https://www.ncbi.nlm.nih.gov/pubmed/37620951
http://dx.doi.org/10.1186/s13036-023-00370-8
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