{"title":"优化用于神经刺激的3D高分辨率植入物的制造。","authors":"Gal Shpun, Nairouz Farah, Yoav Chemla, Amos Markus, Tamar Azrad Leibovitch, Erel Lasnoy, Doron Gerber, Zeev Zalevsky, Yossi Mandel","doi":"10.1186/s13036-023-00370-8","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Approach: </strong>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<sub>2</sub> plasma treatment and the addition of a bio-adhesion molecule.</p><p><strong>Main results: </strong>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.</p><p><strong>Conclusions: </strong>The reported process and optimization steps described here in detail can aid in designing and fabricating retinal prosthetic devices or similar neural implants.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":"17 1","pages":"55"},"PeriodicalIF":5.7000,"publicationDate":"2023-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10463680/pdf/","citationCount":"0","resultStr":"{\"title\":\"Optimizing the fabrication of a 3D high-resolution implant for neural stimulation.\",\"authors\":\"Gal Shpun, Nairouz Farah, Yoav Chemla, Amos Markus, Tamar Azrad Leibovitch, Erel Lasnoy, Doron Gerber, Zeev Zalevsky, Yossi Mandel\",\"doi\":\"10.1186/s13036-023-00370-8\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Approach: </strong>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<sub>2</sub> plasma treatment and the addition of a bio-adhesion molecule.</p><p><strong>Main results: </strong>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.</p><p><strong>Conclusions: </strong>The reported process and optimization steps described here in detail can aid in designing and fabricating retinal prosthetic devices or similar neural implants.</p>\",\"PeriodicalId\":15053,\"journal\":{\"name\":\"Journal of Biological Engineering\",\"volume\":\"17 1\",\"pages\":\"55\"},\"PeriodicalIF\":5.7000,\"publicationDate\":\"2023-08-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10463680/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Biological Engineering\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1186/s13036-023-00370-8\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMICAL RESEARCH METHODS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Biological Engineering","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1186/s13036-023-00370-8","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
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 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 N2 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.
期刊介绍:
Biological engineering is an emerging discipline that encompasses engineering theory and practice connected to and derived from the science of biology, just as mechanical engineering and electrical engineering are rooted in physics and chemical engineering in chemistry. Topical areas include, but are not limited to:
Synthetic biology and cellular design
Biomolecular, cellular and tissue engineering
Bioproduction and metabolic engineering
Biosensors
Ecological and environmental engineering
Biological engineering education and the biodesign process
As the official journal of the Institute of Biological Engineering, Journal of Biological Engineering provides a home for the continuum from biological information science, molecules and cells, product formation, wastes and remediation, and educational advances in curriculum content and pedagogy at the undergraduate and graduate-levels.
Manuscripts should explore commonalities with other fields of application by providing some discussion of the broader context of the work and how it connects to other areas within the field.