优化用于神经刺激的3D高分辨率植入物的制造。

IF 5.7 3区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS
Gal Shpun, Nairouz Farah, Yoav Chemla, Amos Markus, Tamar Azrad Leibovitch, Erel Lasnoy, Doron Gerber, Zeev Zalevsky, Yossi Mandel
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引用次数: 0

摘要

背景:用于神经刺激的组织集成微电子设备在恢复退化器官的功能方面具有巨大的潜力,特别是视网膜假体,旨在恢复视力。高分辨率、高长宽比(AR)的3D聚合物金属器件的制造工艺非常复杂,面临着许多影响其功能的挑战。方法:本文描述了一种生物功能化的3D高分辨率1mm圆形视网膜下植入物的制造工艺优化,该植入物由SU-8聚合物与致密金微电极(23μm间距)集成组成,并与3D微孔样结构(20μm直径,3μm分辨率)钝化。通过逐步规划和优化,同时利用两步双层升降过程,克服了主要挑战;通过N2等离子体处理和添加生物粘附分子进行生物功能化。主要结果:体外和体内研究,包括扫描电镜和FIB横断面检查,显示了良好的结构设计,以及设备在大鼠视网膜下空间的良好长期整合和细胞向孔中的迁移。此外,通过体外大鼠视网膜电激活实验,验证了该装置对视网膜下神经刺激的可行性。结论:本文详细描述的过程和优化步骤可以帮助设计和制造视网膜假体装置或类似的神经植入物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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

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

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

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.

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来源期刊
Journal of Biological Engineering
Journal of Biological Engineering BIOCHEMICAL RESEARCH METHODS-BIOTECHNOLOGY & APPLIED MICROBIOLOGY
CiteScore
7.10
自引率
1.80%
发文量
32
审稿时长
17 weeks
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.
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