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电镀在视网膜下假体上的三维电神经接口。

Three-dimensional electro-neural interfaces electroplated on subretinal prostheses.

作者信息

Butt Emma, Wang Bing-Yi, Shin Andrew, Chen Zhijie Charles, Bhuckory Mohajeet, Shah Sarthak, Galambos Ludwig, Kamins Theodore, Palanker Daniel, Mathieson Keith

机构信息

Institute of Photonics, Department of Physics, University of Strathclyde, Glasgow, Scotland, UK.

Hansen Experimental Physics Laboratory, Stanford University, Stanford, CA, USA.

出版信息

bioRxiv. 2023 Nov 13:2023.11.09.566003. doi: 10.1101/2023.11.09.566003.

Abstract

OBJECTIVE

High-resolution retinal prosthetics offer partial restoration of sight to patients blinded by retinal degenerative diseases through electrical stimulation of the remaining neurons. Decreasing the pixel size enables an increase in prosthetic visual acuity, as demonstrated in animal models of retinal degeneration. However, scaling down the size of planar pixels is limited by the reduced penetration depth of the electric field in tissue. We investigate 3-dimensional structures on top of the photovoltaic arrays for enhanced penetration of electric field to permit higher-resolution implants.

APPROACH

We developed 3D COMSOL models of subretinal photovoltaic arrays that accurately quantify the device electrodynamics during stimulation and verified it experimentally through comparison with the standard (flat) photovoltaic arrays. The models were then applied to optimise the design of 3D electrode structures (pillars and honeycombs) to efficiently stimulate the inner retinal neurons. The return electrodes elevated on top of the honeycomb walls surrounding each pixel orient the electric field inside the cavities vertically, aligning it with bipolar cells for optimal stimulation. Alternatively, pillars elevate the active electrode into the inner nuclear layer, improving proximity to the target neurons. Modelling results informed a microfabrication process of electroplating the 3D electrode structures on top of the existing flat subretinal prosthesis.

MAIN RESULTS

Simulations demonstrate that despite the conductive sidewalls of the 3D electrodes being exposed to electrolyte, most of the charge flows via the high-capacitance sputtered Iridium Oxide film that caps the top of the 3D structures. The 24 μm height of the electroplated honeycomb structures was optimised for integration with the inner nuclear layer cells in rat retina, while 35 μm height of the pillars was optimized for penetrating the debris layer in human patients. Release from the wafer and implantation of the 3D arrays demonstrated that they are mechanically robust to withstand the associated forces. Histology demonstrated successful integration of the 3D structures with the rat retina in-vivo.

SIGNIFICANCE

Electroplated 3D honeycomb structures produce a vertically oriented electric field that offers low stimulation threshold, high spatial resolution and high contrast for the retinal implants with pixel sizes down to 20μm in width. Pillar electrodes offer an alternative configuration for extending the stimulation past the debris layers. Electroplating of the 3D structures is compatible with the fabrication process of the flat photovoltaic arrays, thereby enabling much more efficient stimulation than in their original flat configuration.

摘要

目的

高分辨率视网膜假体通过对剩余神经元进行电刺激,为因视网膜退行性疾病而失明的患者提供部分视力恢复。如在视网膜变性动物模型中所示,减小像素尺寸可提高假体视敏度。然而,平面像素尺寸的缩小受到组织中电场穿透深度降低的限制。我们研究了光伏阵列顶部的三维结构,以增强电场穿透,从而实现更高分辨率的植入。

方法

我们开发了视网膜下光伏阵列的三维COMSOL模型,该模型可在刺激过程中准确量化器件的电动力学特性,并通过与标准(平面)光伏阵列进行比较进行实验验证。然后应用这些模型来优化三维电极结构(柱状和蜂窝状)的设计,以有效刺激视网膜内层神经元。围绕每个像素的蜂窝壁顶部升高的返回电极使腔内电场垂直定向,使其与双极细胞对齐以实现最佳刺激。或者,柱状结构将有源电极提升到内核层,改善与目标神经元的接近度。建模结果为在现有平面视网膜下假体顶部电镀三维电极结构的微制造工艺提供了依据。

主要结果

模拟表明,尽管三维电极的导电侧壁暴露于电解质中,但大部分电荷通过覆盖三维结构顶部的高电容溅射氧化铱薄膜流动。电镀蜂窝结构的24μm高度针对与大鼠视网膜内核层细胞的整合进行了优化,而柱状结构的35μm高度针对穿透人类患者的碎片层进行了优化。从晶圆上释放并植入三维阵列表明它们在机械上具有足够的强度来承受相关力。组织学证明三维结构在体内与大鼠视网膜成功整合。

意义

电镀三维蜂窝结构产生垂直定向的电场,对于宽度低至20μm的像素尺寸的视网膜植入物,该电场具有低刺激阈值、高空间分辨率和高对比度。柱状电极提供了一种替代配置,可将刺激扩展到碎片层之外。三维结构的电镀与平面光伏阵列的制造工艺兼容,从而实现比其原始平面配置更有效的刺激。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af57/10680680/8f000bae267e/nihpp-2023.11.09.566003v1-f0001.jpg

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