Electrical stimulation of neuroretinas with 3D pyrolytic carbon electrodes

IF 3 4区 医学 Q3 ENGINEERING, BIOMEDICAL
Pratik Kusumanchi, Jesper Guldsmed Madsen, Toke Bek, Stephan Sylvest Keller, Rasmus Schmidt Davidsen
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引用次数: 0

Abstract

Retinal prosthesis has been one of the medical strategies aimed at restoring some degree of vision for patients affected by retinal degenerative diseases, such as Retinitis Pigmentosa (RP) and age-related macular degeneration (AMD), which are leading causes of irreversible visual loss. In retinal prosthesis, electrical pulses are typically delivered to the retinal neurons via electrodes on the surface of the implant. In this work, we fabricated 3D carbon pillar electrodes by pyrolysis of SU-8 structures defined photolithographically on Si wafers. We then measured compound action potentials induced in porcine neuroretinas stimulated with electrical pulses. The recorded spikes were validated to be biological in origin by adding the voltage-gated sodium-channel blocking agent tetrodotoxin. The minimum threshold voltage needed to effectively stimulate retinal cells, such as retinal ganglion cells, with 3D electrodes was analyzed through systematic investigation of the spike rate and amplitudes as a function of stimulation voltage. 3D electrodes significantly increased spike rate and amplitudes above spontaneous activity in the tissue during stimulation and outperformed the 2D counterpart, both in terms of spike rate and amplitude. Our results indicate a threshold voltage range of 500-600 mV for 1 ms pulses at a frequency of 10 Hz above which a significant increase in spike count was observed. Furthermore, we report an order of magnitude increase in peak-to-peak amplitude for evoked spikes (> 3 mV), compared to spontaneous spikes (∼ 200 µV). Based on numerical integration, we estimate the area under the curve to be ~14 times larger in evoked compound action potentials compared to spontaneous activity. This indicates the relative increase in number of contributing cells to the compound action potential. At a stimulation voltage of 600 mV the spike rate for 3D electrodes was above 10 spikes/channel/s. We hypothesize that the significant difference between 2D and 3D electrodes is not only caused by the higher active electrode surface area of the 3D micropillar electrodes, but also by more intricate contact and interaction with the inner cell layers of the retinal tissue. Our findings indicate that 3D carbon micropillar electrodes are promising for electrical stimulation of the retina.

三维热解碳电极对神经视网膜的电刺激
视网膜假体已成为恢复视网膜退行性疾病患者一定程度视力的医学策略之一,如色素性视网膜炎(RP)和年龄相关性黄斑变性(AMD),这是导致不可逆视力丧失的主要原因。在视网膜假体中,电脉冲通常通过植入物表面的电极传递到视网膜神经元。在这项工作中,我们通过热解在硅晶片上光刻确定的SU-8结构来制备三维碳柱电极。然后,我们测量了电脉冲刺激下猪神经视网膜的复合动作电位。通过添加电压门控钠通道阻断剂河豚毒素,验证了记录的尖峰是生物起源。通过系统研究脉冲速率和振幅与刺激电压的关系,分析了三维电极有效刺激视网膜细胞(如视网膜神经节细胞)所需的最小阈值电压。在刺激过程中,3D电极显著增加了组织中自发活动的峰值速率和振幅,并且在峰值速率和振幅方面优于2D电极。我们的结果表明,阈值电压范围为500-600 mV,频率为10 Hz,超过该范围,观察到尖峰计数显着增加。此外,我们报告了诱发峰值的峰对峰幅度的数量级增加(>;3 mV),与自发尖峰(~ 200µV)相比。基于数值积分,我们估计,与自发活动相比,诱发复合动作电位的曲线下面积约为14倍。这表明参与复合动作电位的细胞数量相对增加。在600 mV的刺激电压下,三维电极的峰值速率大于10个峰值/通道/s。我们假设2D和3D电极之间的显著差异不仅是由于3D微柱电极的活性电极表面积更高,而且还与视网膜组织内细胞层更复杂的接触和相互作用造成的。我们的研究结果表明,3D碳微柱电极有望用于视网膜的电刺激。
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来源期刊
Biomedical Microdevices
Biomedical Microdevices 工程技术-工程:生物医学
CiteScore
6.90
自引率
3.60%
发文量
32
审稿时长
6 months
期刊介绍: Biomedical Microdevices: BioMEMS and Biomedical Nanotechnology is an interdisciplinary periodical devoted to all aspects of research in the medical diagnostic and therapeutic applications of Micro-Electro-Mechanical Systems (BioMEMS) and nanotechnology for medicine and biology. General subjects of interest include the design, characterization, testing, modeling and clinical validation of microfabricated systems, and their integration on-chip and in larger functional units. The specific interests of the Journal include systems for neural stimulation and recording, bioseparation technologies such as nanofilters and electrophoretic equipment, miniaturized analytic and DNA identification systems, biosensors, and micro/nanotechnologies for cell and tissue research, tissue engineering, cell transplantation, and the controlled release of drugs and biological molecules. Contributions reporting on fundamental and applied investigations of the material science, biochemistry, and physics of biomedical microdevices and nanotechnology are encouraged. A non-exhaustive list of fields of interest includes: nanoparticle synthesis, characterization, and validation of therapeutic or imaging efficacy in animal models; biocompatibility; biochemical modification of microfabricated devices, with reference to non-specific protein adsorption, and the active immobilization and patterning of proteins on micro/nanofabricated surfaces; the dynamics of fluids in micro-and-nano-fabricated channels; the electromechanical and structural response of micro/nanofabricated systems; the interactions of microdevices with cells and tissues, including biocompatibility and biodegradation studies; variations in the characteristics of the systems as a function of the micro/nanofabrication parameters.
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