Retina implant project : chronic implantation of active epiretinal implants

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Wide field epiretinal micro-electrode-design and feature test

This study was aimed to design and fabricate a wide field implantable epi-retinal microelectrode array for the purpose of retinal repair, and to perform electrochemical test on the array. With parylene as flexible substrate material and Pt as electrode and route material, microelectrode array prototypes was designed and fabricated, and electric characteristics of the array was tested with the three-electrode test system. The feature analysis showed that morphological and electrical properties of the array well met the requirements of implantation and electrical stimulation of retina. The microelectrode array can be put in the in vivo electrophysiological experiments on animal and can perform reliably. © 2013 IEEE.published_or_final_versio

Flexible Parylene-based Microelectrode Technology for Intraocular Retinal Prostheses

We present the first single metal layer flexible microelectrode arrays designed for intraocular implantation that utilize parylene C as their primary structural and insulating material. These electrodes are fabricated as a key component of an intraocular retinal prosthesis comprising a radio-frequency coil for power and data transfer, a packaged high lead-count telemetry-recovery and driving application-specific integrated circuit (ASIC), and a high-density epiretinal stimulating microelectrode array for the treatment of retinal degenerative blindness in humans. Electrochemical tests have demonstrated that these thin-film platinum electrodes perform as necessary for neuronal stimulation. A novel bioconformal MEMS geometry for a complete intraocular system with capsular retaining-wings that enables all the components of the system to be implanted and retained within the lens capsule and vitreous cavity of the eye is also presented. The efficacy of this geometry when compared with a previous model without capsular retaining-wings has been verified by surgical implantation in animal models

Flexible Microfabricated Parylene Multielectrode Arrays for Retinal Stimulation and Spinal Cord Field Modulation

The first flexible parylene-based multielectrode arrays (MEAs) designed for functional electrical stimulation (FES) in retinal prostheses, and the extension of this technology toward enabling reflex-arc neuromodulation in cases of spinal cord damage or transection, are presented. A single metal layer 16 × 16 retinal electrode array of 125 μm-diameter thin-film Ti/Pt electrodes and lines of 12 μm-pitch has been fabricated as a demonstration of this technology. To allow for even higher density arrays, a novel dual-layer process has also been implemented that enables leads to pass under overlying electrodes without making electrical contact to them. A biomimetic parylene-based electrode array consisting of 1024 electrodes of highly variable spacing, 60 of which have been connected in this manner, has been fabricated according to this paradigm. A parylene-parylene annealing process has also been developed to increase device longevity under accelerated-lifetime saline soak conditions. Surgical tests of novel anatomically-conformal geometries that enable such parylene-based electrode systems to interact with their neuronal targets of interest while causing minimal mechanical damage to tissues or to the implants are also presented. The use of these flexible electrode arrays in spinal cord stimulation experiments in animal models has proven their efficacy in stimulating neurons

A Novel In Vitro Sensing Configuration for Retinal Physiology Analysis of a Sub-Retinal Prosthesis

This paper presents a novel sensing configuration for retinal physiology analysis, using two microelectrode arrays (MEAs). In order to investigate an optimized stimulation protocol for a sub-retinal prosthesis, retinal photoreceptor cells are stimulated, and the response of retinal ganglion cells is recorded in an in vitro environment. For photoreceptor cell stimulation, a polyimide-substrate MEA is developed, using the microelectromechanical systems (MEMS) technology. For ganglion cell response recording, a conventional glass-substrate MEA is utilized. This new sensing configuration is used to record the response of retinal ganglion cells with respect to three different stimulation methods (monopolar, bipolar, and dual-monopolar stimulation methods). Results show that the geometrical relation between the stimulation microelectrode locations and the response locations seems very low. The threshold charges of the bipolar stimulation and the monopolar stimulation are in the range of 10∼20 nC. The threshold charge of the dual-monopolar stimulation is not obvious. These results provide useful guidelines for developing a sub-retinal prosthesis

High-Density Flexible Parylene-Based Multielectrode Arrays for Retinal and Spinal Cord Stimulation

Novel flexible parylene-based high-density electrode arrays have been developed for functional electrical stimulation in retinal and spinal cord applications. These electrode arrays are microfabricated according to single-metal-layer and, most recently, dual-metal-layer processes. A new heat-molding process has been implemented to conform electrode arrays to approximate the curvature of canine retinas, and chronic implantation studies have been undertaken to study the mechanical effects of parylene-based prostheses on the retina, with excellent results to date. Electrode arrays have also been implanted and tested on the spinal cords of murine models, with the ultimate goal of facilitation of locomotion after spinal cord injury; these arrays provide a higher density and better spatial control of stimulation and recording than is typically possible using traditional fine-wire electrodes. Spinal cord stimulation typically elicited three muscle responses, an early (direct), a middle (monosynaptic), and a late (polysynaptic) response, classified based on latency after stimulation. Stimulation at different rostrocaudal levels of the cord yielded markedly different muscle responses, highlighting the need for such high-density arrays

Systems design of a high resolution retinal prosthesis

Simulations of artificial vision suggest that 1000 electrodes may be required to restore vision to individuals with diseases of the outer retina. In order to achieve such an implant, new technology is needed, since the state-of-the-art implantable neural stimulator has at most 22 contacts with neural tissue. Considerable progress has been made towards that goal with the development of image processing, microelectronics, and polymer based MEMS. An image processing system has been realized that is capable of real-time implementation of image decimation and filtering (for example, edge detection). Application specific integrated circuits (ASICs) have been designed and tested to demonstrate closed loop power control and efficient microstimulation. A novel packaging process has been developed that is capable of simultaneously forming communication coils, interconnects, and stimulating electrodes

Biocompatibility of subretinal parylene-based Ti/Pt microelectrode array in rabbit for further artificial vision studies

To evaluate the biocompatibility of subretinal implanted parylene-based Ti/Pt microelectrode arrays (MEA). Eyes were enucleated 3 months after MEAs were implanted into the subretinal space of rabbits. Morphological changes of the retinas were investigated by H&E staining. Immunohistochemical staining for glial fibrillary acidic protein and opsin were performed to evaluate changes in Muller cells and photoreceptors in the retinas. Retina tissue around the array remained intact. Photoreceptor degeneration and glial cell activation were observed in the retina overlaying the MEA implant. However, the cells in the inner retinal layers were preserved. Photoreceptor degeneration and glial cell activation at the MEA–retina interface are expected to be a normal reaction to implantation. Material used in this experiment has good biocompatibility within the subretinal environment and is expected to be promising in the further retinal prosthesis studies

In Vivo Photovoltaic Performance of a Silicon Nanowire Photodiode-Based Retinal Prosthesis.

Purpose:For more than 20 years, there has been an international, multidisciplinary effort to develop retinal prostheses to restore functional vision to patients blinded by retinal degeneration. We developed a novel subretinal prosthesis with 1512 optically addressed silicon nanowire photodiodes, which transduce incident light into an electrical stimulation of the remaining retinal circuitry. This study was conducted to evaluate the efficacy of optically driving the subretinal prosthesis to produce visual cortex activation via electrical stimulation of the retina. Methods:We measured electrically evoked potential responses (EEPs) in rabbit visual cortex in response to illumination of the subretinal nanowire prosthesis with pulsed 852-nm infrared (IR) light. We compared the EEP responses to visually evoked potential responses (VEPs) to pulsed 532-nm visible light (positive control) and pulsed 852-nm IR light (negative control). Results:Activating the devices with IR light produced EEP responses with a significantly higher trough-to-peak amplitude (54.17 ± 33.4 μV) than IR light alone (24.07 ± 22.1 μV) or background cortical activity (23.22 ± 17.2 μV). EEP latencies were significantly faster than focal VEP latencies. Focal VEPs produced significantly higher amplitudes (94.88 ± 43.3 μV) than EEPs. We also demonstrated how an electrode placed on the cornea can be used as a noninvasive method to monitor the function of the implant. Conclusions:These results show that subretinal electrical stimulation with nanowire electrodes can elicit EEPs in the visual cortex, providing evidence for the viability of a subretinal nanowire prosthetic approach for vision restoration