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Visual prostheses are becoming a reality as a therapy to restore functional vision to the blind. New stimulation strategies and novel electrode designs are contributing to accelerate the development of such devices triggering the interest of scientists, clinicians and the blind community worldwide. In this scenario, there is a need for large animal models that are suitable for preclinical testing of retinal neuroprostheses. This study presents an electrophysiology assessment of an ovine model for single and simultaneous electrode stimulation from the suprachoroidal space, using symmetric biphasic current pulses with a monopolar return configuration. Visually and electrically evoked potentials were recorded using supradural surface electrodes, showing charge thresholds comparable to those in humans. This model represents an alternative to feline or canine models with analogous activation levels and an eye anatomy similar to that of humans.

PURPOSE Research to restore some degree of vision to patients suffering from retinal degeneration is becoming increasingly more promising. Several groups have chosen electrical stimulation of the remaining network of a degenerate retina as a means to generate discrete light percepts (phosphenes). Approaches vary significantly, with the greatest difference being the location of the stimulating electrode itself. METHODS Suprachoroidal positioning offers excellent mechanical stability and surgical simplicity; however, at the cost of activation thresholds and focused stimulation due to the distance from the electrodes to the target neurons. Past studies proposed a hexapolar electrode configuration to focus the cortical activation and minimize cross-talk between electrodes during concurrent stimulation. The high impedance nature of the choroid and pigment epithelium, however, cause current to shunt between the stimulating and return electrodes, resulting in even higher activation thresholds. In our study, we analyzed the effect of stimulating the feline retina using a quasimonopolar stimulation by simultaneously stimulating a hexapolar and distant monopolar return configurations. RESULTS Results of in vivo studies showed that quasimonopolar stimulation can be used to maintain the activation containment properties of hexapolar stimulation, while lowering the activation threshold to values almost equivalent to those of monopolar stimulation. CONCLUSIONS The optimal stimulus was found to be composed of a subthreshold monopolar stimulus combined with a suprathreshold hexapolar stimulation. This resulted in a decrease of activation threshold of 60% with respect to hexapolar alone, but with no discernible deleterious effect on the charge containment of a pure hexapolar stimulation.

The complexity of surgical implantation has always been a significant obstacle in the development of visual prosthetics. Implanting in the epi and sub-retinal spaces allows the prosthesis direct access to the retina, resulting in lower stimulation thresholds, potentially at the expense of robust mechanical stability and interface longevity. Implanting the stimulating electrode in the supra-choroidal space greatly simplifies surgery and improves mechanical stability. This is achieved at the cost of a higher activation threshold and reduced focus of the electric field at the target site of stimulation, given the increased distance between the stimulating electrodes and the target tissue. In order to contain the spread of the stimulating field, the authors proposed a hexagonal arrangement of return electrodes, at a further cost to the stimulation threshold over that of a monopolar stimulation paradigm. This study analyses the effect on activation thresholds of activating simultaneously the hexpolar guard electrodes and the distant monopolar return in what we have termed a quasimonopolar configuration. Results show that introducing a small element of monopolar stimulation significantly lowers the activation threshold otherwise required by a pure hexpolar return.

Objective. Recent interest in the use of conducting polymers (CPs) for neural stimulation electrodes has been growing; however, concerns remain regarding the stability of coatings under stimulation conditions. These studies examine the factors of the CP and implant environment that affect coating stability. The CP poly(ethylene dioxythiophene) (PEDOT) is examined in comparison to platinum (Pt), to demonstrate the potential performance of these coatings in neuroprosthetic applications. Approach. PEDOT is coated on Pt microelectrode arrays and assessed in vitro for charge injection limit and long-term stability under stimulation in biologically relevant electrolytes. Physical and electrical stability of coatings following ethylene oxide (ETO) sterilization is established and efficacy of PEDOT as a visual prosthesis bioelectrode is assessed in the feline model. Main results. It was demonstrated that PEDOT reduced the potential excursion at a Pt electrode interface by 72% in biologically relevant solutions. The charge injection limit of PEDOT for material stability was found to be on average 30× larger than Pt when tested in physiological saline and 20× larger than Pt when tested in protein supplemented media. Additionally stability of the coating was confirmed electrically and morphologically following ETO processing. It was demonstrated that PEDOT-coated electrodes had lower potential excursions in vivo and electrically evoked potentials (EEPs) could be detected within the visual cortex. Significance. These studies demonstrate that PEDOT can be produced as a stable electrode coating which can be sterilized and perform effectively and safely in neuroprosthetic applications. Furthermore these findings address the necessity for characterizing in vitro properties of electrodes in biologically relevant milieu which mimic the in vivo environment more closely.

Conducting polymer (CP) coatings on medical electrodes have the potential to provide superior performance when compared to conventional metallic electrodes, but their stability is strongly dependant on the substrate properties. The aim of this study was to examine the effect of laser roughening of underlying platinum (Pt) electrode surfaces on the mechanical, electrical and biological performance of CP coatings. In addition, the impact of dopant type on electrical performance and stability was assessed. The CP poly(ethylene dioxythiophene) (PEDOT) was coated on Pt microelectrode arrays, with three conventional dopant ions. The in vitro electrical characteristics were assessed by cyclic voltammetry and biphasic stimulation. Results showed that laser roughening of the underlying substrate did not affect the charge injection limit of the coated material, but significantly improved the passive stability and chronic stimulation lifetime without failure of the coating. Accelerated material ageing and long-term biphasic stimulus studies determined that some PEDOT variants experienced delamination within as little as 10 days when the underlying Pt was smooth, but laser roughening to produce a surface index of 2.5 improved stability, such that more than 1.3 billion stimulation cycles could be applied without evidence of failure. PEDOT doped with paratoluene sulfonate (PEDOT/pTS) was found to be the most stable CP on roughened Pt, and presented a surface topography which encouraged neural cell attachment.

Most implantable medical devices such as cochlear implants and visual prostheses require protection of the stimulating electronics. This is achieved by way of a hermetic feedthrough system which typically features three important attributes: biocompatibility with the human body, device hermeticity and density of feedthrough conductors. On the quest for building a visual neuroprosthesis, a high number of stimulating channels is required. This has encouraged new technologies with higher rates of production yield and further miniaturization. An Al(2)O(3) based feedthrough system has been developed comprising up to 20 platinum feedthroughs per square millimeter. Ceramics substrates are shown to have leak rates below 1 × 10(-12) atm × cc/s, thus exceeding the resolution limits of most commercially available leak detectors. A sheet resistance of 0.05 Ω can be achieved. This paper describes the design, fabrication process and hermeticity testing of high density feedthroughs for use in neuroprosthetic implants.

Retinal micro-electrode arrays (MEAs) for a visual prosthesis were fabricated by laser structuring of platinum (Pt) foil and liquid silicone rubber. A new design was created using a folding technique to create a multi-layered array from a single Pt sheet. This method allowed a reduction in both the electrode pitch, and the overall width of the array, while maintaining coplanar connection points for more stable interconnections to other components of the system. The design also included a section which could be rolled to create a cylindrical segment in order to minimise the size of the exit in the sclera after implantation. A picosecond mode-locked 532 nm laser system was investigated as a replacement for the nanosecond Q-switched 1064 nm laser currently in use. Trials showed that the ps system could produce high quality electrode tracks with a minimum pitch of 30 μm, less than 40% the pitch achievable with the ns laser. A method was investigated for the cutting of Pt foils without damaging the underlying silicone by laser machining to a depth just below the thickness of the foil. Initial samples showed promise with full penetration of the foil only occurring at cross points of the laser paths. The ps laser was also used to create roughened surfaces, in order to increase the electrochemical surface area of the electrodes. Surfaces were imaged using a scanning electron microscope, and compared to surfaces roughened with the ns laser. The ps laser was seen to offer a reduction in feature size, as well as an increase in control over the appearance of the electrode surface.

Exploration into electrical stimulation of the retina has thus far focussed primarily upon the development of prostheses targeted at one of two sites of intervention - the epi- and sub-retinal surfaces. These two approaches have sound, logical merit owing to their proximity to retinal neurons and their potential to deliver stimuli via the surviving retinal neural networks respectively. There is increasing evidence, however, that electric field effects, electrode engineering limitations, and electrode-tissue interactions limit the spatial resolution that once was hoped could be elicited from electrical stimulation at epi- and sub-retinal sites. An alternative approach has been proposed that places a stimulating electrode array within the supra-choroidal space - that is, between the sclera and the choroid. Here we investigate whether discrete, cortical activity patterns can be elicited via electrical stimulation of a feline retina using a custom, 14 channel, silicone rubber and Pt electrode array arranged in two hexagons comprising seven electrodes each. Cortical responses from Areas 17/18 were acquired using a silicon-based, multi-channel, penetrating probe developed at IMTEK, University of Freiburg, within the European research project NeuroProbes. Multi-unit spike activity was recorded in synchrony with the presentation of electrical stimuli. Results show that distinct cortical response patterns could be elicited from each hexagon separated by 1.8 mm (center-to-center) with a center-to-center electrode spacing within each hexagon of 0.55 mm. This lends support that higher spatial resolution may also be discerned.

Conducting polymers (CPs) have the potential to provide superior neural interfaces to conventional metal electrodes by introducing more efficient charge transfer across the same geometric area. In this study the conducting polymer poly(ethylene dioxythiophene) (PEDOT) was coated on platinum (Pt) microelectrode arrays. The in vitro electrical characteristics were assessed during biphasic stimulation regimes applied between electrode pairs. It was demonstrated that PEDOT could reduce the potential excursion at a Pt electrode interface by an order of magnitude. The charge injection limit of PEDOT was found to be 15 x larger than Pt. Additionally, PEDOT coated electrodes were acutely implanted in the suprachoroidal space of a cat retina. It was demonstrated that PEDOT coated electrodes also had lower potential excursions in vivo and electrically evoked potentials (EEPs) could be detected within the vision cortex.

Microelectrode arrays for a stimulating retinal prosthesis were fabricated from laser etched platinum (Pt) foil encased in silicone. A total of 12 arrays were fabricated to test performance in saline. Hexagonal arrangements (N=6) with multiple (6) return electrodes, as well as paired electrodes (N=6) with single returns were constructed. Electron microscopy of the electrode's surfaces was performed. Cyclic voltammetry was performed on all electrodes to measure the real surface area. The electrodes were submerged in saline in an incubator and biphasic pulses of ±162 µA and ±280 µA for 400 µs were applied at a rate of 67.1 Hz for 12 weeks. Microscopy and cyclic voltammetry were repeated and changes to the electrode's surfaces were observed both by visual inspection of the micrographs and analysis of the cyclic voltammetry curves. Extensive corrosion to those electrodes subjected to the higher current suggests a charge injection limit of less than the original 350µC/cm2 estimate. Analysis of different corrosion levels between the hexagonal and paired arrangements show that a hexagonally arranged electrode array, with multiple return electrodes, allows a greater stimulation current to be used without reaching the charge injection limit of the electrodes.

Objective. Laser surface modification of platinum (Pt) electrodes was investigated for use in neuroprosthetics. Surface modification was applied to increase the surface area of the electrode and improve its ability to transfer charge within safe electrochemical stimulation limits. Approach. Electrode arrays were laser micromachined to produce Pt electrodes with smooth surfaces, which were then modified with four laser patterning techniques to produce surface structures which were nanosecond patterned, square profile, triangular profile and roughened on the micron scale through structured laser interference patterning (SLIP). Improvements in charge transfer were shown through electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV) and biphasic stimulation at clinically relevant levels. A new method was investigated and validated which enabled the assessment of in vivo electrochemically safe charge injection limits. Main results. All of the modified surfaces provided electrical advantage over the smooth Pt. The SLIP surface provided the greatest benefit both in vitro and in vivo, and this surface was the only type which had injection limits above the threshold for neural stimulation, at a level shown to produce a response in the feline visual cortex when using an electrode array implanted in the suprachoroidal space of the eye. This surface was found to be stable when stimulated with more than 150 million clinically relevant pulses in physiological saline. Significance. Critical to the assessment of implant devices is accurate determination of safe usage limits in an in vivo environment. Laser patterning, in particular SLIP, is a superior technique for improving the performance of implant electrodes without altering the interfacial electrode chemistry through coating. Future work will require chronic in vivo assessment of these electrode patterns.

Restoring vision to the blind by way of medical device technology has been an objective of several research teams for a number of years. It is known that spots of light-phosphenes-can be elicited by way of electrical stimulation of surviving retinal neurons. Beyond this our understanding of prosthetic vision remains rudimentary. We have designed and manufactured an integrated circuit neurostimulator with substantial versatility, able to provide focussed, simultaneous stimulation using current sources and sinks, steering the current to the intended site of stimulation. The ASIC utilizes high-voltage CMOS transistors in key circuits, to manage voltage compliance issues (due to an unknown or changing electrode/tissue interface impedance) given the relatively high stimulation thresholds necessary to elicit physiological excitation of retinal neurons. In addition, a unique multiplexing system comprised of electrodes arranged in a hexagonal mosaic is used, wherein each electrode can be addressed to be a stimulating electrode and all adjacent electrodes serve as the return path. This allows for simultaneous stimulation to be delivered while appropriately managing cross-talk between the stimulating electrodes. Test results indicate highly linear current sources and sinks (differential nonlinearity error of 0.13 least significant bits -2.6 microA), with the ASIC clearly able to provide focussed stimulation using electrodes immersed in a saline solution.