Laser patterning of platinum electrodes for safe neurostimulation.

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.

Performance of conducting polymer electrodes for stimulating neuroprosthetics.

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.

Discrete cortical responses from multi-site supra-choroidal electrical stimulation in the feline retina.

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.

Charge recovery during concurrent stimulation for a vision prosthesis.

Parallel or concurrent stimulation in an epiretinal neuroprosthesis is likely necessary in order to deliver sufficient phosphenes for effective vision. Important issues with concurrent stimulation are the effect of current distribution which introduces current leakage or 'cross talk' between adjacent electrodes and charge recovery which determines balanced charge being delivered/recovered at each electrode from the previous phase. In this paper, we present the effect of concurrent stimulation of two hexagonally arranged platinum electrode arrays on charge recovery. Balanced and imbalanced (unequal) currents were delivered to the hexagonal arrays when they were immersed in physiological saline. Both simulation and experimental results revealed that charge was not recovered at individual electrodes, particularly when imbalanced currents were delivered. However, total charge injected to both hexagonal arrays was recovered.

Microelectronic retinal prosthesis: I. A neurostimulator for the concurrent activation of multiple electrodes.

An application specific integrated circuit (ASIC) capable of delivering charge to multiple electrodes in unison has been developed. The ASIC is designed to function as part of an epi-retinal prosthesis driving an array of electrodes in a hexagonal mosaic. This unique organization of electrodes and the use of current sources and sinks is implemented to reduce the electrical cross-talk that occurs when many electrodes are activated in unison. Due to the large numbers of electrodes needed to provide useful vision to implantees, the interleaving strategies used in cochlear implants will not suffice for a vision prosthesis, where the "frame rate" is important for acceptable perceptual outcomes. This paper describes the design, and architectural approaches and performance testing of the developed ASIC.

The design and testing of an epi-retinal vision prosthesis neurostimulator capable of concurrent parallel stimulation.

An application specific integrated circuit (ASIC) neurostimulator capable of stimulating multiple electrodes in unison has been designed and tested. The ASIC utilizes multiple matched current sinks and sources to provide localized stimulation and is designed to drive electrodes organized in a hexagonal mosaic. This organization allows each stimulating electrode to be surrounded by up to six return electrodes, effectively isolating each stimulation site. The ASIC was manufactured using a high-voltage complementary metal-oxide-semiconductor process, which allows up to 20 V to be applied across the circuitry. This provides the greatest versatility for testing with electrodes and tissues of varying impedances in-situ and allows the device to be used in other neurostimulation applications such as functional electrical stimulation. The design has been thoroughly tested and meets all the design specifications.

Current distribution during parallel stimulation: implications for an epiretinal neuroprosthesis.

A simplified mathematical model has been developed in order to better understand local current spread when multiple simultaneous current sources are used in an epiretinal neuroprosthesis. To test the model, pairs of platinum electrodes of 430 μm diameter and an intra-pair spacing of 1 mm between centers, were arranged either in-line or in parallel, in a bath of physiological saline. Each pair was separated by distances from 1 mm to 6 mm. The currents in each electrode in the bath were measured and compared with the computational model of the same arrangement. This approach allowed us to quantify return current interaction between parallel sources. As predicted, with parallel electrodes and matching currents in each electrode pair, there is no current cross-talk. However with imbalanced current sources, significant cross-talk is evident. The cross-talk decreases as a function of electrode pair separation. The implication of this work in the design of an epiretinal neuroprosthesis is discussed.

An efficient multiplexing method for addressing large numbers of electrodes in a visual neuroprosthesis.

Recent clinical trials using modified cochlear implants employ a small number of electrodes to stimulate surviving retinal neurons in blind patients and indicate that spatially-mapped phosphenes may indeed be elicited through these means. The next obvious step forward in the path toward achieving a useful visual prosthesis for the blind will be to increase the quantity of stimulation sites such that shapes, characters and rudimentary images may be conveyed. An important objective that must be obtained in the pursuit of this task is the ability to configure and deliver the stimulation with sufficient speed so as to avoid delays that are perceived by the patient as flicker within the visual scene. As the quantity of electrodes within the prosthesis increases, so too does the complexity of achieving this objective. This paper describes a means through which large numbers of electrode sites may be efficiently addressed in a neurostimulation circuit so as to increase the rate at which said circuit may be configured for the delivery of stimulation.

A retrospective serological suvey of Royal Marines previously exposed to Pseudomonas pseudomallei in South East Asia.

Following the suggestion that it was possible that cases of melioidosis amongst those who had been exposed abroad in the past, might be escaping notice, 487 Royal Marines were examined by indirect haemagglutination studies. Four hundred and eleven of these subjects had served for variable times in areas where melioidosis has been known to occur in Indonesia and Malaya, between 1960 and 1974, occupied in activities in the jungle and paddy fields during which exposure to the disease was to be expected. No evidence of residual subclinical melioidosis was found and it seems unlikely that recrudescent disease will prove to be a problem in the future for English servicemen who have been in South East Asia.