Micro-Fabrication of Components for a High-Density Sub-Retinal Visual Prosthesis.

We present a retrospective of unique micro-fabrication problems and solutions that were encountered through over 10 years of retinal prosthesis product development, first for the Boston Retinal Implant Project initiated at the Massachusetts Institute of Technology and at Harvard Medical School's teaching hospital, the Massachusetts Eye and Ear-and later at the startup company Bionic Eye Technologies, by some of the same personnel. These efforts culminated in the fabrication and assembly of 256+ channel visual prosthesis devices having flexible multi-electrode arrays that were successfully implanted sub-retinally in mini-pig animal models as part of our pre-clinical testing program. We report on the processing of the flexible multi-layered, planar and penetrating high-density electrode arrays, surgical tools for sub-retinal implantation, and other parts such as coil supports that facilitated the implantation of the peri-ocular device components. We begin with an overview of the implantable portion of our visual prosthesis system design, and describe in detail the micro-fabrication methods for creating the parts of our system that were assembled outside of our hermetically-sealed electronics package. We also note the unique surgical challenges that sub-retinal implantation of our micro-fabricated components presented, and how some of those issues were addressed through design, materials selection, and fabrication approaches.

Communication and Control System for a 15-Channel Hermetic Retinal Prosthesis.

A small, hermetic, wirelessy-controlled retinal prosthesis has been developed for pre-clinical studies in Yucatan minipigs. The device was attached conformally to the outside of the eye in the socket and received both power and data wirelessly from external sources. Based on the received image data, the prosthesis drove a subretinal thin-film polyimide array of sputtered iridium oxide stimulating electrodes. The implanted device included a hermetic titanium case containing a 15-channel stimulator and receiver chip and discrete circuit components. Feedthroughs in the hermetic case connected the chip to secondary power- and data-receiving coils, which coupled to corresponding external power and data coils driven by power amplifiers. Power was delivered by a 125 KHz carrier, and data were delivered by amplitude shift keying of a 15.5 MHz carrier at 100 Kbps. Stimulation pulse strength, duration and frequency were programmed wirelessly from an external computer system. The final assembly was tested in vitro in physiological saline and in vivo in two minipigs for up to five and a half months by measuring stimulus artifacts generated by the implant's current drivers.

A hermetic wireless subretinal neurostimulator for vision prostheses.

A miniaturized, hermetically encased, wirelessly operated retinal prosthesis has been developed for preclinical studies in the Yucatan minipig, and includes several design improvements over our previously reported device. The prosthesis attaches conformally to the outside of the eye and electrically drives a microfabricated thin-film polyimide array of sputtered iridium oxide film electrodes. This array is implanted into the subretinal space using a customized ab externo surgical technique. The implanted device includes a hermetic titanium case containing a 15-channel stimulator chip and discrete circuit components. Feedthroughs in the case connect the stimulator chip to secondary power and data receiving coils on the eye and to the electrode array under the retina. Long-term in vitro pulse testing of the electrodes projected a lifetime consistent with typical devices in industry. The final assembly was tested in vitro to verify wireless operation of the system in physiological saline using a custom RF transmitter and primary coils. Stimulation pulse strength, duration, and frequency were programmed wirelessly from a Peripheral Component Interconnect eXtensions for Instrumentation (PXI) computer. Operation of the retinal implant has been verified in two pigs for up to five and a half months by detecting stimulus artifacts generated by the implanted device.

Contribution of oxygen reduction to charge injection on platinum and sputtered iridium oxide neural stimulation electrodes.

The extent to which oxygen reduction occurs on sputtered iridium oxide (SIROF) and platinum neural stimulation electrodes was quantified by cyclic voltammetry and voltage-transient measurements in oxygen-saturated physiological saline. Oxygen reduction was the dominant charge-admittance reaction on platinum electrodes during slow-sweep-rate cyclic voltammetry, contributing approximately 12 mC/cm(2) (88% of total charge) to overall cathodal charge capacity. For a 300-nm-thick SIROF electrode, oxygen reduction was a minor reaction contributing 1.3 mC/cm(2), approximately 3% of total charge. During current pulsing with platinum electrodes, oxygen reduction was observed at a level of 7% of the total injected charge. There was no indication of oxygen reduction on pulsed SIROF electrodes. A sweep-rate-dependent contribution of oxygen reduction was observed on penetrating SIROF microelectrodes (nominal surface area 2000 microm(2)) and is interpreted in terms of rate-limited diffusion of oxygen in electrolyte that penetrates the junction between the insulation and electrode shaft. For typical neural stimulation pulses, no oxygen reduction could be observed on penetrating SIROF microelectrodes. Based on the in vivo concentration of dissolved oxygen, it is estimated that oxygen reduction on platinum microelectrodes will contribute less than 0.5% of the total injected charge and considerably less on SIROF electrodes.

Realization of a 15-channel, hermetically-encased wireless subretinal prosthesis for the blind.

A miniaturized, hermetically-encased, wirelessly-operated retinal prosthesis has been developed for implantation and pre-clinical studies in Yucatan mini-pig animal models. The prosthesis conforms to the eye and drives a microfabricated polyimide stimulating electrode array with sputtered iridium oxide electrodes. This array is implanted in the subretinal space using a specially-designed ab externo surgical technique that affixes the bulk of the prosthesis to the surface of the sclera. The implanted device includes a hermetic titanium case containing a 15-channel stimulator chip and discrete power supply components. Feedthroughs from the case connect to secondary power- and data-receiving coils. In addition, long-term in vitro pulse testing was performed on the electrodes to ensure their stability for the long lifetime of the hermetic case. The final assembly was tested in vitro to verify wireless operation of the system in biological saline using a custom RF transmitter circuit and primary coils. Stimulation pulse strength, duration and frequency were programmed wirelessly using a custom graphical user interface. Operation of the retinal implant has been verified in vivo in one pig for more than three months by measuring stimulus artifacts on the eye surface using a contact lens electrode.

Development and implantation of a minimally invasive wireless subretinal neurostimulator.

A wirelessly operated, minimally invasive retinal prosthesis was developed for preclinical chronic implantation studies in Yucatan minipig models. The implant conforms to the outer wall of the eye and drives a microfabricated polyimide stimulating electrode array with sputtered iridium oxide electrodes. This array is implanted in the subretinal space using a specially designed ab externo surgical technique that fixes the bulk of the prosthesis to the outer surface of the sclera. The implanted device is fabricated on a host polyimide flexible circuit. It consists of a 15-channel stimulator chip, secondary power and data receiving coils, and discrete power supply components. The completed device is encapsulated in poly(dimethylsiloxane) except for the reference/counter electrode and the thin electrode array. In vitro testing was performed to verify the performance of the system in biological saline using a custom RF transmitter circuit and primary coils. Stimulation patterns as well as pulse strength, duration, and frequency were programmed wirelessly using custom software and a graphical user interface. Wireless operation of the retinal implant has been verified both in vitro and in vivo in three pigs for more than seven months, the latter by measuring stimulus artifacts on the eye surface using contact lens electrodes.