Retinal degenerative diseases lead to blindness due to loss of the “image capturing” photoreceptors, while neurons in the “image processing” inner retinal layers are relatively well preserved. Electronic retinal prostheses seek to restore sight by electrically stimulating surviving neurons. Most implants are powered through inductive coils, requiring complex surgical methods to implant the coil-decoder-cable-array systems, which deliver energy to stimulating electrodes via intraocular cables. We present a photovoltaic subretinal prosthesis, in which silicon photodiodes in each pixel receive power and data directly through pulsed near-infrared illumination and electrically stimulate neurons. Stimulation was produced in normal and degenerate rat retinas, with pulse durations from 0.5 to 4 ms, and threshold peak irradiances from 0.2 to 10 mW/mm2, two orders of magnitude below the ocular safety limit. Neural responses were elicited by illuminating a single 70 μm bipolar pixel, demonstrating the possibility of a fully-integrated photovoltaic retinal prosthesis with high pixel density.

Several aspects of a new silicon-on-insulator technique utilizing bonding of oxidized silicon wafers were investigated. The bonding was achieved by heating in an inert atmosphere a pair of wafers with hydrophilic surfaces contacted face-to-face. A quantitative method for the evaluation of the surface energy of the bond based on crack propagation theory was developed. The bond strength was found to increase with the bonding temperature from about 60–85 erg/cm2 at room temperature to ≂2200 erg/cm2 at 1400 °C. The strength was essentially independent of the bond time. Bonds created during 10-s annealing at 800 °C were mechanically strong enough to withstand the mechanical and/or chemical thinning of the top wafer to the desired thickness and subsequent device processing. A model was proposed to explain three distinct phases of bonding in the temperature domain. Electrical properties of the bond were tested using metal-oxide-semiconductor (MOS) capacitors. The results were consistent with a negative charge density at the bond interface of approximately 1011 cm−2. A double-etch-back procedure was used to thin the device wafer to the desired thickness with ±20 nm thickness uniformity across a 4-in. wafer. The density of threading dislocations in the remaining silicon layer was 102 –103 cm−2, and the residual dopant concentration less than 5×1015 cm−3, both remnants of the etchstop layer. Complimentary metal-oxide-semiconductor (CMOS) devices made in the 20–100 nm silicon thick layers had subthreshold slopes of 68 mV/decade (both n- and p-channel MOS transistors). The effective carrier lifetime was 15–20 μs in 80- and 300-nm-thick Si films and the interface state density at the Si film-buried oxide interface was ≤5×1010 cm−2.

Patients with retinal degeneration lose sight due to gradual demise of photoreceptors. Electrical stimulation of the surviving retinal neurons provides an alternative route for delivery of visual information. We demonstrate that subretinal arrays with 70 μm photovoltaic pixels provide highly localized stimulation, with electrical and visual receptive fields of comparable sizes in rat retinal ganglion cells. Similarly to normal vision, retinal response to prosthetic stimulation exhibits flicker fusion at high frequencies, adaptation to static images and non-linear spatial summation. In rats with retinal degeneration, these photovoltaic arrays provide spatial resolution of 64 ± 11 μm, corresponding to half of the normal visual acuity in pigmented rats. Ease of implantation of these wireless and modular arrays, combined with their high resolution opens the door to functional restoration of sight.

Objective Intra-retinal placement of stimulating electrodes can provide close and stable proximity to target neurons. We assessed improvement in stimulation thresholds and selectivity of the direct and network-mediated retinal stimulation with intraretinal electrodes, compared to epiretinal and subretinal placements. Approach Stimulation thresholds of the retinal ganglion cells (RGCs) in wild-type rat retina were measured using patch-clamp technique. Direct and network-mediated responses were discriminated using various synaptic blockers. Main results Three types of RGC responses were identified: short latency (SL, τ<5ms) originating in RGCs, medium latency (ML, 3<τ<70ms) originating in the inner nuclear layer and long latency (LL, τ>40ms) originating in photoreceptors. Cathodic epiretinal stimulation exhibited the lowest threshold for direct RGC response and the highest direct selectivity (network/direct thresholds ratio), exceeding a factor of 3 with pulse durations below 0.5ms. For network-mediated stimulation, the lowest threshold was obtained with anodic pulses in OPL position, and its network selectivity (direct/network thresholds ratio) increased with pulse duration, exceeding a factor of 4 at 10ms. Latency of all three types of responses decreased with increasing strength of the stimulus. Significance These results define optimal range of pulse durations, pulse polarities and electrode placement for the retinal prostheses aiming at direct or network-mediated stimulation of RGCs.

Epiretinal prostheses for treating blindness activate axon bundles, causing large, arc-shaped visual percepts that limit the quality of artificial vision. Improving the function of epiretinal prostheses therefore requires understanding and avoiding axon bundle activation. This study introduces a method to detect axon bundle activation on the basis of its electrical signature and uses the method to test whether epiretinal stimulation can directly elicit spikes in individual retinal ganglion cells without activating nearby axon bundles. Combined electrical stimulation and recording from isolated primate retina were performed using a custom multielectrode system (512 electrodes, 10-μm diameter, 60-μm pitch). Axon bundle signals were identified by their bidirectional propagation, speed, and increasing amplitude as a function of stimulation current. The threshold for bundle activation varied across electrodes and retinas, and was in the same range as the threshold for activating retinal ganglion cells near their somas. In the peripheral retina, 45% of electrodes that activated individual ganglion cells (17% of all electrodes) did so without activating bundles. This permitted selective activation of 21% of recorded ganglion cells (7% of expected ganglion cells) over the array. In one recording in the central retina, 75% of electrodes that activated individual ganglion cells (16% of all electrodes) did so without activating bundles. The ability to selectively activate a subset of retinal ganglion cells without axon bundles suggests a possible novel architecture for future epiretinal prostheses. Large-scale multielectrode recording and stimulation were used to test how selectively retinal ganglion cells can be electrically activated without activating axon bundles. A novel method was developed to identify axon activation on the basis of its unique electrical signature and was used to find that a subset of ganglion cells can be activated at single-cell, single-spike resolution without producing bundle activity in peripheral and central retina. These findings have implications for the development of advanced retinal prostheses.