Mr. Alexander Forrest Albert Butterwick Profile

Alexander Forrest Albert Butterwick

Graduate Student at Stanford Univ

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Proceedings Article | 18 February 2009 Paper

High resolution optoelectronic retinal prosthesis

Jim Loudin, Rostam Dinyari, Phil Huie, Alex Butterwick, Peter Peumans, Daniel Palanker

Proceedings Volume 7163, 71631B (2009) https://doi.org/10.1117/12.807668

KEYWORDS: Electrodes, Photodiodes, Photovoltaics, Platinum, Diodes, Video processing, Tissues, Iridium, Video, Information visualization

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Electronic retinal prostheses seek to restore sight in patients with retinal degeneration by delivering pulsed electric currents to retinal neurons via an array of microelectrodes. Most implants use inductive or optical transmission of information and power to an intraocular receiver, with decoded signals subsequently distributed to retinal electrodes through an intraocular cable. Surgical complexity could be minimized by an "integrated" prosthesis, in which both power and data are delivered directly to the stimulating array without any discrete components or cables. We present here an integrated retinal prosthesis system based on a photodiode array implant. Video frames are processed and imaged onto the retinal implant by a video goggle projection system operating at near-infrared wavelengths (~ 900 nm). Photodiodes convert light into pulsed electric current, with charge injection maximized by specially optimized series photodiode circuits. Prostheses of three different pixel densities (16 pix/mm², 64 pix/mm², and 256 pix/mm²) have been designed, simulated, and prototyped. Retinal tissue response to subretinal implants made of various materials has been investigated in RCS rats. The resulting prosthesis can provide sufficient charge injection for high resolution retinal stimulation without the need for implantation of any bulky discrete elements such as coils or tethers. In addition, since every pixel functions independently, pixel arrays may be placed separately in the subretinal space, providing visual stimulation to a larger field of view.

Proceedings Article | 5 March 2007 Paper

Progress toward a high-resolution retinal prosthesis

Alex Butterwick, Alex Vankov, Phil Huie, Karthik Vijayraghavan, Jim Loudin, Daniel Palanker

Proceedings Volume 6426, 64260R (2007) https://doi.org/10.1117/12.701787

KEYWORDS: Electrodes, Photodiodes, Visualization, Retina, Eye, LCDs, Neurons, Goggles, Information visualization, Video

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Electronic retinal prostheses represent a potentially effective approach for restoring some degree of sight in blind patients with retinal degeneration. Functional restoration of sight would require hundreds to thousands of electrodes effectively stimulating remaining neurons in the retina. We present a design of an optoelectronic retinal prosthetic system having 3mm diameter retinal implant with pixel sizes down to 25 micrometers, which allows for natural eye scanning for observing a large field of view, as well as spatial and temporal processing of the visual scene to optimize the patient experience. Information from a head mounted video camera is processed in a portable computer and delivered to the implanted photodiode array by projection from the LCD goggles using pulsed IR (810 nm) light. Each photodiode converts pulsed light (0.5 ms in duration) into electric current with efficiency of 0.3 A/W using common bi-phasic power line. Power is provided by the inductively-coupled RF link from the coil on the goggles into a miniature power supply implanted between the sclera and the conjuctiva, and connected to subretinal implant with a thin 2-wire trans-scleral cable. 3-dimensional structures in the subretinal prosthesis induce retinal migration and thus ensure close proximity between stimulating electrodes and the target retinal neurons. Subretinal implantations of the 3-dimentional pillar and chamber arrays in RCS rats with 2 and 6 week follow-up demonstrate achievement of intimate proximity between the stimulation cites and the inner nuclear layer. In some instances formation of a fibrotic seal has been observed.

Proceedings Article | 7 March 2006 Paper

Plasma-mediated transfection of RPE

D. Palanker, T. Chalberg, A. Vankov, P. Huie, F. Molnar, A. Butterwick, M. Calos, M. Marmor, M. Blumenkranz

Proceedings Volume 6138, 61381E (2006) https://doi.org/10.1117/12.649624

KEYWORDS: Electrodes, Retina, Tissues, Content addressable memory, Eye, Ultrasonography, Luminescence, Eye models, In vivo imaging, Animal model studies

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A major obstacle in applying gene therapy to clinical practice is the lack of efficient and safe gene delivery techniques. Viral delivery has encountered a number of serious problems including immunological reactions and malignancy. Non-viral delivery methods (liposomes, sonoporation and electroporation) have either low efficiency in-vivo or produce severe collateral damage to ocular tissues. We discovered that tensile stress greatly increases the susceptibility of cellular membranes to electroporation. For synchronous application of electric field and mechanical stress, both are generated by the electric discharge itself. A pressure wave is produced by rapid vaporization of the medium. To prevent termination of electric current by the vapor cavity it is ionized thus restoring its electric conductivity. For in-vivo experiments with rabbits a plasmid DNA was injected into the subretinal space, and RPE was treated trans-sclerally with an array of microelectodes placed outside the eye. Application of 250-300V and 100-200 μs biphasic pulses via a microelectrode array resulted in efficient transfection of RPE without visible damage to the retina. Gene expression was quantified and monitored using bioluminescence (luciferase) and fluorescence (GFP) imaging. Transfection efficiency of RPE with this new technique exceeded that of standard electroporation by a factor 10,000. Safe and effective non-viral DNA delivery to the mammalian retina may help to materialize the enormous potential of the ocular gene therapy. Future experiments will focus on continued characterization of the safety and efficacy of this method and evaluation of long-term transgene expression in the presence of phiC31 integrase.

Proceedings Article | 7 March 2006 Paper

Dynamic range of safe electrical stimulation of the retina

Alexander Butterwick, Alexander Vankov, Phil Huie, Daniel Palanker

Proceedings Volume 6138, 61380Q (2006) https://doi.org/10.1117/12.650652

KEYWORDS: Electrodes, Laser damage threshold, Retina, Tissues, Glasses, Signal processing, Data modeling, Natural surfaces, In vitro testing, Experimental physics

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Electronic retinal prostheses represent a potentially effective approach for restoring some degree of sight in blind patients with retinal degeneration. However, levels of safe electrical stimulation and the underlying mechanisms of cellular damage are largely unknown. We measured the threshold of cellular damage as a function of pulse duration, electrode size, and number of pulses to determine the safe range of stimulation. Measurements were performed in-vitro on embryonic chicken retina with saline-filled glass pipettes for stimulation electrodes. Cellular damage was detected using Propidium Iodide fluorescent staining. Electrode size varied from 115μm to 1mm, pulse duration from 6μs to 6ms, and number of pulses from 1 to 7,500. The threshold current density was independent of electrode sizes exceeding 400μm. With smaller electrodes the current density was scaling reciprocal to the square of the pipette diameter, i.e. acting as a point source so that the damage threshold was determined by the total current in this regime. The damage threshold current measured with large electrodes (1mm) scaled with pulse duration as t^-0.5, which is characteristic of electroporation. For repeated electrical pulsed exposure on the retina the threshold current density varied between 0.059 A/cm2 at 6ms to 1.3 A/cm2 at 6μs. The dynamic range of safe stimulation, i.e. the ratio of damage threshold to stimulation threshold was found to be duration-dependent, and varied from 10 to 100 at pulse durations varying between 10μs to 10ms. Maximal dynamic range of 100 was observed near 1ms pulse durations.

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