Some applications of the invention relate generally to implantable medical devices and more specifically to a retinal prosthesis.
Retinal malfunction, due to degenerative retinal diseases, is a leading cause of blindness and visual impairment. Implantation of a retinal prosthesis is a technology for restoring some useful vision in individuals suffering from retinal-related blindness.
The retina is a multi-layered light-sensitive structure that lines the posterior, inner part of the eye. The retina contains photoreceptor cells, for example rods and cones, which capture light and convert light signals into neural signals transmitted through the optic nerve to the brain. Rods are responsible for light sensitive, low resolution black and white vision, whereas cones are responsible for high resolution color vision. Most cones lie in the fovea, which defines the center of the retina. A bipolar cell layer exists between the photoreceptors and ganglion cells of the retina. The bipolar cell layer transmits signals from the photoreceptors to the ganglion cells whose axons form the optic nerve and transmit visual information to the brain.
Grill W., et al. describe in an article, entitled “Implanted Neural Interfaces: Biochallenges and Engineered Solutions,” Annu. Rev. Biomed. Eng. 2009. 11:1-24, a regenerative sieve electrode that has holes to allow processes from a severed neuron to grow through. The article includes a schematic illustration of a sieve electrode.
U.S. Pat. No. 6,908,470 to Stieglitz describes a sieve electrode for connection to a nerve stump, which is composed of a thin flexible substrate with a plurality of ports for nerve filaments and several electrodes that are disposed on at least some of said ports on said substrate and adapted for being electrically contacted via conductors on said substrate, as well as of at least one counter-electrode. The substrate presents tabs protruding from the edge for fixing the substrate on a face of the nerve stump, which serve, at the same time, as carrier of the counter electrode. With this sieve electrode a neuro-technological interface is provided that is described as permitting a low-lesion contact with the nerve stump at a maximum of useable surface for the ports.
U.S. Pat. No. 4,969,468 to Byers describes an electrode array device for making multiple electrical contacts with cellular tissue or organs. The electrode array includes a base, a two dimensional array of conducting protuberances arising from the base and serving as electrodes, and conductors embedded onto the base and connected to such protuberances for transmitting electrical signals to and/or from the protuberances. The protuberances may also include an insulating layer which covers either the entire protuberance or which leaves the tips exposed for making focused electrical contact. Electrode arrays may be used singly or in combination with a second electrode array so as to form a sandwich around a target tissue. The sandwich electrode array may employ indexing cones for aligning the opposing electrode arrays and for limiting their vertical proximity. The conductors of the electrode array may be electronically connected or coupled to processing circuitry which amplifies and analyzes the signal received from the tissue and/or which generates signals which are sent to the target tissue and possibly coordinates the generated signals with signals which originate with the tissue.
The following patents and patent application publications may be of interest:
U.S. Pat. No. 1,662,446
U.S. Pat. No. 2,721,316
U.S. Pat. No. 2,760,483
U.S. Pat. No. 4,272,910
U.S. Pat. No. 4,551,149
U.S. Pat. No. 4,601,545
U.S. Pat. No. 4,628,933
U.S. Pat. No. 4,664,117
U.S. Pat. No. 4,837,049
U.S. Pat. No. 4,903,702
U.S. Pat. No. 5,016,633
U.S. Pat. No. 5,024,223
U.S. Pat. No. 5,108,427
U.S. Pat. No. 5,109,844
U.S. Pat. No. 5,133,356
U.S. Pat. No. 5,147,284
U.S. Pat. No. 5,159,927
U.S. Pat. No. 5,397,350
U.S. Pat. No. 5,411,540
U.S. Pat. No. 5,476,494
U.S. Pat. No. 5,526,423
U.S. Pat. No. 5,575,813
U.S. Pat. No. 5,674,263
U.S. Pat. No. 5,575,813
U.S. Pat. No. 5,597,381
U.S. Pat. No. 5,800,533
U.S. Pat. No. 5,800,535
U.S. Pat. No. 5,836,996
U.S. Pat. No. 5,837,995
U.S. Pat. No. 5,865,839
U.S. Pat. No. 5,873,901
U.S. Pat. No. 5,895,415
U.S. Pat. No. 5,935,155
U.S. Pat. No. 5,944,747
U.S. Pat. No. 6,032,062
U.S. Pat. No. 6,230,057
U.S. Pat. No. 6,298,270
U.S. Pat. No. 6,324,429
U.S. Pat. No. 6,368,349
U.S. Pat. No. 6,389,317
U.S. Pat. No. 6,442,431
U.S. Pat. No. 6,473,365
U.S. Pat. No. 6,507,758
U.S. Pat. No. 6,611,716
U.S. Pat. No. 6,658,299
U.S. Pat. No. 6,677,225
U.S. Pat. No. 6,678,458
U.S. Pat. No. 6,755,530
U.S. Pat. No. 6,762,116
U.S. Pat. No. 6,770,521
U.S. Pat. No. 6,923,669
U.S. Pat. No. 6,976,998
U.S. Pat. No. 7,003,354
U.S. Pat. No. 7,006,873
U.S. Pat. No. 7,025,619
U.S. Pat. No. 7,027,874
U.S. Pat. No. 7,031,776
U.S. Pat. No. 7,037,943
U.S. Pat. No. 7,047,080
U.S. Pat. No. 7,081,630
U.S. Pat. No. 7,096,568
U.S. Pat. No. 7,103,416
U.S. Pat. No. 7,107,097
U.S. Pat. No. 7,139,612
U.S. Pat. No. 7,162,308
U.S. Pat. No. 7,251,528
U.S. Pat. No. 7,321,796
US Patent Application Publication 2006/0282128
US Patent Application Publication 2007/0191909
US Patent Application Publication 2010/0174224
PCT WO 2003/32946
PCT WO 2001/91854
PCT WO 2007/09539
The following articles may be of interest:
David C N G, et al., “Pulse frequency modulation based CMOS image sensor for subretinal stimulation” IEEE Transactions on Circuits and Systems-II: Express Briefs, Volume 53, No 6, June 2006.
Jourdain R P., et al., “Fabrication of piezoelectric thick-film bimorph micro-actuators from bulk ceramics using batch-scale methods” Multi-Material Micro Manufacture, S. Dimov and W. Menz (Eds.) 2008 Cardiff University, Cardiff, UK., Whittles Publishing Ltd.
Kim B., “Through-Silicon-Via Copper Deposition for Vertical Chip Integration” Master. Res. Soc. Symp. Proc. Vol. 970, 2007 Material Research Society
Lianga C, et al., “Surface modification of cp-Ti using femtosecond laser micromachining and the deposition of Ca/P layer” Materials Letters Volume 62, Issue 23, 31 Aug. 2008, Pages 3783-3786.
Puech M., et al., “Fabrication of 3D packaging TSV using DRIE” ALCATEL Micro Machining Systems, www.adixen.com
Seo J M., et al., “Biocompatibility of polyimide microelectrode array for retinal stimulation,” Materials Science and Engineering: C, Volume 24, Number 1, 5 Jan. 2004, pp. 185-189(5)”
Sorkin R., et al., “Process entanglement as a neuronal anchorage mechanism to rough surfaces,” Nanotechnology 20 (2009) 015101 (8pp)
Starzyk J A, et al., “A DC-DC charge pump design based on voltage doublers” IEEE Transaction on Circuits and Systems-I: Fundamental theory and applications, Volume 48, No 3 March 2001.
Stein D J, et al., “High voltage with Si series photovoltaics” Proceedings of SPIE, the International Society for Optical Engineering 2006, vol. 6287, pp. 62870D.1-62870D.
Swain P K., et al., “Back-Illuminated Image Sensors Come to the Forefront. Novel materials and fabrication methods increase quality and lower cost of sensors for machine vision and industrial imaging.” Photonics Spectra August 2008.
Vorobyeva A Y. et al., “Metallic light absorbers produced by femtosecond laser pulses,” Advances in Mechanical Engineering, Volume 2010, Article ID 452749, 4 pages doi: 10.1155/2010/452749
Vorobyeva A Y. et al., “Femtosecond laser structuring of titanium implants,” Applied Surface Science, Volume 253, Issue 17, 30 Jun. 2007, Pages 7272-7280.
Wallman L., et al., “The geometric design of micromachined silicon sieve electrodes influences functional nerve regeneration,” Biomaterials 2001 May:22(10):1187-93
Walter P., et al., “Cortical Activation via an implanted wireless retinal prosthesis,” Investigative Ophthalmology and Visual Science. 2005; 46:1780-1785
Wu J T. and Chang K L., “MOS charge pumps for low-voltage operation” IEEE Journal of Solid-State Circuits, Volume 33 No. 4 April 1998.
Zrenner E., 2002, “Will retinal implants restore vision?” Science 295(5557), pp. 1022-5.
http://www.sony.net/SonyInfo/News/Press/200806/08-069E/index.html
In some applications of the present invention, a system is provided for restoring at least partial vision in a subject suffering from a retinal disease. The system comprises an apparatus comprising an external device, comprising a mount that is placed in front of the subject's eye. The mount may be, for example, a pair of eyeglasses. The external device further comprises a power source, for example a laser that is coupled to the mount and is configured to emit radiated energy that is outside the visible range directed toward the subject's eye.
The apparatus additionally comprises an intraocular device, which is implanted entirely in the subject's eye. The intraocular device comprises an intraocular retinal prosthesis, configured to be implanted in the subject's eye in either an epi-retinal or a sub-retinal position.
The intraocular device typically comprises a support substrate and an array of electrodes protruding from the support substrate. (In this context, in the specification and in the claims, “array” is meant to include rectangular as well as non-rectangular arrays (such as circular arrays). The protruding electrodes are shaped to define electrically-exposed tips which penetrate retinal tissue of the subject, bringing the electrodes in contact with the tissue. For some applications, a surface of the electrodes is treated to increase roughness and surface area of the electrodes, thus reducing electrode impendence and facilitating retinal stimulation and/or axon regeneration. Additionally or alternatively, the exposed tips of the electrodes have perforations passing therethrough, further increasing the surface area of the electrodes and allowing neuronal processes, to pass through and intertwine with the electrodes.
For some applications, the support substrate from which the electrodes protrude comprises additional elements of a retinal prosthesis, e.g., an energy receiving layer, a photosensor layer and driving circuitry that is powered by the energy receiving layer. The driving circuitry typically drives electrical charge into the retinal tissue from the tips of the electrodes, in response to sensing by the photosensor layer, in order to stimulate the retinal tissue.
For some applications, the photosensor layer is divided into units, each unit corresponding to a stimulating electrode in the array of electrodes.
The inventors have identified that, for some applications, sufficient stimulation of retinal tissue is a characteristic for consideration in enabling proper function of a retinal prosthesis. In particular, facilitating stimulation of the bipolar cell layer of the retina, which in turn stimulates ganglion cells, is a characteristic for consideration in retinal prosthesis provided by some applications of the present invention. The ganglion cells, whose axons form the optic nerve, further transmit the visual information to the brain resulting in the formation of an image. Penetrating perforated electrodes, in contrast to surface electrodes known in the art which sit on the surface of tissue, are configured to extend from either an epi-retinal or a sub-retinal implantation site and penetrate retinal tissue to directly contact and drive electrical charge into the bipolar cell layer from typically less than 10 um from the nearest bipolar cell. Rough electrode surfaces and perforations passing through the electrodes allow neuronal processes to grow therethrough, further improving cell-electrode coupling and increasing stimulation. Increased and direct contact of the retinal tissue by penetrating perforated electrodes enhances stimulation of the retina resulting in enhanced image resolution.
There is therefore provided in accordance with an application of the present invention, apparatus including:
an external device, including:
the external device is configured to modulate the energy emitted from the power source, and the control unit is configured to demodulate the modulated energy and in response regulate an operation parameter of the intraocular device.
For some applications, the apparatus includes a control element configured to receive an input from the subject, the external device is configured to modulate the energy emitted from the power source in response to the input.
For some applications, the operation parameter includes a characteristic of the electrical charges applied by the electrodes, and the control unit is configured to regulate the characteristic of the electrical charges applied by the electrodes.
For some applications, the characteristic of the electrical charges is a temporal characteristic of the electrical charges.
For some applications, the driving circuitry is configured to drive the electrodes to apply the electrical charges in pulses of electrical charge, and the temporal characteristic of the electrical charges is selected from the group consisting of: a number of the pulses, a frequency of the pulses, a duration of each pulse, and a pulse repetition interval of the pulses.
For some applications, the operation parameters include a sensitivity of the photosensors, and the control unit is configured to control the sensitivity of the photosensors.
For some applications, the sensitivity of the photosensors includes a duration of a sensing period of the photosensors, and the control unit is configured to regulate the duration of the sensing period of the photosensors.
For some applications, the operation parameters include a duration of an energy receiving period of the energy receiver, and the control unit is configured to regulate the duration of the energy receiving period of the energy receiver.
There is further provided, in accordance with an application of the present invention, apparatus including:
an external device, including:
an intraocular device configured to be implanted entirely in the subject's eye, the intraocular device including:
For some applications, the control unit is configured to regulate operation parameters of the intraocular device by applying a logarithmic transformation to the signal received by the photosensors.
For some applications, the operation parameters include a characteristic of the electrical charges applied by the electrodes, and the control unit is configured to regulate the characteristic of the electrical charges applied by the electrodes.
For some applications, the characteristic of the electrical charges is a temporal characteristic of the electrical charges.
For some applications, the driving circuitry is configured to drive the electrodes to apply the electrical charges in pulses of electrical charge, and the temporal characteristic of the electrical charges is selected from the group consisting of: a number of the pulses, a frequency of the pulses, a duration of each pulse, and a pulse repetition interval of the pulses.
For some applications, the operation parameters include a sensitivity of the photosensors, and the control unit is configured to control the sensitivity of the photosensors.
For some applications, the sensitivity of the photosensors includes a duration of a sensing period of the photosensors, and the control unit is configured to regulate the duration of the sensing period of the photosensors.
For some applications, the operation parameters include a duration of an energy receiving period of the energy receiver, and the control unit is configured to regulate the duration of the energy receiving period of the energy receiver.
For some applications, the control unit is configured to perform image processing in response to the signal generated by the plurality of photosensors.
For some applications, the control unit is configured to perform the image processing utilizing a process selected from a group consisting of: edge detection, focusing, light adjustment, averaging, and motion detection.
For some applications, the plurality of photosensors are color sensitive, and the driving circuitry is configured to regulate electrical charges driven through the electrodes in response to a color sensed by the photosensors.
For some applications, the driving circuitry is configured to create distinct stimulation patterns of the electrical charges applied to the retina, in response to the color sensed by the photosensors.
For some applications, the driving circuitry is configured to drive a first one of the electrodes to apply an electrical charge in response to the sensed color being a first color, and the driving circuitry is configured to drive a second one of the electrodes to apply an electrical charge in response to the sensed color being a second color.
There is still further provided, in accordance with an application of the present invention, apparatus configured for implantation in a body of a subject, the apparatus including:
an implantable array of at least 10 subsets of 3 or more electrodes; and
for each subset, a respective common power supply configured to provide current to the electrodes in the subset,
at least some of the electrodes in each subset are configured to drive respective electrical charges into tissue of the subject.
For some applications, the common power supply for each subset includes a common capacitor for each subset.
For some applications, the at least 10 subsets include 10-2500 subsets.
For some applications, a total volume of the apparatus is less than 0.2 cc.
For some applications, an electrode in at least one of the subsets is within 500 um of another electrode in the subset.
For some applications, an electrode in at least one of the subsets is within 300 um of another electrode in the subset.
There is additionally provided, in accordance with an application of the present invention, apparatus including:
an external device, including:
an intraocular device configured to be implanted entirely in the subject's eye, the intraocular device including:
There is yet additionally provided, in accordance with an application of the present invention, apparatus including:
There is yet additionally provided, in accordance with an application of the present invention, apparatus configured for implantation in an eye of a subject, the apparatus including:
an intraocular device including:
For some applications, the control unit is configured such that the electrical charge driven by each electrode in a subset is returned via a plurality of the other electrodes in the subset.
For some applications, the control unit is configured such that the electrical charge driven by each electrode in a subset is returned via all of the other electrodes in the subset.
For some applications, the control unit is configured such that the electrical charge driven by each electrode in a subset is returned via an electrode in the subset that serves as a common return electrode for the other electrodes in the subset.
There is still additionally provided, in accordance with an application of the present invention, apparatus including:
an external device, including:
For some applications, the die includes:
For some applications, the die further includes a charge pump configured to generate a voltage to be supplied to at least one component of the intraocular device.
For some applications, the external device is configured to modulate the energy emitted from the power source, and the die includes a control unit configured to demodulate the modulated energy and, in response, regulate an operation parameter of the intraocular device.
For some applications, the external device is configured to modulate the energy emitted from the power source, and the die includes a demodulator configured to demodulate the modulated energy and, in response, regulate an operation parameter of the intraocular device.
For some applications, the apparatus includes an additional die, the additional die including:
For some applications, the additional die includes a charge pump configured to generate a voltage to be supplied to the intraocular device.
For some applications, the external device is configured to modulate the energy emitted from the power source, and wherein the additional die includes a control unit configured to demodulate the modulated energy and, in response, regulate an operation parameter of the intraocular device.
For some applications, the external device is configured to modulate the energy emitted from the power source, and wherein the additional die includes a demodulator configured to demodulate the modulated energy and, in response, regulate an operation parameter of the intraocular device.
Vision is initiated when light reflecting from objects is focused by lens 2 of eye 4 onto the retina 6.
Bipolar cells 14 typically transmit signals from photoreceptors 10 to ganglion cells 12. The rod and cone photoreceptors transfer a signal to the bipolar cells that lay adjacent to the photoreceptor layer. The bipolar cells then transmit the signal to the ganglion cells whose axons form the optic nerve. The bipolar cell 14 are generally located in a region of the retina that is approximately 130 um-200 um from the inner limiting membrane (ILM), which is the boundary between the vitreous humor in the posterior chamber and the retina itself.
As shown in
For some applications, device 60 is implanted in a sub-retinal position (not shown). As described in Zrenner, 2002, which is incorporated herein by reference, sub-retinal arrays are typically implanted between the pigment epithelial layer 30 and the layer of the retina which contains photoreceptor cells 10.
As provided by some applications of the present invention, device 60 comprises a support substrate 62 and a plurality of electrodes 64 protruding from the support substrate. Support substrate 62 comprises components of an intraocular retinal prosthesis. For example, support substrate 62 may comprise an energy receiving layer, a photosensor layer and driving circuitry. The driving circuitry is powered by the energy receiving layer, which typically receives energy from an external device 600 comprising an external power source 24 (e.g., a laser coupled to the frame of a pair of eyeglasses 25, and/or a radiofrequency (RF) power source, and/or another electromagnetic power source). For some applications a partially-transparent (e.g., half-silvered) mirror 23 is coupled to eyeglasses 25, providing ophthalmoscope functionality to the external device.
It is to be noted that for some applications, techniques and apparatus described herein with reference to the external and intraocular devices may be performed with techniques and apparatus described in U.S. patent application Ser. No. 12/368,150 to Gross, et al., entitled, “Retinal Prosthesis,” filed Feb. 9, 2009, which issued as U.S. Pat. No. 8,150,526 to Gross et al., U.S. patent application Ser. No. 12/687,509 to Gefen et al., entitled “Penetrating electrodes for retinal stimulation, filed Jan. 14, 2010, which published as US 2011/0172736 to Gefen et al., and/or PCT/IL2010/000097 to Gross et al., entitled “Retinal Prosthesis,” filed Feb. 3, 2010, which published as WO/2010/089739 to Gross et al., all of which are assigned to the assignee of the present patent application and are incorporated herein by reference.
The driving circuitry drives electrodes 64 to apply electrical charges to the retina, in response to sensing by the photosensor layer, in order to stimulate the retina 6. Accordingly, system 20 for restoring vision in a subject does not comprise an extraocular camera, and intraocular device 60 does not receive image data from outside the eye, but rather utilizes the intact optics and processing mechanisms of the eye 4.
Intraocular device 60 typically comprises approximately 500-6000, e.g., 1000-4000, typically 1600 electrodes 64. For some applications, the electrodes protrude perpendicularly at least 50 um from the support substrate.
Each electrode is typically 100-1000 um in length e.g., 300-600 um, for example, 400 um, in order to reach the outer plexiform layer (OPL), where connections between the bipolar cells and the adjacent photoreceptor cells occur. For some applications, each electrode comprises an electrically-insulated body portion 68 coupled to an electrically exposed tip portion 70. Insulated portion 68 of the electrode has a length L1 of between 100 um and 650 um, e.g., 150 um. Exposed tip 70 of electrode 64 typically has a length L2 of between 25 um and 100 um, e.g., 50 um. Typically, electrode 64 has an exposed area of 750 um2. The electrodes 64 protrude from support substrate 62, such that when device 60 is implanted in an eye of a subject, electrodes 64 penetrate tissue of retina 6 and exposed tip portions 70 are typically disposed in layer of bipolar cells 14. Other dimensions of the electrodes are described hereinbelow, with reference to
For some applications, each electrode 64 is typically 25-100 um in length e.g., 50 um, in order to penetrate the nerve fiber layer (NFL) and reach the layer of ganglion cells 12 (GCL). Contacting the ganglion cells by electrodes 64 typically enables the use of a reduced amount of power in order to stimulate the ganglion cells. Close proximity to ganglion cells 12 generally results in more focused stimulation that enables higher pixel density for a given amount of electrical charge.
Reference is made to
Typically, a spatial density of the perforations of each pointed tip is 0.001-0.02 perforations/um2, or 0.02 to 0.5 perforations/um2, e.g., 0.1 perforations/um2. For some applications, each perforation has a diameter of 1-10 um. The diameter of the perforations in electrode 64 allows axons of bipolar cells, which typically have an average diameter of 1 um, to penetrate and grow through the perforations.
As mentioned hereinabove, for some applications electrodes 64 are disposed in the layer of ganglion cells 12. In such applications, the axons of the ganglion cells grow through the perforations in electrode tips 70, increasing coupling between the neuronal processes and electrodes 64, and improving stimulation of the ganglion cell layer.
The average diameter of the perforations is typically smaller than the average diameter of a retinal glial cell, which is typically larger than 10 um, preventing glial cells from passing through the perforations in the electrode. Preventing glial cells from passing through the perforations reduces glial encapsulation of the electrodes, and prolongs electrode function.
The perforations are typically created by use of chemical treatments e.g., etching and/or a laser beam. For some applications, the same treatment is used to create the perforations and to increase surface roughness. For some applications, a surface of tip 70 of electrode 64 is coated with carbon nanotubes, attracting neuronal processes to the perforations in tip 70 and increasing adhesion of the neuronal processes to the perforations. Typically, the carbon nanotube coating within the perforation can withstand penetration of neuronal processes into the perforations.
Reference is made to
Reference is made to FIGS. 1 and 2A-B. As shown in
Reference is again made to FIGS. 1 and 2A-B. As mentioned hereinabove, for some applications, electrodes 64 comprise bipolar electrodes that are configured to penetrate retinal tissue of a subject. Penetrating bipolar electrodes, which are typically implanted such that both the stimulating and return electrodes are in close proximity to a neuronal retinal cell, require a smaller potential between the electrodes and enable reaching a higher potential drop across a given cell, resulting in enhanced stimulation of the cell. This is in contrast to many epi-retinal implants known in the art in which neuronal cells of the retina are stimulated by a surface electrode on the ILM layer.
For some applications, an array 90 of electrodes 64 is divided into subsets of electrodes. For such applications, a subset of three or more, e.g., 3-6, stimulating electrodes, by way of illustration and not limitation, surround and share a common return electrode 8. Each electrode in the subset receives a signal, through driving circuitry, from a discrete, respective, photosensor in support substrate 62, and in response, stimulates the retina of the subject. In such applications, the return electrode typically has a sufficiently large surface area in order to accommodate the electric charge returning from the subset of stimulating electrodes. Generally, such an arrangement of array of electrodes 64 enables the use of a reduced number of electrodes, since several stimulating electrodes share a common return electrode. For some applications, the stimulating electrodes are configured to drive electrical charges into the cells of retina non-simultaneously. Such staggering of the driving of each electrode in the subset reduces the amount of return electrical charge that is driven through the return electrode at a given time. For some applications, array 90 comprises at least 10 subsets of electrodes, e.g., 100-500 subsets. For some applications, array 90 comprises 500-1500 subsets of electrodes.
Reference is again made to
Reference is now made to
Tip 70 may be shaped to define a tip having an angle alpha of 30-60 degrees. As shown in
As shown in
Typically, tip 70 of electrode 64 is treated to increase surface roughness of tip 70. For some applications, an area 73 of tip 70 is treated to increase roughness, whereas another area 75 of tip 70 remains untreated in order to maintain structural strength of the tip.
Reference is made to
For some applications, electrodes 64 are coated with carbon nanotubes. Typically, carbon nanotubes create a rough surface in electrode 64, including tip portion 70. Rough surfaces in general and carbon nanotube surfaces in particular have been shown to attract neurons and promote neuronal growth. As described in Sorkin et al., 2009 (referenced above) neurons were found to bind and preferentially anchor to carbon nanotube rough surfaces. Thus, adhesion of retinal neurons, e.g., bipolar cells, to carbon nanotube electrodes provided by these applications of the present invention, promotes cell-electrode coupling and/or axon regeneration, leading to improved stimulation of the retina. For some applications, the carbon nanotube coating of electrode 64 is glued to the electrode surface and/or grown on a selected surface of the electrode by using doping techniques known in the art.
For some applications, a femtosecond laser is used to increase surface roughness of electrodes 64. Femtosecond laser treatment produces rough surface structures on titanium possibly for the use of implants and other biomedical applications treatments (Vorobyev et al., 2007 referenced above). As described in Vorobyev et al., femtosecond laser treatment increases the roughness of a titanium substrate in the range of 1-15 um. Additionally, femtosecond laser treatment was shown to produce a variety of surface nanostructures, such as nanoprotrusions and nanopores on the titanium substrate. Liang et al., 2007, (referenced above), report good bioactivity of a pure titanium substrate that was treated with a femtosecond laser to increase roughness of its surface.
For some application, a blanket etch MEMS procedure is used to increase surface roughness of electrodes 64. For such applications, the entire electrode 64 is blanketed and tip 70 is etched to increase surface roughness and achieve a desired aspect ratio in a similar procedure to that described in U.S. Pat. No. 6,770,521 to Visokay.
Reference is made to
Electrodes 1064 comprise any suitable material e.g., palladium and/or titanium, and/or silicon electrodes. For some applications, electrodes 1064 comprise a metal alloy and/or doped electrodes. Typically, a silicon wafer 1030 forms the base of array 1090 from which electrodes 1064 protrude. For some applications, wafer 1030 is selectively etched to a desired depth by using any suitable technique known in the art, e.g., techniques of Deep Reactive Ion Etching (DRIE). For some applications, following bonding of the silicon wafer, electrodes 1064 are etched by using any suitable technique known in the art, e.g., techniques of Deep Reactive Ion Etching (DRIE), to have desired dimensions and aspect ratios. For some applications, additional metals such as platinum, and/or palladium, are deposited on electrodes 1064 by using, for example, a shadow mask technique. An attaching titanium ring frame 1020 is typically electroplated with electrodes 1064 to form structure that can subsequently be welded to the metal ring case 2020 (shown in
Typically, device 60 additionally comprises a CMOS chip 1040 including through-silicon vias. For some applications, solder bumps 1050 are deposited on an upper side of CMOS chip 1040, electrically connecting chip 1040 to silicon wafer 1030. Additionally, for some applications, device 60 comprises a layer 1060. Layer 1060 typically comprises additional elements of an intraocular retinal prosthesis, e.g., an energy receiving layer, a photosensor layer and driving circuitry that is powered by the energy receiving layer. The driving circuitry typically drives electrical charge into the retinal tissue from the rough tips 1070 of electrodes 1064, in response to sensing by the photosensor layer, in order to stimulate the retinal tissue. The electrical signal generated by layer 1060 is typically routed through silicon wafer 1030 to electrodes 1064, providing sealing on one side and electrical contact on the other.
For some applications, a back side of the titanium wafer is bound to a glass cap 80 which, as shown in
Reference is made to
Reference is now made to
As described hereinabove with reference to
Typically, intraocular device 60 is configured to match the natural curvature of the retina to facilitate implantation and anchoring of intraocular device 60 to the retina. Accordingly, electrodes 1064 typically vary in length, and as indicated by
Reference is made to
Intraocular device 60 and electrodes 1064 are typically configured to match the natural curvature of a human organ and/or tissue in which it is implanted, e.g., the retina. As shown in
Reference is made to
For other applications, one electrode (either the + or the −) protrudes from intraocular device 60 and is configured to penetrate tissue of retina 6, and the other electrode, of opposite polarity, is a surface electrode that is not configured to penetrate tissue of retina 6, but rather functions as a return electrode (application not shown). Typically, intraocular device 60 comprises at least 100 short or surface electrodes, and at least 400 long electrodes.
For some applications, electrodes 1064 comprise hook electrodes configured to anchor to retinal tissue of a subject, increasing coupling between the target cells and the electrode.
Reference is made to
Reference is again made to
It is to be noted that a system comprising penetrating electrodes with rough and/or perforated tips as described hereinabove with reference to
For some applications, a system comprising penetrating electrodes as described hereinabove may be used to stimulate organs such as the liver or the pancreas. Implanting an array of such electrodes in, for example, selected areas of pancreatic tissue (e.g., insulin-secreting areas) enables specific and more effective stimulation of these areas.
Reference is again made to
Reference is made to
Typically, photosensors 34 are arranged as an array of photosensors 34. In some configurations of device 60, each photosensor in the array of photosensors corresponds to a stimulating electrode in the array of electrodes 1064. For some applications, each photosensor functions independently, i.e., each photosensor receives photons 33 and in response sends signals to driving circuitry 36, whereupon the driving circuitry drives the corresponding electrode to apply electrical charge to the retina 6. Thus, intraocular device 60 comprises an array of photosensor units, each photosensor unit comprising a photosensor and a corresponding electrode. Accordingly, the degree of retinal stimulation applied by each photosensor unit in the intraocular device is dictated by the light received by that unit. For some applications, each photosensor unit translates the level of light received by that unit into a train of stimulation pulses that is applied to the retina by the electrode. Additionally, such conversion of intensity of received light to frequency of stimulation can include a log transformation, such that for example: × photons received by the photosensor unit translate into one stimulation pulse applied by the electrode, while 10× photons correspond to only 2 stimulation pulses applied by the electrode.
Although functioning independently from one another, for some applications, a central control unit 200 regulates the function of each photosensor and corresponding electrode unit. Additionally or alternatively, each photosensor unit is configured to communicate with other units located in close proximity, and to modulate the electrical charge it drives into the retina in response to the functioning of neighboring units. Regulation of the electrical charge applied by each unit in the array of photosensors 34 with respect to other units in the array facilitates regulation of diverse features of visual perception. Varying the electrical charges applied to retinal neurons allows improved processing of the electrical charge by the retinal neurons e.g., bipolar cells.
For some applications, processing is performed by control unit 200. In some configurations of intraocular device 60, there is a larger number of photosensors than stimulating electrodes. For example, processing by control unit 200 can include disabling a bad pixel, improving focus of an image, sharpening, level adjustment, edge enhancement, and motion detection. Typically, this is performed using the data provided by the significantly larger number of photosensors than stimulating electrodes. Thus, edge detection and enhancement (or other image processing techniques) are performed using the hundreds of data points (or more), which are available to the control unit after having been sampled by the individual photosensors. This processing is used to allow the smaller number of stimulating electrodes to apply a more meaningful form of retinal stimulation, which reflects the output of the image processing (e.g., by showing an enhanced edge, emphasizing motion, or sharpening individual elements of an image). The scope of the present invention includes performing any of the image processing techniques described herein, even if the number of photosensors is not smaller than the number of stimulating electrodes. For some applications, a standard process is utilized in order to, e.g., enhance sensitivity by summation, edge detection for a clearer image, noise reduction in time and space, and/or adaptive dynamic range. Alternatively, the control unit facilitates processing, such as edge enhancement, by horizontal and/or amacrine cells of the retina, by providing a simpler image than that imaged by the photosensors. This simpler image is more easily processed by the retina neuron network.
For some applications, intraocular device 60 comprises protruding electrodes which are sufficient in length to contact bipolar cells 14 (shown in
For some applications, device 60 may comprise protruding electrodes that are shorter in length (e.g., 50-200 um, e.g., 100-150 um) and configured to directly contact the layer of ganglion cells 12 (shown in
Reference is again made to
Additionally or alternatively, central control unit 200 sets the duration of an energy receiving period, i.e., the amount of time in which energy receiver 32 receives energy from external power source 24 before that energy is passed to driving circuitry 36 to drive the electrodes to drive electrical charges into retinal tissue (e.g., 1-10 ms, or 10-100 ms). For example, control unit 200 may increase the duration of an energy receiving period to supply device 60 with a sufficient amount of energy, e.g., if the subject increases the intensity such that a larger amount of electrical charge is applied through the electrodes, resulting in device 60 requiring an increased amount of energy. Further additionally or alternatively, central control unit 200 regulates the stimulation timing.
Reference is still made to
For example, if the subject determines that the overall stimulation being applied by device 60 to the retina is too strong, then he can adjust a setting on the control element to reduce the stimulation strength. Similarly, if he senses that his entire visual field is over-stimulated, indicating that the sensitivity of photosensors 34 is too high (e.g., resulting in the entire array of electrodes activating the retina at high intensity), then he can adjust another setting on the control element to reduce the sensitivity. In response to the subject's input, the energy emitted by the power source is modulated to regulate operating parameters of device 60, e.g., to increase or decrease intensity and/or sensitivity. An example of a suitable modulation protocol includes a first train of six short pulses from power source 24, indicating that stimulation intensity is going to be changed, followed by a train of between one and ten longer pulses indicating a subject-selected desired level of stimulation intensity. To change sensitivity, a first train of six long pulses is emitted from power source 24, followed by a train of between one and ten longer pulses indicating a subject-selected desired level of sensitivity. A person of ordinary skill in the art will appreciate that other encoding protocols may be used, as well.
Typically, central control unit 200 receives modulated energy from energy receiver 32, and demodulates the energy to regulate operation of device 60 accordingly. For example, based on the subject's input, the energy emitted by power source 24 is modulated to signal to device 60 to decrease or increase sensitivity of photosensors 34. (For example, the modulation may include changes in pulse timing of pulses emitted by power source 24.) Control unit 200 is configured to demodulate the energy received by energy receiver 32 and, for example, accordingly determine the duration of a sensing period of the photosensors, i.e., the amount of time in which the photosensors receive photons before the driving circuitry drives the corresponding electrode to drive electrical charge into retinal tissue (e.g., 0.1 ms-5 ms, or 5 ms-100 ms). This thereby increases or decreases the sensitivity of the photosensors according to the subject's input. Additionally or alternatively, control unit 200 is configured to demodulate the energy received by energy receiver 32 and accordingly regulate the driving circuitry to alter the intensity of electrical charge applied to the retina by altering a stimulation parameter such as a number of the pulses, a frequency of the pulses, duration of each pulse, and a pulse repetition interval of the pulses.
Alternatively, the function of elements and/or arrays and/or sub-arrays of device 60 are controlled by several distributed control units.
For example, for some applications, each photosensor and corresponding electrode unit is controlled by an individual control unit which regulates system parameters, such as parameters of the photosensor. In an application, the sensitivity of the photosensors is regulated, for example, by setting the duration of a sensing period of each photosensor (i.e., the amount of time in which the photosensor receives photons before the driving circuitry drives the corresponding electrode to drive electrical charge into retinal tissue). For other applications, separate control units regulate the function of each subset of electrodes and corresponding photosensors.
Reference is made to
Reference is again made to
Reference is still made to
Typically each subset 3002 of electrodes shares a common power supply, e.g., a common capacitor 3004, which provides current (typically non-simultaneously) to all of the electrodes in a respective subset. In such applications, the capacitor in each subset is sufficiently large (e.g., 0.01-0.1 nf, or 0.1 nf-1 nf) to allow charging to less than 50% of full-charge of the capacitor during each charging of the capacitor. Using a large capacitor generally enhances the efficiency of intraocular device 60, since it allows for the capacitor to quickly recharge once it has provided currents to the electrodes. In contrast, using a single small capacitor in order to drive a single electrode typically requires a longer recharging period and is therefore less efficient. However, it is generally not possible to have one large capacitor per electrode, in an array of 100-1000 electrodes. As provided by some applications of the present invention, an array of several subsets of electrodes, in which each subset is driven by a respective common large capacitor, allows for the use of a reduced number of large capacitors, thus allowing the use of a large capacitor to drive a plurality of electrodes and thereby improving efficiency of the device.
For some applications, electrodes 1064 are arranged in subsets of stimulating electrodes which surround and share a common return electrode (as described hereinabove). At least some of the stimulating electrodes 1064 in each subset are configured to drive electrical charges into the neurons of the retina in non-simultaneous time periods. Consequently, for such applications, the common return electrode receives electrical charges from at least some of the stimulating electrodes in the subset non-simultaneously. Such staggering of the driving of each electrode and of the returning current generally reduces interference and neuron load. Such staggering also reduces tissue damage and/or prolongs the lifetime of the return electrode: Additionally, for applications in which the electrodes are arranged in subsets of electrodes, staggering of the driving of each electrode generally reduces the charge density per subset. Additionally or alternatively, staggering of the driving of each electrode generally reduces interference between adjacent neuron fibers, typically leading to improved sensation of vision.
For some applications, no dedicated return electrode is provided, but instead while one electrode in a subset drives electrical charges into the retina, some or all of the remaining electrodes in the subset act, collectively, as a return electrode.
Typically, application of electrical charges to the cells may be programmed such that generation of sub-harmonics and/or beat frequencies, and/or artificial frequencies and/or sensations of a flicker are reduced. For example intraocular device 60 may be configured to apply electrical charge through electrodes 1064 in a subset using changing sequences. For example, apparatus 60 may be configured to apply electrical charge through four electrodes in a subset using the sequence 1-2-3-4, followed by applying the electrical charge in a different sequence (3-1-2-4), by way of illustration and not limitation. Alternatively, the electrical charge is applied using time-based jittering of at least some of the electrical charge applications, to reduce the generation of sub-harmonics and/or beat frequencies, and/or artificial frequencies and/or sensations of a flicker. For example, instead of applying electrical charge pulses separated by a standard time gap, the time gap can be “jittered” by introducing a time variation in the frequency of these successive electrical charge pulses. Alternatively or additionally, other signal parameters may be jittered, such as pulse duration and amplitude. For some applications, a fuzzy logic, multi-value, concept is applied. For example, instead of having a single fixed parameter for power amplitude or jitter, the system has a range of each parameter and it will scan through this range in a regular or pseudorandom procedure. (In biological systems, the exact parameter that will produce an optimal response at any time is changing, but the range of the parameter is generally known.)
For some applications, system 20 is configured to restore at least some color vision in a subject suffering from damaged retinal photoreceptor cells, e.g., cones, by stimulating intact portions of the retina, e.g., the bipolar cells. Most cones lie in the fovea, which defines the center of the retina. Humans normally have three types of cones responding to different wavelengths. A different signal is applied by the different cone types, allowing perception of different colors. A typical cone cell forms a synapse with a neuron such as the bipolar cell. Intraocular device 60 is configured to drive the electrodes to directly stimulate different bipolar cells resulting in perception of different colors. Additionally or alternatively, the electrical charge driven by the electrodes into the retina is modulated such that different stimulation patterns are applied to the retina resulting in the perception of color (e.g., red, green and/or blue). Intraocular device 60 can then be calibrated based on the subject's input as to which stimulation pattern (typically based on varying pulse parameters) creates an optimal perception of color.
Additionally, photosensors 34 are color sensitive and configured to distinguish between certain colors (e.g., red, green and/or blue). Accordingly, electrodes 1064 are typically designated red, green and/or blue (by way of illustration and not limitation), corresponding to the colors sensed by photosensors 34. According to the sensing of different colors, the driving circuitry in intraocular device 60 drives electrical charges through the corresponding electrodes, resulting in the sensation of different colors (typically after an acclimation and/or training period).
Reference is still made to
For some applications, power source 24 of the external device comprises an RF emitting power source. For such applications in which the power source comprises an RF emitting power source, an intraocular lens (IOL) is implanted in the eye of the subject, replacing the native lens. Typically, an RF receiving coil configured to receive RF energy emitted from the power source is incorporated into the IOL (configuration not shown). Incorporation of the RF receiving coil in the IOL, instead of implanting such a coil in a small epi-retinal space, generally enables the use of a large diameter RF receiving coil (e.g., 8-14 mm in diameter). Additionally, an RF receiving coil which is located in the IOL is in relative close proximity to the RF power source, enabling the use of a reduced amount of energy. Typically, the macula of the retina is spaced about 4-5 cm from eyeglasses 25 (eyeglasses 25 are shown in
Reference is made to
The photosensor signal is transmitted to driving circuitry 36 which drives electrode 1064 to apply electrical charges to cells of the retina. As shown, for some applications, electrodes 1064 are coupled to a custom-made ASIC die 260. Typically, device 60 comprises a custom-made ASIC die 260 which additionally includes a charge pump 280, a demodulator 290, a control unit 2000, and an image processor 310. Energy from external power source 24 reaches energy receiver 32 and is passed via charge pump 280 to power components of intraocular device 60. The charge pump generates a higher voltage to be supplied to digital components of device 60. In addition to supplying power to components of ASIC die 260, charge pump 280 supplies power to imager die 240. Alternatively or additionally, photovoltaic cell dies of energy receiver 32 can be cascade wired, and thereby configured to increase voltage and enhance power supply to device 60. Energy from the energy receiver and charge pump is additionally passed to demodulator 290 and control unit 2000 in ASIC die 260. The demodulator typically receives modulated energy from energy receiver 32, and demodulates the energy to regulate, together with the control unit, operation of device 60 as described hereinabove with reference to
ASIC die 260 further comprises an image processor 310 and is coupled to stimulating electrodes 1064 via driving circuitry 36 (including, for example, analog amplification functionality). The control unit typically regulates processing of the signal generated by photosensors 34 by image processor 310 in accordance with the now demodulated information. The processed photosensor signal is passed to driving circuitry 36, which drives stimulating electrodes 1064 to apply electrical charge to the retina of a subject.
For other applications, custom-made ASIC die 260 may, additionally to the above-mentioned components, also comprise energy receiver 32 and/or photosensors 34 or any combination thereof.
In an additional configuration, intraocular device 60 comprises custom-made ASIC die 260 and at least one photovoltaic die which comprises energy receiver 32 and photosensors 34.
Typically, ASIC die 260 comprises an integral BIT (built-in test), configured to generate an output when device 60 is implanted in an eye of a subject and transfer the output either in a wired or wireless manner, enabling calibration of device 60 after implantation. Alternatively, the output is used to calibrate device 60 prior to implantation, e.g., during manufacturing or pre-implantation processing.
Reference is now made to
CMOS imager die 240 and energy receiving photovoltaic dies 32 are typically arranged in an array 900, which comprises the front side 910 of device 60 (the anterior side, when implanted). Typically, the imager die and the photovoltaic dies include a back side thereof, which forms the active surface 400 of these components. Solder bumps 1050 are deposited on a back side of array 900, electrically connecting array 900 to custom-made ASIC die 260 which typically includes through-silicon vias 1055. Alternatively the dies can be connected with wire bonding techniques. As shown in
Reference is made to
Reference is made to
For some applications, intraocular device 60 comprises a plurality of fully functional cells 500 as described hereinabove with reference to
For some applications, the plurality of cells 500 are arranged in clusters of cells. Typically, the receiving of energy from the power source, and the receiving of visible light from an object, occur in two phases. For example, during a first phase, cells 500 in a cluster receive visible light and during a second phase receive energy from the power source, e.g., IR energy. The visible light received during the first phase is then used to define tissue stimulation during the second phase. Typically, the stimulation of each electrode in a given cluster occurs in sequence, in order to reduce short-term power requirements. Thus, for example, if there are four cells in a cluster, then during the second phase, each cell is actuated, in turn, to apply tissue stimulation in accordance with the light sensed by the photosensor of that cell.
Reference is made to
Reference is made to
Reference is made to
The scope of the present invention includes embodiments described in the following patent applications, which is incorporated herein by reference. For some applications, techniques and apparatus described in the following patent application are combined with techniques and apparatus described herein:
For some applications, techniques described herein are practiced in combination with techniques described in one or more of the references cited in the Background section of the present patent application, which are incorporated herein by reference.
It will be appreciated by persons skilled in the art that the present invention is not limited to what has been particularly shown and described hereinabove. Rather, the scope of the present invention includes both combinations and subcombinations of the various features described hereinabove, as well as variations and modifications thereof that are not in the prior art, which would occur to persons skilled in the art upon reading the foregoing description.
Number | Name | Date | Kind |
---|---|---|---|
1662446 | Wappler | Mar 1928 | A |
2721316 | Shaw | Oct 1955 | A |
2760483 | Edward | Aug 1956 | A |
4272910 | Danz | Jun 1981 | A |
4551149 | Sciarra | Nov 1985 | A |
4601545 | Kern | Jul 1986 | A |
4628933 | Michelson | Dec 1986 | A |
4664117 | Beck | May 1987 | A |
4786818 | Mead et al. | Nov 1988 | A |
4837049 | Byers et al. | Jun 1989 | A |
4903702 | Putz | Feb 1990 | A |
4914738 | Oda et al. | Apr 1990 | A |
4969468 | Byers et al. | Nov 1990 | A |
5016633 | Chow | May 1991 | A |
5024223 | Chow | Jun 1991 | A |
5081378 | Watanabe | Jan 1992 | A |
5108427 | Majercik et al. | Apr 1992 | A |
5109844 | de Juan, Jr. et al. | May 1992 | A |
5133356 | Bryan et al. | Jul 1992 | A |
5147284 | Fedorov et al. | Sep 1992 | A |
5159927 | Schmid | Nov 1992 | A |
5215088 | Normann et al. | Jun 1993 | A |
5397350 | Chow et al. | Mar 1995 | A |
5411540 | Edell et al. | May 1995 | A |
5476494 | Edell et al. | Dec 1995 | A |
5526423 | Ohuchi et al. | Jun 1996 | A |
5575813 | Edell et al. | Nov 1996 | A |
5597381 | Rizzo, III | Jan 1997 | A |
5608204 | Hofflinger et al. | Mar 1997 | A |
5674263 | Yamamoto et al. | Oct 1997 | A |
5769875 | Peckham et al. | Jun 1998 | A |
5800478 | Chen et al. | Sep 1998 | A |
5800533 | Eggleston et al. | Sep 1998 | A |
5800535 | Howard, III | Sep 1998 | A |
5835250 | Kanesaka | Nov 1998 | A |
5836996 | Doorish | Nov 1998 | A |
5837995 | Chow et al. | Nov 1998 | A |
5865839 | Doorish | Feb 1999 | A |
5873901 | Wu et al. | Feb 1999 | A |
5895415 | Chow et al. | Apr 1999 | A |
5935155 | Humayun et al. | Aug 1999 | A |
5944747 | Greenberg et al. | Aug 1999 | A |
5949064 | Chow et al. | Sep 1999 | A |
6020593 | Chow et al. | Feb 2000 | A |
6032062 | Nisch | Feb 2000 | A |
6035236 | Jarding et al. | Mar 2000 | A |
6043437 | Schulman et al. | Mar 2000 | A |
6069365 | Chow et al. | May 2000 | A |
6075251 | Chow et al. | Jun 2000 | A |
6201234 | Chow et al. | Mar 2001 | B1 |
6230057 | Chow et al. | May 2001 | B1 |
6259937 | Schulman et al. | Jul 2001 | B1 |
6287372 | Briand et al. | Sep 2001 | B1 |
6298270 | Nisch et al. | Oct 2001 | B1 |
6324429 | Shire et al. | Nov 2001 | B1 |
6347250 | Nisch et al. | Feb 2002 | B1 |
6368349 | Wyatt et al. | Apr 2002 | B1 |
6389317 | Chow et al. | May 2002 | B1 |
6400989 | Eckmiller | Jun 2002 | B1 |
6427087 | Chow et al. | Jul 2002 | B1 |
6442431 | Veraart et al. | Aug 2002 | B1 |
6458157 | Suaning | Oct 2002 | B1 |
6472122 | Schulman et al. | Oct 2002 | B1 |
6473365 | Joh et al. | Oct 2002 | B2 |
6498043 | Schulman et al. | Dec 2002 | B1 |
6507758 | Greenberg et al. | Jan 2003 | B1 |
6533798 | Greenberg et al. | Mar 2003 | B2 |
6574022 | Chow et al. | Jun 2003 | B2 |
6611716 | Chow et al. | Aug 2003 | B2 |
6647297 | Scribner | Nov 2003 | B2 |
6658299 | Dobelle | Dec 2003 | B1 |
6677225 | Ellis et al. | Jan 2004 | B1 |
6678458 | Ellis et al. | Jan 2004 | B2 |
6683645 | Collins et al. | Jan 2004 | B1 |
6738672 | Schulman et al. | May 2004 | B2 |
6755530 | Loftus et al. | Jun 2004 | B1 |
6758823 | Pasquale et al. | Jul 2004 | B2 |
6761724 | Zrenner et al. | Jul 2004 | B1 |
6762116 | Skidmore | Jul 2004 | B1 |
6770521 | Visokay et al. | Aug 2004 | B2 |
6785303 | Holzwarth et al. | Aug 2004 | B1 |
6792314 | Byers et al. | Sep 2004 | B2 |
6804560 | Nisch et al. | Oct 2004 | B2 |
6821154 | Canfield et al. | Nov 2004 | B1 |
6844023 | Schulman et al. | Jan 2005 | B2 |
6847847 | Nisch et al. | Jan 2005 | B2 |
6888571 | Koshizuka et al. | May 2005 | B1 |
6904239 | Chow et al. | Jun 2005 | B2 |
6908470 | Stieglitz et al. | Jun 2005 | B2 |
6923669 | Tsui et al. | Aug 2005 | B1 |
6935897 | Canfield et al. | Aug 2005 | B2 |
6949763 | Ovadia et al. | Sep 2005 | B2 |
6961619 | Casey | Nov 2005 | B2 |
6970745 | Scribner | Nov 2005 | B2 |
6974533 | Zhou | Dec 2005 | B2 |
6976998 | Rizzo et al. | Dec 2005 | B2 |
6990377 | Gliner et al. | Jan 2006 | B2 |
7001608 | Fishman et al. | Feb 2006 | B2 |
7003354 | Chow et al. | Feb 2006 | B2 |
7006873 | Chow et al. | Feb 2006 | B2 |
7025619 | Tsui et al. | Apr 2006 | B2 |
7027874 | Sawan et al. | Apr 2006 | B1 |
7031776 | Chow et al. | Apr 2006 | B2 |
7035692 | Maghribi et al. | Apr 2006 | B1 |
7037943 | Peyman | May 2006 | B2 |
7047080 | Palanker et al. | May 2006 | B2 |
7058455 | Huie, Jr. et al. | Jun 2006 | B2 |
7071546 | Fey et al. | Jul 2006 | B2 |
7079881 | Schulman et al. | Jul 2006 | B2 |
7081630 | Saini et al. | Jul 2006 | B2 |
7096568 | Nilsen et al. | Aug 2006 | B1 |
7103416 | Ok et al. | Sep 2006 | B2 |
7107097 | Stern et al. | Sep 2006 | B2 |
7127286 | Mech et al. | Oct 2006 | B2 |
7127301 | Okandan et al. | Oct 2006 | B1 |
7130693 | Montalbo | Oct 2006 | B1 |
7133724 | Greenberg et al. | Nov 2006 | B2 |
7139612 | Chow et al. | Nov 2006 | B2 |
7147865 | Fishman et al. | Dec 2006 | B2 |
7149586 | Greenberg et al. | Dec 2006 | B2 |
7158834 | Paul, Jr. | Jan 2007 | B2 |
7158836 | Suzuki | Jan 2007 | B2 |
7160672 | Schulman et al. | Jan 2007 | B2 |
7162308 | O'Brien et al. | Jan 2007 | B2 |
7177697 | Eckmiller et al. | Feb 2007 | B2 |
7190051 | Mech et al. | Mar 2007 | B2 |
7191010 | Ohta et al. | Mar 2007 | B2 |
7224300 | Dai et al. | May 2007 | B2 |
7224301 | Dai et al. | May 2007 | B2 |
7235350 | Schulman et al. | Jun 2007 | B2 |
7242597 | Shodo | Jul 2007 | B2 |
7244027 | Sumiya | Jul 2007 | B2 |
7248928 | Yagi | Jul 2007 | B2 |
7251528 | Harold | Jul 2007 | B2 |
7255871 | Huie, Jr. et al. | Aug 2007 | B2 |
7257446 | Greenberg et al. | Aug 2007 | B2 |
7263403 | Greenberg et al. | Aug 2007 | B2 |
7271525 | Byers et al. | Sep 2007 | B2 |
7272447 | Stett et al. | Sep 2007 | B2 |
7291540 | Mech et al. | Nov 2007 | B2 |
7295872 | Kelly et al. | Nov 2007 | B2 |
7302598 | Suzuki et al. | Nov 2007 | B2 |
7314474 | Greenberg et al. | Jan 2008 | B1 |
7321796 | Fink et al. | Jan 2008 | B2 |
7342427 | Fensore et al. | Mar 2008 | B1 |
7377646 | Suzuki | May 2008 | B2 |
7379000 | Dai et al. | May 2008 | B2 |
7388288 | Solzbacher et al. | Jun 2008 | B2 |
7400021 | Wu et al. | Jul 2008 | B2 |
7447547 | Palanker | Nov 2008 | B2 |
7447548 | Eckmiller | Nov 2008 | B2 |
7480988 | Ok et al. | Jan 2009 | B2 |
7481912 | Stelzle et al. | Jan 2009 | B2 |
7482957 | Dai et al. | Jan 2009 | B2 |
7483751 | Greenberg et al. | Jan 2009 | B2 |
7493169 | Greenberg et al. | Feb 2009 | B2 |
7499754 | Greenberg et al. | Mar 2009 | B2 |
7539544 | Greenberg et al. | May 2009 | B2 |
7555328 | Schulman et al. | Jun 2009 | B2 |
7556621 | Palanker et al. | Jul 2009 | B2 |
7565202 | Greenberg et al. | Jul 2009 | B2 |
7565203 | Greenberg et al. | Jul 2009 | B2 |
7571004 | Roy et al. | Aug 2009 | B2 |
7571011 | Zhou et al. | Aug 2009 | B2 |
7574263 | Greenberg et al. | Aug 2009 | B2 |
7610098 | McLean | Oct 2009 | B2 |
7622702 | Wu et al. | Nov 2009 | B2 |
7630771 | Cauller | Dec 2009 | B2 |
7631424 | Greenberg et al. | Dec 2009 | B2 |
7638032 | Zhou et al. | Dec 2009 | B2 |
7666523 | Zhou | Feb 2010 | B2 |
7676274 | Hung et al. | Mar 2010 | B2 |
7691252 | Zhou et al. | Apr 2010 | B2 |
7706887 | Tai et al. | Apr 2010 | B2 |
7706893 | Hung et al. | Apr 2010 | B2 |
7709961 | Greenberg et al. | May 2010 | B2 |
7725191 | Greenberg et al. | May 2010 | B2 |
7734352 | Greenberg et al. | Jun 2010 | B2 |
7738962 | Greenberg et al. | Jun 2010 | B2 |
7749608 | Laude et al. | Jul 2010 | B2 |
7750076 | Laude et al. | Jul 2010 | B2 |
7751896 | Graf et al. | Jul 2010 | B2 |
7765009 | Greenberg et al. | Jul 2010 | B2 |
7766903 | Blumenkranz et al. | Aug 2010 | B2 |
7776197 | Zhou | Aug 2010 | B2 |
7831309 | Humayun et al. | Nov 2010 | B1 |
7834767 | Shodo | Nov 2010 | B2 |
7835798 | Greenberg et al. | Nov 2010 | B2 |
7840273 | Schmid | Nov 2010 | B2 |
7846285 | Zhou et al. | Dec 2010 | B2 |
7853330 | Bradley et al. | Dec 2010 | B2 |
7871707 | Laude et al. | Jan 2011 | B2 |
7877866 | Greenberg et al. | Feb 2011 | B1 |
7881799 | Greenberg et al. | Feb 2011 | B2 |
7887681 | Zhou | Feb 2011 | B2 |
7894909 | Greenberg et al. | Feb 2011 | B2 |
7894911 | Greenberg et al. | Feb 2011 | B2 |
7904148 | Greenberg et al. | Mar 2011 | B2 |
7908011 | McMahon et al. | Mar 2011 | B2 |
7912556 | Greenberg et al. | Mar 2011 | B2 |
7914842 | Greenberg et al. | Mar 2011 | B1 |
7937153 | Zhou et al. | May 2011 | B2 |
7957811 | Caspi et al. | Jun 2011 | B2 |
7962221 | Greenberg et al. | Jun 2011 | B2 |
7979134 | Chow et al. | Jul 2011 | B2 |
7989080 | Greenberg et al. | Aug 2011 | B2 |
8000804 | Wessendorf et al. | Aug 2011 | B1 |
8010202 | Shah et al. | Aug 2011 | B2 |
8010206 | Dai et al. | Aug 2011 | B2 |
8014868 | Greenberg et al. | Sep 2011 | B2 |
8014869 | Greenberg et al. | Sep 2011 | B2 |
8014878 | Greenberg et al. | Sep 2011 | B2 |
8024022 | Schulman et al. | Sep 2011 | B2 |
8034229 | Zhou et al. | Oct 2011 | B2 |
8046078 | Greenberg et al. | Oct 2011 | B2 |
8060211 | Greenberg et al. | Nov 2011 | B2 |
8060216 | Greenberg et al. | Nov 2011 | B2 |
8068913 | Greenberg et al. | Nov 2011 | B2 |
8078284 | Greenberg et al. | Dec 2011 | B2 |
8090447 | Tano et al. | Jan 2012 | B2 |
8090448 | Greenberg et al. | Jan 2012 | B2 |
8103352 | Fried et al. | Jan 2012 | B2 |
8121697 | Greenberg et al. | Feb 2012 | B2 |
8131375 | Greenberg et al. | Mar 2012 | B2 |
8131378 | Greenberg et al. | Mar 2012 | B2 |
8145322 | Yao et al. | Mar 2012 | B1 |
8150526 | Gross et al. | Apr 2012 | B2 |
8150534 | Greenberg et al. | Apr 2012 | B2 |
8160713 | Greenberg et al. | Apr 2012 | B2 |
8165680 | Greenberg et al. | Apr 2012 | B2 |
8170676 | Greenberg et al. | May 2012 | B2 |
8170682 | Greenberg et al. | May 2012 | B2 |
8180453 | Greenberg et al. | May 2012 | B2 |
8180454 | Greenberg et al. | May 2012 | B2 |
8180460 | Nevsmith et al. | May 2012 | B2 |
8190267 | Greenberg et al. | May 2012 | B2 |
8195266 | Whalen, III et al. | Jun 2012 | B2 |
8197539 | Nasiatka et al. | Jun 2012 | B2 |
8200338 | Grennberg et al. | Jun 2012 | B2 |
8226661 | Balling et al. | Jul 2012 | B2 |
8239034 | Greenberg et al. | Aug 2012 | B2 |
8244362 | Yonezawa | Aug 2012 | B2 |
8249716 | Tano et al. | Aug 2012 | B2 |
20020091421 | Greenberg et al. | Jul 2002 | A1 |
20030023297 | Byers et al. | Jan 2003 | A1 |
20030032946 | Fishman et al. | Feb 2003 | A1 |
20030132946 | Gold | Jul 2003 | A1 |
20040054407 | Tashiro et al. | Mar 2004 | A1 |
20040078064 | Suzuki | Apr 2004 | A1 |
20040088026 | Chow et al. | May 2004 | A1 |
20040098067 | Ohta et al. | May 2004 | A1 |
20040181265 | Palanker et al. | Sep 2004 | A1 |
20040189940 | Kutschbach et al. | Sep 2004 | A1 |
20050015120 | Seibel et al. | Jan 2005 | A1 |
20050119605 | Sohn | Jun 2005 | A1 |
20050146954 | Win et al. | Jul 2005 | A1 |
20060106432 | Sawan et al. | May 2006 | A1 |
20060111757 | Greenberg et al. | May 2006 | A9 |
20060184245 | Graf et al. | Aug 2006 | A1 |
20060282128 | Tai et al. | Dec 2006 | A1 |
20060287688 | Yonezawa | Dec 2006 | A1 |
20070005116 | Lo | Jan 2007 | A1 |
20070123766 | Whalen et al. | May 2007 | A1 |
20070142877 | McLean | Jun 2007 | A1 |
20070142878 | Krulevitch et al. | Jun 2007 | A1 |
20070191909 | Ameri et al. | Aug 2007 | A1 |
20080114230 | Addis | May 2008 | A1 |
20080234791 | Arle et al. | Sep 2008 | A1 |
20080262571 | Greenberg et al. | Oct 2008 | A1 |
20080288036 | Greenberg et al. | Nov 2008 | A1 |
20090002034 | Westendorp et al. | Jan 2009 | A1 |
20090005835 | Greenberg et al. | Jan 2009 | A1 |
20090024182 | Zhang et al. | Jan 2009 | A1 |
20090118805 | Greenberg et al. | May 2009 | A1 |
20090192571 | Stett et al. | Jul 2009 | A1 |
20090204207 | Blum et al. | Aug 2009 | A1 |
20090204212 | Greenberg et al. | Aug 2009 | A1 |
20090216295 | Zrenner et al. | Aug 2009 | A1 |
20090228069 | Dai et al. | Sep 2009 | A1 |
20090287275 | Suaning et al. | Nov 2009 | A1 |
20090326623 | Greenberg et al. | Dec 2009 | A1 |
20100174224 | Sohn | Jul 2010 | A1 |
20100204754 | Gross et al. | Aug 2010 | A1 |
20100249878 | McMahon et al. | Sep 2010 | A1 |
20100331682 | Stein et al. | Dec 2010 | A1 |
20110054583 | Litt et al. | Mar 2011 | A1 |
20110172736 | Gefen et al. | Jul 2011 | A1 |
20120035725 | Gefen et al. | Feb 2012 | A1 |
20120035726 | Gross et al. | Feb 2012 | A1 |
20120041514 | Gross et al. | Feb 2012 | A1 |
20120209350 | Taylor et al. | Aug 2012 | A1 |
20120221103 | Liran et al. | Aug 2012 | A1 |
20120259410 | Gefen et al. | Oct 2012 | A1 |
Number | Date | Country |
---|---|---|
WO-0191854 | Dec 2001 | WO |
WO-03032946 | Apr 2003 | WO |
WO-2007009539 | Jan 2007 | WO |
WO-2007095395 | Aug 2007 | WO |
WO-2010035173 | Apr 2010 | WO |
WO-2010089739 | Aug 2010 | WO |
WO-2011086545 | Jul 2011 | WO |
WO-2011086545 | Jul 2011 | WO |
WO-2012017426 | Feb 2012 | WO |
WO-2012114327 | Aug 2012 | WO |
WO-2012153325 | Nov 2012 | WO |
Entry |
---|
Delbrubk et al.: “Analog VLSI Adaptive, Logarithmic, wide-dynamic-Range Photoreceptor,” 1994 International Symposium on Circuits and Systems (London, 1994), p. 339-342. |
An Office Action dated Aug. 24, 2011 issued during the prosecution of Applicant's U.S. Appl. No. 12/368,150. |
An International Search Report and Written Opinion dated Aug. 12, 2011 issued during the prosecution of Applicant's International Application No. PCT/IL2011/00022. |
International Search Report and Written Opinion dated Dec. 12, 2011 issued on International Application No. PCT/IL2011/00609. |
U.S. Appl. No. 12/687,509, Gefen. |
Zrenner E., 2002. “Will retinal implants restore vision?” Science 295(5557), pp. 1022-1025. |
Jourdain R P., et al., “Fabrication of piezoelectric thick-film bimorph micro-actuators from bulk ceramics using batch-scale methods” Multi-Material Micro Manufacture, S. Dimov and W. Menz (Eds.) 2008 Cardiff University, Cardiff, UK., Whittles Publishing Ltd. |
Lianga C, et al., “Surface modification of cp-Ti using femtosecond laser micromachining and the deposition of Ca/P layer” Materials Letters vol. 62, Issue 23, Aug. 31, 2008, pp. 3783-3786—an abstract. |
Seo J M., et al., “Biocompatibility of polyimide microelectrode array for retinal stimulation,” Materials Science and Engineering: C, vol. 24, No. 1, Jan. 5, 2004, pp. 185-189(5). |
Sorkin R., et al., “Process entanglement as a neuronal anchorage mechanism to rough surfaces,” Nanotechnology 20 (2009) 015101 (8pp). |
Vorobyeva A Y. et al., “Metallic light absorbers produced by femtosecond laser pulses,” Advances in Mechanical Engineering vol. 2010, Article ID 452749, 4 pages doi:10.1155/2010/452749, Hindawi Publishing Corporation. |
Vorobyeva A Y. et al., “Femtosecond laser structuring of titanium implants,” Applied Surface Science vol. 253, Issue 17, Jun. 30, 2007, pp. 7272-7280—an abstract. |
Wallman L., et al., “The geometric design of micromachined silicon sieve electrodes influences functional nerve regeneration,” Biomaterials May 2001:22(10):1187-93, (an abstract). |
Warren M. Grill, et al. “Implanted Neural Interfaces: Biochallenges and Engineered Solutions”, Annu. Rev. Biomed. Eng. 2009, 11:1. |
Grill W., et al., “Implanted Neural Interfaces: Biochallenges and Engineered Solutions”, Annu. Rev. Biomed. Eng. 2009. 11:1-2—an abstract. |
An International Search Report dated Aug. 17, 2010, which issued during the prosecution of Applicant's PCT/IL10/00097. |
Kim B., “Through-Silicon-Via Copper Deposition for Vertical Chip Integration” Master. Res. Soc. Symp. Proc. vol. 970, 2007 Material Research Society. |
Puech M., et al., “Fabrication of 3D packaging TSV using DRIE” ALCATEL Micro Machining Systems, www.adixen.com 2007. |
Stein DJ, et al., “High voltage with Si series photovoltaics” Proceedings of SPIE, the International Society for Optical Engineering 2006, vol. 6287, pp. 62870D.1-62870D. |
Starzyk JA, et al., “A DC-DC charge pump design based on voltage doublers” IEEE Transaction on Circuits and Systems -I: Fundamental theory and applications, vol. 48, No. 3 Mar. 2001. |
Walter P., et al., “Cortical Activation via an implanted wireless retinal prosthesis,” Investigative Ophthalmology and Visual Science. 2005;46:1780-1785. |
Wu J T. and Chang K L., “MOS charge pumps for low-voltage operation” IEEE Journal of Solid-State Circuits, vol. 33 No. 4 Apr. 1998. |
Swain P K., et al., “Back-Illuminated Image Sensors Come to the Forefront. Novel materials and fabrication methods increase quality and lower cost of sensors for machine vision and industrial imaging.” Photonics Spectra Aug. 2008. |
News Release—Sony develops back-illuminated CMOS image sensor, realizing high picture quality, nearly twofold sensitivity (*1) and low noise, Jun. 2008 http://www.sony.net/SonyInfo/News/Press/200806/08-069E/index.html. |
David C Ng, et al., “Pulse frequency modulation based CMOS image sensor for subretinal stimulation” IEEE Transactions on Circuits and Systems-II: Express Briefs, vol. 53, No. 6, Jun. 2006. |
An Office Action dated Sep. 28, 2012, which issued during the prosecution of U.S. Appl. No. 13/103,264. |
An International Preliminary Report on Patentability dated Jul. 17, 2012, which issued during the prosecution of Applicant's PCT/IL2011/000022. |
A Supplementary European Search Report dated Aug. 10, 2012, which issued during the prosecution of Applicant's European Application No. 10 73 8277. |
Palanker D. et al., “Design of a high-resolution optoelectric retinal prosthesis”. Journal of Neural Engineering, Institute of physics publishing, Bristol, GB. vol. 2, No. 1, Mar. 1, 2005, pp. S105-S120, XP002427333, ISSN: 17412552, DOI: 10.1088/1741-2560/2/1/012. |
Cortical Visual Neuro-Prosthesis for the Blind: Retina-Like Software/Hardware Preprocessor, F.J. Pelayol, A. Martinezl, S. Romerol, Ch.A. Morillasl, E. Rosl , E. Fernandez2 1Dept. of Computer Architecture and Technology, University of Granada, Spain 2Dept. of Histology and Institute of Bioengineering, University Miguel Hernandez, Alicante, Spain Neural Engineering, 2003. Conference Proceedings. First International IEEE EMBS Conference. |
“Single-Chip CMOS Image Sensors for a Retina Implant System”, Markus Schwarz, Ralf Hauschild, Bedrich J. Hosticka, Senior Member, IEEE, Jurgen Huppertz, Student Member, IEEE, Thorsten Kneip, Member, IEEE, Stephan Kolnsberg, Lutz Ewe, and Hoc Khiem Trieu, 2000. |
An International Search Report dated Aug. 12, 2011, which issued during the prosecution of Applicant s PCT/IL2011/000022. |
An International Search Report and a Written Opinion both dated Sep. 17, 2012, which issued during the prosecution of Applicant's PCT/IL12/00057. |
An Official Action dated Dec. 7, 2012, issued during prosecution of U.S. Appl. No. 12/678,509. |
An Official Action dated Dec. 14, 2012, which issued during the prosecution of U.S. Appl. No. 13/034,516. |
International Search Report dated Sep. 4, 2012, during prosecution of PCT/IL2012/000186. |
Humayun, et al, “Visual Pereception in a Blind Subject with a Chronic Microelectric Retinal Prosthesis”, Vision Research 43 (2003), pp. 2573-2581. |
Walter, et al., “Cortical Activation via an Implanted Wireless Retinal Prosthesis”, Investigative Ophthalmology & Visual Science, vol. 46. No. 5 (May 2005) pp. 1780-1785. |
Ganesan et al, “Diamond Penetrating Electrode Array for Epi-Retinal Prothesis”, 3rd Annual International Conference of IEEE EMBS, Buenos Aires, Argentina (Aug. 31-Sep. 4, 2010), pp. 6757-6760. |
Schwarz et al, “Hardware Architecture of Neural Net Based Retina Implant for Patients Suffering from Retinitis Pigementosa”, Fraunhofer Institute of Microelectric Circuits and Systems Finkenstr. 61, IEEE (1996), pp. 653-658. |
Number | Date | Country | |
---|---|---|---|
20120035725 A1 | Feb 2012 | US |