DOE Artificial Retina Program
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DOE Artificial Retina Program
Mark S. Humayun, M.D. Ph.D.Professor of Ophthalmology, Biomedical Engineering, and Cell & Neurobiology
Doheny Eye InstituteKeck School of Medicine
University of Southern California
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Overview
Artificial Retina Research Update Doheny Retina-DOE Research
Implants Electrophysiology
Bioelectronic Research Lab Surgical/Imaging/Histology Resource ftp host site for DOE Artificial Vision
Project
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Human Visual System and Retinal Blindness•
• Retina is a light sensitive neural network
• Diseases such as Retinitis Pigmentosa (RP) and Age-related Macular Degeneration (AMD) primarily affect the photoreceptors, are both presently incurable, and render 100,000s blind each year
Webvision, Kolb, Fernandez, and Nelson, 2003.
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Retinal Prosthesis – Epiretinal vs. Subretinal
Epiretinal Less disruptive to the
retina. More flexibility in
component placement More complex stimulus
algorithms required Subretinal
In natural position of photoreceptors
Disruptive to retina Devices relying on
incident light for power cannot generate effective stimulus
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State of the Art – Retinal Prostheses
• Epiretinal and Subretinal at Investigational Device Exemption Stage
• Epiretinal - encouraging results, but better technology required
• Subretinal – No direct evidence demonstrating functional electrical stimulation, but patients report subjective improvements in vision
Optobionics ASRTM
Second Sight Retinal StimulatorTM
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20 months
16 months
8 months
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Rows and Columns
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Computer Controlled Testing
Test type HEC01 YSL02 CS03
Sequential activation
4AFC (25%)
6/8, 6/8, 4/8 (67%)
9/10, 9/10, 10/10 (93%)
2/10, 6/10, 6/10, 6/10 (50%)
Form vision (Row vs. column)
2AFC (50%)
1/4, 2/4, 5/8, 7/8, 4/8 (55%)
10/10, 9/10, 10/10 (97%)
4/10, 9/10, 10/10 (77%)
Spatial Location (Right vs. left)
2AFC (50%)
4/10, 6/10, 10/12, 4/5, 8/10 (69%)
10/10, 10/10, 10/10 (100%)
4/10, 7/10, 6/10 (57%)
Spatial Location (Up vs. down)
2AFC (50%)
12/12, 8/8, 5/8, 3/8, 8/8, 8/8, 5/10 (79%)
10/10, 10/10, 10/10 (100%)
4/10, 10/10, 9/10 (77%)
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Camera Tests
Camera still
Test type HEC01 YSL02 CS03
Lights on/off
2AFC (50%)
10/10 (100%)
10/10, 10/10 (100%)
9/10 (90%)
Moving directions
4AFC (25%)
4/8 (50%) 7/10, 9/10, 10/10 (87%)
5/10, 5/10, 2/10 (40%)
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Camera TestsScanning Test Type HEC01 YSL02 CS03
Finding objects (Ø, R, L)
3AFC (33%)
9/10 (90%) 10/10, 10/10, 10/10 (100%)
9/10, 7/10, 7/10 (77%)
Counting/finding objects (Ø, R, L, R+L)
4AFC (25%)
8/10, 7/10, 8/10 (77%)
10/10, 8/10, 7/10, 9/10 (90%)
8/10, 8/10, 7/10, 8/10 (77%)
Objects recognition (plate, knife and cup)
3AFC (33%)
8/10, 7/10, 4/10, 5/10, 8/10, 8/10 (67%)
8/10, 7/10, 7/10 (73%)
7/10, 8/10, 4/10 (63%)
L position 4AFC (25%)
5/10 (50%) 7/10, 6/10, 9/10 (73%)
4/10, 6/10, 9/10 (63%)
Considering only results with multiple pixels setting.
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Camera Tests: Multiple vs. Single pixel
Scanning Test Type Multipixel Single pixel
Finding objects (Ø, R, L)
3AFC (33%)
62/70 (89%) 54/70 (77%)
Counting/finding objects (Ø, R, L, R+L)
4AFC (25%)
88/111 (79%)
77/110 (70%)
Objects recognition (plate, knife and cup)
3AFC (33%)
81/120 (68%)
45/80 (56%)
L position 4AFC (25%)
46/70 (66%) 61/104 (59%)
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Design Requirements for Higher Resolution Artificial Retina
Unaided Mobility 256-600 pixels
Reading Large Print/Recognizing faces 1024 pixels
Reading regular print at regular reading speed 10,000 pixels
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Design Implications for Future Implants
Stimulus Threshold Electrode Size
Best Case: 6 uA -> 15 micron diameter (irOx, 1 mC/cm2) Conservative: 100 uA - > 200 micron diameter (Pt, 0.1
mC/cm2) Device Power
Smaller electrode size will lead to higher impedance, but P=I2R, so lowering threshold stimulus has large effect on decreasing power
Image Processing Eye tracking system, digital zooming, digital
saccading, automated optimization System layout and packaging
Extraocular component placement is feasible
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DOE’s Unique Role in Artificial Retina Development
DOE LABS have sophisticated design and fabrication capabilites (ORNL, LLNL, SNL, ANL, LANL)
DOE labs have the ability to work cooperatively with Universities (USC, UCSC, NCSU) and Industry (Second Sight)-- CRADA
DOE has the ability to provide sustained support for high risk, high payoff projects
DOE is used to managing large projects (Genome)
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DOE Implants
PDMS conformable electrode array from LLNL
MEMs spring electrode array from SNL
UNCD hermetic coating from ANL
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OCT measurementsFront of eye
Retina
ExcitationReflection
Pt
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DOE Implants – PDMS electrode
Goal: To develop a PDMS substrate stimulating electrode
Progress: Four normal sighted dogs were
implanted. Three of them have been followed for 3 months, 2 months and 1 month.
Multilayer cable PDMS test devices were received and evaluated.
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Implantation of LLNL device #4
Postoperative 1st month OCT imaging (horizontal scan)
Postoperative 1st month OCT imaging (vertical scan)
DOE Implants – PDMS Electrode
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#2 LLNL dog, postoperative 2nd month, OCT imaging
#2 LLNL dog, postoperative 3rd month, OCT imaging
#3 LLNL dog, postoperative 1st month, OCT imaging
#3 LLNL dog, postoperative 2nd month, OCT imaging
DOE Implants – PDMS Electrode
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Retinal Implant – MEMS Component
microelectronics
electroplated or assembled electrodes
bulk micromachinedelectrode seats
surface micromachinedsprings(polymer) frame
flexible frame for attachment
micromachined electrode array (silicon substrate)
retina
posts for assembly and electrical interconnect
electrodes
flexibleinterconnect
tack
antenna
inner-eyeelectronics
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Bulk Micromachined Components
Bosch etched single crystal silicon electrodes
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Polymer frame / test parts
9x9 electrode array(test part/ no posts)
array placed in the polymer frame
3D modeland fabricatedpolymer mold
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INITIAL WORK ON COATING OF SNL MEMS ELECTRODE STRUCTURES WITH UNCD LAYERS
SEM picture of SNL MEMS SEM picture of SNL MEMS Si electrode test structuresSi electrode test structures
SEM pictures of ANL Si tips and posts SEM pictures of ANL Si tips and posts coated with UNCD filmcoated with UNCD film
SEM pictures of SNL MEMS Si electrode SEM pictures of SNL MEMS Si electrode test structure coated with UNCD filmtest structure coated with UNCD film
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SCALING OF UNCD GROWTH PROCESS
Next Generation 11” Microwave Next Generation 11” Microwave Plasma System Suitable for Plasma System Suitable for Scaling to 6” and 8” Substrates Scaling to 6” and 8” Substrates (On order-Available January 2004)(On order-Available January 2004)
New Substrate holder with New Substrate holder with heating and cooling capabilities heating and cooling capabilities under design to achieve better under design to achieve better control of low temperature control of low temperature growthgrowth
Next Generation 11” Microwave Next Generation 11” Microwave Plasma System Suitable for Plasma System Suitable for Scaling to 6” and 8” Substrates Scaling to 6” and 8” Substrates (On order-Available January 2004)(On order-Available January 2004)
New Substrate holder with New Substrate holder with heating and cooling capabilities heating and cooling capabilities under design to achieve better under design to achieve better control of low temperature control of low temperature growthgrowth
(FURTHER FUTURE ALREADY HERE: 16” SYSTEM DEMONSTRATED - 2003!(FURTHER FUTURE ALREADY HERE: 16” SYSTEM DEMONSTRATED - 2003!
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8 - 9 ” ” CH4 / Ar Plasma
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Bioelectronics Lab at Doheny
Implant Testing - Digital Ophthalmic Photography and Microscopy.
Accelerated testing of devices (in conjunction with Second Sight under CRADA).
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Bioelectronics Lab Use established methods of retinal
neurobiology to investigate electrically elicited vision Multichannel extracellular recording Intracellular recording
Retinal and ocular tissue properties ftp://doheny.ws/doeretina
Conference call minutes/action items Data repository to facilitate conference calls