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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 Institute Keck School of Medicine University of Southern California. Overview. Artificial Retina Research Update Doheny Retina-DOE Research
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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 Institute Keck School of Medicine University of Southern California
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
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.
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
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 Second Sight Retinal StimulatorTM Optobionics ASRTM
20 months 16 months 8 months
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%) Computer Controlled Testing
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%) Camera Tests
Camera Tests Considering only results with multiple pixels setting.
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
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
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)
DOE Implants • PDMS conformable electrode array from LLNL • MEMs spring electrode array from SNL • UNCD hermetic coating from ANL
OCT measurements Front of eye Excitation Reflection Pt Retina
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.
Postoperative 1st month OCT imaging (horizontal scan) Postoperative 1st month OCT imaging (vertical scan) Implantation of LLNL device #4 DOE Implants – PDMS Electrode
DOE Implants – PDMS Electrode #2 LLNL dog, postoperative 2nd month, OCT imaging #3 LLNL dog, postoperative 1st month, OCT imaging #2 LLNL dog, postoperative 3rd month, OCT imaging #3 LLNL dog, postoperative 2nd month, OCT imaging
antenna inner-eye electronics flexible interconnect tack electrodes Retinal Implant – MEMS Component posts for assembly and electrical interconnect flexible frame for attachment microelectronics surface micromachined springs (polymer) frame bulk micromachined electrode seats micromachined electrode array (silicon substrate) retina electroplated or assembled electrodes
Bulk Micromachined Components Bosch etched single crystal silicon electrodes
Polymer frame / test parts 3D model and fabricated polymer mold 9x9 electrode array (test part/ no posts) array placed in the polymer frame
INITIAL WORK ON COATING OF SNL MEMS ELECTRODE STRUCTURES WITH UNCD LAYERS SEM picture of SNL MEMS Si electrode test structures SEM pictures of SNL MEMS Si electrode test structure coated with UNCD film SEM pictures of ANL Si tips and posts coated with UNCD film
Next Generation 11” Microwave Plasma System Suitable for Scaling to 6” and 8” Substrates (On order-Available January 2004)New Substrate holder with heating and cooling capabilities under design to achieve better control of low temperature growth SCALING OF UNCD GROWTH PROCESS 8 - 9 ” CH4 / Ar Plasma (FURTHER FUTURE ALREADY HERE: 16” SYSTEM DEMONSTRATED - 2003!
Bioelectronics Lab at Doheny • Implant Testing - Digital Ophthalmic Photography and Microscopy. • Accelerated testing of devices (in conjunction with Second Sight under CRADA).
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