Multiple-Unit Artificial Retina Chipset Dr. Elliot McGucken Physics University of North Carolina at Chapel Hill NC State University A computer-chip based device that can provide limited-resolution vision for people with retinal-based blindness. Beneficiaries would be 10,000,000 people worldwide suffering from forms of blindness including retinal pigmentosa and age-related macular degeneration.
MERRILL LYNCH "INNOVATION GRANTS" AWARDED TO FIVE DOCTORAL STUDENTS DOCTORAL RESEARCH YIELDS GROUNDBREAKING PROPOSALS RANGING FROM NEW COMPUTER CHIPS TO A MALE ORAL CONTRACEPTIVE NEW YORK, Sept.16 -- The Merrill Lynch Forum today announced the first winners of the Innovation Grants Competition -- its global competition challenging doctoral students to craft commercial applications of their dissertation research. The winners were recognized at an awards dinner at Merrill Lynch headquarters last night (Sept. 15), hosted by Merrill Lynch Chairman and CEO David H. Komansky. Dr. Jan Mark Noworolski, from the University of California at Berkeley, received the top prize in the competition for creating a new type of power converter, a key element in virtually all electronic devices. This technology would greatly reduce the size, parts count and weight of power supplies for the increasingly pervasive array of portable electronic products such as cell phones and laptop computers, as well as enabling the design of new mobile electronic products. "Power management is one of the major constraints in personal electronics," he said. "An integrated design using this technology could offer a 10-fold improvement in device performance." A total of 213 proposals from 16 countries were submitted to the competition, which was open to new Ph.D. recipients in the sciences, liberal arts, and engineering disciplines. Entries were judged by a distinguished panel of nine entrepreneurs, venture capitalists, journalists, and innovators and were considered without knowledge of the applicants' identity or academic affiliation. "Academic research is a significant and often untapped source of intellectual capital in our society, and a tremendous economic resource," said Merrill Lynch Chairman and CEO David H. Komansky. "The winning proposals from this competition are all excellent examples of how new knowledge can be transformed into new value simply by encouraging researchers to look at their research from a different perspective. We hope that these Innovation Grants will help foster a closer interaction between world-class science and the world of commerce," Mr. Komansky added. The judging panel consisted of: John Seely Brown, Chief Scientist, Xerox Corporation, and Director, Xerox Palo Alto Research Center Edgar W. K. Cheng, former Chairman, The Stock Exchange of Hong Kong John Doerr, Partner, Kleiner Perkins Caufield & Byers Esther Dyson, Chairman, EDventure Holdings, Inc. Peter C. Goldmark, Chairman and Chief Executive, The International Herald Tribune William Haseltine, Chairman & CEO, Human Genome Sciences, Inc. John Markoff, Technology Correspondent, The New York Times Edward McKinley, President, E.M. Warburg, Pincus & Company International, Ltd. Arati Prabhakar, former Chief Technology Officer, Raychem Corporation In evaluating the applications, the judges sought to identify proposals with the potential to affect real change in industries and in the way people live their lives. "The Innovation Grants Competition is a terrific idea," said judge John Doerr, of venture-capital firm Kleiner Perkins Caufield & Byers. "I was impressed with many of the proposals and thought that several of the ideas would merit a venture-capital follow-up." The five winning entries: First Place, $50,000 -- Single-Chip Power Converter. Dr. Jan Mark Noworolski, University of California at Berkeley. A unique, one-chip power converter that uses electromechanical energy instead of inductive energy storage. This technology could dramatically reduce the size and complexity of portable electronic devices such as laptop computers, cellular phones, and pagers. Second Place, $20,000 -- Membrane Chips. Dr. Jay T. Groves, Stanford University. A technology that enables biological membranes to be incorporated into computer chips. These chips could be used by the medical diagnostic industry, particularly for AIDS research, and leukemia. Second Place, $20,000 -- Multiple-Unit Artificial Retina Chipset (MARC). Dr. Elliot McGucken, University of North Carolina at Chapel Hill/NC State University. A computer-chip based device that can provide limited-resolution vision for people with retinal-based blindness. This device could benefit the more than 10,000,000 people worldwide suffering from blindness originating from various causes. Third Place, $10,000 -- Male Oral Contraceptive. Dr. Bruce Lahn, Whitehead Institute of Biomedical Research, Massachusetts Institute of Technology. This research led to the development of an understanding of the role of the gene CDY in producing an essential enzyme for sperm production. This research could produce a male oral contraceptive that would chemically inhibit the production of the sperm-producing enzyme. Third Place, $10,000 -- Artificially Engineered Quantum Solid Materials. Dr. Alexander Balandin, University of Notre Dame. This study of new materials based on quantum confinement properties suggests opportunities for the engineering of a new generation of electronic devices. The most significant market application would be the improvement of devices such as semiconductor lasers, CD players, digital cameras, and optical drives. Additional grants of $5,000 were awarded to each of the winners' universities and discretionary grants of $3,000 each were awarded to five additional proposals. The 1998 Innovation Grants Competition was directed by Michael Schrage, a Research Associate at the MIT Media Lab, and a leading expert on issues surrounding innovation and new business development. "What fuels the 'new economy' of the information age is ideas," said Schrage. "This competition takes great ideas that might otherwise have languished for years in academia and brings them to the attention of people who can translate them into transformative technologies. Anyone looking at these proposals can see that they contain truly exciting possibilities." The competition was open to doctoral students who successfully defended their dissertations between January 1, 1996, and July 1, 1998. Entrants were required to submit a 3,000-word explanation of how their dissertation topic could be translated into a commercial product or service. The description had to include: a summary of the dissertation, a description of the most significant commercial idea embodied in it, an analysis of the potential market for the product or service, and a discussion of technical steps necessary to bring the innovation to market. The Merrill Lynch Forum is a "virtual" think tank established by the global financial services company to bring together leading experts to consider and explore issues of worldwide importance in the areas of technology, economics, and international relations. Those interested in additional information, should visit the Competition's web site, http://www.ml.com/innovation, or call 1-888-33Forum. Additional information is also available by sending e-mail to:InnovationGrants@ml.com BIOGRAPHIES DR. ELLIOT MCGUCKEN -------------------------------------------------------------------------------- Dr. Elliot McGucken was born and raised in Akron, Ohio, and he has studied and taught physics ever since he left Akron to attend Princeton University as an undergraduate. He recently received his Ph.D. in physics from the University of North Carolina at Chapel Hill (1998), where his research on the Multiple Unit Artificial Retina Chipset To Aid The Visually Impaired often led him down the road to North Carolina State University. He is currently continuing his involvement with the retinal prosthesis's prototype development at NCSU, while also teaching physics and astronomy as an assistant professor of physics at the neighboring Elon College. His favorite hobbies are celestial navigation, sailing and windsurfing, reading the classics, and writing poetry. Dr. McGucken received the Tanner Award for Excellence in Undergraduate Teaching while at the University of North Carolina at Chapel Hill, where he also received an honorary membership in the the American Society of Physics Teachers.
Multiple Unit Artificial Retina Chipset (MARC) to Aid the Visually Impaired By Elliot McGucken -------------------------------------------------------------------------------- 1. Summary of the dissertation Engineering progress relating to the development of the multiple-unit artificial retina chipset (MARC) prosthesis to benefit the visually impaired is presented in my dissertation, "Multiple Unit Artificial Retina Chipset to Aid the Visually Impaired and Enhanced CMOS Phototransistors." The design, fabrication, and testing of the first generation MARC VLSI chips are reported on. A synthesis of the engineering, biological, medical, and physical research is offered within the presentation of methods and means for the overall design engineering, powering, bonding, packaging, and hermetic sealing of the MARC retinal prosthesis. The retinal prosthesis is based on the fundamental concept of replacing photoreceptor function with an electronic device1, which was initiated by2 and has been extensively developed3,4 by MARC team-members Dr. Humayun et al. The use of an inductive link for power and telemetric communications is explored, and an experimental study of RF coil configurations, showing their feasibility for this retinal implant, is offered. An enhanced CMOS phototransistor with a holed emitter (HEP), used in the first generation MARC, is presented, along with a numerical model which also predicts its enhanced quantum efficiency. Due to the small size of the intraocular cavity, the extreme delicacy of the retina, and the fact that the eye is mobile, an artificial retinal implant poses difficult engineering challenges. Over the past several years all of these factors and contrasts have been taken into consideration in the engineering research of an implantable retinal device. Initial steps3 towards fabricating a commercially available, implantable MARC device have been taken by our team of engineers, physicists, and doctors. 2. Description of the most significant commercial aspect A multiple-unit artificial retina chipset (MARC) would create a new marketplace by offering a cure for forms of blindness including retinal pigmentosa (RP) and age-related macular degeneration (AMD), which afflict over 10,000,000 people worldwide. Clinical studies4 have shown that controlled electrical signals applied to a small area of a dysfunctional retina with a microelectrode can be used to initiate a local neural response in the remaining retinal cells. The neural response, or phosphene, is perceived by otherwise completely blind patients as a small spot of light, about the size of a match-head held out at arm's length. When multiple electrodes are activated in a two-dimensional electrode array, an image may be stimulated upon the retina. The MARC system consists of an extraocular means for acquiring and processing visual information, a means for power and signal transceiving via RF telemetry, and a multiple-until artificial retina chipset. The stimulating electrode array is mounted on the retina with metal-alloy retinal tacks while the power and signal transceiver is mounted in close proximity to the cornea. An external miniature low-power CMOS camera worn in an eyeglass frame captures an image and transfers the visual information and power to the intraocular components via RF telemetry. The intraocular prosthesis will decode the signal and electrically stimulate the retinal neurons through the electrodes in a manner that corresponds to the original image perceived by the CMOS Camera. 3. Description of the market for the proposed product and the competition The multiple-unit artificial retina chipset (MARC) is designed to provide useful vision to over 10,000,000 people blind because of photoreceptor loss due to partial retinal degeneration from diseases such as Age Related Macular Degeneration (AMD) and Retinitis Pigmentosa (RP). People who are completely blind will initially gain the ability to discern shapes and pictures, and even to read, with limited resolutions of 15x15 pixels. Future MARC generations will provide greater resolutions, and the device will chart a brand new marketplace a s a prosthetic device to aid the visually impaired. 3.1 Unique value derived by the customer Before embarking on the MARC chip design, it was necessary to assess how useful a limited-resolution view would b to the blind. Simple visual feasibility experiments have been conducted at NCSU so as to determine how well sight could be restored with a 15x15 array of pixels, each of which would be capable of four-bit stimulation, or sixteen gray levels. A picture from a video camera was projected onto a television screen at the low resolution of 15x15 pixels. When subjects who wore glasses removed their glasses, or when those with good sight intentionally blurred their vision, the natural spatial-temporal processing of the brain allowed them to actually distinguish features and recognize people. When the subject focused on the screen, it appeared as a 15x15 array of gray blocks, but when the subject "trained" themselves to unfocus their vision, they were able to "learn" to see definitive edges and details such as beard, teeth, and opened or closed eyes. These results are reminiscent of the experiences with the artificial cochlear implant. When the artificial cochlear was originally being designed, it was believed that over 2,400 electrodes would be needed to stimulate the nerves in a manner that would be conducive to hearing. Today, however, within a few weeks of receiving an implant, a patient can understand phone conversations with an artificial cochlear that has only six electrodes. One of the advantages of this project is that the MARC device will be interfaced with the world's greatest computer - the brain. The MARC won't be duplicating the exact functioning of the retina, but rather the device will be an entity that the brain will "learn" to use. A good analogy to think of is that in attempting flight, the Wright brothers did not attempt to imitate nature by building a plane which flapped its wings, but rather they did it in a way that had not yet appeared in the natural world. Thus we believe that a 15x15 pixel array will facilitate a level of sight which will be of significant value to the patient. And after the initial prototype is developed, there will be few barriers to stepping up the resolution. 3.2 Prior art, competition, and MARC advantages The current design of the MARC clears several hurdles that exist is prior inventions and research. Much of the prior art has relied upon structures so complicated or biologically intrusive as to make their implementation impractical, and thus, to date, an operating implantable artificial retina has not been achieved. Several international teams are actively pursuing a prosthetic device, including formidable competitors from MIT, a German team of over 20 scientists and engineers who have received over $14,000,000 for the German government and a team from Japan who have recently received government funding. To date, members of the MARC team Dr. Humayun et al. have been the only ones to electrically stimulate1,2,4 controlled visual percepts human patients. Chapter 2 of my dissertation provides a treatment of the papers, patents, and prior art embodied by the various teams' progress, but due to space limitations, only the advantages of the MARC are presented here. MARC Component Size: The novel multiple-until intraocular transceiver processing and electrode array-processing visual prosthesis allows for larger processing chips (6x6 mm), and thus more complex circuitry. Also, by splitting the chips up into smaller components, and utilizing techniques such as solder bumping to connect the chips with kapton substrates, we shall keep the sizes to a minimum. MARC Heat Dissipation: The power transfer and rectification, primary sources of heat generation, occur near the corneal surface, or at least remotely from the retina, rather than in close proximity to the more delicate retina. MARC Powering: The novel multiple-until intraocular transceiver-processing and electrode array-processing visual prosthesis provides a more direct means for power and signal transfer, as the transceiver microprocessing unit is placed in close proximity to the cornea, making it more accessible to electromagnetic radiation in either the visible wavelength range or radio waves. Solar powering and especially RF powering are made more feasible. MARC Diagnostic Capability: The transceiver unit is positioned close to the cornea, and thus it can send and receive radio waves, granting it the capability of being programmed to perform different functions as well as giving diagnostic feedback to an external control system. Diagnostic feedback would be much more difficult with the solar powering. MARC Physiological Functionality: Our device was designed in conformance with the physiological data gained during tests on blind patients. We are the only group who has yet created a visual percept (with electrical stimulation) in a patient. Therefore, we have the unique advantage of designing around parameters which are guaranteed to work. Reduction of Stress Upon The Retina: Our device would reduce the stress upon the retina, as it would only necessitate the mounting of the electrode array upon the delicate surface, while the signal processing and power transfer could be performed off the retina. Also, buoyancy could be added to the electrode array, to give it the same average density as the surrounding fluid. Approximately 10,000,000 people worldwide are severely visually handicapped due to photoreceptor degeneration5 experienced in end-stage age-related macular retinal degeneration and retinitis pigmentosa. In addition to benefiting the visually impaired, restoring vision to a large subset of blind patients promises to have a positive impact on government spending. 4. Description of the five most important technical steps The honing and development of several aspects of the MARC system must yet be fully realized so as to optimize the final device's functionality and performance. Concurrent engineering tasks which are both touched upon and elaborated in chapters of my dissertation include the following: The design, fabrication, and testing of the signal-processing and stimulus-driving MARC2, MARC3 and MARC46 VLSI chips and the video-processing chip. These are VLSI chips endowed with microprocessing circuitry to encode and decode visual information, and drive the stimulating electrodes. The enhancement of the CMOS photodetectors and the Holed Emitter Phototransistor. These are the fundamental building blocks of silicon photosensors. The final designs and optimization of the kapton/polyimide or silicon stimulating electrode array. Kapton polyimide flexible polymer which would allow for the fabrication of an electrode array which could conform to the curvature of the retinal surface. So far it has proven to be biocompatible. The design and refinement of the RF telemetry system and video protocol. RF Telemetry is utilized to transmit both power and signal without the presence of physical wires. Thus the device is entirely self-contained within the eye. The bonding, packaging, and hermetic sealing of the CMOS signal-processing chips with the kapton electrode array. The hermetic packaging of a chronic device with over 100 electrical feedthroughs is a challenge. The integration of microelectronics with damaged or degenerated biological systems in order to provide some of the lost function is a rapidly emerging field, and we have been and will continue to share technologies with other groups also working on biological prosthesises. 5. Description of how best to test prototypes Extensive laboratory and clinical testing will be conducted before functioning MARC is realized. The doctors on our team are conducting the biocompatability and threshold-stimulation experiments within both humans and animals, while the engineers at NCSU-ECE are concentrating on the testing of the functionality of the computer chips, and the performance of the RF telemetry transfer of power and signal. Hermeticity may be tested by submerging device in saline baths for extended periods. In order to test MARC1, which was endowed with HEP photosensors, the image of a while paper E mounted on black paper was focused onto the MARC chip. An adjustable incandescent light was shone onto both black and white paper, and the difference in reflected power was measured, and found to be around a factor of ten. This order of magnitude difference is easily recognized by Mead's logarithmic photodetector circuit. Even though the image of E was focused down to about 20% of its original size, so as to fit upon the chip, the difference between the intensities of the neighboring light and dark areas remained the same, as they were both multiplied by the same factor. All the pixels which were subject to the light of the E's image fired, while those beyond the border remained off. The output from the "on" pixels, which resulted in 250 mA, 2ms pulses at a 50 Hz clock rate, were sufficient for retinal stimulation. The photosensing and current-generating partition of the artificial retina chip has been tested, and it ahs been demonstrated to work. These results suggest that the chip would facilitate the perception of outlines where sharp contrast existed, such as for windows or illuminated text. The Doctors have demonstrated that the 5x5 electrode array functions, and the next step towards an artificial retinal prosthesis is to connect the dual unit visual prosthesis to the 5x5 electrode array, and implant the dual unit device in an animal, so as to test biocompatibility. 6. Description of the limitations and challenges in the MARC project The MARC project spreads itself across a diverse array of scientific, engineering, and medical disciplines. Perhaps one of the greatest challenges associated with this project is the interdisciplinary nature of the device's design, which requires the devotion from members of a large, unified team from a wide array of disciplines and distant institutions. One of the goals of my dissertation was to aid the project by providing an overview or synthesis of the wide-ranging research, within the presentation of the complete system engineering of the MARC implantable prosthesis. The inter-disciplinary challenge involves the fabrication of the processing chips, the acquisition and transmission of visual data in a way that is meaningful to the device and to the patient, a wireless power source, and a form of biocompatible, hermetically-sealed packaging. The MARC designs presented throughout my dissertation attempt to integrate the multifaceted technologies in a final device that will be beneficial to a visually-impaired patient. As we approach a functioning MARC prosthesis, the design will continue to evolve, as the refinement of any one parameter affects all the rest. For instance, should the main intraocular chip be subdivided into smaller individually-sealed chips so as to reduce the risk of realizing a complete system failure if one chip should malfunction, the basic chip design, as well as the hermetic packaging, will have to be altered. An alteration in the hermetic packaging will affect where the chip may be mounted. A different chip design will require a different power source and thus telemetry configuration. And a different telemetry configuration may alter the coil designs, which would affect the size of the external battery. Thus an alteration in any one aspect of the design resounds throughout the entire system. The purpose of this dissertation was to offer an overview of all the parameters affecting the design of the MARC, elaborate on all the engineering progress that has been made, anticipate design and engineering hurdles, and suggest approaches for future research. The photosensing/current-generating component of the artificial retina chip has been tested, and it has been demonstrated to work. Investigations into the feasibility of RF powering have so far been positive. The electrode design is being honed, and the Doctors have demonstrated that a 5x5 electrode array can stimulate simple pictures upon a patient's retina. The doctors are currently investigating ways of stimulating the retina with lower currents, which will have a positive impact on the design of the chip and RF powering system. The next step towards an artificial retinal prosthesis will be to develop the second and third generation MARCs which will be capable of driving a 15x15 electrode array and 25x25 electrode arrays, and testing the devices for short periods within a human. The implications of this research may extend beyond this immediate project, as contributions to the overall field of implantable prosthetic devices and hermetic packaging. The observations and clinical and engineering experiments performed should lend insight into the actual functioning of the human retina. The feedback gained by these studies should provide a vehicle for further understanding of the retinal/vision/perception process. In addition, a CMOS phototransistor which exhibits an enhanced quantum efficiency was also developed, and a numerical model was presented which also predicts its enhanced efficiency. The enhanced performance is accounted for via the physics of transistor operation. The CMOS phototransistor may find an application in the emerging field of CMOS photodetectors, wherein researchers are attempting to create low-powered inexpensive cameras. -------------------------------------------------------------------------------- References: 1 E.D. Juan, Jr. Mark S. Humayun, Howard D. Phillips; "Retinal Microstimulation," US Patent #5109844, 1993 2 M. Humayun, "Is Surface Electrical Stimulation of the Retina a Feasible Approach Towards The Development of a Visual Prosthesis?" Ph.D. Dissertation UNCCH BME 1994 3 W. Liu, E. McGucken, K. Vichiechom, M. Clements, E. De Juan, and M. Humayun, "Dual Unit Retinal Prosthesis," IEEE EMBS97 4 M.S. Humayun, E.D. Juan Jr, G. Dagnelie, R.J. Greenberg, R.H. Propst and H. Phillips, "Visual Preception Elicited by Electrical Stimulation of Retina in Blind Humans by Electrical Stimulation of Retina in Blind Humans," Arch. Ophthalmol, pp. 40-46, vol. 114, Jan. 1996. 5 Research to Prevent Blindness, Progress Report 1993. 6 K. Vichiechom, M. Clemments, E. McGucken, C. Demarco, C. Hughes, W. Liu, MARC2 and MARC3 (Retina2 and Retina3), Technical Report, February, 1998