Leverage Artificial Retina Project—
Create Spinoff Technologies
Department of Energy's national laboratories are incubators
Chu, Secretary of Energy
to the DOE national labs is like going to a high-tech extravaganza.
Their revolutionary technologies are enabling completely
DOE Artificial Retina Project
in many frontier scientific research projects, the U.S. Department
of Energy’s (DOE) Artificial Retina Project has led to cutting-edge
innovations as well as several unanticipated discoveries and spinoffs
that are increasing the value of these investments.
same microelectronics and feedback mechanisms used in the artificial
retina to enable neural cells to communicate with machines could
be adapted to interface with other cell types such as those of
plants and bacteria. Applications include remote sensors that
monitor for environmental contamination, assist with environmental
remediation, or counter bioterrorism. A wide range of other biomedical
devices also could be enabled by this technology.
are only looking at the tip of the iceberg right now as we move
into higher-density abiotic-biotic surfaces,” says Satinderpall
Pannu, group leader for advanced materials and processing technologies
at DOE’s Lawrence Livermore National Laboratory (LLNL) and
one of the primary technology developers for the artificial retina.
below are several of the leading-edge technologies developed for
and/or as a result of the Artificial Retina Project. Full descriptions
polymer-based, field-deployable biodetection system with
embedded microelectronics and radio frequency-based power
and data communication. [Credit: Satinderpall
research at LLNL is furthering the development of remote-sensing
platforms to detect biothreats in harsh environments such as oceans,
rivers, and wastewater streams.
Similar to the artificial retina, these polymer-based biodetection
systems contain embedded electronics and electrodes (see photo
at right). But instead of stimulating retinal tissue, the electrodes
can be functionalized for multiple chemical or biological agents
like anthrax or small pox. Whenever those particular substances
are detected—for example, in a drinking water supply or
at an air monitoring station—the electrical
signal changes, and the information can be sent to a local agency
or the Centers for Disease Control and Prevention, alerting them
to the potential threat.
technologies developed for the artificial retina are enabling
such advanced detection devices. Because the technology was designed
for the saline environment in the eye, these sensors can tolerate
harsh surroundings. Moreover, communication and power transmission
occur via a radio-frequency link. Miniaturized for the artificial
retina, this technology permits the deployment of multiple sensors
that can relay signals to each other. Operating with very low
power requirements, such a distributed network of sensors permits
long-range communication capabilities with a low detection risk.
flexible substrate allows these detection devices to be molded
for attachment to any curved surface. They could be affixed inside
a channel, pipe, tube, or even a soldier’s helmet. In a
battlefield setting, such sensors could be deployed virtually
everywhere—on soldiers, tanks, planes, and Humvees—permitting
communication as the sensors actively search the surrounding environment
for chemical and biological threats.
such rugged, flexible sensors could be distributed anywhere in
any situation and be counted on to work for the lifetime of an
The advanced, implantable microelectronic
system developed for the artificial retina has the potential to
revolutionize other medical implants that could help people with
combat injuries (e.g., soldiers who suffer traumatic brain injuries),
spinal cord injuries, Parkinson’s disease, deafness, and
many other neurological disorders.
artificial retina demonstrates that an electronic-tissue interface
is capable of communicating
with the brain to provide information that the local tissue is
unable to provide because of disease or injury. By selectively
stimulating neural or muscular tissue, the brain can be retrained
to understand bioelectronic inputs or to control the movement
of muscles or electromechanical actuators.
technology platform also could be useful for drug delivery. The
flexible circuit could be adapted so that instead of carrying
electrical current, it would carry fluids via microfluidic channels,
Pannu says. In the case of diabetics, for example, such a smart,
implantable system could serve as an artificial pancreas, continually
measuring glucose levels and dispensing the appropriate amounts
of insulin in response to any foods being consumed (see photo
this technology might be used to administer narcotics or pain
relievers to people with chronic pain such as migraine headaches.
In addition, preventative systems could be implanted in people
who have been diagnosed with a particular disease or have a history
of cancer in their family. If the device picks up any change in
the level of a certain biomarker, an alarm would be triggered
to alert the patient to see a doctor immediately. Not only could
such a system improve and save lives, Pannu says, it also would
cut down on healthcare costs because patients would need to see
a doctor only if an issue arises.
scene as it might be viewed by a person with normal vision.
[Credit: National Eye Institute, National Institutes of Health]
same scene as it might be viewed by a person with diabetic
retinopathy. [Credit: National Eye Institute, National Institutes
Prosthesis for Diabetics
In addition to age-related macular degeneration and retinitis
pigmentosa, diabetic retinopathy is another leading cause of blindness.
It results from poor blood circulation, particularly
in the retina, which is a complicating factor of diabetes. As
blood flow is restricted, retinal tissue is deprived of oxygen.
Subsequently, neovascularization can occur, with abnormal or excessive
blood vessels forming to compensate for the lack of oxygen. Eventually,
these vessels can burst, leaking blood into the vitreous and causing
blindness (see photos at right). The longer a person has diabetes,
the greater his or her chances of developing this eye disease.
could be provided to retinal tissue with poor blood flow before
the onset of neovascularization,
progression of this condition might be stopped and perhaps reversed.
An extension of the technology developed for DOE’s artificial
retina could supply the needed oxygen via a metabolic prosthesis.
The first publication of this new idea, including experimental
data, appeared in the February 2009 issue of IEEE Transactions
on Biomedical Engineering.
The procedure would involve surgically implanting
a feedback-controlled, three-electrode electrolysis system that
stimulates oxygen production
near the retina. The electrodes would provide small amounts of
current in very short, repetitive pulses that last about 200 microseconds.
This would result in rapid production of oxygen and suppressed
production of chlorine, a potentially harmful byproduct.
vitreous humor has a chemical composition very similar to seawater,
and if you perform ordinary electrolysis of saltwater, you’ll
make bleach and alkali, which are very harsh byproducts,”
explains Elias Greenbaum, who is leading this study at Oak Ridge
National Laboratory (ORNL) in collaboration with the University
of Southern California (USC) and University of Tennessee. “We’ve
discovered that if you perform pulsed or charge-limited electrolysis
of the vitreous, it’s possible to produce oxygen and suppress
the formation of chlorine.”
in the IEEE paper, the three-electrode and feedback loop configuration—made
possible by implanting a second cathode behind a patient’s
ear—would enable a constant pH to be maintained in the area
to be treated. If any pH drift occurs, it can be exported to a
surface-accessible region for treatment, thereby avoiding any
adverse internal irritants.
this technique could preserve the retina. Currently, neovascularization
treatment is destructive. “You apply a laser to the peripheral
retina, essentially destroying it to create less oxygen demand
in that region in order to supply more oxygen to the central retina,”
explains Mark Humayun, a vitreoretinal surgeon and associate director
of research at USC’s Doheny Eye Institute. “If we
can supply oxygen, we can hopefully sustain the entire retina.”
Much of what
has been learned through DOE’s Artificial Retina Project—practical
biomedical engineering, surgical techniques, and electrode fabrication—carries
directly over to oxygenation of ischemic tissue for diabetic retinopathy.
And in many respects, the surgery and electrode fabrication are
simpler, and the potential for neural tissue damage is eliminated
because no neural tissue is stimulated. Instead, the vitreous
humor is oxygenated.
research has demonstrated proof of principle of the metabolic
prosthesis concept. The next step is to build and test a device.
Electrodes to Molecular Photovoltaics
studies algae being used to produce hydrogen from water
in an illuminated flask. [Image: ORNL
numerous spinoff technologies have been spawned by DOE’s
artificial retina, other national laboratory technologies have
helped to advance the retinal implant. One of these,
from ORNL, evolved from DOE-supported research using photosynthesis
in spinach and algae to split water molecules to produce oxygen
and hydrogen, the energy-rich gas.
using metal electrodes to stimulate retinal neurons, a light-sensitive
protein from green plants could be used because it generates a
small electrical voltage after capturing the energy of incoming
light. This technology could make future artificial retinas more
efficient than previously believed possible.
membranes, which measure 5 nanometers across, are where plants
convert light energy to chemical energy. As photons are absorbed
in specialized reaction centers, they trigger a charge separation
that generates a voltage which might be sufficient to trigger
a neural response. If these reaction centers are inserted into
retinal neural cells, the resulting stimulation could be much
more effective than that applied with external electrodes, where
voltage is lost at the interface between the electrode and liquid
interface, says Greenbaum, a physicist at ORNL.
offers other advantages as well. For one, these systems are already
at the nanoscale, so a high density of them could be packed into
the roughly 5 mm by 5 mm area of the retina targeted by the prosthesis
for stimulation. In contrast, an equivalent number of metal electrodes
would require hair-like dimensions, leading to fabrication and
no metal is stable when you get down to those hair-like dimensions
because the electrical voltages applied to them cause corrosion
and loss of metal,” Greenbaum explains.
the lens of the eye itself could be used to capture images, eliminating
the need for an external camera mounted in eyeglasses. Likewise,
no battery would be needed because the voltages would be self-powered
by the photosynthetic reaction centers in the retinal cells.
group has shown that these nanoscale protein structures can be
harvested from plant materials and reconstituted in liposomes,
with their full photovoltaic properties preserved. Liposomes are
artificial membranes made of lipids that mimic the membrane composition
of a living cell. Using the liposomes as delivery vehicles, the
researchers have inserted these photosynthetic reaction centers
into mammalian cells and elicited optical activity where there
was none before.
information on this spinoff topic, see articles from Discovery
advanced artificial retinas are relying on miniaturized electronics
for processing incoming images and activating the corresponding
electrodes to communicate with retinal cells and ultimately the
brain. The goal of these devices, being developed through a U.S.
Department of Energy (DOE) collaboration, is to continually improve
their visual resolution so that implanted individuals eventually
will be able to read large print, recognize faces, and move about
without aid. Sandia National Laboratories’ expertise in
the development, fabrication, and production of microsystems is
helping to make this goal a reality.
Biocompatible electronics packages currently used in medical devices
require only a small number of electrical interfaces to operate
them. For example, pacemakers at most have four electrical contacts,
and cochlear implants for the hearing impaired use 22 or fewer.
Additionally, the volume of these packages is typically more than
5 cm3. By comparison, DOE’s artificial retina requires a
much smaller electronics package but one to two orders of magnitude
more electrical feed-throughs to communicate with retinal cells.
is beyond conventional packaging technology. The compact size
of the artificial retina’s electronics package makes it
difficult to mechanically and electrically interconnect the microelectronics
inside. The package also has to withstand the human eye’s
harsh saline environment for the lifetime of the patient, so the
electronics have to be hermetically sealed, preventing all transfer
of moisture and gases between the components inside the package
and the human body.
we’re trying to cram more and more things into smaller and
smaller spaces,” says Kurt Wessendorf, an analog circuit
designer and leader of Sandia’s artificial retina efforts.
If more electrodes, and hence more capabilities, can be packed
into the system, the images that implanted individuals see will
be of higher resolution. This is the area benefitted by Sandia’s
expertise in microsystems.
1. An application-specific integrated circuit being developed
for advanced artificial retinas. A four-way switch allows
each incoming signal to go to one of four places as an output,
enabling more electrodes to be stimulated. Click on image
devices smaller than a human hair are built on silicon wafers
or chips. They contain electrical circuitry and microelectromechanical
systems (MEMS), which are miniature machines.
retina’s custom-designed integrated circuit (IC) is the
system’s brain. Its job is to take signals from the external
camera and convert them into stimuli that are transferred to the
electrode array. The IC performs this function via a series of
interconnected, nanosize nodes, whose locations on the chip’s
surface are important because they can minimize the wire length
along which the signal travels (see figure 1 at right).
2. Three-dimensional model and cross section of a dual-sided
integrated circuit. The circuit enables high-density interconnects
on both top and bottom surfaces. Click on image to enlarge.
current method for achieving higher electrode currents involves
assembly with a lot of bond wires and other interconnects,”
says Sean Pearson, an IC design engineer at Sandia. “This
makes the device tedious to build and very difficult to yield
full functionality.” Consequently, he and his colleagues
are developing a novel, dual-sided IC to simplify how data are
routed and to better integrate the electronics package with the
electrode array (see figure 2 at right). “We’re using
one side to bring the signals in and the other side to put them
out,” Pearson explains.
electronics substrate, the researchers are using a Sandia-patented
MEMS technique to selectively etch away parts of the silicon chip
or add new structural layers to create tiny features that cannot
be made any other way. This micromachining process allows wiring
of the electrical connections through the chip for access to both
using that bottom surface, which adds interconnect space instead
of eliminating it, we’re able to get higher interconnect
densities,” thereby allowing the number of electrodes on
the array to be increased without making the device bigger, says
Murat Okandan, a microsystems engineer on the Sandia team.
3. High-density hermetic electronics packaging with a dual-sided
electronic circuit. Click on image to enlarge.
Sandia researchers are developing state-of-the-art packaging technologies
to assemble and integrate the microelectronic components with
the thin-film electrode array. Biocompatibility issues are driving
much of this effort, requiring the high-density interconnects
to be insulated with a nonconductive film to prevent moisture
and ionic and biological contamination from causing device failure
(see figure 3 at right).
Sandia has a long history of pioneering microelectronics research,
which feeds into several defense-related systems, including sensor
technologies and satellite applications. Spinoffs of the Artificial
Retina Project—such as the silicon interconnect and higher-density
packaging of components—are being evaluated for potential
applications in some of these ongoing projects.
kind of exposure seen in the eye is not unlike the harsh, corrosive
environments in which many defense-related components are required
to survive for many years,” Wessendorf says. Moreover, “We’re
always looking at miniaturizing and increasing function, and these
efforts will help in those directions.”
Laboratories is operated by Sandia Corporation, a Lockheed Martin
company, for the U.S. Department of Energy’s National Nuclear
Simulator Image Processing Software System: Seeing is Processing
novel software system not only processes incoming images in real
time but also enhances what retinal implant recipients perceive
palette of Artificial Retinal Implant Vision Simulator (ARVIS)
image-processing modules that are applied in real time to
the video camera stream driving the artificial retina. [Credit:
California Institute of Technology]. Click on image to enlarge.
retina is not just a detector of light that sends optical information
to the brain. It also performs complex image processing to provide
the brain with optimized visual information. Replacing diseased
photoreceptors with the electrodes of an artificial retina thus
not only reduces the number of pixels, it also disrupts this necessary
that lost function, researchers at the California Institute of
Technology’s Visual and Autonomous Exploration Systems Research
Laboratory under the direction of Wolfgang Fink are developing
software to pre-process the information from implant patients’
miniature cameras before it is fed to their retinal prostheses.
Dubbed the Artificial Retinal Implant Vision Simulator (ARIVS),
this software system provides real-time image processing and enhancement
to improve the limited vision afforded by the camera-driven device.
The preservation and enhancement of contrast differences and transitions,
such as edges, are especially important compared to picture details
like object texture.
exactly what blind subjects may be able to perceive is difficult,
ARIVS offers a wide variety of image processing filters. They
include contrast and brightness enhancement, grayscale equalization
for luminance control under severe lighting conditions, user-defined
grayscale levels for reducing the data volume transmitted to the
visual prosthesis, blur algorithms, and edge detection (see graphic
at right). These filters are not unlike what a person experiences
in a regular eye exam during which a battery of tests is performed
to determine the proper eyeglass prescription. In this case, retinal
implant recipients can choose among these different filters to
further fine tune, optimize, and customize their individual visual
perception by actively manipulating parameters of individual image-processing
filters or altering the sequence of these filters.
greater challenge exists in predicting how to electrically stimulate
the retina of a blind subject via the retinal prosthesis to elicit
a visual perception that matches an object or scene as captured
by the camera system that drives the prosthesis. This requires
the efficient translation of the camera stream, pre-processed
by ARIVS, into patterns of electrical stimulation of retinal tissue
by the implanted electrode array. The Caltech researchers on the
U.S. Department of Energy’s team are addressing this challenge
by developing and testing multivariate optimization algorithms
based on evolutionary principles. These algorithms are used to
modify the electrical stimulation patterns administered by the
electrode array to optimize visual perception. Operational tests
with Argus™ I users currently are under way.
artificial retina team at Lawrence Livermore National Laboratory
includes: Front row (left) Julie Hamilton and (right) Terri
Delima. Back row, from left to right: Phillipe Tabada, Satinderpall
Pannu, and William Benett.
work with polymer-based microfabrication methods at Lawrence Livermore
National Laboratory (LLNL) is feeding into the primary component
of the Artificial Retina Project—namely, development of
a flexible, biocompatible microelectrode array.
A key LLNL
technique for making thin metal lines “allows us to pack
many more electrodes into a much smaller device than previous
models,” says Satinderpall Pannu, who is leading the LLNL
effort. This technique, coupled with integrated-circuit and wireless
technologies, drives the Department of Energy’s advanced
retina prosthesis. The current goal is to develop an array with
hundreds of electrodes.
As part of LLNL’s Center for Micro- and Nano-Technology,
Pannu and his team are applying their expertise to microelectromechanical
systems (called MEMS) that integrate micrometer-sized mechanical
elements, sensors, actuators, and electronics through microfabrication
traces forming the electrodes and electronics in the array are
less than a micrometer thick, less than 1% the thickness of a
human hair. Embedded in such soft, moldable substrates as silicone,
the array conforms easily to the curved shape of the retina.
view of the neural microelectrodes that make up the artificial
group also is developing methods for integrating complementary
metal oxide silicon (called CMOS) electronics into the retinal
prosthesis to reduce its overall size and complexity.
send electrical signals to microelectrodes to stimulate the retina,
a function normally generated by the eye’s photoreceptor
cells. In blind people suffering from retinitis pigmentosa and
age-related macular degeneration, however, this process has broken
down. The microelectrode array mimics the function of the photoreceptor
cells by electrically stimulating the remaining healthy bipolar
and ganglion cell layers.
LLNL’s expertise is being tapped to develop advanced ocular
surgical tools that will allow surgeons to place the microelectrode
array precisely on the retina with minimal tissue damage.
Many of the technological advances forming the basis of this research
stem from LLNL’s role as a national security laboratory.
project is a great example of LLNL’s multidisciplinary approach
to science,” says Cherry Murray, LLNL’s deputy director
of Science and Technology.
LLNL researchers used silicone as a substrate for microfluidic
devices such as biosensors to detect and identify chemical and
biological pathogens in waterways. Since silicone is a biocompatible
material, more recent work has focused on developing processes
for embedding metal microelectrodes and electronics within silicone
for use in biomedical devices.
ocular surgical tools developed at LLNL are used to tack the
thin-film electrode array into the retinal tissue.
leveraging a lot of the technologies we’ve developed for
biodetection systems onto the retinal prosthesis, and vice versa,”
for the flexible electrode array go beyond the artificial retina.
LLNL researchers are working to integrate this technology into
next-generation devices such as the cochlear implant for hearing.
The array also might be used one day to stimulate the deep brain
for treating such diseases as Parkinson’s and chronic depression,
and the spinal cord to relieve chronic pain.
hope is that this technology will evolve into a general-purpose
neural electrode array,” Pannu says, “helping to restore
eyesight in blind people and revolutionizing treatment for all
kinds of neurologically based diseases.”
LLNL is managed
by the University of California for the U.S. Department of Energy’s
National Nuclear Security Administration.
Scans Show Brain Responses to Light, Electrical Stimulation
study measuring metabolic changes in the brains of sighted people
is showing similar responses to both light and electrical stimulations.
Researchers at the U.S. Department of Energy’s Brookhaven
National Laboratory, Doheny Eye Institute at the University of
Southern California, and Columbia University now are taking this
study a step further to demonstrate that the visual cortex in
patients with retinitis pigmentosa (RP) can respond to electrical
emission tomography (PET) scanning and a glucose analogue called
FDG, the researchers evaluated and compared what happens to the
visual processing part of the brain following different stimuli.
Eight healthy volunteers with normal vision participated in the
study. Each underwent three PET scans on three different days
to represent baseline conditions, responses to light stimulation,
and responses to electrical stimulation.
scans showing brain activity in response to light (upper)
stimulation and electrical (lower) stimulation. Click on
image to enlarge.
each scan, the volunteers sat quietly in a darkened room for 30
minutes to dark adapt before receiving the FDG injection. For
the baseline scan, both eyes were blindfolded. During the light
stimulation scan, the person’s right eye was exposed to
light flashes from a computer monitor. For the electrical stimulation
experiment, a fiber electrode was placed on the right eye and
a stream of electrical pulses with the same duty cycle was delivered.
The results show similar activation and inactivation patterns
between the light and electrical stimulations.
the study to RP patients implanted with retinal prostheses, the
researchers will analyze what happens to the visual part of the
brain over time as the device is used more by patients. Ultimately,
the researchers hope to use the results to examine the effect
of cortical reorganization
in retinal degenerative diseases.
work was funded by the U.S. Department of Energy, and the RP patient
work is being funded by the National Science Foundation (NSF grant
John Carlisle (left) and Orlando Auciello (right) are developing
an ultrathin biocompatible coating for the device.
Diamond Coatings for the Retinal Implant
Laboratory (ANL) plays a critical role in the success of the electrode
implants used in the Artificial Retina Project. That’s where
researchers Orlando Auciello and colleague John Carlisle are using
their patented ultrananocrystalline diamond (UNCD) technology
to apply a revolutionary new coating to the retinal prosthetic
device. The new packaging promises to provide a very thin, ultrasmooth
film that will be far more compact and biocompatible than the
bulky materials used to encase the earlier prototypes (models
1 and 2).
like wearing a skin instead of a space suit,” says Mark
Humayun (Doheny Eye Institute at the University of Southern California),
leader of the Artificial Retina Project.
Ultrathin Diamond Coating
UNCD is a
form of carbon that captures many of the properties of diamond
and can be deposited on a wide variety of surfaces in thin layers.
The diamond grains used in the coating are only 2 to 5 nanometers
in size (a nanometer is about 10,000 times narrower than a human
hair). These films are as hard as single-crystal diamond, the
hardest known material on earth. Unlike natural diamond, however,
its properties can be adjusted and optimized for a given application.
to be a platform technology, UNCD has numerous potential beneficial
applications in such areas as medicine, transportation, and industrial
production. It is chemically inert (nonreactive) and compatible
with biological tissues, traits that make it useful in retinal
prosthetic implants as well as other biodevices such as an artificial
pancreas. Additionally, the material is a superb electrical insulator
but also can be made to be highly conductive, and this conductivity
can be tuned. This work has led to the use of UNCD for biosensors
that use electrochemical reactions to detect biomolecules.
Parts of the
UNCD technology received a 2003 R&D 100 award, an honor given
to the most innovative developments that occur in a particular
year. The technology has been licensed to Advanced Diamond Technologies
(Champaign, Il.), a company founded by Carlisle and Auciello.
the National Labs to the Public
A goal of
the national laboratories is to provide benefits to industry and
the public by moving discoveries into everyday use, a process
called technology transfer. This practice leads to benefits for
everyone and demonstrates the value of using tax dollars to support
early-stage scientific research. In recognition of their efforts
toward that end, Carlisle and Auciello received the 2006 Award
for Excellence in Technology Transfer from the Federal Laboratory
first national laboratory, ANL conducts basic and applied scientific
research across a wide spectrum of disciplines, ranging from high-energy
physics to climatology and biotechnology. Since 1990, Argonne
has worked with more than 600 companies and numerous federal agencies
and other organizations to help advance America’s scientific
leadership and prepare the nation for the future.
Argonne is managed by the University of Chicago for the U.S. Department
of Energy’s Office of Science.