New Retinal Implant Technology Expected to Help Restore Sight

In an effort to improve retinal implant technology, researchers have developed a new method that uses microsecond pulses, on-chip counter-electrodes, and controlled firing of electrodes to shape the electrical field, which could help people who have lost their sight see more than just light and vague shapes.

Researchers at the University of Arizona and University of Tübingen have made a breakthrough in retinal implant technology that could help people who have lost their sight see more than just light and vague shapes.

Wolfgang Fink, an associate professor in the UA departments of electrical and computer engineering and biomedical engineering, is researching new implant design and methods of electrical stimulation of the retina that will enable retinal implants to produce much clearer images.

Fink conducted the research jointly with Erich Schmid, professor emeritus of theoretical atomic and nuclear physics at the University of Tübingen, Germany. Fink will present the team’s findings in San Diego during the November 6-8, 2013 IEEE International Conference on Neural Engineering, organized by the Engineering in Medicine & Biology Society.

Only a handful of companies and research institutions worldwide are developing retinal implants, which stimulate surviving retinal cells in people who have lost their sight due to common degenerative diseases such as macular degeneration and retinitis pigmentosa. Implant patients can usually detect the presence of light, but the images they perceive are very low resolution.

“Current technologies and methods are far behind what can be done,” said Fink, who is working with Tech Launch Arizona to patent the new technology and license it to retinal implant developers.

The conference presentations – “Simultaneous vs. Sequential and Unipolar vs. Multipolar Stimulation in Retinal Prostheses” and “Electric Stimulation of Neurons and Neural Networks in Retinal Prostheses” – will reflect the team’s view that implants on the market don’t work, and will propose new methods for achieving higher resolution images so implant patients can see in greater detail.

The low-level visual acuity currently achievable, Fink said, enables implant patients to make out white stripes on a black computer screen, or to distinguish between white objects such as a cup and a plate on a black background in a darkened room. “But only if the patients are told in advance that they are to choose between a cup and a plate,” Fink said.

The level of restored vision the research team thinks is achievable, using its discoveries, is for an implant patient to be able to make out a bird flying in the sky. To accomplish that level of detail, the team’s novel method of electrical stimulation uses microsecond pulses, on-chip counter-electrodes, and controlled firing of electrodes to shape the electrical field.

The technology of retinal implants

Retinal implants consist of an array of electrodes that are activated – either by light entering the eye or by a signal from a camera mounted outside the eye – to emit electric fields, which in turn stimulate retinal cells that send signals to the brain.

In an attempt to achieve greater resolution, some companies are developing implants with more densely packed electrodes while maintaining the array’s same small footprint. Just adding more electrodes, however, is not the answer, Fink said, stressing that without the stimulation methodology he and Schmid propose, the vision achievable with hundreds or even thousands of electrodes would be no better than that achieved using tens of electrodes.

“Stimulation methodology is what achieves the improved vision, not electrode density,” Fink said.

Stimulation methodology, not electrode density, is key

One problem with current implants, Fink explained, is that the return electrode, or counter-electrode, is too far from the electrode array, or chip, often somewhere within the patient’s head. This configuration does not allow fine-tuned stimulation of retinal cells that are just microns above the chip.

The research team’s solution is to use electrodes on the chip as return electrodes, so the electrical stimulation can be more focused.

Some electrodes are programmed to fire in short bursts – it is these microsecond high-voltage pulses that stimulate retinal cells – while others are programmed to fire for longer periods. The team has discovered that the field emitted by the longer-firing electrodes can be used to shape the field emitted by the electrodes firing in short bursts.

It’s easy, but erroneous, to visualize a one-to-one relationship between the electrodes on a chip and the retinal cells they stimulate to form a pixel. An electrode cannot emit an electric field with laser-like focus – the laws of physics dictate otherwise. In reality, each electrode, when firing alone, emits a hemispherical field that stimulates all retinal cells in its vicinity. When all the electrodes on an array are fired up simultaneously, the fields bunch together but never overlap, again due to physics. However, the shape of the electrical field can be controlled by selectively firing the electrodes in specific patterns.

For example, an electrode’s stimulating field can be shaped by fields from adjacent electrodes into what the team calls a “fountain” – a tall, focused electric field that pushes upward directly into a localized region of the retina and then cascades down, fountain-like, to the return electrodes on the chip.

Chip-level field shaping improves visual perception

Unlike the technology developed by Fink and Schmid, current retinal implants rely on longer pulses, typically measured in milliseconds, and a single distant counter-electrode. They also lack the firing-sequence control that enables fields to be shaped.

“If you look at the electrode array in the cup and plate scenario, only a few electrodes of the entire array are firing and stimulating the retina – all the other electrodes are quiescent,” Schmid said. “This is why current implants appear to work well.”

Conversely, Schmid said, being able to see a bird flying – a small, dark shape traversing an expanse of blue and white – is a highly complex task for a retinal implant. And it’s a negative of the cup and plate scenario: Every single electrode is firing except for those tracking the bird.

“With every electrode firing simultaneously, the fields are forced into very thin, almost parallel electric field lines. There is so much bunching going on that no electric current can leave the chip. You’re basically strangling the stimulation being emitted from the chip,” said Schmid, likening the effect to squeezing around the middle of a bunch of straws.

In the artificial vision generated by the implant, that bird is represented by non-firing electrodes. However, the absence of an electrical field above those electrodes leaves a vacuum into which adjacent fields readily enter, thus obliterating the image of the bird. The team’s novel field-shaping and neural stimulation methods would allow the bird to be perceived.

Beyond Retinal Implants

Taken in its wider context, Fink and Schmid’s research is about neural stimulation.

“We believe this same methodology could work for all forms of neural stimulation,” said Fink. “It could be applied to paralysis, deep brain stimulation, things like that. There are definitely some cool ideas to explore that go way beyond vision.”

Fink is the founding director of the Visual and Autonomous Exploration Systems Research Laboratory, and the inaugural holder of the Edward and Maria Keonjian Endowed Chair. He holds joint appointments in the UA departments of electrical and computer engineering, biomedical engineering, systems and industrial engineering, aerospace and mechanical engineering, and ophthalmology and vision science.

In 2012 he was elected to the College of Fellows of the American Institute for Medical and Biological Engineering for his outstanding contributions in the field of ophthalmology and vision sciences with particular focus on diagnostics and artificial vision systems.

The U.S. Department of Energy and the National Science Foundation have funded Fink’s research into artificial vision, and his research contribution to the DOE Artificial Retina project involved developing a real-time image-processing system, determining the most effective electric stimulation patterns (awarded two patents to date), and designing a robotic surrogate for patients with a vision implant. In 2009, the DOE Artificial Retina project won R&D Magazine’s R&D 100 Award and the Editors’ Choice Award as one of the top three of the 100 award winners that year.

Source: Pete Brown, College of Engineering, University of Arizona

Image: University of Arizona

Surprise Discovery Could Revolutionize Solar Energy

This is the experimental setup used to generate femtosecond laser pulses which serve as an ultrafast “flash ” for the camera so that very rapid phenomenon can be filmed. Credit: Simon Gelinas

In a newly published study, researchers from Cambridge’s Cavendish Laboratory detail the surprise discovery that could revolutionize solar energy.

Researchers have been able to tune ‘coherence’ in organic nanostructures due to the surprise discovery of wavelike electrons in organic materials, revealing the key to generating “long-lived charges” in organic solar cells – material that could revolutionize solar energy.

By using an ultrafast camera, scientists say they have observed the very first instants following the absorption of light into artificial yet organic nanostructures and found that charges not only formed rapidly but also separated very quickly over long distances – phenomena that occur due to the wavelike nature of electrons which are governed by fundamental laws of quantum mechanics.

This result surprised scientists as such phenomena were believed to be limited to “perfect” – and expensive – inorganic structures; rather than the soft, flexible organic material believed by many to be the key to cheap, ‘roll-to-roll’ solar cells that could be printed at room temperatures – a very different world from the traditional but costly processing of current silicon technologies.

The study,sheds new light on the mystery mechanism that allows positive and negative charges to be separated efficiently – a critical question that continues to puzzle scientists – and takes researchers a step closer to effectively mimicking the highly efficient ability to harvest sunlight and convert into energy, namely photosynthesis, which the natural world evolved over the course of millennia.

“This is a very surprising result. Such quantum phenomena are usually confined to perfect crystals of inorganic semiconductors, and one does not expect to see such effects in organic molecules – which are very disordered and tend to resemble a plate of cooked spaghetti rather than a crystal,” said Dr Simon Gélinas, from Cambridge’s Cavendish Laboratory, who led the research with colleagues from Cambridge as well as the University of California in Santa Barbara.

During the first few femtoseconds (one millionth of one billionth of a second) each charge spreads itself over multiple molecules rather than being localized to a single one. This phenomenon, known as spatial coherence, allows a charge to travel very quickly over several nanometers and escape from its oppositely charged partner – an initial step which seems to be the key to generating long-lived charges, say the researchers. This can then be used to generate electricity or for chemical reactions.

By carefully engineering the way molecules pack together, the team found that it was possible to tune the spatial coherence and to amplify – or reduce – this long-range separation. “Perhaps most importantly the results suggest that because the process is so fast it is also energy efficient, which could result in more energy out of the solar cell,” said Dr Akshay Rao, a co-author on the study from the Cavendish Laboratory.

Dr Alex Chin, who led the theoretical part of the project, added that, if you look beyond the implications of the study for organic solar cells, this is a clear demonstration of “how fundamental quantum-mechanical processes, such as coherence, play a crucial role in disordered organic and biological systems and can be harnessed in new quantum technologies”.

The work at Cambridge forms part of a broader initiative to harness high tech knowledge in the physics sciences to tackle global challenges such as climate change and renewable energy. This initiative is backed by both the UK Engineering and Physical Sciences Research Council (EPSRC) and the Cambridge Winton Program for the Physics of Sustainability. The work at the University of California in Santa Barbara was supported by the Center for Energy Efficient Materials, an Energy Frontier Research Center funded by the U.S. Department of Energy, Office of Science, Basic Energy Sciences under Award #DC0001009.

Publication: Simon Gélinas, et al., “Ultrafast Long-Range Charge Separation in Organic Semiconductor Photovoltaic Diodes,” Science, 2013; DOI: 10.1126/science.1246249

Source: University of Cambridge

Image: Simon Gelinas

Inactivating AGPS Enzyme Reduces Tumor Growth, Cripples Cancer Cells

Illustration of an aggressive cancer cell. Image by O’Reilly Science Art

In a newly published study, researchers tested the effects of reducing ether lipids on human skin cancer cells and primary breast tumors, finding that inactivating an enzyme critical to the formation of ether lipids substantially reduced the aggressiveness of the cancer cells.

Berkeley — Knocking out a single enzyme dramatically cripples the ability of aggressive cancer cells to spread and grow tumors, offering a promising new target in the development of cancer treatments, according to a new study by researchers at the University of California, Berkeley.

The paper, sheds new light on the importance of lipids, a group of molecules that includes fatty acids and cholesterol, in the development of cancer.

Researchers have long known that cancer cells metabolize lipids differently than normal cells. Levels of ether lipids – a class of lipids that are harder to break down – are particularly elevated in highly malignant tumors, although the nature of that correlation has been unclear for decades.

“Cancer cells make and use a lot of fat and lipids, and that makes sense because cancer cells divide and proliferate at an accelerated rate, and to do that, they need lipids, which make up the membranes of the cell,” said study principal investigator Daniel Nomura, assistant professor in UC Berkeley’s Department of Nutritional Sciences and Toxicology. “Lipids have a variety of uses for cellular structure, but what we’re showing with our study is that lipids can also send signals that fuel cancer growth.”

In the study, Nomura and his team tested the effects of reducing ether lipids on human skin cancer cells and primary breast tumors. They targeted an enzyme, alkylglycerone phosphate synthase, or AGPS, known to be critical to the formation of ether lipids.

The researchers first confirmed that AGPS expression increased when normal cells turned cancerous. They then found that inactivating AGPS substantially reduced the aggressiveness of the cancer cells.

“The cancer cells were less able to move and invade,” said Nomura.

The researchers also compared the impact of disabling the AGPS enzyme in mice that had been injected with cancer cells.

“Among the mice that had the AGPS enzyme inactivated, the tumors were nonexistent,” said Nomura. “The mice that did not have this enzyme disabled rapidly developed tumors.”

The researchers determined that inhibiting AGPS expression depleted the cancer cells of ether lipids. They also found that AGPS altered levels of other types of lipids important to the ability of the cancer cells to survive and spread, including prostaglandins and acyl phospholipids.

“The effect on other lipids was unexpected and previously unknown,” said study lead author Daniel Benjamin, doctoral student in the Nomura Research Group. “Other studies have investigated specific lipid signaling pathways, but what makes AGPS stand out as a treatment target is that the enzyme seems to simultaneously regulate multiple aspects of lipid metabolism important for tumor growth and malignancy.”

Future steps include the development of AGPS inhibitors for use in cancer therapy, said Nomura.

“This study sheds considerable light on the important role that AGPS plays in ether lipid metabolism in cancer cells, and it suggests that inhibitors of this enzyme could impair tumor formation,” said Benjamin Cravatt, professor and chair of chemical physiology at The Scripps Research Institute, who is not part of the UC Berkeley study. Cravatt is an expert in the role enzymes play in human diseases.

Other study co-authors include Kunxin Luo, UC Berkeley professor of molecular and cell biology and faculty scientist at the Lawrence Berkeley National Laboratory.

The National Institutes of Health and the Searle Scholar Foundation helped support this research.

Publication: Daniel I. Benjamin, et al., “Ether lipid generating enzyme AGPS alters the balance of structural and signaling lipids to fuel cancer pathogenicity,” PNAS, 2013; doi: 10.1073/pnas.1310894110

Source: Sarah Yang, UC Berkeley News

Image: O’Reilly Science Art

New System Converts Sun’s Energy into Hydrogen Fuel

Tom Meyer at the Energy Frontier Research Center at the University of North Carolina at Chapel Hill built a device that converts the sun’s energy not into electricity but hydrogen fuel and stores it for later use. The device, a dye-sensitized photoelectrosynthesis cell generates hydrogen fuel by using the sun’s energy to split water into its component parts. After the split, hydrogen is sequestered and stored, while the byproduct, oxygen, is released into the air.

A new system designed by researchers at UNC and NC State converts the sun’s energy into hydrogen fuel and stores it for later use.

Solar energy has long been used as a clean alternative to fossil fuels such as coal and oil, but it could only be harnessed during the day when the sun’s rays were strongest. Now researchers led by Tom Meyer at the Energy Frontier Research Center at the University of North Carolina at Chapel Hill have built a system that converts the sun’s energy not into electricity but hydrogen fuel and stores it for later use, allowing us to power our devices long after the sun goes down.

“So called ‘solar fuels’ like hydrogen offer a solution to how to store energy for nighttime use by taking a cue from natural photosynthesis,” said Meyer, Arey Distinguished Professor of Chemistry at UNC’s College of Arts and Sciences. “Our new findings may provide a last major piece of a puzzle for a new way to store the sun’s energy – it could be a tipping point for a solar energy future.”

In one hour, the sun puts out enough energy to power every vehicle, factory and device on the planet for an entire year. Solar panels can harness that energy to generate electricity during the day. But the problem with the sun is that it goes down at night—and with it the ability to power our homes and cars. If solar energy is going to have a shot at being a clean source for powering the planet, scientists had to figure out how to store it for night-time use.

The new system designed by Meyer and colleagues at UNC and with Greg Parsons’ group at North Carolina State University does exactly that. It is known as a dye-sensitized photoelectrosynthesis cell, or DSPEC, and it generates hydrogen fuel by using the sun’s energy to split water into its component parts. After the split, hydrogen is sequestered and stored, while the byproduct, oxygen, is released into the air.

“But splitting water is extremely difficult to do,” said Meyer. “You need to take four electrons away from two water molecules, transfer them somewhere else, and make hydrogen, and, once you have done that, keep the hydrogen and oxygen separated. How to design molecules capable of doing that is a really big challenge that we’ve begun to overcome.”

Meyer had been investigating DSPECs for years at the Energy Frontier Research Center at UNC and before. His design has two basic components: a molecule and a nanoparticle. The molecule, called a chromophore-catalyst assembly, absorbs sunlight and then kick starts the catalyst to rip electrons away from water. The nanoparticle, to which thousands of chromophore-catalyst assemblies are tethered, is part of a film of nanoparticles that shuttles the electrons away to make the hydrogen fuel.

However, even with the best of attempts, the system always crashed because either the chromophore-catalyst assembly kept breaking away from the nanoparticles or because the electrons couldn’t be shuttled away quickly enough to make hydrogen.

To solve both of these problems, Meyer turned to the Parsons group to use a technique that coated the nanoparticle, atom by atom, with a thin layer of a material called titanium dioxide. By using ultra-thin layers, the researchers found that the nanoparticle could carry away electrons far more rapidly than before, with the freed electrons available to make hydrogen. They also figured out how to build a protective coating that keeps the chromophore-catalyst assembly tethered firmly to the nanoparticle, ensuring that the assembly stayed on the surface.

With electrons flowing freely through the nanoparticle and the tether stabilized, Meyer’s new system can turn the sun’s energy into fuel while needing almost no external power to operate and releasing no greenhouse gases. What’s more, the infrastructure to install these sunlight-to-fuel converters is in sight based on existing technology. A next target is to use the same approach to reduce carbon dioxide, a greenhouse gas, to a carbon-based fuel such as formate or methanol.

“When you talk about powering a planet with energy stored in batteries, it’s just not practical,” said Meyer. “It turns out that the most energy dense way to store energy is in the chemical bonds of molecules. And that’s what we did – we found an answer through chemistry.”

Related Studies:

• Leila Alibabaeia, et al., “Solar water splitting in a molecular photoelectrochemical cell,” PNAS, vol. 110 no. 50, 20008–20013; doi: 10.1073/pnas.1319628110
• Hanlin Luo, et al., “A Sensitized Nb2O5 Photoanode for Hydrogen Production in a Dye-Sensitized Photoelectrosynthesis Cell,” Chem. Mater., 2013, 25 (2), pp 122–131; DOI: 10.1021/cm3027972

Source: University of North Carolina at Chapel Hill

Image: Yan Liang

Engineers Convert Yeast Cells into Biofuel

Left: Starting cells with around 15 percent lipid content. Right: Engineered cells with nearly 90 percent lipid content.

Using genetically engineered yeast cells and ordinary table sugar, engineers from the Cockrell School of Engineering developed a new biofuel.

Austin, Texas — Researchers at The University of Texas at Austin’s Cockrell School of Engineering have developed a new source of renewable energy, a biofuel, from genetically engineered yeast cells and ordinary table sugar. This yeast produces oils and fats, known as lipids, that can be used in place of petroleum-derived products.

Assistant professor Hal Alper, in the Cockrell School’s McKetta Department of Chemical Engineering, along with his team of students, created the new cell-based platform. Given that the yeast cells grow on sugars, Alper calls the biofuel produced by this process “a renewable version of sweet crude.”

The researchers’ platform produces the highest concentration of oils and fats reported through fermentation, the process of culturing cells to convert sugar into products such as alcohol, gases or acids.

The UT Austin research team was able to rewire yeast cells to enable up to 90 percent of the cell mass to become lipids, which can then be used to produce biodiesel.

“To put this in perspective, this lipid value is approaching the concentration seen in many industrial biochemical processes,” Alper said. “You can take the lipids formed and theoretically use it to power a car.”

Since fatty materials are building blocks for many household products, this process could be used to produce a variety of items made with petroleum or oils — from nylon to nutrition supplements to fuels. Biofuels and chemicals produced from living organisms represent a promising portion of the renewable energy market. Overall, the global biofuels market is expected to double during the next several years, going from $82.7 billion in 2011 to $185.3 billion in 2021.

“We took a starting yeast strain of Yarrowia lipolytica, and we’ve been able to convert it into a factory for oil directly from sugar,” Alper said. “This work opens up a new platform for a renewable energy and chemical source.”

The biofuel the researchers formulated is similar in composition to biodiesel made from soybean oil. The advantages of using the yeast cells to produce commercial-grade biodiesel are that yeast cells can be grown anywhere, do not compete with land resources and are easier to genetically alter than other sources of biofuel.

“By genetically rewiring Yarrowia lipolytica, Dr. Alper and his research group have created a near-commercial biocatalyst that produces high levels of bio-oils during carbohydrate fermentation,” said Lonnie O. Ingram, director of the Florida Center for Renewable Chemicals and Fuels at the University of Florida. “This is a remarkable demonstration of the power of metabolic engineering.”

So far, high-level production of biofuels and renewable oils has been an elusive goal, but the researchers believe that industry-scale production is possible with their platform.

In a large-scale engineering effort spanning over four years, the researchers genetically modified Yarrowia lipolytica by both removing and overexpressing specific genes that influence lipid production. In addition, the team identified optimum culturing conditions that differ from standard conditions. Traditional methods rely on nitrogen starvation to trick yeast cells into storing fat and materials. Alper’s research provides a mechanism for growing lipids without nitrogen starvation. The research has resulted in a technology for which UT Austin has applied for a patent.

“Our cells do not require that starvation,” Alper said. “That makes it extremely attractive from an industry production standpoint.”

The team increased lipid levels by nearly 60-fold from the starting point.

At 90 percent lipid levels, the platform produces the highest levels of lipid content created so far using a genetically engineered yeast cell. To compare, other yeast-based platforms yield lipid content in the 50 to 80 percent range. However, these alternative platforms do not always produce lipids directly from sugar as the UT Austin technology does.

Alper and his team are continuing to find ways to further enhance the lipid production levels and develop new products using this engineered yeast.

This research was funded by the Office of Naval Research Young Investigator Program, the DuPont Young Professor Grant and the Welch Foundation under grant F-1753.

Publication: John Blazeck, et al., “Harnessing Yarrowia lipolytica lipogenesis to create a platform for lipid and biofuel production,” Nature Communications 5, Article number: 3131; doi:10.1038/ncomms4131

Source: University of Texas at Austin’s Cockrell School of Engineering

Image: University of Texas at Austin’s Cockrell School of Engineering