Looking blue can mean feeling sad or it can indicate that you have argyria, a condition caused by ingesting too much silver. An Oct. 29, 2012 news item on Nanowerk about research on argyria taking place at Brown University reveals the latest insight on the cause for this condition,
Researchers from Brown University have shown for the first time how ingesting too much silver can cause argyria, a rare condition in which patients’ skin turns a striking shade of grayish blue.
“It’s the first conceptual model giving the whole picture of how one develops this condition,” said Robert Hurt, professor of engineering at Brown and part of the research team. “What’s interesting here is that the particles someone ingests aren’t the particles that ultimately cause the disorder.”
Scientists have known for years argyria had something to do with silver. The condition has been documented in people who (ill advisedly) drink antimicrobial health tonics containing silver nanoparticles and in people who have had extensive medical treatments involving silver. Tissue samples from patients showed silver particles actually lodged deep in the skin, but it wasn’t clear how they got there.
As it turns out, argyria is caused by a complex series of chemical reactions, Hurt said. His paper on the subject, authored with Brown colleagues Jingyu Liu, Zhongying Wang, Frances Liu, and Agnes Kane, is published in the journal ACS Nano (“Chemical Transformations of Nanosilver in Biological Environments” [behind a paywall]).
Hurt and his team have been studying the environmental impact of silver, specifically silver nanoparticles, for years. They’ve found that nanosilver tends to corrode in acidic environments, giving off charged ions — silver salts — that can be toxic in large amounts. Hurt’s graduate student, Jingyu Liu (now a postdoctoral fellow at the National Institute of Standards and Technology), thought those same toxic ions might also be produced when silver enters the body, and could play a role in argyria.
To find out, the researchers mixed a series chemical treatments that could simulate what might happen to silver inside the body. One treatment simulated the acidic environment in the gastrointestinal tract; one mimicked the protein content of the bloodstream; and a collagen gel replicated the base membranes of the skin.
They found that nanosilver corrodes in stomach acid in much the same way it does in other acidic environments. Corrosion strips silver atoms of electrons, forming positively charged silver salt ions. Those ions can easily be taken into the bloodstream through channels that absorb other types of salt. That’s a crucial step, Hurt said. Silver metal particles themselves aren’t terribly likely to make it from the GI tract to the blood, but when they’re transformed into a salt, they’re ushered right through.
From there, Hurt and his team showed that silver ions bind easily with sulfur present in blood proteins, which would give them a free ride through the bloodstream. Some of those ions would eventually end up in the skin, where they’d be exposed to light.
To re-create this end stage, the researchers shined ultraviolet light on collagen gel containing silver ions. The light caused electrons from the surrounding materials to jump onto the unstable ions, returning them to their original state — elemental silver. This final reaction is ultimately what turns patients’ skin blue. The photoreaction is similar to the way silver is used in black and white photography [emphasis mine]. When exposed to light, silver salts on a photographic film reduce to elemental silver and darken, creating an image.
While I find the notion that the body’s reaction to silver is similar to the processing of silver in black and white photography, it’s the discussion about toxicity that most interests me. The scientists at Brown are suggesting that standard ‘ingestable’ silver could be more dangerous than silver nanoparticles when they are consumed in the body,
This research, however, “would be one piece of evidence that you could treat nanoparticles in the same way as other forms of silver,” Hurt says.
That’s because the bioavailable form of silver — the form that is absorbed into the bloodstream — is the silver salt that’s made in the stomach. Any elemental silver that’s ingested is just the raw material to make that bioavailable salt. So ingesting silver in any form, be it nano or not, would have basically the same effect, Hurt said.
“The concern in this case is the total dose of silver, not what form it’s in,” Hurt said. “This study implies that silver nanoparticles will be less toxic than an equivalent amount of silver salt, at least in this exposure scenario [emphasis mine].”
This research provides more evidence supporting Dr. Andrew Maynard’s contention that creating definitions and regulations for nanomaterials based on size may not be the best approach. Here’s his response to my question (in an Oct. 24, 2011 posting) about the then newly adopted Health Canada definition (which includes size) for nanomaterials,
The problem is that, while the Health Canada is a valiant attempt to craft a definition based on the current state of science, it is still based on a premise – that size within a well defined range is a robust indicator of novel risk – that is questionable [emphasis mine]. Granted, they try to compensate for the limitations of this premise, but the result still smacks of trying to shoehorn the science into an assumption of what is important.
One can only wait as the evidence continues to mount on one side or the other. In the meantime, I don’t one can ever go wrong with BB King, one of the great blues guitar players (Blues Boys Tune),
The Aug. 22, 2012 news item on Nanowerk by way of Feedzilla features some research at the University of Edinburgh which determined that short nanofibres do not have the same effect on lung cells as longer fibres do. From the news item, here’s a description of why this research was undertaken
Nanofibres, which can be made from a range of materials including carbon, are about 1,000 times smaller than the width of a human hair and can reach the lung cavity when inhaled.
This may lead to a cancer known as mesothelioma, which is known to be caused by breathing in asbestos fibres, which are similar to nanofibres.
I wrote about research at Brown University which explained why some fibres get stuck in lung cells in a Sept. 22, 2011 posting titled, Why asbestos and carbon nanotubes are so dangerous to cells. The short answer is: if the tip is rounded, the cell mistakes the fibre for a sphere and, in error, it attempts to absorb it. Here’s some speculation on my part about what the results might mean (from my Sept. 22, 2011 posting),
The whole thing has me wondering about long vs. short carbon nanotubes. Does this mean that short carbon nanotubes can be ingested successfully? If so, at what point does short become too long to ingest?
The University study found that lung cells were not affected by short fibres that were less than five-thousandths of a millimetre long.
However, longer fibres can reach the lung cavity, where they become stuck and cause disease.
We knew that long fibres, compared with shorter fibres, could cause tumours but until now we did not know the cut-off length at which this happened. Knowing the length beyond which the tiny fibres can cause disease is important in ensuring that safe fibres are made in the future as well as helping to understand the current risk from asbestos and other fibres, [said] Ken Donaldson, Professor of Respiratory Toxicology.
Sometimes, I surprise myself. I think I’ll take a moment to bask. … Done now!
Here’s my final thought, while this research suggests short length nanofibres won’t cause mesothelioma, this doesn’t rule out other potential problems. So, let’s celebrate this new finding and then get back to investigating nanofibres and their impact on health.
They’ve been using platinum catalysts, in fuel cells and metal-air batteries, which over the last five years has ranged in cost from just under $800/oz to over $2200/oz. My March 13, 2012 posting about fuel cells noted that the use of expensive metals that are not very efficient catalysts was holding back their development and entry into the marketplace,
Advances in fuel-cell technology have been stymied by the inadequacy of metals studied as catalysts. The drawback to platinum, other than cost, is that it absorbs carbon monoxide in reactions involving fuel cells powered by organic materials like formic acid. A more recently tested metal, palladium, breaks down over time.
Now chemists at Brown University have created a triple-headed metallic nanoparticle that they say outperforms and outlasts all others at the anode end in formic-acid fuel-cell reactions.
Another group of researchers at Stanford University and other institutions is suggesting an alternative to a platinum catalyst, a multi-walled carbon nanotube. From the May 27, 2012 news release written by Mark Shwartz on EurekAlert,
Multi-walled carbon nanotubes riddled with defects and impurities on the outside could replace some of the expensive platinum catalysts used in fuel cells and metal-air batteries, according to scientists at Stanford University. Their findings are published in the May 27 online edition of the journal Nature Nanotechnology.
“Platinum is very expensive and thus impractical for large-scale commercialization,” said Hongjie Dai, a professor of chemistry at Stanford and co-author of the study. “Developing a low-cost alternative has been a major research goal for several decades.”
…
For the study, the Stanford team used multi-walled carbon nanotubes consisting of two or three concentric tubes nested together. The scientists showed that shredding the outer wall, while leaving the inner walls intact, enhances catalytic activity in nanotubes, yet does not interfere with their ability to conduct electricity.
“A typical carbon nanotube has few defects,” said Yanguang Li, a postdoctoral fellow at Stanford and lead author of the study. “But defects are actually important to promote the formation of catalytic sites and to render the nanotube very active for catalytic reactions.”
Here’s how it works, from the May 27, 2012 news release on EurekAlert,
For the study, Li and his co-workers treated multi-walled nanotubes in a chemical solution. Microscopic analysis revealed that the treatment caused the outer nanotube to partially unzip and form nanosized graphene pieces that clung to the inner nanotube, which remained mostly intact.
“We found that adding a few iron and nitrogen impurities made the outer wall very active for catalytic reactions,” Dai said. “But the inside maintained its integrity, providing a path for electrons to move around. You want the outside to be very active, but you still want to have good electrical conductivity. If you used a single-wall carbon nanotube you wouldn’t have this advantage, because the damage on the wall would degrade the electrical property.”
These are two different perspectives on the reason for why fuel cells and other batteries have not had the expected impact on the marketplace. The team at Brown University states the problem as an issue with the effectiveness of the metal catalysts where the Stanford-led team states the problem as being the cost of the metal used. Dexter Johnson in a March 9, 2012 posting on the Nanoclast blog on the IEEE (Institute of Electrical and Electronics Engineers) website suggested a third issue,
One of the fundamental problems with fuel cells has been the cost of producing hydrogen. While hydrogen is, of course, the most abundant element, it attaches itself to other elements like nitrogen or fluorine, and perhaps most ubiquitously to oxygen to create the water molecule. The process used to separate hydrogen out into hydrogen gas for powering fuel cells now relies on electricity produced from fossil fuels, negating some of the potential environmental benefits.
In his May 30, 2012 posting about this new work from Stanford, Dexter notes yet another issue impeding widespread commercialization,
… but the two main issues that have prevented fuel cells from gaining wider adoption—at least in the area of powering automobiles—are the costs of isolating hydrogen and building an infrastructure that would deliver that hydrogen to the automobiles.
Dexter mentions another application (metal-air batteries) that may benefit more from this latest work (from Dexter’s May 30, 2012 posting),
I think it’s all together possible that researchers at IBM and the US national labs who have been working on metal-air batteries for years now might be somewhat more interested in this line of research than fuel-cell manufacturers.
As one of the researchers notes (from the May 27, 2012 news release on EurekAlert),
“Lithium-air batteries are exciting because of their ultra-high theoretical energy density, which is more than 10 times higher than today’s best lithium ion technology,” Dai said. “But one of the stumbling blocks to development has been the lack of a high-performance, low-cost catalyst. Carbon nanotubes could be an excellent alternative to the platinum, palladium and other precious-metal catalysts now in use.”
The Stanford team made one other discovery as they were testing the carbon nanotubes,
The Stanford study might also have resolved a long-standing scientific controversy about the chemical structure of catalytic active sites where oxygen reactions occur. “One group of scientists believes that iron impurities are bonded to nitrogen at the active site,” Li said. “Another group believes that iron contributes virtually nothing, except to promote active sites made entirely of nitrogen.”
To address the controversy, the Stanford team enlisted scientists at Oak Ridge National Laboratory to conduct atomic-scale imaging and spectroscopy analysis of the nanotubes. The results showed clear, visual evidence of iron and nitrogen atoms in close proximity.
“For the first time, we were able to image individual atoms on this kind of catalyst,” Dai said. “All of the images showed iron and nitrogen close together, suggesting that the two elements are bonded. This kind of imaging is possible, because the graphene pieces are just one-atom thick.”
Dai noted that the iron impurities, which enhanced catalytic activity, actually came from metal seeds that were used to make the nanotubes and were not intentionally added by the scientists. The discovery of these accidental yet invaluable bits of iron offered the researchers an important lesson. “We learned that metal impurities in nanotubes must not be ignored,” Dai said.
The video shows a woman getting herself a cup of coffee for the first time in 15 years. She’s tetraplegic (aka quadraplegic) and is participating in a research project funded by DARPA (US Defense Advanced Research Projects Agency) for developing neuroprostheses.
Kudos to the researchers and to the woman for her courage and persistence. The May 17, 2012 news item on Nanowerk provides some background,
DARPA launched the Revolutionizing Prosthetics program in 2006 to advance the state of upper-limb prosthetic technology with the goals of improving quality of life for service-disabled veterans and ultimately giving them the option of returning to duty. [emphasis mine] Since then, Revolutionizing Prosthetics teams have developed two anthropomorphic advanced modular prototype prosthetic arm systems, including sockets, which offer increased range of motion, dexterity and control options. Through DARPA-funded work and partnerships with external researchers, the arm systems and supporting technology continue to advance.
The newest development on this project (Revolutionizing Prosthetics) comes from the BrainGate team (mentioned in my April 19, 2012 posting [scroll down about 1/5th of the way) many of whom are affiliated with Brown University. Alison Abbott’s May 16, 2012 Nature article provides some insight into the latest research,
The study participants — known as Cathy and Bob — had had strokes that damaged their brain stems and left them with tetraplegia and unable to speak. Neurosurgeons implanted tiny recording devices containing almost 100 hair-thin electrodes in the motor cortex of their brains, to record the neuronal signals associated with intention to move.
…
The work is part of the BrainGate2 clinical trial, led by John Donoghue, director of the Brown Institute for Brain Science in Providence. His team has previously reported a trial in which two participants were able to move a cursor on a computer screen with their thoughts.
The neuroscientists are working closely with computer scientists and robotics experts. The BrainGate2 trial uses two types of robotic arm: the DEKA Arm System, which is being developed for prosthetic limbs in collaboration with US military, and a heavier robot arm being developed by the German Aerospace Centre (DLR) as an external assistive device.
In the latest study, the two participants were given 30 seconds to reach and grasp foam balls. Using the DEKA arm, Bob — who had his stroke in 2006 and was given the neural implant five months before the study —- was able to grasp the targets 62% of the time. Cathy had a 46% success rate with the DEKA arm and a 21% success rate with the DLR arm. She successfully raised the bottled coffee to her lips in four out of six trials.
Nature has published the research paper (citation):
Reach and grasp by people with tetraplegia using a neurally controlled robotic arm
Authors: Leigh R. Hochberg, Daniel Bacher, Beata Jarosiewicz, Nicolas Y. Masse, John D. Simeral, Joern Vogel, Sami Haddadin, Jie Liu, Sydney S. Cash, Patrick van der Smagt and John P. Donoghue
Nature, 485, 372–375 (17 May 2012) doi:10.1038/nature11076
The paper is behind a paywall but if you have access, it’s here.
In the excess emotion after watching that video, I forgot for a moment that the ultimate is to repair soldiers and hopefully get them back into the field.
Last time I wrote about soldiers, equipment, and energy-efficiency (April 5, 2012 posting) the soldiers in question were British. Today’s posting focuses on US soldiers. From the May 7, 2012 news item on Nanowerk,
U.S. soldiers are increasingly weighed down by batteries to power weapons, detection devices and communications equipment. So the Army Research Laboratory has awarded a University of Utah-led consortium almost $15 million to use computer simulations to help design materials for lighter-weight, energy efficient devices and batteries.
“We want to help the Army make advances in fundamental research that will lead to better materials to help our soldiers in the field,” says computing Professor Martin Berzins, principal investigator among five University of Utah faculty members who will work on the project. “One of Utah’s main contributions will be the batteries.”
Of the five-year Army grant of $14,898,000, the University of Utah will retain $4.2 million for research plus additional administrative costs. The remainder will go to members of the consortium led by the University of Utah, including Boston University, Rensselaer Polytechnic Institute, Pennsylvania State University, Harvard University, Brown University, the University of California, Davis, and the Polytechnic University of Turin, Italy.
…
The new research effort is based on the idea that by using powerful computers to simulate the behavior of materials on multiple scales – from the atomic and molecular nanoscale to the large or “bulk” scale – new, lighter, more energy efficient power supplies and materials can be designed and developed. Improving existing materials also is a goal.
“We want to model everything from the nanoscale to the soldier scale,” Berzins says. “It’s virtual design, in some sense.”
“Today’s soldier enters the battle space with an amazing array of advanced electronic materials devices and systems,” the University of Utah said in its grant proposal. “The soldier of the future will rely even more heavily on electronic weaponry, detection devices, advanced communications systems and protection systems. Currently, a typical infantry soldier might carry up to 35 pounds of batteries in order to power these systems, and it is clear that the energy and power requirements for future soldiers will be much greater.” [emphasis mine]
“These requirements have a dramatic adverse effect on the survivability and lethality of the soldier by reducing mobility as well as the amount of weaponry, sensors, communication equipment and armor that the soldier can carry. Hence, the Army’s desire for greater lethality and survivability of its men and women in the field is fundamentally tied to the development of devices and systems with increased energy efficiency as well as dramatic improvement in the energy and power density of [battery] storage and delivery systems.”
Up to 35 lbs. of batteries? I’m trying to imagine what the rest of the equipment would weigh. In any event, they seem to be more interested in adding to the weaponry than reducing weight. At least, that’s how I understand “greater leathality.” Nice of them to mention greater survivability too.
The British project is more modest, they are weaving e-textiles that harvest energy allowing British soldiers to carry fewer batteries. I believe field trials were scheduled for May 2012.
The boxes in question self-assemble although why anyone would consider the image of small boxes in one’s bloodstream appealing escapes me. Well, we are talking about engineers and mathematicians so perhaps it’s understandable. From the April 23, 2012 news item on Nanowerk,
… now, interdisciplinary research by engineers at Johns Hopkins University in Baltimore, Md., and mathematicians at Brown University in Providence, R.I., has led to a breakthrough showing that higher order polyhedra can indeed fold up and assemble themselves.
“What is remarkable here is not just that a structure folds up on its own, but that it folds into a very precise, three-dimensional shape, and it happens without any tweezers or human intervention,” says David Gracias, a chemical and biomolecular engineer at Johns Hopkins. “Much like nature assembles everything from sea shells to gem stones from the bottom up, the idea of self-assembly promises a new way to manufacture objects from the bottom up.”
Here’s a video from the US National Science Foundation about the work being done by David Gracias and his colleague at Brown University, mathematician Govind Menon,
Miles O’Brien of the NSF’s Science Nation magazine notes in his April 23, 2012 article that there are many applications for these structures,
Imagine thousands of precisely structured, tiny, biodegradable, boxes rushing through the bloodstream en route to a sick organ. Once they arrive at their destination, they can release medicine with pinpoint accuracy. That’s the vision for the future. For now, the more immediate concern is getting the design of the structures just right so that they can be manufactured with high yields.
“Our process is also compatible with integrated circuit fabrication, so we envision that we can use it to put silicon-based logic and memory chips onto the faces of 3-D polyhedra. Our methodology opens the door to the creation of truly three-dimensional ‘smart’ and multi-functional particles on both micro- and nano- length scales,” says Gracias.
Here’s more about the structures themselves, as mentioned in the video and in O’Brien’s article,
Menon’s team at Brown began designing these tiny 3-D structures by first flattening them out. They worked with a number of shapes, such as 12-sided interconnected panels, which can potentially fold into a dodecahedron shaped container. “Imagine cutting it up and flattening out the faces as you go along,” says Menon. “It’s a two-dimensional unfolding of the polyhedron.”
And not all flat shapes are created equal; some fold better than others. “The best ones are the ones which are most compact. There are 43,380 ways to fold a dodecahedron,” notes Menon.
The researchers developed an algorithm to sift through all of the possible choices, narrowing the field to a few compact shapes that easily fold into 3-D structures. Menon’s team sent those designs to Gracias and his team at Johns Hopkins who built the shapes, and validated the hypothesis.
“We deposit a material in between the faces and the edges, and then heat them up, which creates surface tension and pulls the edges together, fusing the structure shut,” explains Gracias. “The angle between adjacent panels in a dodecahedron is 116.6 degrees and in our process, pentagonal panels precisely align at these remarkably precise angles and seal themselves; all on their own.”
As noted earlier, I’m not thrilled with the idea of tiny boxes in my bloodstream but, analogy aside, the medical applications are appealing. As for Gracias’ smart and multifunctional particles, I look forward to hearing more about them.
I’ve decided to do a roundup of the various brain-related projects I’ve been coming across in the last several months. I was inspired by this article (Real-life Jedi: Pushing the limits of mind control) by Katia Moskvitch,
You don’t have to be a Jedi to make things move with your mind.
Granted, we may not be able to lift a spaceship out of a swamp like Yoda does in The Empire Strikes Back, but it is possible to steer a model car, drive a wheelchair and control a robotic exoskeleton with just your thoughts.
…
We are standing in a testing room at IBM’s Emerging Technologies lab in Winchester, England.
On my head is a strange headset that looks like a black plastic squid. Its 14 tendrils, each capped with a moistened electrode, are supposed to detect specific brain signals.
In front of us is a computer screen, displaying an image of a floating cube.
As I think about pushing it, the cube responds by drifting into the distance.
Moskvitch goes on to discuss a number of projects that translate thought into movement via various pieces of equipment before she mentions a project at Brown University (US) where researchers are implanting computer chips into brains,
Headsets and helmets offer cheap, easy-to-use ways of tapping into the mind. But there are other,
Imagine some kind of a wireless computer device in your head that you’ll use for mind control – what if people hacked into that”
…
At Brown Institute for Brain Science in the US, scientists are busy inserting chips right into the human brain.
The technology, dubbed BrainGate, sends mental commands directly to a PC.
Subjects still have to be physically “plugged” into a computer via cables coming out of their heads, in a setup reminiscent of the film The Matrix. However, the team is now working on miniaturising the chips and making them wireless.
The purpose of the first phase of the pilot clinical study of the BrainGate2 Neural Interface System is to obtain preliminary device safety information and to demonstrate the feasibility of people with tetraplegia using the System to control a computer cursor and other assistive devices with their thoughts. Another goal of the study is to determine the participants’ ability to operate communication software, such as e-mail, simply by imagining the movement of their own hand. The study is invasive and requires surgery.
Individuals with limited or no ability to use both hands due to cervical spinal cord injury, brainstem stroke, muscular dystrophy, or amyotrophic lateral sclerosis (ALS) or other motor neuron diseases are being recruited into a clinical study at Massachusetts General Hospital (MGH) and Stanford University Medical Center. Clinical trial participants must live within a three-hour drive of Boston, MA or Palo Alto, CA. Clinical trial sites at other locations may be opened in the future. The study requires a commitment of 13 months.
They have been recruiting since at least November 2011, from the Nov. 14, 2011 news item by Tanya Lewis on MedicalXpress,
Stanford University researchers are enrolling participants in a pioneering study investigating the feasibility of people with paralysis using a technology that interfaces directly with the brain to control computer cursors, robotic arms and other assistive devices.
…
The pilot clinical trial, known as BrainGate2, is based on technology developed at Brown University and is led by researchers at Massachusetts General Hospital, Brown and the Providence Veterans Affairs Medical Center. The researchers have now invited the Stanford team to establish the only trial site outside of New England.
Under development since 2002, BrainGate is a combination of hardware and software that directly senses electrical signals in the brain that control movement. The device — a baby-aspirin-sized array of electrodes — is implanted in the cerebral cortex (the outer layer of the brain) and records its signals; computer algorithms then translate the signals into digital instructions that may allow people with paralysis to control external devices.
Confusingly, there seemto be two BrainGate organizations. One appears to be a research entity where a number of institutions collaborate and the other is some sort of jointly held company. From the About Us webpage of the BrainGate research entity,
In the late 1990s, the initial translation of fundamental neuroengineering research from “bench to bedside” – that is, to pilot clinical testing – would require a level of financial commitment ($10s of millions) available only from private sources. In 2002, a Brown University spin-off/startup medical device company, Cyberkinetics, Inc. (later, Cyberkinetics Neurotechnology Systems, Inc.) was formed to collect the regulatory permissions and financial resources required to launch pilot clinical trials of a first-generation neural interface system. The company’s efforts and substantial initial capital investment led to the translation of the preclinical research at Brown University to an initial human device, the BrainGate Neural Interface System [Caution: Investigational Device. Limited by Federal Law to Investigational Use]. The BrainGate system uses a brain-implantable sensor to detect neural signals that are then decoded to provide control signals for assistive technologies. In 2004, Cyberkinetics received from the U.S. Food and Drug Administration (FDA) the first of two Investigational Device Exemptions (IDEs) to perform this research. Hospitals in Rhode Island, Massachusetts, and Illinois were established as clinical sites for the pilot clinical trial run by Cyberkinetics. Four trial participants with tetraplegia (decreased ability to use the arms and legs) were enrolled in the study and further helped to develop the BrainGate device. Initial results from these trials have been published or presented, with additional publications in preparation.
While scientific progress towards the creation of this promising technology has been steady and encouraging, Cyberkinetics’ financial sponsorship of the BrainGate research – without which the research could not have been started – began to wane. In 2007, in response to business pressures and changes in the capital markets, Cyberkinetics turned its focus to other medical devices. Although Cyberkinetics’ own funds became unavailable for BrainGate research, the research continued through grants and subcontracts from federal sources. By early 2008 it became clear that Cyberkinetics would eventually need to withdraw completely from directing the pilot clinical trials of the BrainGate device. Also in 2008, Cyberkinetics spun off its device manufacturing to new ownership, BlackRock Microsystems, Inc., which now produces and is further developing research products as well as clinically-validated (510(k)-cleared) implantable neural recording devices.
Beginning in mid 2008, with the agreement of Cyberkinetics, a new, fully academically-based IDE application (for the “BrainGate2 Neural Interface System”) was developed to continue this important research. In May 2009, the FDA provided a new IDE for the BrainGate2 pilot clinical trial. [Caution: Investigational Device. Limited by Federal Law to Investigational Use.] The BrainGate2 pilot clinical trial is directed by faculty in the Department of Neurology at Massachusetts General Hospital, a teaching affiliate of Harvard Medical School; the research is performed in close scientific collaboration with Brown University’s Department of Neuroscience, School of Engineering, and Brown Institute for Brain Sciences, and the Rehabilitation Research and Development Service of the U.S. Department of Veteran’s Affairs at the Providence VA Medical Center. Additionally, in late 2011, Stanford University joined the BrainGate Research Team as a clinical site and is currently enrolling participants in the clinical trial. This interdisciplinary research team includes scientific partners from the Functional Electrical Stimulation Center at Case Western Reserve University and the Cleveland VA Medical Center. As was true of the decades of fundamental, preclinical research that provided the basis for the recent clinical studies, funding for BrainGate research is now entirely from federal and philanthropic sources.
The BrainGate Research Team at Brown University, Massachusetts General Hospital, Stanford University, and Providence VA Medical Center comprises physicians, scientists, and engineers working together to advance understanding of human brain function and to develop neurotechnologies for people with neurologic disease, injury, or limb loss.
The BrainGate™ Co. is a privately-held firm focused on the advancement of the BrainGate™ Neural Interface System. The Company owns the Intellectual property of the BrainGate™ system as well as new technology being developed by the BrainGate company. In addition, the Company also owns the intellectual property of Cyberkinetics which it purchased in April 2009.
Meanwhile, in Europe there are two projects BrainAble and the Human Brain Project. The BrainAble project is similar to BrainGate in that it is intended for people with injuries but they seem to be concentrating on a helmet or cap for thought transmission (as per Moskovitch’s experience at the beginning of this posting). From the Feb. 28, 2012 news item on Science Daily,
In the 2009 film Surrogates, humans live vicariously through robots while safely remaining in their own homes. That sci-fi future is still a long way off, but recent advances in technology, supported by EU funding, are bringing this technology a step closer to reality in order to give disabled people more autonomy and independence than ever before.
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“Our aim is to give people with motor disabilities as much autonomy as technology currently allows and in turn greatly improve their quality of life,” says Felip Miralles at Barcelona Digital Technology Centre, a Spanish ICT research centre.
Mr. Miralles is coordinating the BrainAble* project (http://www.brainable.org/), a three-year initiative supported by EUR 2.3 million in funding from the European Commission to develop and integrate a range of different technologies, services and applications into a commercial system for people with motor disabilities.
In terms of HCI [human-computer interface], BrainAble improves both direct and indirect interaction between the user and his smart home. Direct control is upgraded by creating tools that allow controlling inner and outer environments using a “hybrid” Brain Computer Interface (BNCI) systemable to take into account other sources of information such as measures of boredom, confusion, frustration by means of the so-called physiological and affective sensors.
Furthermore, interaction is enhanced by means of Ambient Intelligence (AmI) focused on creating a proactive and context-aware environments by adding intelligence to the user’s surroundings. AmI’s main purpose is to aid and facilitate the user’s living conditions by creating proactive environments to provide assistance.
Human-Computer Interfaces are complemented by an intelligent Virtual Reality-based user interface with avatars and scenarios that will help the disabled move around freely, and interact with any sort of devices. Even more the VR will provide self-expression assets using music, pictures and text, communicate online and offline with other people, play games to counteract cognitive decline, and get trained in new functionalities and tasks.
Perhaps this video helps,
Another European project, NeuroCare, which I discussed in my March 5, 2012 posting, is focused on creating neural implants to replace damaged and/or destroyed sensory cells in the eye or the ear.
The Human Brain Project is, despite its title, a neuromorphic engineering project (although the researchers do mention some medical applications on the project’s home page) in common with the work being done at the University of Michigan/HRL Labs mentioned in my April 19, 2012 posting (A step closer to artificial synapses courtesy of memritors) about that project. From the April 11, 2012 news item about the Human Brain Project on Science Daily,
Researchers at the EPFL [Ecole Polytechnique Fédérale de Lausanne] have discovered rules that relate the genes that a neuron switches on and off, to the shape of that neuron, its electrical properties and its location in the brain.
The discovery, using state-of-the-art informatics tools, increases the likelihood that it will be possible to predict much of the fundamental structure and function of the brain without having to measure every aspect of it. That in turn makes the Holy Grail of modelling the brain in silico — the goal of the proposed Human Brain Project — a more realistic, less Herculean, prospect. “It is the door that opens to a world of predictive biology,” says Henry Markram, the senior author on the study, which is published this week in PLoS ONE.
Here’s a bit more about the Human Brain Project (from the home page),
Today, simulating a single neuron requires the full power of a laptop computer. But the brain has billions of neurons and simulating all them simultaneously is a huge challenge. To get round this problem, the project will develop novel techniques of multi-level simulation in which only groups of neurons that are highly active are simulated in detail. But even in this way, simulating the complete human brain will require a computer a thousand times more powerful than the most powerful machine available today. This means that some of the key players in the Human Brain Project will be specialists in supercomputing. Their task: to work with industry to provide the project with the computing power it will need at each stage of its work.
The Human Brain Project will impact many different areas of society. Brain simulation will provide new insights into the basic causes of neurological diseases such as autism, depression, Parkinson’s, and Alzheimer’s. It will give us new ways of testing drugs and understanding the way they work. It will provide a test platform for new drugs that directly target the causes of disease and that have fewer side effects than current treatments. It will allow us to design prosthetic devices to help people with disabilities. The benefits are potentially huge. As world populations grow older, more than a third will be affected by some kind of brain disease. Brain simulation provides us with a powerful new strategy to tackle the problem.
The project also promises to become a source of new Information Technologies. Unlike the computers of today, the brain has the ability to repair itself, to take decisions, to learn, and to think creatively – all while consuming no more energy than an electric light bulb. The Human Brain Project will bring these capabilities to a new generation of neuromorphic computing devices, with circuitry directly derived from the circuitry of the brain. The new devices will help us to build a new generation of genuinely intelligent robots to help us at work and in our daily lives.
The Human Brain Project builds on the work of the Blue Brain Project. Led by Henry Markram of the Ecole Polytechnique Fédérale de Lausanne (EPFL), the Blue Brain Project has already taken an essential first towards simulation of the complete brain. Over the last six years, the project has developed a prototype facility with the tools, know-how and supercomputing technology necessary to build brain models, potentially of any species at any stage in its development. As a proof of concept, the project has successfully built the first ever, detailed model of the neocortical column, one of the brain’s basic building blocks.
The Human Brain Project is a flagship project in contention for the 1B Euro research prize that I’ve mentioned in the context of the GRAPHENE-CA flagship project (my Feb. 13, 2012 posting gives a better description of these flagship projects while mentioned both GRAPHENE-CA and another brain-computer interface project, PRESENCCIA).
Part of the reason for doing this roundup, is the opportunity to look at a number of these projects in one posting; the effect is more overwhelming than I expected.
For anyone who’s interested in Markram’s paper (open access),
Georges Khazen, Sean L. Hill, Felix Schürmann, Henry Markram. Combinatorial Expression Rules of Ion Channel Genes in Juvenile Rat (Rattus norvegicus) Neocortical Neurons. PLoS ONE, 2012; 7 (4): e34786 DOI: 10.1371/journal.pone.0034786
I do have earlier postings on brains and neuroprostheses, one of the more recent ones is this March 16, 2012 posting. Meanwhile, there are new announcements from Northwestern University (US) and the US National Institutes of Health (National Institute of Neurological Disorders and Stroke). From the April 18, 2012 news item (originating from the National Institutes of Health) on Science Daily,
An artificial connection between the brain and muscles can restore complex hand movements in monkeys following paralysis, according to a study funded by the National Institutes of Health.
In a report in the journal Nature, researchers describe how they combined two pieces of technology to create a neuroprosthesis — a device that replaces lost or impaired nervous system function. One piece is a multi-electrode array implanted directly into the brain which serves as a brain-computer interface (BCI). The array allows researchers to detect the activity of about 100 brain cells and decipher the signals that generate arm and hand movements. The second piece is a functional electrical stimulation (FES) device that delivers electrical current to the paralyzed muscles, causing them to contract. The brain array activates the FES device directly, bypassing the spinal cord to allow intentional, brain-controlled muscle contractions and restore movement.
A new Northwestern Medicine brain-machine technology delivers messages from the brain directly to the muscles — bypassing the spinal cord — to enable voluntary and complex movement of a paralyzed hand. The device could eventually be tested on, and perhaps aid, paralyzed patients.
…
The research was done in monkeys, whose electrical brain and muscle signals were recorded by implanted electrodes when they grasped a ball, lifted it and released it into a small tube. Those recordings allowed the researchers to develop an algorithm or “decoder” that enabled them to process the brain signals and predict the patterns of muscle activity when the monkeys wanted to move the ball.
These experiments were performed by Christian Ethier, a post-doctoral fellow, and Emily Oby, a graduate student in neuroscience, both at the Feinberg School of Medicine. The researchers gave the monkeys a local anesthetic to block nerve activity at the elbow, causing temporary, painless paralysis of the hand. With the help of the special devices in the brain and the arm — together called a neuroprosthesis — the monkeys’ brain signals were used to control tiny electric currents delivered in less than 40 milliseconds to their muscles, causing them to contract, and allowing the monkeys to pick up the ball and complete the task nearly as well as they did before.
“The monkey won’t use his hand perfectly, but there is a process of motor learning that we think is very similar to the process you go through when you learn to use a new computer mouse or a different tennis racquet. Things are different and you learn to adjust to them,” said Miller [Lee E. Miller], also a professor of physiology and of physical medicine and rehabilitation at Feinberg and a Sensory Motor Performance Program lab chief at the Rehabilitation Institute of Chicago.
The National Institutes of Health news item supplies a little history and background for this latest breakthrough while the Northwestern University news item offers more technical details more technical details.
You can find the researchers’ paper with this citation (assuming you can get past the paywall,
C. Ethier, E. R. Oby, M. J. Bauman, L. E. Miller. Restoration of grasp following paralysis through brain-controlled stimulation of muscles. Nature, 2012; DOI: 10.1038/nature10987
I was surprised to find the Health Research Fund of Québec listed as one of the funders but perhaps Christian Ethier has some connection with the province.
There’s a lot of interest in fuel cells where I live due primarily to the existence of Ballard Power Systems, which was founded here in the province of British Columbia, Canada. Here’s what it says on the About Ballard page,
Ballard Power Systems, Inc. is a global leader in PEM (proton exchange membrane) fuel cell technology. We provide clean energy fuel cell products enabling optimized power systems for a range of applications. Ballard offers smarter solutions for a clean energy future.
We are actively putting fuel cells to work in high-value commercial uses every day. In fact, Ballard has designed and shipped close to 150 MW of hydrogen fuel cell technology to date.
In addition to Ballard, Canada’s National Research Council located its Institute for Fuel Cell Innovation in Vancouver, British Columbia (after much lobbying from the province).
Despite all the excitement over the years (especially in the beginning), the fuel cell industry in British Columbia has yet to become the revenue producer that was promised.
According to some observers, one of the keys issues has been the metals used as catalysts and once the situation is resolved, fuel cells will come into their own. Researchers at Brown University have developed a nanoparticle that outperforms other metallic catalysts. From the March 12, 2012 news item on Nanowerk,
Advances in fuel-cell technology have been stymied by the inadequacy of metals studied as catalysts. The drawback to platinum, other than cost, is that it absorbs carbon monoxide in reactions involving fuel cells powered by organic materials like formic acid. A more recently tested metal, palladium, breaks down over time.
Now chemists at Brown University have created a triple-headed metallic nanoparticle that they say outperforms and outlasts all others at the anode end in formic-acid fuel-cell reactions. In a paper published in the Journal of the American Chemical Society (“Structure-Induced Enhancement in Electrooxidation of Trimetallic FePtAu Nanoparticles”), the researchers report a 4-nanometer iron-platinum-gold nanoparticle (FePtAu), with a tetragonal crystal structure, generates higher current per unit of mass than any other nanoparticle catalyst tested. Moreover, the trimetallic nanoparticle at Brown performs nearly as well after 13 hours as it did at the start. By contrast, another nanoparticle assembly tested under identical conditions lost nearly 90 percent of its performance in just one-quarter of the time.
Gold plays key roles in the reaction. First, it acts as a community organizer of sorts, leading the iron and platinum atoms into neat, uniform layers within the nanoparticle. The gold atoms then exit the stage, binding to the outer surface of the nanoparticle assembly. Gold is effective at ordering the iron and platinum atoms because the gold atoms create extra space within the nanoparticle sphere at the outset. When the gold atoms diffuse from the space upon heating, they create more room for the iron and platinum atoms to assemble themselves. Gold creates the crystallization chemists want in the nanoparticle assembly at lower temperature.
Gold atoms create orderly places for iron and platinum atoms, then retreat to the periphery of the fuel cell, where they scrub carbon monoxide from fuel reactions. The tighter organization and cleaner reactions extend the cell's performance life. Credit: Sun Lab/Brown University
The researchers note that other metals may be substituted for gold as the best combinations are tested for combination and durability. (You can find more technical details in either the news item on Nanowerk or the news release at Brown University.)
Dexter Johnson at his Nanoclast blog (on the Institute of Electrical and Electronics Engineers [IEEE] website) provides a contrasting opinion as to why fuel cells have not become popular in his March 9, 2012 posting,
One of the fundamental problems with fuel cells has been the cost of producing hydrogen. While hydrogen is, of course, the most abundant element, it attaches itself to other elements like nitrogen or fluorine, and perhaps most ubiquitously to oxygen to create the water molecule. The process used to separate hydrogen out into hydrogen gas for powering fuel cells now relies on electricity produced from fossil fuels, negating some of the potential environmental benefits. So in the last few years, a new line of research has emerged that uses nanomaterials to imitate photosynthesis and break water down into hydrogen and oxygen thereby creating a more cost-effective and environmentally-friendly method for producing hydrogen.
If you’re interested, Dexter goes on to describe some promising areas of research that mimic photosynthesis.
In that odd area where coincidences meet, the latest work that Dexter discusses is taking place in California, a major centre for the gold rush of the 1800s. As it turns out, British Columbia was also a major destination in the days of the gold rush.
Here’s an intriguing approach to self-assembly for manufacturing purposes from scientists at Brown and Johns Hopkins Universities, respectively. From the Dec. 7, 2011 news item on Nanowerk,
In a paper published in the Proceedings of National Academy of Sciences (“Algorithmic design of self-folding polyhedra”), researchers from Brown and Johns Hopkins University determined the best 2-D arrangements, called planar nets, to create self-folding polyhedra with dimensions of a few hundred microns, the size of a small dust particle. The strength of the analysis lies in the combination of theory and experiment. The team at Brown devised algorithms to cut through the myriad possibilities and identify the best planar nets to yield the self-folding 3-D structures. Researchers at Johns Hopkins then confirmed the nets’ design principles with experiments.
Here’s the magnitude of the problem these scientists were solving (from the news item),
Material chemists and engineers would love to figure out how to create self-assembling shells, containers or structures that could be used as tiny drug-carrying containers or to build 3-D sensors and electronic devices.
There have been some successes with simple 3-D shapes such as cubes, but the list of possible starting points that could yield the ideal self-assembly for more complex geometric configurations gets long fast. For example, while there are 11 2-D arrangements for a cube, there are 43,380 for a dodecahedron (12 equal pentagonal faces). Creating a truncated octahedron (14 total faces – six squares and eight hexagons) has 2.3 million possibilities.
Associate professor of applied mathematics at Brown University, Govind Menon, says (from the news item),
“The issue is that one runs into a combinatorial explosion. … How do we search efficiently for the best solution within such a large dataset? This is where math can contribute to the problem.”
Here’s how they solved the problem (from the news item),
“Using a combination of theory and experiments, we uncovered design principles for optimum nets which self-assemble with high yields,” said David Gracias, associate professor in of chemical and biomolecular engineering at Johns Hopkins and a co-corresponding author on the paper.
“In doing so, we uncovered striking geometric analogies between natural assembly of proteins and viruses and these polyhedra, which could provide insight into naturally occurring self-assembling processes and is a step toward the development of self-assembly as a viable manufacturing paradigm.”
“This is about creating basic tools in nanotechnology,” said Menon, co-corresponding author on the paper. “It’s important to explore what shapes you can build. The bigger your toolbox, the better off you are.” While the approach has been used elsewhere to create smaller particles at the nanoscale, the researchers at Brown and Johns Hopkins used larger sizes to better understand the principles that govern self-folding polyhedra.
The news item on Nanowerk features more details, a video of a self-assembling dodecahedron, and an image of various options for 2-D nets that can be used to create 3-D shapes.
“Using a combination of theory and experiments, we uncovered design principles for optimum nets which self-assemble with high yields,” said David Gracias, associate professor in of chemical and biomolecular engineering at Johns Hopkins and a co-corresponding author on the paper. “In doing so, we uncovered striking geometric analogies between natural assembly of proteins and viruses and these polyhedra, which could provide insight into naturally occurring self-assembling processes and is a step toward the development of self-assembly as a viable manufacturing paradigm.”
“This is about creating basic tools in nanotechnology,” said Menon, co-corresponding author on the paper. “It’s important to explore what shapes you can build. The bigger your toolbox, the better off you are.”
While the approach has been used elsewhere to create smaller particles at the nanoscale, the researchers at Brown and Johns Hopkins used larger sizes to better understand the principles that govern self-folding polyhedra.
Sphere or spear? Apparently cells can’t tell that an asbestos fibre or long carbon nanotube are spears due to their rounded tips according to researchers at Brown University. From the Sept. 18, 2011 news item on Nanowerk,
Through molecular simulations and experiments, the team reports in Nature Nanotechnology that certain nanomaterials, such as carbon nanotubes, enter cells tip-first and almost always at a 90-degree angle. The orientation ends up fooling the cell; by taking in the rounded tip first, the cell mistakes the particle for a sphere, rather than a long cylinder. By the time the cell realizes the material is too long to be fully ingested, it’s too late.
Here’s a representation of what the scientists mean,
Something perpendicular this way comes Cells ingest things by engulfing them. When a long perpendicular fiber comes near, the cell senses only its tip, mistakes it for a sphere, and begins engulfing something too long to handle. Credit: Gao Lab/Brown University
Here’s what happens when a cell encounters a carbon nanotube, asbestos fibre, gold nanowires, and other materials that are long and perpendicular with rounded tips,
Like asbestos fibers, commercially available carbon nanotubes and gold nanowires have rounded tips that often range from 10 to 100 nanometers in diameter. Size is important here; the diameter fits well within the cell’s parameters for what it can handle. Brushing up against the nanotube, special proteins called receptors on the cell spring into action, clustering and bending the membrane wall to wrap the cell around the nanotube tip in a sequence that the authors call “tip recognition.” As this occurs, the nanotube is tipped to a 90-degree angle, which reduces the amount of energy needed for the cell to engulf the particle.
Once the engulfing — endocytosis — begins, there is no turning back. Within minutes, the cell senses it can’t fully engulf the nanostructure and essentially dials 911. “At this stage, it’s too late,” Gao [Huajian Gao] said. “It’s in trouble and calls for help, triggering an immune response that can cause repeated inflammation.”
I gather this is the starting point for mesothelioma. Here’s a description of the process (from the Brown University Sept. 18, 2011 news release,
“We thought the tube was going to lie on the cell membrane to obtain more binding sites. However, our simulations revealed the tube steadily rotating to a high-entry degree, with its tip being fully wrapped,” said Xinghua Shi, first author on the paper who earned his doctorate at Brown and is at the Chinese Academy of Sciences in Beijing. “It is counter-intuitive and is mainly due to the bending energy release as the membrane is wrapping the tube.”
Here’s a video from Brown illustrating the process,
The whole thing has me wondering about long vs. short carbon nanotubes. Does this mean that short carbon nanotubes can be ingested successfully? If so, at what point does short become too long to ingest? It doesn’t seem like my questions are going to be answered too soon since the team would like to go in this direction (from the Brown news release),
The team would like to study whether nanotubes without rounded tips — or less rigid nanomaterials such as nanoribbons — pose the same dilemma for cells.
“Interestingly, if the rounded tip of a carbon nanotube is cut off (meaning the tube is open and hollow), the tube lies on the cell membrane, instead of entering the cell at a high-degree-angle,” Shi said.
