Tag Archives: Brown University

Brain, brains, brains: a roundup

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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 researchers are recruiting for human clinical trials, from the BrainGate Clinical Trials webpage,

Clinical Trials – Now Recruiting

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.

I think they’re saying there was a reverse takeover of Cyberkinetics, from the BrainGate company About webpage,

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.

…

“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.

Here’s more from the BrainAble home page,

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) system able 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.

From the April 19, 2012 news item (originating from Northwestern University) on Science Daily,

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.

Gold in them thar fuel cells

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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.

The March 12, 2012 news release from Brown University describes how gold improves performance,

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.

3-D and self-assembly

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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.

Why asbestos and carbon nanotubes are so dangerous to cells

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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,

Cells bite off more than they can chew from Brown PAUR on Vimeo.

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.

Cutting carbon nanotubes

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I’ve been meaning to get to this news item about cutting carbon nanotubes for a few days. From the Dec. 17, 2010 news item on Nanowerk,

“We can now design the cutting rate and the diameters we want to cut,” said Kyung-Suk Kim, professor of engineering in the School of Engineering at Brown and the corresponding author on the paper.

The basics of carbon nanotube manufacturing are known. Single-atom thin graphene sheets are immersed in solution (usually water), causing them to look like a plate of tangled spaghetti. The jumbled bundle of nanotubes is then blasted by high-intensity sound waves that create cavities (or partial vacuums) in the solution. The bubbles that arise from these cavities expand and collapse so violently that the heat in each bubble’s core can reach more than 5,000 degrees Kelvin, close to the temperature on the surface of the sun. Meanwhile, each bubble compresses at an acceleration 100 billion times greater than gravity. Considering the terrific energy involved, it’s hardly surprising that the tubes come out at random lengths. Technicians use sieves to get tubes of the desired length. The technique is inexact partly because no one was sure what caused the tubes to fracture.

German researchers had hypothesized that the tube fractures were due to the action of sonic boomlets yanking the tubes apart violently (like taking hold of the two opposite ends of a rope and pulling the rope apart from each end so that it breaks somewhere along its length). Apparently, this was not the case,

They [researchers from Brown University and Korea Institute of Science and Technology] found that rather than being pulled apart, as the German researchers had thought, the tubes were being compressed mightily from both ends. This caused a buckling in a roughly five-nanometer section along the tubes called the compression-concentration zone. In that zone, the tube is twisted into alternating 90-degree-angle folds, so that it fairly resembles a helix.

That discovery still did not explain fully how the tubes are cut. Through more computerized simulations, the group learned the mighty force exerted by the bubbles’ sonic booms caused atoms to be shot off the tube’s lattice-like foundation like bullets from a machine gun.

“It’s almost as if an orange is being squeezed, and the liquid is shooting out sideways,” Kim said. “This kind of fracture by compressive atom ejection has never been observed before in any kind of materials.”

Here’s where the paper was published and why they hope this is an important discovery,

In a paper published this month in the British journal Proceedings of the Royal Society A, researchers at Brown University and in Korea document for the first time how single-walled carbon nanotubes are cut, a finding that could lead to producing more precise, higher-quality nanotubes. Such manufacturing improvements likely would make the nanotubes more attractive for use in automotive, biomedicine, electronics, energy, optics and many other fields.

I didn’t see any projections for when these “more precise, higher-quality nanotubes” might reach the marketplace. It seems to me that they aren’t that sure about the prospects.

Arxis, healing with liquid bone

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I spotted this Dec. 8, 2010 news item about liquid bone on the Azonano website,

Here’s the vision: an elderly woman comes into the emergency room after a fall. She has broken her hip. The orthopaedic surgeon doesn’t come with metal plates or screws or shiny titanium ball joints.

Instead, she pulls out a syringe filled with a new kind of liquid that will solidify in seconds and injects into the break. Over time, new bone tissue will take its place, encouraged by natural growth factors embedded in the synthetic molecules of the material.

Although still early in its development, the liquid is real. In the Brown engineering lab of professor Thomas Webster it’s called TBL, for the novel DNA-like “twin-base linker” molecules that give it seemingly ideal properties. The biotech company Audax Medical Inc., based in Littleton, Mass., announced on Dec. 7 an exclusive license of the technology from Brown. It brands the technology as Arxis and sees similar potential for repairing broken vertebrae.

In chasing down more information about this particular liquid bone technology, I went to Brown University’s website to find an article by David Orenstein,

In some of his work, Webster employs nanotechnology to try to bridge metals to bone better than traditional bone cement. But TBL is an entirely new material, co-developed with longtime colleague and chemist Hicham Fenniri at the University of Alberta. [emphasis mine] Fenniri synthesized the molecules, while Webster’s research has focused on ensuring that TBL becomes viable material for medical use.

The molecules are artificial, but made from elements that are no strangers to the body: carbon, nitrogen, and oxygen. At room temperature their aggregate form is a liquid, but the material they form solidifies at body temperature. The molecules look like nanoscale tubes (billionths of a meter wide), and when they come together, it is in a spiraling ladder-shaped arrangement reminiscent of DNA or collagen. That natural structure makes it easy to integrate with bone tissue.

Yes, there is a University of Alberta connection! In fact, Fenniri (his university webpage is here) also works for Canada’s National Institute of Nanotechnology (NINT) in the Supramolecular Nanoscale Assembly group (webpage here). Why isn’t NINT making some sort of an announcement about this? (I digress.)

Back to the bone. You can see a video demonstration of the liquid bone by visiting the  Orenstein article on the Brown University website. The following image is also from the Orenstein article,

Buttressing bones Twin-based linker molecules, top left, self-assemble into six-molecule rings. Stacked in a tube shape, the rings of molecules not only provide a new scaffold for bone growth, but can also store growth factors and helpful drugs inside. Credit: Websterlab/Brown University

While this is a promising development, there are yet to be any clinical trials,

The molecules are artificial, but made from elements that are no strangers to the body: carbon, nitrogen, and oxygen. At room temperature their aggregate form is a liquid, but the material they form solidifies at body temperature. The molecules look like nanoscale tubes (billionths of a meter wide), and when they come together, it is in a spiraling ladder-shaped arrangement reminiscent of DNA or collagen. That natural structure makes it easy to integrate with bone tissue.

In the space within the nanotubes, the team, which includes graduate student Linlin Sun, has managed to stuff in various drugs including antibiotics, anti-inflammatory agents, and bone growth factors, which the tubes release over the course of months. Even better, different recipes of TBL, or Arxis, can be chemically tuned to become as hard as bone or as soft as cartilage, and can solidify in seconds or minutes, as needed. Once it is injected, nothing else is needed.

“We really like the fact that it doesn’t need anything other than temperature to solidify,” Webster said. Other compounds that people have developed require exposure to ultraviolet light and cannot therefore be injected through a tiny syringe hole. They require larger openings to be created.

For all of TBL’s apparent benefits, they have only been demonstrated in cow bone fragments in incubators on the lab bench top, Webster said. TBL still needs to be proven in vivo and, ultimately, in human trials.

I gather it will be years before we can expect to experience the scenario (breaking a hip and being injected with liquid bone) that opened this posting.