Posts Tagged ‘Northwestern University’

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DARPA (US Defense Advanced Research Projects Agency), nanoparticles, and your traumatized brain

Friday, May 10th, 2013

According to the May 10, 2013 news item on Nanowerk,

DARPA, the U.S. Defense Advanced Research Projects Agency, has awarded $6 million to a team of researchers to develop nanotechnology therapies for the treatment of traumatic brain injury and associated infections.

Led by Professor Michael J. Sailor, Ph.D., from the University of California San Diego [UC San Diego], the award brings together a multi-disciplinary team of renowned experts in laboratory research, translational investigation and clinical medicine, including Erkki Ruoslahti, M.D., Ph.D. of Sanford-Burnham Medical Research Institute, Sangeeta N. Bhatia, M.D., Ph.D. of Massachusetts Institute of Technology and Clark C. Chen, M.D., Ph.D. of UC San Diego School of Medicine.

Ballistics injuries that penetrate the skull have amounted to 18 percent of battlefield wounds sustained by men and women who served in the campaigns in Iraq and Afghanistan, according to the most recent estimate from the Joint Theater Trauma Registry, a compilation of data collected during Operation Iraqi Freedom and Operation Enduring Freedom.

“A major contributor to the mortality associated with a penetrating brain injury is the elevated risk of intracranial infection,” said Chen, a neurosurgeon with UC San Diego Health System, noting that projectiles drive contaminated foreign materials into neural tissue.

The May 9, 2013 UC San Diego news release by Susan Brown, which originated the news item, describes the reasons why DARPA wants to use nanoparticles in therapies for people suffering from traumatic brain injury,

Under normal conditions, the brain is protected from infection by a physiological system called the blood-brain barrier. “Unfortunately, those same natural defense mechanisms make it difficult to get antibiotics to the brain once an infection has taken hold,” said Chen, associate professor and vice-chair of research in the Division of Neurosurgery at UC San Diego School of Medicine.

DARPA hopes to meet these challenges with nanotechnology. The agency awarded this grant under its In Vivo Nanoplatforms for Therapeutics program to construct nanoparticles that can find and treat infections and other damage associated with traumatic brain injuries.

“Our approach is focused on porous nanoparticles that contain highly effective therapeutics on the inside and targeting molecules on the outside,” said Sailor, the UC San Diego materials chemist who leads the team. “When injected into the blood stream, we have found that these silicon-based particles can target certain tissues very effectively.”

Several types of nanoparticles have already been approved for clinical use in patients, but none for treatment of trauma or diseases in the brain. This is due in part to the inability of nanoparticle formulations to cross the blood-brain barrier and reach their intended targets.

“Poor penetration into tissues limits the application of nanoparticles to the treatment of many types of diseases,” said Ruoslahti, distinguished professor at Sanford-Burnham and partner in the research. “We are trying to overcome this limitation using targeting molecules that activate tissue-specific transport pathways to deliver nanoparticles.”

There is another major hurdle for treating brain injuries (from the news release),

Treating brain infections is becoming more difficult as drug-resistant strains of viruses and bacteria have emerged. Because drug-resistant strains mutate and evolve rapidly, researchers must constantly adjust their approach to treatment.

In an attempt to hit this moving target, the team is making their systems modular, so they can be reconfigured “on-the-fly” with the latest therapeutic advances.

Nanocomplexes that contain genetic material known as short interfering RNA, or siRNA, developed by Bhatia’s research group at MIT, will be key to this aspect of the team’s approach.

“The function of this type of RNA is that it specifically intereferes with processes in a diseased cell. The advantage of RNA therapies are that they can be quickly and easily modified when a new disease target emerges,” said Bhatia, a bioengineering professor at MIT and partner in the research.

But effective delivery of siRNA-based therapeutics in the body has proven to be a challenge because the negative charge and chemical structure of naked siRNA makes it very unstable in the body and it has difficulty crossing into diseased cells. To solve these problems, Bhatia has developed nanoparticles that form a protective coating around siRNA.

“The nanocomplexes we are developing shield the negative charge of RNA and protect it from nucleases that would normally destroy it. Adding Erkki’s tissue homing and cell-penetrating peptides allows the nanocomplex to transport deep into tissue and enter the diseased cells,” she said.

Bhatia has previously used the cell-penetrating nanocomplex to deliver siRNA to a tumor cell and shut down its protein production machinery. Although her group’s effort has focused on cancer, the team is now going after two other hard-to-treat cell types: drug-resistant bacteria and inflammatory cells in the brain.

“The work proposed by this multi-disciplinary team should provide new tools to mitigate the debilitating effects of penetrating brain injuries and offer our warfighters the best chance of meaningful recovery,” Chen said. [emphasis mine]

BTW, the term ‘warfighters’ is new to me; are we replacing the word ‘soldier’?

Returning to the matter at hand, I found DARPA’s In Vivo Nanoplatforms for Therapeutics program which is described this way on its home page,

Disease limits soldier readiness and creates healthcare costs and logistics burdens. Diagnosing and treating disease faster can help limit its impact. [emphasis mine] Current technologies and products for diagnosing disease are principally relegated to in vitro (in the lab) medical devices, which are often expensive, bulky and fragile.

DARPA’s In Vivo Nanoplatforms (IVN) program seeks to develop new classes of adaptable nanoparticles for persistent, distributed, unobtrusive physiologic and environmental sensing as well as the treatment of physiologic abnormalities, illness and infectious disease.

The IVN Diagnostics (IVN:Dx) program effort aims to develop a generalized in vivo platform that provides continuous physiological monitoring for the warfighter. [emphasis mine] Specifically, IVN:Dx will investigate technologies that may provide:

  • Implantable nanoplatforms using bio-compatible and nontoxic materials
  • In vivo sensing of small and large molecules of biological interest
  • Multiplexed detection of analytes at clinically relevant concentrations
  • External interrogation of the nanoplatform free from any implanted communications electronics
  • Complete system demonstration in a large animal

The IVN Therapeutics (IVN:Tx) program effort will seek unobtrusive nanoplatforms for rapidly treating disease in warfighters.

(I see DARPA is using both soldier and warfighter’.)

This team is not the only one wishing to deliver drug therapies in a targeted fashion to the brain. My Feb. 19, 2013 posting mentioned Chad Mirkin (Northwestern University) and his team’s efforts with spherical nucleic acids (SNAs), from the posting,

Potential applications include using SNAs to carry nucleic acid-based therapeutics to the brain for the treatment of glioblastoma, the most aggressive form of brain cancer, as well as other neurological disorders such as Alzheimer’s and Parkinson’s diseases. Mirkin is aggressively pursuing treatments for such diseases with Alexander H. Stegh, an assistant professor of neurology at Northwestern’s Feinberg School of Medicine. (originally excerpted from this the Feb. 15, 2013 news release on EurekAlert)

Coincidentally, Mirkin has just been named ‘Chemistry World Entrepreneur of the Year’ by the UK’s Royal Society of Chemistry, from the May 10, 2013 news item on Nanowerk,

Northwestern University scientist Chad A. Mirkin, a world-renowned leader in nanotechnology research and its application, has been named 2013 Chemistry World Entrepreneur of the Year by the Royal Society of Chemistry (RSC). The award recognizes an individual’s contribution to the commercialization of research.

The RSC is honoring Mirkin for his invention of spherical nucleic acids (SNAs), new globular forms of DNA and RNA. These structures form the basis for more than 300 products commercialized by licensees of the technology.

I’m never quite sure what to make of researchers who receive public funding then patent and license the results of that research.

Getting back to soldiers/warfighters, I’m glad to see this research being pursued. Years ago, a physician mentioned to me that soldiers in Iraq were surviving injuries that would have killed them in previous conflicts. The problem is that the same protective gear which insulates soldiers against many injuries makes them vulnerable to abusive head trauma (same principle as ‘shaken baby syndrome’). For example, imagine having a high velocity bullet hit your helmet. You’re protected from the bullet but the impact shakes your head so violently, your brain is injured.

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Bend it, twist it, any way you want to—a foldable lithium-ion battery

Thursday, February 28th, 2013

A Feb. 26, 2013 news item on ScienceDaily features an extraordinary lithium-ion battery,

Northwestern University’s Yonggang Huang and the University of Illinois’ John A. Rogers are the first to demonstrate a stretchable lithium-ion battery — a flexible device capable of powering their innovative stretchable electronics.

No longer needing to be connected by a cord to an electrical outlet, the stretchable electronic devices now could be used anywhere, including inside the human body. The implantable electronics could monitor anything from brain waves to heart activity, succeeding where flat, rigid batteries would fail.

Huang and Rogers have demonstrated a battery that continues to work — powering a commercial light-emitting diode (LED) — even when stretched, folded, twisted and mounted on a human elbow. The battery can work for eight to nine hours before it needs recharging, which can be done wirelessly.

The researchers at Northwestern have produced a video where they demonstrate the battery’s ‘stretchability’,

The Northwestern University Feb. 26, 2013 news release by Megan Fellman, which originated the news item, offers this detail,

“We start with a lot of battery components side by side in a very small space, and we connect them with tightly packed, long wavy lines,” said Huang, a corresponding author of the paper. “These wires provide the flexibility. When we stretch the battery, the wavy interconnecting lines unfurl, much like yarn unspooling. And we can stretch the device a great deal and still have a working battery.”

…

The power and voltage of the stretchable battery are similar to a conventional lithium-ion battery of the same size, but the flexible battery can stretch up to 300 percent of its original size and still function.

…

Huang and Rogers have been working together for the last six years on stretchable electronics, and designing a cordless power supply has been a major challenge. Now they have solved the problem with their clever “space filling technique,” which delivers a small, high-powered battery.

For their stretchable electronic circuits, the two developed “pop-up” technology that allows circuits to bend, stretch and twist. They created an array of tiny circuit elements connected by metal wire “pop-up bridges.” When the array is stretched, the wires — not the rigid circuits — pop up.

This approach works for circuits but not for a stretchable battery. A lot of space is needed in between components for the “pop-up” interconnect to work. Circuits can be spaced out enough in an array, but battery components must be packed tightly to produce a powerful but small battery. There is not enough space between battery components for the “pop-up” technology to work.

Huang’s design solution is to use metal wire interconnects that are long, wavy lines, filling the small space between battery components. (The power travels through the interconnects.)

The unique mechanism is a “spring within a spring”: The line connecting the components is a large “S” shape and within that “S” are many smaller “S’s.” When the battery is stretched, the large “S” first stretches out and disappears, leaving a line of small squiggles. The stretching continues, with the small squiggles disappearing as the interconnect between electrodes becomes taut.

“We call this ordered unraveling,” Huang said. “And this is how we can produce a battery that stretches up to 300 percent of its original size.”

The stretching process is reversible, and the battery can be recharged wirelessly. The battery’s design allows for the integration of stretchable, inductive coils to enable charging through an external source but without the need for a physical connection.

Huang, Rogers and their teams found the battery capable of 20 cycles of recharging with little loss in capacity. The system they report in the paper consists of a square array of 100 electrode disks, electrically connected in parallel.

I’d like to see this battery actually powering a device even though the stretching is quite alluring in its way. For those who are interested here’s a citation and a link to the research paper,

Stretchable batteries with self-similar serpentine interconnects and integrated wireless recharging systems by Sheng Xu, Yihui Zhang, Jiung Cho, Juhwan Lee, Xian Huang, Lin Jia, Jonathan A. Fan, Yewang Su, Jessica Su, Huigang Zhang, Huanyu Cheng, Bingwei Lu,           Cunjiang Yu, Chi Chuang, Tae-il Kim, Taeseup Song, Kazuyo Shigeta, Sen Kang, Canan Dagdeviren, Ivan Petrov  et al.   Nature Communications 4, Article number: 1543 doi: 10.1038/ncomms2553  Published 26 February 2013

The article is behind a paywall.

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Chad Mirkin, spherical nucleic acids, and a new ‘periodic table’

Tuesday, February 19th, 2013

There was a big splash in July 2012 with the announcement that Chad Mirkin’s team at Northwestern University (Chicago, Illinois) had devised a skin cream that penetrated the skin barrier to deliver medication (my July 4, 2012 posting),

A team led by a physician-scientist and a chemist — from the fields of dermatology and nanotechnology — is the first to demonstrate the use of commercial moisturizers to deliver gene regulation technology that has great potential for life-saving therapies for skin cancers.

The topical delivery of gene regulation technology to cells deep in the skin is extremely difficult because of the formidable defenses skin provides for the body. The Northwestern approach takes advantage of drugs consisting of novel spherical arrangements of nucleic acids. These structures, each about 1,000 times smaller than the diameter of a human hair, have the unique ability to recruit and bind to natural proteins that allow them to traverse the skin and enter cells.

Mirkin has just finished presenting (Feb. 15, 2013 and Feb. 17, 2013) more information about spherical nucleic acids and their implications at the AAAS  (American Association for the Advancement of Science) 2013 meeting in Boston, Massachusetts. From the Feb. 15, 2013 news release on EurekAlert,

Northwestern University’s Chad A. Mirkin, a world-renowned leader in nanotechnology research and its application, has invented and developed a powerful material that could revolutionize biomedicine: spherical nucleic acids (SNAs).

…

Potential applications include using SNAs to carry nucleic acid-based therapeutics to the brain for the treatment of glioblastoma, the most aggressive form of brain cancer, as well as other neurological disorders such as Alzheimer’s and Parkinson’s diseases. Mirkin is aggressively pursuing treatments for such diseases with Alexander H. Stegh, an assistant professor of neurology at Northwestern’s Feinberg School of Medicine.

“These structures are really quite spectacular and incredibly functional,” Mirkin said. “People don’t typically think about DNA in spherical form, but this novel arrangement of nucleic acids imparts interesting chemical and physical properties that are very different from conventional nucleic acids.”

Spherical nucleic acids consist of densely packed, highly oriented nucleic acids arranged on the surface of a nanoparticle, typically gold or silver.  [emphasis mine] The tiny non-toxic balls, each roughly 15 nanometers in diameter, can do things the familiar but more cumbersome double helix can’t do:

  • SNAs can naturally enter cells and effect gene knockdown, making SNAs a superior tool for treating genetic diseases using gene regulation technology.
  • SNAs can easily cross formidable barriers in the human body, including the blood-brain barrier and the layers that make up skin.
  • SNAs don’t elicit an immune response, and they resist degradation, resulting in longer lifetimes in the body.

“The field of medicine needs new constructs and strategies for treating disease,” Mirkin said. “Many of the ways we treat disease are based on old methods and materials. Nanotechnology offers the ability to rapidly create new structures with properties that are very different from conventional forms of matter.”

…

“We now can go after a whole new set of diseases,” Mirkin said. “Thanks to the Human Genome Project and all of the genomics research over the last two decades, we have an enormous number of known targets. And we can use the same tool for each, the spherical nucleic acid. We simply change the sequence to match the target gene. That’s the power of gene regulation technology.”

###

A member of President Obama’s Council of Advisors on Science and Technology, Mirkin is known for invention and development of biological and chemical diagnostic systems based upon nanomaterials. He is the inventor and chief developer of Dip-Pen Nanolithography, a groundbreaking nanoscale fabrication and analytical tool, and is the founder of four Chicago-based companies: AuraSense, AuraSense Therapeutics, Nanosphere and NanoInk.

Mirkin, in addition to his work with spherical nucleic acids, has been busy with other nanoparticles and possible dreams of a new ‘periodic table of elements’, from the Feb. 17, 2013 news release on EurekAlert,

Forging a new periodic table using nanostructures

Northwestern University’s Chad A. Mirkin, …, has developed a completely new set of building blocks that is based on nanoparticles and DNA. Using these tools, scientists will be able to build — from the bottom up, just as nature does — new and useful structures.

…

“We have a new set of building blocks,” Mirkin said. “Instead of taking what nature gives you, we can control every property of the new material we make. We’ve always had this vision of building matter and controlling architecture from the bottom up, and now we’ve shown it can be done.”

Using nanoparticles and DNA, Mirkin has built more than 200 different crystal structures with 17 different particle arrangements. Some of the lattice types can be found in nature, but he also has built new structures that have no naturally occurring mineral counterpart.

…

Mirkin can make new materials and arrangements of particles by controlling the size, shape, type and location of nanoparticles within a given particle lattice. He has developed a set of design rules that allow him to control almost every property of a material.

New materials developed using his method could help improve the efficiency of optics, electronics and energy storage technologies. “These same nanoparticle building blocks have already found wide-spread commercial utility in biology and medicine as diagnostic probes for markers of disease,” Mirkin added.

With this present advance, Mirkin uses nanoparticles as “atoms” and DNA as “bonds.” He starts with a nanoparticle, which could be gold, silver, platinum or a quantum dot, for example. The core material is selected depending on what physical properties the final structure should have.

He then attaches hundreds of strands of DNA (oligonucleotides) to the particle. The oligonucleotide’s DNA sequence and length determine how bonds form between nanoparticles and guide the formation of specific crystal lattices.

“This constitutes a completely new class of building blocks in materials science that gives you a type of programmability that is extraordinarily versatile and powerful,” Mirkin said. “It provides nanotechnologists for the first time the ability to tailor properties of materials in a highly programmable way from the bottom up.”

If I read these two news releases rightly, the process (nanoparticles as atoms and DNA as bonds), Mirkin uses to create new structures is the same process he has used to create spherical nucleic acids. Given Mirkin’s entrepreneurial inclinations, I am curious as to how many and what kind of patents might be ‘protecting’ this work.

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Love, hate, and the whole damn thing affect batteries, semiconductors, and electronic memory

Friday, January 25th, 2013

A Jan. 24, 2013 news item on ScienceDaily features love triumphing over hate where tetracationic rings are concerned,

Northwestern University graduate student Jonathan Barnes had a hunch for creating an exotic new chemical compound, and his idea that the force of love is stronger than hate proved correct. He and his colleagues are the first to permanently interlock two identical tetracationic rings that normally are repelled by each other. Many experts had said it couldn’t be done.

On the surface, the rings hate each other because each carries four positive charges (making them tetracationic). But Barnes discovered by introducing radicals (unpaired electrons) onto the scene, the researchers could create a love-hate relationship in which love triumphs.

The Jan. 24, 2013 Northwestern University news release by Megan Fellman, which originated the news item, probes into the nature of the problem and its solution (Note: A link has been removed),

Unpaired electrons want to pair up and be stable, and it turns out the attraction of one ring’s single electrons to the other ring’s single electrons is stronger than the repelling forces.

The process links the rings not by a chemical bond but by a mechanical bond, which, once in place, cannot easily be torn asunder.

The study detailing this new class of stable organic radicals will be published Jan. 25 [2013] by the journal Science.

“It’s not that people have tried and failed to put these two rings together — they just didn’t think it was possible,” said Sir Fraser Stoddart, a senior author of the paper. “Now this molecule has been made. I cannot overemphasize Jonathan’s achievement — it is really outside the box. Now we are excited to see where this new chemistry leads us.”

…

The rings repel each other like the positive poles of two magnets. Barnes saw an opportunity where he thought he could tweak the chemistry by using radicals to overcome the hate between the two rings.

“We made these rings communicate and love each other under certain conditions, and once they were mechanically interlocked, the bond could not be broken,” Barnes said.

Barnes’ first strategy — adding electrons to temporarily reduce the charge and bring the two rings together — worked the first time he tried it. He, Stoddart and their colleagues started with a full ring and a half ring that they then closed up around the first ring (using some simple chemistry), creating the mechanical bond.

When the compound is oxidized and electrons lost, the strong positive forces come roaring back — “It’s hate on all the time,” Barnes said — but then it is too late for the rings to be parted. “That’s the beauty of this system,” he added.

Most organic radicals possess short lifetimes, but this unusual radical compound is stable in air and water. The compound tucks the electrons away inside the structure so they can’t react with anything in the environment. The tight mechanical bond endures despite the unfavorable electrostatic interactions.

The two interlocked rings house an immense amount of charge in a mere cubic nanometer of space. The compound, a homo[2]catenane, can adopt one of six oxidation states and can accept up to eight electrons in total.

“Anything that accepts this many electrons has possibilities for batteries,” Barnes said.

“Applications beckon,” Stoddart agreed. “Now we need to spend more time with materials scientists and people who make devices to see how this amazing compound can be used.”

For anyone interested in the details of the work, here’s a citation and link to the paper published in Science,

A Radically Configurable Six-State Compound by Jonathan C. Barnes, Albert C. Fahrenbach, Dennis Cao, Scott M. Dyar, Marco Frasconi, Marc A. Giesener, Diego Benítez, Ekaterina Tkatchouk, Oleksandr Chernyashevskyy, Weon Ho Shin, Hao Li, Srinivasan Sampath, Charlotte L. Stern, Amy A. Sarjeant, Karel J. Hartlieb, Zhichang Liu, Raanan Carmieli, Youssry Y. Botros, Jang Wook Choi, Alexandra M. Z. Slawin, John B. Ketterson, Michael R. Wasielewski, William A. Goddard III, J. Fraser Stoddart. Science 25 January 2013: Vol. 339 no. 6118 pp. 429-433 DOI: 10.1126/science.1228429

This is paper is behind a paywall.

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Multiple sclerosis stopped by a biodegradable nanoparticle?

Monday, November 19th, 2012

Researchers at Northwestern University (Chicago, Illinois) have halted the progress of multiple sclerosis in mice. The Nov. 18, 2012 Northwestern University news release on EurekAlert provides more details,

In a breakthrough for nanotechnology and multiple sclerosis, a biodegradable nanoparticle turns out to be the perfect vehicle to stealthily deliver an antigen that tricks the immune system into stopping its attack on myelin and halt a model of relapsing remitting multiple sclerosis (MS) in mice, according to new Northwestern Medicine research.

…

In MS, the immune system attacks the myelin membrane that insulates nerves cells in the brain, spinal cord and optic nerve. When the insulation is destroyed, electrical signals can’t be effectively conducted, resulting in symptoms that range from mild limb numbness to paralysis or blindness. About 80 percent of MS patients are diagnosed with the relapsing remitting form of the disease.

The Northwestern nanotechnology does not suppress the entire immune system as do current therapies for MS, which make patients more susceptible to everyday infections and higher rates of cancer. Rather, when the nanoparticles are attached to myelin antigens and injected into the mice, the immune system is reset to normal. The immune system stops recognizing myelin as an alien invader and halts its attack on it.

“This is a highly significant breakthrough in translational immunotherapy,” said Stephen Miller, a corresponding author of the study and the Judy Gugenheim Research Professor of Microbiology-Immunology at Northwestern University Feinberg School of Medicine. “The beauty of this new technology is it can be used in many immune-related diseases. We simply change the antigen that’s delivered.”

“The holy grail is to develop a therapy that is specific to the pathological immune response, in this case the body attacking myelin,” Miller added. “Our approach resets the immune system so it no longer attacks myelin but leaves the function of the normal immune system intact.”

The nanoparticle, made from an easily produced and already FDA-approved substance, was developed by Lonnie Shea, professor of chemical and biological engineering at Northwestern’s McCormick School of Engineering and Applied Science.

There are human clinical trials taking place now (from the news release),

The study’s method is the same approach now being tested in multiple sclerosis patients in a phase I/II clinical trial — with one key difference. The trial uses a patient’s own white blood cells — a costly and labor intensive procedure — to deliver the antigen. The purpose of the new study was to see if nanoparticles could be as effective as the white blood cells as delivery vehicles. They were.

For interested parties, here’s the full citation for the article and a link,

“Microparticles bearing encephalitogenic peptides induce T-cell tolerance and ameliorate experimental autoimmune encephalomyelitis” by Daniel R Getts, Aaron J Martin, Derrick P McCarthy, Rachael . Terry, Zoe N Hunter, Woon Teck Yap, Meghann Teague Getts, Michael Pleiss, Zunrong Luo, Nicholas JC King, Lonnie D Shea and Stephen D Miller in Nature Biotechnology (2012) doi:10.1038/nbt.2434

The article is behind a paywall.  I found these details  in the news release about how the antigen and nanoparticles work with the immune system particularly interesting,

In the study, researchers attached myelin antigens to the nanoparticles and injected them intravenously into the mice. The particles entered the spleen, which filters the blood and helps the body dispose of aging and dying blood cells. There, the particles were engulfed by macrophages, a type of immune cell, which then displayed the antigens on their cell surface. The immune system viewed the nanoparticles as ordinary dying blood cells and nothing to be concerned about. This created immune tolerance to the antigen by directly inhibiting the activity of myelin responsive T cells and by increasing the numbers of regulatory T cells which further calmed the autoimmune response.

“The key here is that this antigen/particle-based approach to induction of tolerance is selective and targeted. Unlike generalized immunosuppression, which is the current therapy used for autoimmune diseases, this new process does not shut down the whole immune system,” said Christine Kelley, National Institute of Biomedical Imaging and Bioengineering director of the division of Discovery Science and Technology at the National Institutes of Health, which supported the research.

All in all, this seems a gentler approach to the disease.

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Nano crafts class: get out your ‘paper’ and scissors

Thursday, November 15th, 2012

It’s not all atomic force microscopy and nanotweezers as scientists keep reminding us that the techniques we learned in kindergarten can be all the high technology we need even when working at the nanoscale. From the Nov. 14, 2012 news item on ScienceDaily,

Two Northwestern University researchers have discovered a remarkably easy way to make nanofluidic devices: using paper and scissors. And they can cut a device into any shape and size they want, adding to the method’s versatility.

The Nov. 14, 2012 Northwestern University news release by Megan Fellman explains both nanofluidic devices and the new technique,

Nanofluidic devices are attractive because their thin channels can transport ions — and with them a higher than normal electric current — making the devices promising for use in batteries and new systems for water purification, harvesting energy and DNA sorting.

The “paper-and-scissors” method one day could be used to manufacture large-scale nanofluidic devices without relying on expensive lithography techniques.

The Northwestern duo found that simply stacking up sheets of the inexpensive material graphene oxide creates flexible “paper” with tens of thousands of very useful channels. A tiny gap forms naturally between neighboring sheets, and each gap is a channel through which ions can flow.

Using a pair of regular scissors, the researchers simply cut the paper into a desired shape, which, in the case of their experiments, was a rectangle.

“In a way, we were surprised that these nanochannels actually worked, because creating the device was so easy,” said Jiaxing Huang, who conducted the research with postdoctoral fellow Kalyan Raidongia. “No one had thought about the space between sheet-like materials before. Using the space as a flow channel was a wild idea. We ran our experiment at least 10 times to be sure we were right.”

The process is a little more complex than kindergarten crafts (from Fellman’s news release),

To create a working device, the researchers took a pair of scissors and cut a piece of their graphene oxide paper into a centimeter-long rectangle. They then encased the paper in a polymer, drilled holes to expose the ends of the rectangular piece and filled up the holes with an electrolyte solution (a liquid containing ions) to complete the device.

Next they put electrodes at both ends and tested the electrical conductivity of the device. Huang and Raidongia observed higher than normal current, and the device worked whether flat or bent.

The nanochannels have significantly different — and desirable — properties from their bulk channel counterparts, Huang said. The nanochannels have a concentrating effect, resulting in an electric current much higher than those in bulk solutions.

Graphene oxide is basically graphene sheets decorated with oxygen-containing groups. It is made from inexpensive graphite powders by chemical reactions known for more than a century.

Scaling up the size of the device is simple. Tens of thousands of sheets or layers create tens of thousands of nanochannels, each channel approximately one nanometer high. There is no limit to the number of layers — and thus channels — one can have in a piece of paper.

To manufacture very massive arrays of channels, one only needs to put more graphene oxide sheets in the paper or to stack up many pieces of paper. A larger device, of course, can handle larger quantities of electrolyte.

Kindergarten techniques worked well for Andre Geim and Konstantin Novoselov who received Nobel prizes for their work on graphene (from my Oct. 7,2010 posting),

The technique that Geim and Novoselov used to create the first graphene sheets both amuses and fascinates me (from the article by Kit Eaton on the Fast Company website),

The two scientists came up with the technique that first resulted in samples of graphene–peeling individual atoms-deep sheets of the material from a bigger block of pure graphite. The science here seems almost foolishly simple, but it took a lot of lateral thinking to dream up, and then some serious science to investigate: Geim and Novoselo literally “ripped” single sheets off the graphite by using regular adhesive tape.

Then, there’s the ‘Shrinky Dinks’ nanopatterning technique (from my Aug. 16,2010 posting),

Scientists at a Northwestern University laboratory have taken to using a children’s arts and crafts product, Shrinky Dinks, for a new way to create large area nanoscale patterns on the cheap.

It’s good to be reminded that science at its heart is not about expensive equipment and complicated techniques but a means of exploring the world around us with the means at hand.

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Can nanoparticles pass through the skin or not?

Wednesday, October 3rd, 2012

Researchers at the University of Bath (England) have proved that nanoparticles do not penetrate the skin, according to the Oct. 1, 2012 news item on Nanowerk,

 Research by scientists at the University of Bath is challenging claims that nanoparticles in medicated and cosmetic creams are able to transport and deliver active ingredients deep inside the skin.
Nanoparticles, which are tiny particles that are less than one hundredth of the thickness of a human hair, are used in sunscreens and some cosmetic and pharmaceutical creams.
The Bath study (“Objective assessment of nanoparticle disposition in mammalian skin after topical exposure”) discovered that even the tiniest of nanoparticles did not penetrate the skin’s surface.
These findings have implications for pharmaceutical researchers and cosmetic companies that design skin creams with nanoparticles that are supposed to transport ingredients to the deeper layers of the skin. [emphasis mine]

Back in July 2012, a research team at Northwestern University claimed to have successfully delivered gene regulation technology using moisturizers to penetrate the skin barrier, excerpted from my July 4, 2012 posting,

The news item originated from a July 2, 2012 news release, by Marla Paul for Northwestern University, which provides more details about the researchers,

“The technology developed by my collaborator Chad Mirkin and his lab is incredibly exciting because it can break through the skin barrier,” said co-senior author Amy S. Paller, M.D., the Walter J. Hamlin Professor, chair of dermatology and professor of pediatrics at Northwestern University Feinberg School of Medicine. She also is director of Northwestern’s Skin Disease Research Center.

…

A co-senior author of the paper, Mirkin is the George B. Rathmann Professor of Chemistry in the Weinberg College of Arts and Sciences and professor of medicine, chemical and biological engineering, biomedical engineering and materials science and engineering. He also is the director of Northwestern’s International Institute for Nanotechnology.

…

Interdisciplinary research is a hallmark of Northwestern. Paller and Mirkin said their work highlights the power of physician-scientists and scientists and engineers from other fields coming together to address a difficult medical problem.

“This all happened because of our world-class presence in both cancer nanotechnology and skin disease research,” Paller said. “In putting together the Skin Disease Research Center proposal, I reached out to Chad to see if his nanostructures might be applied to skin disease. We initially worked together through a pilot project of the center, and now the rest is history.”

There’s more about how the nanoscale structures make their way through the skin but it seems the team from the University of Bath are prepared to contradict this claim, from the University of Bath’s Oct. 1,2012 news release (which originated the news item on Nanowerk),

Research by scientists at the University of Bath is challenging claims that nanoparticles in medicated and cosmetic creams are able to transport and deliver active ingredients deep inside the skin.

…

The Bath study discovered that even the tiniest of nanoparticles did not penetrate the skin’s surface.

These findings have implications for pharmaceutical researchers and cosmetic companies that design skin creams with nanoparticles that are supposed to transport ingredients to the deeper layers of the skin.

However the findings will also allay safety concerns that potentially harmful nanoparticles such as those used in sunscreens can be absorbed into the body.

The scientists used a technique called laser scanning confocal microscopy to examine whether fluorescently-tagged polystyrene beads, ranging in size from 20 to 200 nanometers, were absorbed into the skin. [emphasis mine]

They found that even when the skin sample had been partially compromised by stripping the outer layers with adhesive tape, the nanoparticles did not penetrate the skin’s outer layer, known as the stratum corneum.

I note they tested nanostructures larger than 20 nanometers so it’s possible that nanostructures that measure less than 20 nanometers could penetrate skin, non? However, it seems the structure used to ‘penetrate’ the skin by the team Northwestern University are considerably larger (excerpted from my July 4, 2012 posting),

The topical delivery of gene regulation technology to cells deep in the skin is extremely difficult because of the formidable defenses skin provides for the body. The Northwestern approach takes advantage of drugs consisting of novel spherical arrangements of nucleic acids. These structures, each about 1,000 times smaller than the diameter of a human hair, have the unique ability to recruit and bind to natural proteins that allow them to traverse the skin and enter cells.

(Side note: I believe a structure 1,000 times smaller than the diameter of a human hair would be measured in microns not nanometers.) I gather it’s the use of the nucleic acids in specialized formulations by the Northwestern team which make nanoparticle entry past the skin possible which contrasts with the work done by the University of Bath researchers who tested nanoparticles in standard cosmetic formulations.

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Hands off the bubbles in my boiling water!

Friday, September 14th, 2012

The discovery that boiling water bubbled was important to me. I’ve never really thought about it until now when researchers at Northwestern University have threatened to take my bubbles away, metaphorically speaking. From the Sept. 13, 2012 news item on ScienceDaily,

Every cook knows that boiling water bubbles, right? New research from Northwestern University turns that notion on its head.

“We manipulated what has been known for a long, long time by using the right kind of texture and chemistry to prevent bubbling during boiling,” said Neelesh A. Patankar, professor of mechanical engineering at Northwestern’s McCormick School of Engineering and Applied Science and co-author of the study.

This discovery could help reduce damage to surfaces, prevent bubbling explosions and may someday be used to enhance heat transfer equipment, reduce drag on ships and lead to anti-frost technologies.

The Sept. 13, 2012 news release from McCormick University (which originated the news item) provides details,

This phenomenon is based on the Leidenfrost effect. In 1756 the German scientist Johann Leidenfrost observed that water drops skittered on a sufficiently hot skillet, bouncing across the surface of the skillet on a vapor cushion or film of steam. The vapor film collapses as the surface falls below the Leidenfrost temperature. When the water droplet hits the surface of the skillet, at 100 degrees Celsius, boiling temperature, it bubbles.

To stabilize a Leidenfrost vapor film and prevent bubbling during boiling, Patankar collaborated with Ivan U. Vakarelski of King Abdullah University of Science and Technology, Saudi Arabia. Vakarelski led the experiments and Patankar provided the theory. The collaboration also included Derek Chan, professor of mathematics and statistics from the University of Melbourne in Australia.

In their experiments, the stabilization of the Leidenfrost vapor film was achieved by making the surface of tiny steel spheres very water-repellant. The spheres were sprayed with a commercially available hydrophobic coating — essentially self-assembled nanoparticles — combined with other water-hating chemicals to achieve the right amount of roughness and water repellency. At the correct length scale this coating created a surface texture full of tiny peaks and valleys.

When the steel spheres were heated to 400 degrees Celsius and dropped into room temperature water, water vapors formed in the valleys of the textured surface, creating a stable Leidenfrost vapor film that did not collapse once the spheres cooled to the temperature of boiling water. In the experiments, researchers completely avoided the bubbly phase of boiling.

To contrast, the team also coated tiny steel spheres with a water-loving coating, heated the objects to 700 degrees Celsius, dropped them into room temperature water and observed that the Leidenfrost vapor collapsed with a vigorous release of bubbles.

The scientists have provided a video illustrating their work,

This movie shows the cooling of 20 mm hydrophilic (left) and superhydrophobic (right) steel spheres in 100 C water. The spheres’ initial temperature is about 380 C. The bubbling phase of boiling is completely eliminated for steel spheres with superhydrophobic coating. (from Vimeo, http://vimeo.com/49391913)

I understand there are advantages to not having bubbles in hot water but it somehow seems wrong. I’ve given up a lot over the years: gravity, boundaries between living and non-living (that was a very big thing to give up), and other distinctions that I have made based on traditional science but, today, this is one step too far.

It may seem silly but that memory of my mother explaining that you identify boiling water by its bubbles is important to me. It was one of my first science lessons. I imagine I will recover from this moment but it does remind me of how challenging it can be when your notions of reality/normalcy are challenged by various scientific endeavours. The process can get quite exhausting as you keep recalibrating everything you ‘know’ all the time.

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Test your tuna for mercury and other heavy metals with nano-velcro

Monday, September 10th, 2012

Scientists Francesco Stellacci at the École Polytechnique Fédérale de Lausanne (EPFL) and Bartosz Grzybowski at Northwestern University have devised an easy and economical way to test for mercury and other heavy metals in fish. From the Sept. 9, 2012 news release on EurekAlert,

Mercury, when dumped in lakes and rivers, accumulates in fish, and often ends up on our plates. A Swiss-American team of researchers led by Francesco Stellacci at the Ecole Polytechnique Fédérale de Lausanne (EPFL) and Bartosz Grzybowski at Northwestern University has devised a simple, inexpensive system based on nanoparticles, a kind of nano-velcro, to detect and trap this toxic pollutant as well as others. The particles are covered with tiny hairs that can grab onto toxic heavy metals such as mercury and cadmium. This technology makes it possible to easily and inexpensively test for these substances in water and, more importantly, in the fish that we eat. Their new method can measure methyl mercury, the most common form of mercury pollution, at unprecedentedly small attomolar concentrations.

Here’s a description of how the technique works, from the Sept. 12, 2012 news release on the EPFL website,

The technology developed by the Swiss-American team is simple to use. A strip of glass covered with a film of “hairy”nanoparticles is dipped into the water. When an ion – a positively charged particle, such as a methyl mercury or cadmium ion – gets in between two hairs, the hairs close up, trapping the pollutant.

A voltage-measuring device reveals the result; the more ions there are trapped in the nano-velcro, the more electricity it will conduct. So to calculate the number of trapped particles, all one needs to do is measure the voltage across the nanostructure.

By varying the length of the nano-hairs, the scientists can target a particular kind of pollutant. “The procedure is empirical,” explains Stellacci. Methyl mercury, fortunately, has properties that make it extremely easy to trap without accidentally trapping other substances at the same time; thus the results are very reliable.

The interesting aspect of this approach is that the ‘reading’ glass strip could costs less than 10 dollars, while the measurement device will cost only a few hundreds of dollars. The analysis can be done in the field, so the results are immediately available. “With a conventional method, you have to send samples to the laboratory, and the analysis equipment costs several million dollars,” notes Stellacci.

They have tested the system in the field,

The researchers tested the system in Lake Michigan, near Chicago. Despite the high level of industry in the region, mercury levels were extremely low. “The goal was to compare our measurements to FDA [US Food and Drug Administration] measurements done using conventional methods,” explains Stellacci. “Our results fell within an acceptable range.”

A mosquito fish from the Everglades in Florida was also tested. This species is not very high on the food chain and thus does not accumulate high levels of mercury in its tissues. “We measured tissue that had been dissolved in acid. The goal was to see if we could detect even minuscule quantities.” says Bartosz Grzybowski, Burgess Professor of Chemistry and Director of Non-Equilibrium Energy Research Center at Northwestern University. The United States Geological Survey reported near-identical results after analyzing the same sample.

…

“I think it is quite incredible,” Grzybowski adds, “how the complex principles of quantum tunneling underlying our device translate into such an accurate and practically useful device. It is also notable that our system – through some relatively simple chemical modifications – can be readily adapted to detect other toxic species” Researchers have already demonstrated the detection of cadmium with a very high femtomolar sensitivity.

“With this technology, it will be possible to conduct tests on a much larger scale in the field, or even in fish before they are put on the market,” says lead author Eun Seon Cho. This is a necessary public health measure, given the toxic nature of methyl mercury and the extremely complex manner in which it spreads in the environment and accumulates in living tissues.

Northwestern University provided an illustration of the nano-velcro trapping an ion of heavy metal,

Nano-velcro (Courtesy Northwestern University & EPFL; downloaded from http://actu.epfl.ch/news/nano-velcro-clasps-heavy-metal-molecules-in-its-gr/)

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Surgery with fingertip control

Friday, August 10th, 2012

In the future, ‘surgery at your fingertips’ could be literally true. Researchers at the University of Illinois at Urbana-Champaign have created a silicon nanomembrane that can be fitted onto the fingertips and could, one day, be used in surgical procedures. From the Aug. 9, 2012 news item on ScienceDaily,

The intricate properties of the fingertips have been mimicked and recreated using semiconductor devices in what researchers hope will lead to the development of advanced surgical gloves.

The devices, shown to be capable of responding with high precision to the stresses and strains associated with touch and finger movement, are a step towards the creation of surgical gloves for use in medical procedures such as local ablations [excising or removing tissue] and ultrasound scans.

Researchers from the University of Illinois at Urbana-Champaign, Northwestern University and Dalian University of Technology have published their study August 10, in IOP [Institute of Physics] Publishing’s journal Nanotechnology.

The Aug. 10,2012 posting on the IOP website  offers this detail about the research,

The electronic circuit on the ‘skin’ is made of patterns of gold conductive lines and ultrathin sheets of silicon, integrated onto a flexible polymer called polyimide. The sheet is then etched into an open mesh geometry and transferred to a thin sheet of silicone rubber moulded into the precise shape of a finger.

This electronic ‘skin’, or finger cuff, was designed to measure the stresses and strains at the fingertip by measuring the change in capacitance – the ability to store electrical charge – of pairs of microelectrodes in the circuit.  Applied forces decreased the spacing in the skin which, in turn, increased the capacitance.

The fingertip device could also be fitted with sensors for measuring motion and temperature, with small-scale heaters as actuators for ablation and other related operations

The researchers experimented with having the electronics on the inside of the device, in contact with wearer’s skin, and also on the outside. They believe that because the device exploits materials and fabrication techniques adopted from the established semiconductor industry, the processes can be scaled for realistic use at reasonable cost.

“Perhaps the most important result is that we are able to incorporate multifunctional, silicon semiconductor device technologies into the form of soft, three-dimensional, form-fitting skins, suitable for integration not only with the fingertips but also other parts of the body,” continued Professor Rogers [John Rogers, co-author of the study].

Here’s what an image of these e-fingertips,

Virtual touch. Electronic fingertips could one day allow us to feel virtual sensations. Credit: John Rogers/University of Illinois at Urbana-Champaign

Krystnell A offers a more detailed description of the e-fingetips in an Aug. 9, 2012 story for Science NOW,

Hoping to create circuits with the flexibility of skin, materials scientist John Rogers of the University of Illinois, Urbana-Champaign, and colleagues cut up nanometer-sized strips of silicon; implanted thin, wavy strips of gold to conduct electricity; and mounted the entire circuit in a stretchable, spider web-type mesh of polymer as a support. They then embedded the circuit-polyimide structure onto a hollow tube of silicone that had been fashioned in the shape of a finger. Just like turning a sock inside out, the researchers flipped the structure so that the circuit, which was once on the outside of the tube, was on the inside where it could touch a finger placed against it.

To test the electronic fingers, the researchers put them on and pressed flat objects, such as the top of their desks. The pressure created electric currents that were transferred to the skin, which the researchers felt as mild tingling. That’s a first step in creating electrical signals that could be sent to the fingers, which could virtually recreate sensations such as heat, pressure, and texture, the team reports online today in Nanotechnology.

…

Rogers says another application of the technology is to custom fit the “electronic skin” around entire organs, allowing doctors to remotely monitor changes in temperature and blood flow. Electronic skin could also restore sensation to people who have lost their natural skin, he says, such as burn victims or amputees.

Here’s a link to the article which is freely accessible for 30 days after publication, from the Aug. 9, 2012 news item on ScienceDaily,

Ming Ying, Andrew P Bonifas, Nanshu Lu, Yewang Su, Rui Li, Huanyu Cheng, Abid Ameen, Yonggang Huang, John A Rogers. Silicon nanomembranes for fingertip electronics. Nanotechnology, 2012; 23 (34): 344004 DOI: 10.1088/0957-4484/23/34/344004

My best guess is that free access will no longer be available by Sept. 7 (or so) , 2012. I last wrote about John Rogers’ work in an Aug. 12, 2011 posting about electronic tattoos.

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