Fascinating work out of Finland shows that a minor change in the number of gold atoms in your gold nanoparticle can mean the difference between a metal and a molecule (coincidentally, this phenomenon is alluded to in my April 14, 2015 post (Nature’s patterns reflected in gold nanoparticles); more about that at the end of this piece. Getting back to Finland and when gold is metal and when it’s a molecule, here’s more from an April 10, 2015 news item on ScienceDaily,
Researchers at the Nanoscience Center at the University of Jyväskylä, Finland, have shown that dramatic changes in the electronic properties of nanometre-sized chunks of gold occur in well-defined size range. Small gold nanoclusters could be used, for instance, in short-term storage of energy or electric charge in the field of molecular electronics. Funded by the Academy of Finland, the researchers have been able to obtain new information which is important, among other things, in developing bioimaging and sensing based on metal-like clusters.
Two recent papers by the researchers at Jyväskylä (1, 2) demonstrate that the electronic properties of two different but still quite similar gold nanoclusters can be drastically different. The clusters were synthesised by chemical methods incorporating a stabilising ligand layer on their surface. The researchers found that the smaller cluster, with up to 102 gold atoms, behaves like a giant molecule while the larger one, with at least 144 gold atoms, already behaves, in principle, like a macroscopic chunk of metal, but in nanosize.
The fundamentally different behaviour of these two differently sized gold nanoclusters was demonstrated by shining a laser light onto solution samples containing the clusters and by monitoring how energy dissipates from the clusters into the surrounding solvent.
“Molecules behave drastically different from metals,” said Professor Mika Pettersson, the principal investigator of the team conducting the experiments. “The additional energy from light, absorbed by the metal-like clusters, transfers to the environment extremely rapidly, in about one hundred billionth of a second, while a molecule-like cluster is excited to a higher energy state and dissipates the energy into the environment with a rate that is at least 100 times slower. This is exactly what we saw: the 102-gold atom cluster is a giant molecule showing even a transient magnetic state while the 144-gold atom cluster is already a metal. We’ve thus managed to bracket an important size region where this fundamentally interesting change in the behaviour takes place.”
“These experimental results go together very well with what our team has seen from computational simulations on these systems,” said Professor Hannu Häkkinen, a co-author of the studies and the scientific director of the nanoscience centre. “My team predicted this kind of behaviour back in 2008-2009 when we saw big differences in the electronic structure of exactly these nanoclusters. It’s wonderful that robust spectroscopic experiments have now proved these phenomena. In fact, the metal-like 144-atom cluster is even more interesting, since we just published a theoretical paper where we saw a big enhancement of the metallic properties of just a few copper atoms mixed with gold.” (3)
Molecule-like Photodynamics of Au102(pMBA)44 Nanocluster by Satu Mustalahti, Pasi Myllyperkiö, Sami Malola, Tanja Lahtinen, Kirsi Salorinne, Jaakko Koivisto, Hannu Häkkinen, and Mika Pettersson. ACS Nano, 2015, 9 (3), pp 2328–2335 DOI: 10.1021/nn506711a Publication Date (Web): February 22, 2015
A 133 atom gold nanoparticle bears a resemblance to the Milky Way and to DNA’s (deoxyribonucleic acid) double helix according to an April 9, 2015 news item on ScienceDaily,
Our world is full of patterns, from the twist of a DNA molecule to the spiral of the Milky Way. New research from Carnegie Mellon chemists has revealed that tiny, synthetic gold nanoparticles exhibit some of nature’s most intricate patterns.
Unveiling the kaleidoscope of these patterns was a Herculean task, and it marks the first time that a nanoparticle of this size has been crystallized and its structure mapped out atom by atom. The researchers report their work in the March 20  issue of Science Advances.
“As you broadly think about different research areas or even our everyday lives, these kinds of patterns, these hierarchical patterns, are universal,” said Rongchao Jin, associate professor of chemistry. “Our universe is really beautiful and when you see this kind of information in something as small as a 133-atom nanoparticle and as big as the Milky Way, it’s really amazing.”
Gold nanoparticles, which can vary in size from 1 to 100 nanometers, are a promising technology that has applications in a wide range of fields including catalysis, electronics, materials science and health care. But, in order to use gold nanoparticles in practical applications, scientists must first understand the tiny particles’ structure.
“Structure essentially determines the particle’s properties, so without knowing the structure, you wouldn’t be able to understand the properties and you wouldn’t be able to functionalize them for specific applications,” said Jin, an expert in creating atomically precise gold nanoparticles.
With this latest research, Jin and his colleagues, including graduate student Chenjie Zeng, have solved the structure of a nanoparticle, Au133, made up of 133 gold atoms and 52 surface-protecting molecules—the biggest nanoparticle structure ever resolved with X-ray crystallography. While microscopy can reveal the size, shape and the atomic lattice of nanoparticles, it can’t discern the surface structure. X-ray crystallography can, by mapping out the position of every atom on the nanoparticles’ surface and showing how they bond with the gold core. Knowing the surface structure is key to using the nanoparticles for practical applications, such as catalysis, and for uncovering fundamental science, such as the basis of the particle’s stability.
The crystal structure of the Au133 nanoparticle divulged many secrets.
“With X-ray crystallography, we were able to see very beautiful patterns, which was a very exciting discovery. These patterns only show up when the nanoparticle size becomes big enough,” Jin said.
During production, the Au133 particles self-assemble into three layers within each particle: the gold core, the surface molecules that protect it and the interface between the two. In the crystal structure, Zeng discovered that the gold core is in the shape of an icosahedron. At the interface between the core and the surface-protecting molecules is a layer of sulfur atoms that bind with the gold atoms. The sulfur-gold-sulfur combinations stack into ladder-like helical structures. Finally, attached to the sulfur molecules is an outer layer of surface-protecting molecules whose carbon tails self-assemble into fourfold swirls.
“The helical features remind us of a DNA double helix and the rotating arrangement of the carbon tails is reminiscent of the way our galaxy is arranged. It’s really amazing,” Jin said.
These particular patterns are responsible for the high stability of Au133 compared to other sizes of gold nanoparticles. The researchers also tested the optical and electronic properties of Au133 and found that these gold nanoparticles are not metallic. [emphasis mine] Normally, gold is one of the best conductors of electrical current, but the size of Au133 is so small that the particle hasn’t yet become metallic. Jin’s group is currently testing the nanoparticles for use as catalysts, substances that can increase the rate of a chemical reaction.
Catherine J Murphy, professor of chemistry at the University of Illinois at Urbana-Champaign (UIUC), contributed to Inside Higher Education’s Academic Minute audio podcast series according to an April 9, 2015 news item on the organization’s website.
Murphy provides a very good beginner’s description of gold nanoparticles.
Inside Higher Education offers a transcript of the ‘minute’ by Matthew on its Academic Minute website’s Catherine Murphy webpage,
Introduction: Atomic element #79 is the precious metal more commonly known as gold.
Transcript: Nanotechnology is the study of matter on the 1-100 nanometer scale – about ten to a thousand atoms across. Many elements in the periodic table are metals, and chemists like me are figuring out ways to create tiny metal nanoparticles of different shapes and sizes – spheres, cylinders, stars, you name it. We focus on gold. The cool thing is that each shape and size of gold nanoparticle absorbs and scatters light at different wavelengths, so each size and shape has a different color. So all the colors of the rainbow, and then some, are possible with gold nanoparticles.
The reasons for these neat colors go back to understanding the fundamental nature of light. We know from Maxwell’s equations that light is an electromagnetic wave. If light impinges on a “small conducting sphere,” then there are conditions under which certain wavelengths of light lead to huge oscillations in the electron cloud around the metal, for any metal in the periodic table, as a function of the size of the sphere, the dielectric constant of the metal, and the refractive index of the medium. These equations were worked out by Gustav Mie in the early 1900’s and give us a fundamental understanding of where these brilliant colors come from. In the last 30 years, scientists have adapted his equation for all kinds of shapes beyond spheres.
But gold nanoparticles are not just pretty to look at: they can do a lot of interesting things. For instance, these gold nanoparticles also scatter light, making them easy to find in a simple optical microscope; and since gold is environmentally benign compared to other metals, people are using gold nanoparticles to image biological systems. When you shine light on gold, the absorption of light is very strong at the right wavelengths. Once the particles have absorbed all this energy, what do they do with it? They dump it out as heat to the environment, and so can raise the temperature of their surroundings by many degrees. This is the basis for what scientists call “photothermal therapy,” the idea that if you could target gold nanoparticles to cancer cells, or pathogens, then you could shine light at the wavelength you desire and kill the cancer cells or pathogens. Finally, if you make gold nanoparticles really really small, like 10 atoms across, they no longer act like a noble, unreactive metal at all; they become very active catalysts, like the catalytic converter in your car. So chemists are also very interested in figuring out the transition between unreactive and reactive nanoparticles.
For anyone who might be interested in the series, the Academic Minute covers a wide variety of topics ranging from ‘addiction vaccines’ to ‘digital transgender archives’ to ‘aeroponic gardening’ to ‘a science of the voice’ to ‘Viking social standing’ and more. The series seems to have been started in January 2011 and they’ve been adding to the list of podcasts at a lively rate (lately, it’s one per day). There are over 200 pages of audio podcasts available for your listening pleasure.
The simple test developed by University of Central Florida scientist Qun “Treen” Huo holds the promise of earlier detection of one of the deadliest cancers among men. It would also reduce the number of unnecessary and invasive biopsies stemming from the less precise PSA test that’s now used.
“It’s fantastic,” said Dr. Inoel Rivera, a urologic oncologist at Florida Hospital Cancer Institute, which collaborated with Huo on the recent pilot studies. “It’s a simple test. It’s much better than the test we have right now, which is the PSA, and it’s cost-effective.”
When a cancerous tumor begins to develop, the body mobilizes to produce antibodies. Huo’s test detects that immune response using gold nanoparticles about 10,000 times smaller than a freckle.
When a few drops of blood serum from a finger prick are mixed with the gold nanoparticles, certain cancer biomarkers cling to the surface of the tiny particles, increasing their size and causing them to clump together.
Among researchers, gold nanoparticles are known for their extraordinary efficiency at absorbing and scattering light. Huo and her team at UCF’s NanoScience Technology Center developed a technique known as nanoparticle-enabled dynamic light scattering assay (NanoDLSay) to measure the size of the particles by analyzing the light they throw off. That size reveals whether a patient has prostate cancer and how advanced it may be.
And although it uses gold, the test is cheap. A small bottle of nanoparticles suspended in water costs about $250, and contains enough for about 2,500 tests.
“What’s different and unique about our technique is it’s a very simple process, and the material required for the test is less than $1,” Huo said. “And because it’s low-cost, we’re hoping most people can have this test in their doctor’s office. If we can catch this cancer in its early stages, the impact is going to be big.”
After lung cancer, prostate cancer is the second-leading killer cancer among men, with more than 240,000 new diagnoses and 28,000 deaths every year. The most commonly used screening tool is the PSA, but it produces so many false-positive results – leading to painful biopsies and extreme treatments – that one of its discoverers recently called it “hardly more effective than a coin toss.”
Pilot studies found Huo’s technique is significantly more exact. The test determines with 90 to 95 percent confidence that the result is not false-positive. When it comes to false-negatives, there is 50 percent confidence – not ideal, but still significantly higher than the PSA’s 20 percent – and Huo is working to improve that number.
The results of the pilot studies were published recently in ACS Applied Materials & Interfaces. Huo is also scheduled to present her findings in June at the TechConnect World Innovation Summit & Expo in suburban Washington, D.C.
Huo’s team is pursuing more extensive clinical validation studies with Florida Hospital and others, including the VA Medical Center Orlando. She hopes to complete major clinical trials and see the test being used by physicians in two to three years.
Huo also is researching her technique’s effectiveness as a screening tool for other tumors.
“Potentially, we could have a universal screening test for cancer,” she said. “Our vision is to develop an array of blood tests for early detection and diagnosis of all major cancer types, and these blood tests are all based on the same technique and same procedure.”
Huo co-founded Nano Discovery Inc., a startup company headquartered in a UCF Business Incubator, to commercialize the new diagnostic test. The company manufacturers a test device specifically for medical research and diagnostic purposes.
Happily, I’m getting more nanotechnology (for the most part) information from Japan. Given Japan’s prominence in this field of endeavour I’ve long felt FrogHeart has not adequately represented Japanese contributions. Now that I’m receiving English language translations, I hope to better address the situation.
This morning (March 26, 2015), there were two news releases from Kawasaki INnovation Gateway at SKYFRONT (KING SKYFRONT), Coastal Area International Strategy Office, Kawasaki City, Japan in my mailbox. Before getting on to the news releases, here’s a little about the city of Kawasaki and about its innovation gateway. From the Kawasaki, Kanagawa entry in Wikipedia (Note: Links have been removed),
Kawasaki (川崎市 Kawasaki-shi?) is a city in Kanagawa Prefecture, Japan, located between Tokyo and Yokohama. It is the 9th most populated city in Japan and one of the main cities forming the Greater Tokyo Area and Keihin Industrial Area.
Kawasaki occupies a belt of land stretching about 30 kilometres (19 mi) along the south bank of the Tama River, which divides it from Tokyo. The eastern end of the belt, centered on JR Kawasaki Station, is flat and largely consists of industrial zones and densely built working-class housing, the Western end mountainous and more suburban. The coastline of Tokyo Bay is occupied by vast heavy industrial complexes built on reclaimed land.
There is a 2014 video about Kawasaki’s innovation gateway, which despite its 14 mins. 39 secs. running time I am embedding here. (Caution: They highlight their animal testing facility at some length.)
Now on to the two news releases. The first concerns research on gold nanoparticles that was published in 2014. From a March 26, 2015 Kawasaki INnovation Gateway news release,
Gold nanoparticles size up to cancer treatment
Incorporating gold nanoparticles helps optimise treatment carrier size and stability to improve delivery of cancer treatment to cells.
Treatments that attack cancer cells through the targeted silencing of cancer genes could be developed using small interfering RNA molecules (siRNA). However delivering the siRNA into the cells intact is a challenge as it is readily degraded by enzymes in the blood and small enough to be eliminated from the blood stream by kidney filtration. Now Kazunori Kataoka at the University of Tokyo and colleagues at Tokyo Institute of Technology have designed a protective treatment delivery vehicle with optimum stability and size for delivering siRNA to cells.
The researchers formed a polymer complex with a single siRNA molecule. The siRNA-loaded complex was then bonded to a 20 nm gold nanoparticle, which thanks to advances in synthesis techniques can be produced with a reliably low size distribution. The resulting nanoarchitecture had the optimum overall size – small enough to infiltrate cells while large enough to accumulate.
In an assay containing heparin – a biological anti-coagulant with a high negative charge density – the complex was found to release the siRNA due to electrostatic interactions. However when the gold nanoparticle was incorporated the complex remained stable. Instead, release of the siRNA from the complex with the gold nanoparticle could be triggered once inside the cell by the presence of glutathione, which is present in high concentrations in intracellular fluid. The glutathione bonded with the gold nanoparticles and the complex, detaching them from each other and leaving the siRNA prone to release.
The researchers further tested their carrier in a subcutaneous tumour model. The authors concluded that the complex bonded to the gold nanoparticle “enabled the efficient tumor accumulation of siRNA and significant in vivo gene silencing effect in the tumor, demonstrating the potential for siRNA-based cancer therapies.”
The news release provides links to the March 2015 newsletter which highlights this research and to the specific article and video,
The second March 26, 2015 Kawasaki INnovation Gateway news release concerns a DNA chip and food-borne pathogens,
Rapid and efficient DNA chip technology for testing 14 major types of food borne pathogens
Conventional methods for testing food-borne pathogens is based on the cultivation of pathogens, a process that is complicated and time consuming. So there is demand for alternative methods to test for food-borne pathogens that are simpler, quick and applicable to a wide range of potential applications.
Now Toshiba Ltd and Kawasaki City Institute for Public Health have collaborated in the development of a rapid and efficient automatic abbreviated DNA detection technology that can test for 14 major types of food borne pathogens. The so called ‘DNA chip card’ employs electrochemical DNA chips and overcomes the complicated procedures associated with genetic testing of conventional methods. The ‘DNA chip card’ is expected to find applications in hygiene management in food manufacture, pharmaceuticals, and cosmetics.
The so-called automatic abbreviated DNA detection technology ‘DNA chip card’ was developed by Toshiba Ltd and in a collaboration with Kawasaki City Institute for Public Health, used to simultaneously detect 14 different types of food-borne pathogens in less than 90 minutes. The detection sensitivity depends on the target pathogen and has a range of 1E+01~05 cfu/mL.
Notably, such tests would usually take 4-5 days using conventional methods based on pathogen cultivation. Furthermore, in contrast to conventional DNA protocols that require high levels of skill and expertise, the ‘DNA chip card’ only requires the operator to inject nucleic acid, thereby making the procedure easier to use and without specialized operating skills.
Examples of pathogens associated with food poisoning that were tested with the “DNA chip card”
Enterohemorrhagic Escherichia coli
Enterotoxigenic Escherichia coli
Enteroaggregative Escherichia coli
Enteropathogenic Escherichia coli
I think 14 is the highest number of tests I’ve seen for one of these chips. This chip is quite an achievement.
One final bit from the news release about the DNA chip provides a brief description of the gateway and something they call King SkyFront,
About KING SKYFRONT
The Kawasaki INnovation Gateway (KING) SKYFRONT is the flagship science and technology innovation hub of Kawasaki City. KING SKYFRONT is a 40 hectare area located in the Tonomachi area of the Keihin Industrial Region that spans Tokyo and Kanagawa Prefecture and Tokyo International Airport (also often referred to as Haneda Airport).
KING SKYFRONT was launched in 2013 as a base for scholars, industrialists and government administrators to work together to devise real life solutions to global issues in the life sciences and environment.
I find this emphasis on the city interesting. It seems that cities are becoming increasingly important and active where science research and development are concerned. Europe seems to have adopted a biannual event wherein a city is declared a European City of Science in conjunction with the EuroScience Open Forum (ESOF) conferences. The first such city was Dublin in 2012 (I believe the Irish came up with the concept themselves) and was later adopted by Copenhagen for 2014. The latest city to embrace the banner will be Manchester in 2016.
I have two items about implants and brains and an item about being able to exert remote control of the brain, all of which hint at a cyborg future for at least a few of us.
e-Dura, the spinal column, and the brain
The first item concerns some research, at the École Polytechnique de Lausanne (EPFL) which features flexible electronics. From a March 24, 2015 article by Ben Schiller for Fast Company (Note: Links have been removed),
Researchers at the Swiss Federal Institute of Technology, in Lausanne, have developed the e-Dura—a tiny skinlike device that attaches directly to damaged spinal cords. By sending out small electrical pulses, it stimulates the cord as if it were receiving signals from the brain, thus allowing movement.
“The purpose of the neuro-prosthesis is to excite the neurons that are on the spinal cord below the site of the injury and activate them, just like if they were receiving information from the brain,” says Stéphanie Lacour, a professor at the institute.
EPFL scientists have managed to get rats walking on their own again using a combination of electrical and chemical stimulation. But applying this method to humans would require multifunctional implants that could be installed for long periods of time on the spinal cord without causing any tissue damage. This is precisely what the teams of professors Stéphanie Lacour and Grégoire Courtine have developed. Their e-Dura implant is designed specifically for implantation on the surface of the brain or spinal cord. The small device closely imitates the mechanical properties of living tissue, and can simultaneously deliver electric impulses and pharmacological substances. The risks of rejection and/or damage to the spinal cord have been drastically reduced. An article about the implant will appear in early January  in Science Magazine.
So-called “surface implants” have reached a roadblock; they cannot be applied long term to the spinal cord or brain, beneath the nervous system’s protective envelope, otherwise known as the “dura mater,” because when nerve tissues move or stretch, they rub against these rigid devices. After a while, this repeated friction causes inflammation, scar tissue buildup, and rejection.
Here’s what the implant looks like,
The press release describes how the implant is placed (Note: A link has been removed),
Flexible and stretchy, the implant developed at EPFL is placed beneath the dura mater, directly onto the spinal cord. Its elasticity and its potential for deformation are almost identical to the living tissue surrounding it. This reduces friction and inflammation to a minimum. When implanted into rats, the e-Dura prototype caused neither damage nor rejection, even after two months. More rigid traditional implants would have caused significant nerve tissue damage during this period of time.
The researchers tested the device prototype by applying their rehabilitation protocol — which combines electrical and chemical stimulation – to paralyzed rats. Not only did the implant prove its biocompatibility, but it also did its job perfectly, allowing the rats to regain the ability to walk on their own again after a few weeks of training.
“Our e-Dura implant can remain for a long period of time on the spinal cord or the cortex, precisely because it has the same mechanical properties as the dura mater itself. This opens up new therapeutic possibilities for patients suffering from neurological trauma or disorders, particularly individuals who have become paralyzed following spinal cord injury,” explains Lacour, co-author of the paper, and holder of EPFL’s Bertarelli Chair in Neuroprosthetic Technology.
The press release goes on to describe the engineering achievements,
Developing the e-Dura implant was quite a feat of engineering. As flexible and stretchable as living tissue, it nonetheless includes electronic elements that stimulate the spinal cord at the point of injury. The silicon substrate is covered with cracked gold electric conducting tracks that can be pulled and stretched. The electrodes are made of an innovative composite of silicon and platinum microbeads. They can be deformed in any direction, while still ensuring optimal electrical conductivity. Finally, a fluidic microchannel enables the delivery of pharmacological substances – neurotransmitters in this case – that will reanimate the nerve cells beneath the injured tissue.
The implant can also be used to monitor electrical impulses from the brain in real time. When they did this, the scientists were able to extract with precision the animal’s motor intention before it was translated into movement.
“It’s the first neuronal surface implant designed from the start for long-term application. In order to build it, we had to combine expertise from a considerable number of areas,” explains Courtine, co-author and holder of EPFL’s IRP Chair in Spinal Cord Repair. “These include materials science, electronics, neuroscience, medicine, and algorithm programming. I don’t think there are many places in the world where one finds the level of interdisciplinary cooperation that exists in our Center for Neuroprosthetics.”
For the time being, the e-Dura implant has been primarily tested in cases of spinal cord injury in paralyzed rats. But the potential for applying these surface implants is huge – for example in epilepsy, Parkinson’s disease and pain management. The scientists are planning to move towards clinical trials in humans, and to develop their prototype in preparation for commercialization.
EPFL has provided a video of researcher Stéphanie Lacour describing e-Dura and expressing hopes for its commercialization,
Here’s a link to and a citation for the paper,
Electronic dura mater for long-term multimodal neural interfaces by Ivan R. Minev, Pavel Musienko, Arthur Hirsch, Quentin Barraud, Nikolaus Wenger, Eduardo Martin Moraud, Jérôme Gandar, Marco Capogrosso, Tomislav Milekovic, Léonie Asboth, Rafael Fajardo Torres, Nicolas Vachicouras, Qihan Liu, Natalia Pavlova, Simone Duis, Alexandre Larmagnac, Janos Vörös, Silvestro Micera, Zhigang Suo, Grégoire Courtine, Stéphanie P. Lacour. Science 9 January 2015: Vol. 347 no. 6218 pp. 159-163 DOI: 10.1126/science.1260318
This paper is behind a paywall.
Carbon nanotube fibres could connect to the brain
Researchers at Rice University (Texas, US) are excited about the possibilities that carbon nanotube fibres offer in the field of implantable electronics for the brain. From a March 25, 2015 news item on Nanowerk,
Carbon nanotube fibers invented at Rice University may provide the best way to communicate directly with the brain.
The fibers have proven superior to metal electrodes for deep brain stimulation and to read signals from a neuronal network. Because they provide a two-way connection, they show promise for treating patients with neurological disorders while monitoring the real-time response of neural circuits in areas that control movement, mood and bodily functions.
New experiments at Rice demonstrated the biocompatible fibers are ideal candidates for small, safe electrodes that interact with the brain’s neuronal system, according to the researchers. They could replace much larger electrodes currently used in devices for deep brain stimulation therapies in Parkinson’s disease patients.
They may also advance technologies to restore sensory or motor functions and brain-machine interfaces as well as deep brain stimulation therapies for other neurological disorders, including dystonia and depression, the researchers wrote.
The fibers created by the Rice lab of chemist and chemical engineer Matteo Pasquali consist of bundles of long nanotubes originally intended for aerospace applications where strength, weight and conductivity are paramount.
The individual nanotubes measure only a few nanometers across, but when millions are bundled in a process called wet spinning, they become thread-like fibers about a quarter the width of a human hair.
“We developed these fibers as high-strength, high-conductivity materials,” Pasquali said. “Yet, once we had them in our hand, we realized that they had an unexpected property: They are really soft, much like a thread of silk. Their unique combination of strength, conductivity and softness makes them ideal for interfacing with the electrical function of the human body.”
The simultaneous arrival in 2012 of Caleb Kemere, a Rice assistant professor who brought expertise in animal models of Parkinson’s disease, and lead author Flavia Vitale, a research scientist in Pasquali’s lab with degrees in chemical and biomedical engineering, prompted the investigation.
“The brain is basically the consistency of pudding and doesn’t interact well with stiff metal electrodes,” Kemere said. “The dream is to have electrodes with the same consistency, and that’s why we’re really excited about these flexible carbon nanotube fibers and their long-term biocompatibility.”
Weeks-long tests on cells and then in rats with Parkinson’s symptoms proved the fibers are stable and as efficient as commercial platinum electrodes at only a fraction of the size. The soft fibers caused little inflammation, which helped maintain strong electrical connections to neurons by preventing the body’s defenses from scarring and encapsulating the site of the injury.
The highly conductive carbon nanotube fibers also show much more favorable impedance – the quality of the electrical connection — than state-of-the-art metal electrodes, making for better contact at lower voltages over long periods, Kemere said.
The working end of the fiber is the exposed tip, which is about the width of a neuron. The rest is encased with a three-micron layer of a flexible, biocompatible polymer with excellent insulating properties.
The challenge is in placing the tips. “That’s really just a matter of having a brain atlas, and during the experiment adjusting the electrodes very delicately and putting them into the right place,” said Kemere, whose lab studies ways to connect signal-processing systems and the brain’s memory and cognitive centers.
Doctors who implant deep brain stimulation devices start with a recording probe able to “listen” to neurons that emit characteristic signals depending on their functions, Kemere said. Once a surgeon finds the right spot, the probe is removed and the stimulating electrode gently inserted. Rice carbon nanotube fibers that send and receive signals would simplify implantation, Vitale said.
The fibers could lead to self-regulating therapeutic devices for Parkinson’s and other patients. Current devices include an implant that sends electrical signals to the brain to calm the tremors that afflict Parkinson’s patients.
“But our technology enables the ability to record while stimulating,” Vitale said. “Current electrodes can only stimulate tissue. They’re too big to detect any spiking activity, so basically the clinical devices send continuous pulses regardless of the response of the brain.”
Kemere foresees a closed-loop system that can read neuronal signals and adapt stimulation therapy in real time. He anticipates building a device with many electrodes that can be addressed individually to gain fine control over stimulation and monitoring from a small, implantable device.
“Interestingly, conductivity is not the most important electrical property of the nanotube fibers,” Pasquali said. “These fibers are intrinsically porous and extremely stable, which are both great advantages over metal electrodes for sensing electrochemical signals and maintaining performance over long periods of time.”
The paper is open access provided you register on the website.
Remote control for stimulation of the brain
Mo Costandi, neuroscientist and freelance science writer, has written a March 24, 2015 post for the Guardian science blog network focusing on neuronal remote control,
Two teams of scientists have developed new ways of stimulating neurons with nanoparticles, allowing them to activate brain cells remotely using light or magnetic fields. The new methods are quicker and far less invasive than other hi-tech methods available, so could be more suitable for potential new treatments for human diseases.
Researchers have various methods for manipulating brain cell activity, arguably the most powerful being optogenetics, which enables them to switch specific brain cells on or off with unprecedented precision, and simultaneously record their behaviour, using pulses of light.
This is very useful for probing neural circuits and behaviour, but involves first creating genetically engineered mice with light-sensitive neurons, and then inserting the optical fibres that deliver light into the brain, so there are major technical and ethical barriers to its use in humans.
Nanomedicine could get around this. Francisco Bezanilla of the University of Chicago and his colleagues knew that gold nanoparticles can absorb light and convert it into heat, and several years ago they discovered that infrared light can make neurons fire nervous impulses by heating up their cell membranes.
Polina Anikeeva’s team at the Massachusetts Institute of Technology adopted a slightly different approach, using spherical iron oxide particles that give off heat when exposed to an alternating magnetic field.
Although still in the experimental stages, research like this may eventually allow for wireless and minimally invasive deep brain stimulation of the human brain. Bezanilla’s group aim to apply their method to develop treatments for macular degeneration and other conditions that kill off light-sensitive cells in the retina. This would involve injecting nanoparticles into the eye so that they bind to other retinal cells, allowing natural light to excite them into firing impulses to the optic nerve.
Costandi’s article is intended for an audience that either understands the science or can deal with the uncertainty of not understanding absolutely everything. Provided you fall into either of those categories, the article is well written and it provides links and citations to the papers for both research teams being featured.
Taken together, the research at EPFL, Rice University, University of Chicago, and Massachusetts Institute of Technology provides a clue as to how much money and intellectual power is being directed at the brain.
A March 16, 2015 news item on Nanowerk features research from the University of Illinois and the song ‘Twinkle, Twinkle Little Star’,
Researchers from the University of Illinois at Urbana-Champaign have demonstrated the first-ever recording of optically encoded audio onto a non-magnetic plasmonic nanostructure, opening the door to multiple uses in informational processing and archival storage.
“The chip’s dimensions are roughly equivalent to the thickness of human hair,” explained Kimani Toussaint, an associate professor of mechanical science and engineering, who led the research.
Specifically, the photographic film property exhibited by an array of novel gold, pillar-supported bowtie nanoantennas (pBNAs)–previously discovered by Toussaint’s group–was exploited to store sound and audio files. Compared with the conventional magnetic film for analog data storage, the storage capacity of pBNAs is around 5,600 times larger, indicating a vast array of potential storage uses.
The researchers have provide a visual image illustrating their work,
Nano piano concept: Arrays of gold, pillar-supported bowtie nanoantennas (bottom left) can be used to record distinct musical notes, as shown in the experimentally obtained dark-field microscopy images (bottom right). These particular notes were used to compose ‘Twinkle, Twinkle, Little Star.’ Courtesy of University of Illinois at Urbana-Champaign
To demonstrate its abilities to store sound and audio files, the researchers created a musical keyboard or “nano piano,” using the available notes to play the short song, “Twinkle, Twinkle, Little Star.”
“Data storage is one interesting area to think about,” Toussaint said. “For example, one can consider applying this type of nanotechnology to enhancing the niche, but still important, analog technology used in the area of archival storage such as using microfiche. In addition, our work holds potential for on-chip, plasmonic-based information processing.”
The researchers demonstrated that the pBNAs could be used to store sound information either as a temporally varying intensity waveform or a frequency varying intensity waveform. Eight basic musical notes, including middle C, D, and E, were stored on a pBNA chip and then retrieved and played back in a desired order to make a tune.
“A characteristic property of plasmonics is the spectrum,” said Hao Chen, a former postdoctoral researcher in Toussaint’s PROBE laboratory and the first author of the paper, “Plasmon-Assisted Audio Recording,” appearing in the Nature Publishing Group’s Scientific Reports. “Originating from a plasmon-induced thermal effect, well-controlled nanoscale morphological changes allow as much as a 100-nm spectral shift from the nanoantennas. By employing this spectral degree-of-freedom as an amplitude coordinate, the storage capacity can be improved. Moreover, although our audio recording focused on analog data storage, in principle it is still possible to transform to digital data storage by having each bowtie serve as a unit bit 1 or 0. By modifying the size of the bowtie, it’s feasible to further improve the storage capacity.”
The team previously demonstrated that pBNAs experience reduced thermal conduction in comparison to standard bowtie nanoantennas and can easily get hot when irradiated by low-powered laser light. Each bowtie antenna is approximately 250 nm across in dimensions, with each supported on 500-nm tall silicon dioxide posts. A consequence of this is that optical illumination results in subtle melting of the gold, and thus a change in the overall optical response. This shows up as a difference in contrast under white-light illumination.
“Our approach is analogous to the method of ‘optical sound,’ which was developed circa 1920s as part of the effort to make ‘talking’ motion pictures,” the team said in its paper. “Although there were variations of this process, they all shared the same basic principle. An audio pickup, e.g., a microphone, electrically modulates a lamp source. Variations in the intensity of the light source is encoded on semi-transparent photographic film (e.g., as variation in area) as the film is spatially translated. Decoding this information is achieved by illuminating the film with the same light source and picking up the changes in the light transmission on an optical detector, which in turn may be connected to speakers. In the work that we present here, the pBNAs serve the role of the photographic film which we can encode with audio information via direct laser writing in an optical microscope.”
In their approach, the researchers record audio signals by using a microscope to scan a sound-modulated laser beam directly on their nanostructures. Retrieval and subsequent playback is achieved by using the same microscope to image the recorded waveform onto a digital camera, whereby simple signal processing can be performed.
Here’s a link to and a citation for the paper,
Plasmon-Assisted Audio Recording by Hao Chen, Abdul M. Bhuiya, Qing Ding, & Kimani C. Toussaint, Jr. Scientific Reports 5, Article number: 9125 doi:10.1038/srep09125 Published 16 March 2015
This is an open access paper and here is a sample recording courtesy of the researchers and the University of Illinois at Urbana-Champaign,
Caption: Low-cost experiments to test the toxicity of nanomaterials focused on populations of roundworms. Rice University scientists were able to test 20 nanomaterials in a short time, and see their method as a way to determine which nanomaterials should undergo more extensive testing. Credit: Zhong Lab/Rice University
Until now, ‘cute’ and ‘adorable’ are not words I would have associated with worms of any kind or with Rice University, for that matter. It’s amazing what a single image can do, eh?
A Feb. 3, 2015 news item on Azonano describes how roundworms have been used in research investigating the toxicity of various kinds of nanoparticles,
The lowly roundworm is the star of an ambitious Rice University project to measure the toxicity of nanoparticles.
The low-cost, high-throughput study by Rice scientists Weiwei Zhong and Qilin Li measures the effects of many types of nanoparticles not only on individual organisms but also on entire populations.
The Rice researchers tested 20 types of nanoparticles and determined that five, including the carbon-60 molecules (“buckyballs”) discovered at Rice in 1985, showed little to no toxicity.
Others were moderately or highly toxic to Caenorhabditis elegans, several generations of which the researchers observed to see the particles’ effects on their health.
The results were published by the American Chemical Society journal Environmental Sciences and Technology. They are also available on the researchers’ open-source website.
“Nanoparticles are basically new materials, and we don’t know much about what they will do to human health and the health of the ecosystem,” said Li, an associate professor of civil and environmental engineering and of materials science and nanoengineering. “There have been a lot of publications showing certain nanomaterials are more toxic than others. So before we make more products that incorporate these nanomaterials, it’s important that we understand we’re not putting anything toxic into the environment or into consumer products.
“The question is, How much cost can we bear?” she said. “It’s a long and expensive process to do a thorough toxicological study of any chemical, not just nanomaterials.” She said that due to the large variety of nanomaterials being produced at high speed and at such a large scale, there is “an urgent need for high-throughput screening techniques to prioritize which to study more extensively.”
Rice’s pilot study proves it is possible to gather a lot of toxicity data at low cost, said Zhong, an assistant professor of biosciences, who has performed extensive studies on C. elegans, particularly on their gene networks. Materials alone for each assay, including the worms and the bacteria they consumed and the culture media, cost about 50 cents, she said.
The researchers used four assays to see how worms react to nanoparticles: fitness, movement, growth and lifespan. The most sensitive assay of toxicity was fitness. In this test, the researchers mixed the nanoparticles in solutions with the bacteria that worms consume. Measuring how much bacteria they ate over time served as a measure of the worms’ “fitness.”
“If the worms’ health is affected by the nanoparticles, they reproduce less and eat less,” Zhong said. “In the fitness assay, we monitor the worms for a week. That is long enough for us to monitor toxicity effects accumulated through three generations of worms.” C. elegans has a life cycle of about three days, and since each can produce many offspring, a population that started at 50 would number more than 10,000 after a week. Such a large number of tested animals also enabled the fitness assay to be highly sensitive.
The researchers’ “QuantWorm” system allowed fast monitoring of worm fitness, movement, growth and lifespan. In fact, monitoring the worms was probably the least time-intensive part of the project. Each nanomaterial required specific preparation to make sure it was soluble and could be delivered to the worms along with the bacteria. The chemical properties of each nanomaterial also needed to be characterized in detail.
The researchers studied a representative sampling of three classes of nanoparticles: metal, metal oxides and carbon-based. “We did not do polymeric nanoparticles because the type of polymers you can possibly have is endless,” Li explained.
They examined the toxicity of each nanoparticle at four concentrations. Their results showed C-60 fullerenes, fullerol (a fullerene derivative), titanium dioxide, titanium dioxide-decorated nanotubes and cerium dioxide were the least damaging to worm populations.
Their “fitness” assay confirmed dose-dependent toxicity for carbon black, single- and multiwalled carbon nanotubes, graphene, graphene oxide, gold nanoparticles and fumed silicon dioxide.
They also determined the degree to which surface chemistry affected the toxicity of some particles. While amine-functionalized multiwalled nanotubes proved highly toxic, hydroxylated nanotubes had the least toxicity, with significant differences in fitness, body length and lifespan.
A complete and interactive toxicity chart for all of the tested materials is available online.
Zhong said the method could prove its worth as a rapid way for drug or other companies to narrow the range of nanoparticles they wish to put through more expensive, dedicated toxicology testing.
“Next, we hope to add environmental variables to the assays, for example, to mimic ultraviolet exposure or river water conditions in the solution to see how they affect toxicity,” she said. “We also want to study the biological mechanism by which some particles are toxic to worms.”
Here’s a citation for the paper and links to the paper and to the researchers’ website,
Scientists are hoping they’ve found a better way to detect early signs of a heart attack according to a Jan. 15, 2015 news item on Nanotechnology Now,
NYU [New York University] Polytechnic School of Engineering professors have been collaborating with researchers from Peking University on a new test strip that is demonstrating great potential for the early detection of certain heart attacks.
Kurt H. Becker, a professor in the Department of Applied Physics and the Department of Mechanical and Aerospace Engineering, and WeiDong Zhu, a research associate professor in the Department of Mechanical and Aerospace Engineering, are helping develop a new colloidal gold test strip for cardiac troponin I (cTn-I) detection. The new strip uses microplasma-generated gold nanoparticles (AuNPs) and shows much higher detection sensitivity than conventional test strips. The new cTn-I test is based on the specific immune-chemical reactions between antigen and antibody on immunochromatographic test strips using AuNPs.
Compared to AuNPs produced by traditional chemical methods, the surfaces of the gold nanoparticles generated by the microplasma-induced liquid chemical process attract more antibodies, which results in significantly higher detection sensitivity.
cTn-I is a specific marker for myocardial infarction. The cTn-I level in patients experiencing cardiac infarction is several thousand times higher than in healthy people. The early detection of cTn-I is therefore a key factor of heart attack diagnosis and therapy.
The use of microplasmas to generate AuNP is yet another application of the microplasma technology developed by Becker and Zhu. Microplasmas have been used successfully in dental applications (improved bonding, tooth whitening, root canal disinfection), biological decontamination (inactivation of microorganisms and biofilms), and disinfection and preservation of fresh fruits and vegetables.
The microplasma-assisted synthesis of AuNPs has great potential for other biomedical and therapeutic applications such as tumor detection, cancer imaging, drug delivery, and treatment of degenerative diseases such as Alzheimer’s.
The routine use of gold nanoparticles in therapy and disease detection in patients is still years away: longer for therapeutic applications and shorter for biosensors. The biggest hurdle to overcome is the fact that the synthesis of monodisperse, size-controlled gold nanoparticles, even using microplasmas, is still a costly, time-consuming, and labor-intensive process, which limits their use currently to small-scale clinical studies, Becker explained.
For anyone curious about the more common chemical methods of producing gold nanoparticles, there’s this video produced in Australia by TechNyou Education. There’s a specific technique described which I believe is one of the most commonly used and I think this can be generalized to other gold nanoparticle chemical production processes,
One more thing, this video runs over my 5 min. policy limit for videos. To do this, I battled my inclination to include something that I think is useful for understanding more about nanoparticles and my desire to make sure that my blog doesn’t get too bloated.
There’s a Jan. 14, 2015 news item on Nanowerk from the Virginia Polytechnic Institute (Virginia Tech) which is largely a personal profile featuring some basic information (useful for those new to the topic) about airborne nanoparticles (Note: A link has been removed),
The Harvard educated undergraduate [Linsey Marr, professor of civil and environmental engineering, Virginia Tech] who obtained her Ph.D. from University of California at Berkeley and trained as a postdoctoral researcher with a Nobel laureate of chemistry at MIT is now among a handful of researchers in the world who are addressing concerns about engineered nanomaterials in the atmosphere.
Marr is part of the National Science Foundation’s Center for the Environmental Implications of Nanotechnology and her research group has characterized airborne nanoparticles at every point of their life cycle. This cycle includes production at a commercial manufacturing facility, use by consumers in the home, and disposal via incineration.
“Results have shown that engineered nanomaterials released into the air are often aggregated with other particulate matter, such as combustion soot or ingredients in consumer spray products, and that the size of such aggregates may range from smaller than 10 nanometers to larger than 10 microns,” Marr revealed. She was referring to studies completed by research group members Marina Quadros Vance of Florianopolis, Brazil, a research scientist with the Virginia Tech Institute of Critical Technology and Applied Science, and Eric Vejerano, of Ligao, Philippines, a post-doctoral associate in civil and environmental engineering.
Size matters if these aggregates are inhaled.
Another concern is the reaction of a nanomaterial such as a fullerene with ozone at environmentally relevant concentration levels. Marr’s graduate student, Andrea Tiwari, of Mankato, Minnesota, said the resulting changes in fullerene could lead to enhanced toxicity.
The story then segues into airborne pathogens and viruses eventually honing in on virus microbiomes and bacterial microbiomes (from the news release),
Marr is a former Ironman triathlete who obviously has strong interests in what she is breathing into her own body. So it would be natural for her to expand her study of engineered nanoparticles traveling in the atmosphere to focus on airborne pathogens.
She did so by starting to consider the influenza virus as an airborne pollutant. She applied the same concepts and tools used for studying environmental contaminants and ambient aerosols to the examination of the virus.
She looked at viruses as “essentially self-assembled nanoparticles that are capable of self-replication.”
Her research team became the first to measure influenza virus concentrations in ambient air in a children’s day care center and on airplanes. When they conducted their studies, the Virginia Tech researchers collected samples from a waiting room of a health care center, two toddlers’ rooms and one babies’ area of a childcare center, as well as three cross-country flights between Roanoke, Virginia., and San Francisco. They collected 16 samples between Dec. 10, 2009 and Apr. 22, 2010.
“Half of the samples were confirmed to contain aerosolized influenza A viruses,” Marr said. The childcare samples were the most infected at 75 percent. Next, airplane samples reached 67 percent contamination, and health center numbers came in at 33 percent.
This study serves as a foundation for new work started about a year ago in her lab.
Marr collaborated with Aaron J. Prussin II, of Blacksburg, Virginia, and they successfully secured for him a postdoctoral fellowship from the Alfred P. Sloan Foundation to characterize the bacterial and viral microbiome — the ecological community of microorganisms — of the air in a daycare center.
They are now attempting to determine seasonal changes of both the viral microbiome and the bacterial microbiome in a daycare setting, and examine how changes in the microbiome are related to naturally occurring changes in the indoor environment.
“Little is known about the viral component of the microbiome and it is important because viruses are approximately 10 times more abundant than bacteria, and they help shape the bacterial community. Research suggests that viruses do have both beneficial and harmful interactions with bacteria,” Prussin said.
With Prussin and Marr working together they hope to verify their hypothesis that daycare centers harbor unique, dynamic microbiomes with plentiful bacteria and viruses. They are also looking at what seasonal changes might bring to a daycare setting.
They pointed to the effect of seasonal changes because in previous work, Marr, her former graduate student Wan Yang, of Shantou, China, and Elankumaran Subbiah, a virologist in the biomedical sciences and pathobiology department of the Virginia-Maryland College of Veterinary Medicine, measured the influenza A virus survival rate at various levels of humidity.
Their 2012 study presented for the first time the relationship between the influenza A virus viability in human mucus and humidity over a large range of relative humidities, from 17 percent to 100 percent. They found the viability of the virus was highest when the relative humidity was either close to 100 percent or below 50 percent. The results in human mucus may help explain influenza’s seasonality in different regions.
According to the news release Marr and her colleagues have developed a fast and cheap technology for detection of airborne pathogens (Note: A link has been removed),
With the urgent need to understand the dynamics of airborne pathogens, especially as one considers the threats of bioterrorism, pandemic influenza, and other emerging infectious diseases, Marr said “a breakthrough technology is required to enable rapid, low-cost detection of pathogens in air.”
Along with Subbiah and Peter Vikesland, professor of civil and environmental engineering, they want to develop readily deployable, inexpensive, paper-based sensors for airborne pathogen detection.
In 2013 they received funding of almost $250,000 from Virginia Tech’s Institute for Critical Technology and Applied Science, a supporter of the clustering of research groups, to support their idea of creating paper-based sensors based on their various successes to date.
Marr explained the sensors “would use a sandwich approach. The bottom layer is paper containing specialized DNA that will immobilize the virus. The middle layer is the virus, which sticks to the specialized DNA on the bottom layer. The top layer is additional specialized DNA that sticks to the virus. This DNA is attached to gold nanoparticles that are easily detectable using a technique known as Raman microscopy.”
They key to their approach is that it combines high-tech with low-tech in the hopes of keeping the assay costs low. Their sampling method will use a bicycle pump, and low cost paper substrates. They hope that they will be able to incorporate smart-phone based signal transduction for the detection. Using this approach, they believe “even remote corners of the world” would be able to use the technique.
Vikesland previously received funding from the Gates Foundation to detect the polio virus via paper-based diagnostics. Polio is still found in countries on the continents of Asia and Africa.
I have previously mentioned Linsey Marr in an Oct. 18, 2013 post about the revival of the Nanotechnology Consumer Products Inventory (originally developed by the Project for Emerging Nanotechnologies) by academics at Virginia Tech and first mentioned CEINT in an Aug. 15, 2011 post about a special project featuring a mesocosm at Duke University (North Carolina).