Drug combination delivered by nanoparticles may help in melanoma treatment


Melenoma 170314140859_1_540x360Gavin Robertson, professor of pharmacology, pathology, dermatology, and surgery; director of the Penn State Melanoma and Skin Cancer Center and member of Penn State Cancer Institute, works with associates in the Melanoma Center.
Credit: Penn State College of Medicine

Summary: The first of a new class of medication that delivers a combination of drugs by nanoparticle may keep melanoma from becoming resistant to treatment, according to Penn State College of Medicine researchers.

CelePlum-777 combines a special ratio of the drugs Celecoxib, an anti-inflammatory, and Plumbagin, a toxin. By combining the drugs, the cells have difficulty overcoming the effect of having more than one active ingredient.

Celecoxib and Plumbagin work together to kill melanoma cells when used in a specific ratio. Researchers used microscopic particles called nanoparticles to deliver the drugs directly to the cancer cells. These particles are several hundred times smaller than the width of a hair and can be loaded with medications.

“Loading multiple drugs into nanoparticles is one innovative approach to deliver multiple cancer drugs to a particular site where they need to act and have them released at that optimal cancer cell killing ratio,” said Raghavendra Gowda, assistant professor of pharmacology, who is the lead author on the study. “Another advantage is that by combining the drugs, lower concentrations of each that are more effective and less toxic can be used.”

Celecoxib and Plumbagin cannot be taken by mouth because the drugs do not enter the body well this way and cannot be used together in the ratio needed because of toxicity.

CelePlum-777 can be injected intravenously without toxicity. Because of its small size, it also accumulates inside the tumors where it then releases the drugs to kill the cancer cells. Researchers report their results in the journals Molecular Cancer Therapeutics and Cancer Letters.

“This drug is the first of a new class, loaded with multiple agents to more effectively kill melanoma cells, that has potential to reduce the possibility of resistance development,” said senior author Gavin Robertson, professor of pharmacology, pathology, dermatology, and surgery; director of the Penn State Melanoma and Skin Cancer Center and member of Penn State Cancer Institute. “There is no drug like it in the clinic today and it is likely that the next breakthrough in melanoma treatment will come from a drug like this one.”

The researchers showed the results of CelePlum-777 on killing cancer cells growing in culture dishes and in tumors growing in mice following intravenous injection. The drug prevented tumor development in mice with no detectable side effects and also prevented proteins from enabling uncontrolled cancer cell growth.

More research is required by the Food and Drug Administration before CelePlum-777 can be tested in humans through clinical trials. Penn State has patented this discovery and licensed it to Cipher Pharmaceuticals, which will perform the next series of FDA-required tests.


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Materials provided by Penn State College of Medicine. Note: Content may be edited for style and length.

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New, carbon-nanotube tool for ultra-sensitive-early virus detection and identification (HIV/Aids – Ebola – Zika)



Scanning electron microscope image (scale bar, 200 nm) of the H5N2 avian influenza virus (purple) trapped inside the aligned carbon nanotube. Credit: Penn State University

A new tool that uses a forest-like array of vertically-aligned carbon nanotubes that can be finely tuned to selectively trap viruses by their size can increase the detection threshold for viruses and speed the process of identifying newly-emerging viruses. The research, by an interdisciplinary team of scientists at Penn State, is published in the October 7, 2016 edition of the journal Science Advances.

Detecting viruses early in an infection before symptoms appear, or from field samples, is difficult because the concentration of the viruses could be very low—often below the threshold of current detection methods,” said Mauricio Terrones, professor of physics, chemistry, and materials science and engineering at Penn State, and one of the corresponding authors of the research. 

Early detection is important because a virus can begin to spread before we have the ability to detect it

The device we have developed allows us to selectively trap and concentrate viruses by their size—smaller than human cells and bacteria, but larger than most proteins and other macromolecules—in incredibly dilute samples. It further increases our ability to detect small amounts of a virus by more than a hundred times.”

The research team developed and tested a small, portable device that increases the sensitivity of virus detection by trapping and concentrating viruses in an array of carbon nanotubes.

 Dilute samples collected from patients or the environment are passed through a filter to remove large particles such as bacteria and human cells, then through the array of carbon nanotubes in the device. Viruses get trapped and build up to usable concentrations within the forest of nanotubes, while other smaller particles pass through and are eliminated. 

The concentrated virus captured in the device can then be put through a panel of tests to identify it, including molecular diagnosis by polymerase chain reaction (PCR), immunological methods, virus isolation, and genome sequencing.


Illustration of size-based virus enrichment by the aligned carbon nanotube array. Credit: Penn State University

“Because our device isolates and concentrates viruses purely by size, we can capture viruses that we don’t know anything about biologically—we don’t need any antibody or other molecular label,” said Terrones. “Once we capture and concentrate the virus, we can then use other techniques such as whole-genome sequencing to characterize it.”

“Most lethal viral outbreaks in the past two decades were caused by newly emerging viruses. This size-based virus-enrichment technology can be particularly powerful in identification of emerging viruses and discovery of new viruses that do not have antibodies and sequence information available,” said Si-Yang Zheng, associate professor of biomedical engineering at Penn State, the other corresponding author on the paper. 

“Not only does our new technology enrich viruses by at least one hundred times, but it also removes host and environmental contaminants, and enables direct virus identification by next-generation sequencing from field-collected samples without virus culture.”
 

Viruses—such as influenza, HIV/AIDS, Ebola, and Zika—can cause sudden, unpredictable outbreaks that lead to severe public-health crises. Currently available techniques for isolating and identifying the viruses that cause these outbreaks are slow, expensive, and use equipment and reagents that can be expensive, bulky, and require specialized storage. 

Additionally, many recent outbreaks have been caused by newly emerging viruses for which there are no established ways to selectively isolate them for identification and characterization.

 

Tunable inter-tubular distance of carbon nanotubes for matching virus dimensions — Scale bars, top 100 nm middle 10 μm bottom 200 nm. Credit: Penn State University

“We developed the technology to grow a forest of nanotubes and we can control the distance between the trunks,” said Zheng. “The intertube distance can range from about 17 nanometers to over 300 nanometers to selectively capture viruses. 

The unique properties of the carbon-nanotube forest allow us to integrate it into a robust, scalable, and portable microdevice that can be adapted for use in the field without the need for bulky instruments and specialized storage of reagents.”

The researchers validated the ability of their newly developed device to capture viruses from dilute samples using known concentrations of previously identified viruses as well as field samples of emerging and unknown viruses. “We developed a portable platform to enrich and isolate viruses based on their physical sizes,” said Yin-Ting Yeh, a postdoctoral researcher at Penn State and first author of the paper. “This tunable size-based approach provides rapid virus enrichment directly from field samples without the use of antibodies. 

The device enables early detection of emerging diseases and potentially allows for vaccine development much sooner in the process of an outbreak.”

 Explore further: Sensing viruses by exploring their electrical properties

More information: “Tunable and label-free virus enrichment for ultrasensitive virus detection using carbon nanotube arrays,” Science Advances, advances.sciencemag.org/content/2/10/e1601026 

Journal reference: Science Advances  

Provided by: Pennsylvania State University  

Genesis Nanotechnology – “Great Things from Small Things”

Penn State: New clues could help scientists harness the power of photosynthesis


Photsynth 070716 newcluescoul.jpgThis illustration is a model of Chl f synthase, potentially a ChlF dimer, based on the known X-ray structure of the core of the Photosystem II reaction center. Photosystem II is the light-driven enzyme that oxidizes water to produce oxygen …more

Identification of a gene needed to expand light harvesting in photosynthesis into the far-red-light spectrum provides clues to the development of oxygen-producing photosynthesis, an evolutionary advance that changed the history of life on Earth. “Knowledge of how photosynthesis evolved could empower scientists to design better ways to use light energy for the benefit of mankind,” said Donald A. Bryant, the Ernest C. Pollard Professor of Biotechnology and professor of biochemistry and molecular biology at Penn State University and the leader of the research team that made the discovery.

This discovery, which could enable scientists to engineer crop plants that more efficiently harness the energy of the Sun, will be published online by the journal Science on Thursday July 7, 2016.

“Photosynthesis usually ranks about third after the origin of life and the invention of DNA in lists of the greatest inventions of evolution,” said Bryant. “Photosynthesis was such a powerful invention that it changed the Earth’s atmosphere by producing oxygen, allowing diverse and complex life forms—algae, plants, and animals—to evolve.”

The researchers identified the gene that converts chlorophyll a—the most abundant -absorbing pigment used by plants and other organisms that harness energy through —into chlorophyll f—a type of chlorophyll that absorbs light in the far-red range of the light spectrum. There are several different types of chlorophyll, each tuned to absorb light in different wavelengths. Most organisms that get their energy from photosynthesis use light in the visible range, wavelengths of about 400 to 700 nanometers. Bryant’s lab previously had shown that chlorophyll f allows certain cyanobacteria—bacteria that use photosynthesis and that are sometimes called blue-green algae—to grow efficiently in light just outside of the usual human visual range—far-red light (700 to 800 nanometers). The ability to use light wavelengths other than those absorbed by plants, algae, and other cyanobacteria confers a powerful advantage to those organisms that produce chlorophyll f—they can survive and grow when the visible light they normally use is blocked.

New clues could help scientists harness the power of photosynthesis
This illustration shows the newly discovered evolutionary scheme for the type-1 and type-2 reaction centers of photosynthesis. Reaction centers are protein machines that convert light energy into stable reductants that can be used by cells …more

 

“There is nearly as much energy in the far-red and near-infrared light that reaches the Earth from the Sun as there is in visible light,” said Bryant. “Therefore, the ability to extend in plants into this range would allow the plants to more efficiently use the energy from the Sun and could increase plant productivity.”

The gene the researchers identified encodes an enzyme that is distantly related to one of the main components of the protein machinery used in oxygen-producing photosynthesis. The researchers showed that the conversion of chlorophyll a to chlorophyll f requires only this one enzyme in a simple system that could represent an early intermediate stage in the evolution of photosynthesis. Understanding the mechanism by which the enzyme functions could provide clues that enable scientists to design better ways to use light energy.

“There is intense interest in creating as an alternative energy source,” said Bryant. “Understanding the evolutionary trajectory that nature used to create oxygen production in photosynthesis is one component that will help scientists design an efficient and effective system. The difficulty is that photosynthesis is an incredibly complex process with hundreds of components and, until now, there were few known intermediate stages in its evolution. The simple system that we describe in this paper provides a model that can be further manipulated experimentally for studying those early stages in the evolution of photosynthesis.”

By disabling the gene that encodes the enzyme in two cyanobacteria that normally produce chlorophyll f, the researchers demonstrated that the enzyme is required for the production of chlorophyll f. The experiment showed that, without this enzyme, these cyanobacteria could no longer synthesize chlorophyll f. By artificially adding the gene that encodes the enzyme, the researchers also showed that this one enzyme is all that is necessary to convert cyanobacteria that normally do not produce chlorophyll f into ones that can produce it.

Another clue that the newly identified enzyme could represent an early stage in the evolution of photosynthesis is that the enzyme requires light to catalyze its reaction and may not require oxygen, as scientists had previously suspected. “Because the enzyme that synthesizes chlorophyll f requires light but may not require oxygen for its activity, it is possible that it evolved before Photosystem II, the photosynthetic complex that produces oxygen and to which the enzyme is related. If the enzyme is an evolutionary predecessor of Photosystem II, then evolution borrowed an enzyme that was originally used for synthesis and used it to evolve an that could produce oxygen, which ultimately led to changes in Earth’s atmosphere,” said Bryant.

Explore further: Hot-spring bacteria reveal ability to use far-red light for photosynthesis

More information: “Light-dependent chlorophyll f synthase is a highly divergent paralog of PsbA of photosystem II,” Science, science.sciencemag.org/cgi/doi/10.1126/science.aaf9178

 

Penn State: Biomimetic Membranes that Self-Assemble for Water Filtration


Penn St Water M id40923A synthetic membrane that self assembles and is easily produced may lead to better gas separation, water purification, drug delivery and DNA recognition, according to an international team of researchers. This biomimetic membrane is composed of lipids — fat molecules — and protein-appended molecules that form water channels that transfer water at the rate of natural membranes, and self-assembles into 2-dimensional structures with parallel channels.

“Nature does things very efficiently and transport proteins are amazing machines present in biological membranes,” said Manish Kumar, assistant professor of chemical engineering, Penn State. “They have functions that are hard to replicate in synthetic systems.”
The researchers developed a second-generation synthetic water channel that improves on earlier attempts to mimic aquaporins – natural water channel proteins — by being more stable and easier to manufacture. The peptide-appended pillar[5]arenes (PAP) are also more easily produced and aligned than carbon nanotubes, another material under investigation for membrane separation. Kumar and co-authors report their development in a recent issue of the Proceedings of the National Academy of Science (“Highly permeable artificial water channels that can self-assemble into two-dimensional arrays”).

Penn St Water M id40923

An artificial analogue of the water channel protein, aquaporin, was shown to have permeabilities approaching that of aquaporins and carbon nanotubes. They also arrange in tight two dimensional arrays. (Image: Karl Decker / University of Illinois at Urbana-Champaign, and Yuexiao Shen / Penn State)

“We were surprised to see transport rates approaching the ‘holy grail’ number of a billion water molecules per channel per second,” said Kumar. “We also found that these artificial channels like to associate with each other in a membrane to make 2-dimentional arrays with a very high pore density.”
The researchers consider that the PAP membranes are an order of magnitude better than the first-generation artificial water channels reported to date. The propensity for these channels to automatically form densely packed arrays leads to a variety of engineering applications.
“The most obvious use of these channels is perhaps to make highly efficient water purification membranes,” said Kumar.
Source: Penn State

Scientists use ‘smallest possible diamonds’ to form ultra-thin nanothreads: Video: Will A Space Elevator Be Possible?


Diamonds 10-scientistsusFor the first time, scientists have discovered how to produce ultra-thin “diamond nanothreads” that promise extraordinary properties, including strength and stiffness greater than that of today’s strongest nanotubes and polymers. A paper describing this discovery by a research team led by John V. Badding, a professor of chemistry at Penn State, was published in the Sept. 21 issue of the journal Nature Materials.

“From a fundamental-science point of view, our discovery is intriguing because the threads we formed have a structure that has never been seen before,” Badding said. The core of the nanothreads that Badding’s team made is a long, thin strand of arranged just like the fundamental unit of a diamond’s structure—zig-zag “cyclohexane” rings of six carbon atoms bound together, in which each carbon is surrounded by others in the strong triangular-pyramid shape of a tetrahedron. “It is as if an incredible jeweler has strung together the smallest possible diamonds into a long miniature necklace,” Badding said. “Because this thread is diamond at heart, we expect that it will prove to be extraordinarily stiff, extraordinarily strong, and extraordinarily useful.”

The team’s discovery comes after nearly a century of failed attempts by other labs to compress separate carbon-containing molecules like liquid benzene into an ordered, diamond-like nanomaterial. “We used the large high-pressure Paris-Edinburgh device at Oak Ridge National Laboratory to compress a 6-millimeter-wide amount of benzene—a gigantic amount compared with previous experiments,” said Malcolm Guthrie of the Carnegie Institution for Science, a co-author of the research paper. “We discovered that slowly releasing the pressure after sufficient compression at normal room temperature gave the carbon atoms the time they needed to react with each other and to link up in a highly ordered chain of single-file carbon tetrahedrons, forming these diamond-core nanothreads.”

John Badding, professor of chemistry at Penn State, leads a research team that has discovered how to produce super-strong, super-thin “diamond nanothreads” that promise extraordinary properties such as strength and stiffness higher than that of carbon nanotubes or conventional high-strength polymers.

Badding’s team is the first to coax molecules containing carbon atoms to form the strong tetrahedron shape, then link each tetrahedron end to end to form a long, thin nanothread. He describes the thread’s width as phenomenally small, only a few atoms across, hundreds of thousands of times smaller than an optical fiber, enormously thinner that an average human hair. “Theory by our co-author Vin Crespi suggests that this is potentially the strongest, stiffest material possible, while also being light in weight,” he said.

Diamonds 10-scientistsus

The molecule they compressed is benzene—a flat ring containing six carbon atoms and six hydrogen atoms. The resulting diamond-core nanothread is surrounded by a halo of . During the compression process, the scientists report, the flat benzene molecules stack together, bend and break apart. Then, as the researchers slowly release the pressure, the atoms reconnect in an entirely different yet very orderly way. The result is a structure that has carbon in the tetrahedral configuration of diamond with hydrogens hanging out to the side and each tetrahedron bonded with another to form a long, thin, nanothread.

“It really is surprising that this kind of organization happens,” Badding said. “That the atoms of the benzene molecules link themselves together at room temperature to make a thread is shocking to chemists and physicists. Considering earlier experiments, we think that, when the benzene molecule breaks under very high pressure, its atoms want to grab onto something else but they can’t move around because the pressure removes all the space between them. This benzene then becomes highly reactive so that, when we release the pressure very slowly, an orderly polymerization reaction happens that forms the diamond-core nanothread.”

The scientists confirmed the structure of their diamond nanothreads with a number of techniques at Penn State, Oak Ridge, Arizona State University and the Carnegie Institution for Science, including X-ray diffraction, neutron diffraction, Raman spectroscopy, first-principle calculations, transmission electron microscopy and solid-state nuclear magnetic resonance (NMR). Parts of these first diamond nanothreads appear to be somewhat less than perfect, so improving their structure is a continuing goal of Badding’s research program. He also wants to discover how to make more of them. “The high pressures that we used to make the first diamond nanothread material limit our production capacity to only a couple of cubic millimeters at a time, so we are not yet making enough of it to be useful on an industrial scale,” Badding said. “One of our science goals is to remove that limitation by figuring out the chemistry necessary to make these diamond nanothreads under more practical conditions.”

The nanothread also may be the first member of a new class of diamond-like nanomaterials based on a strong tetrahedral core. “Our discovery that we can use the natural alignment of the benzene molecules to guide the formation of this new diamond nanothread material is really interesting because it opens the possibility of making many other kinds of molecules based on carbon and hydrogen,” Badding said. “You can attach all kinds of other atoms around a core of carbon and hydrogen. The dream is to be able to add other atoms that would be incorporated into the resulting nanothread. By pressurizing whatever liquid we design, we may be able to make an enormous number of different materials.”

                                          Credit: Enshi Xu, Vincent H Crespi lab, Penn State

Potential applications that most interest Badding are those that would be vastly improved by having exceedingly strong, stiff and light materials—especially those that could help to protect the atmosphere, including lighter, more fuel-efficient and therefore less-polluting vehicles. “One of our wildest dreams for the nanomaterials we are developing is that they could be used to make the super-strong, lightweight cables that would make possible the construction of a “space elevator”, which so far has existed only as a science-fiction idea,” Badding said.

Explore further: Smallest possible diamonds form ultra-thin nanothreads

Space Elevators? Super Strong Materials? All from Diamonds Ultra-Thin Nanothreads


Nano Diamonds 201409229914891For the first time, scientists have discovered how to produce ultra-thin “diamond nanothreads” that promise extraordinary properties, including strength and stiffness greater than that of today’s strongest nanotubes and polymers. A paper describing this discovery by a research team led by John V. Badding, a professor of chemistry at Penn State University, will be published in the 21 September 2014 issue of the journal Nature Materials. “From a fundamental-science point of view, our discovery is intriguing because the threads we formed have a structure that has never been seen before,” Badding said.

The core of the nanothreads that Badding’s team made is a long, thin strand of carbon atoms arranged just like the fundamental unit of a diamond’s structure — zig-zag “cyclohexane” rings of six carbon atoms bound together, in which each carbon is surrounded by others in the strong triangular-pyramid shape of a tetrahedron. “It is as if an incredible jeweler has strung together the smallest possible diamonds into a long miniature necklace,” Badding said. “Because this thread is diamond at heart, we expect that it will prove to be extraordinarily stiff, extraordinarily strong, and extraordinarily useful.”

The team’s discovery comes after nearly a century of failed attempts by other labs to compress separate carbon-containing molecules like liquid benzene into an ordered, diamondlike nanomaterial. “We used the large high-pressure Paris-Edinburgh device at Oak Ridge National Laboratory to compress a 6-millimeter-wide amount of benzene — a gigantic amount compared with previous experiments,” said Malcolm Guthrie of the Carnegie Institution for Science, a coauthor of the research paper. “We discovered that slowly releasing the pressure after sufficient compression at normal room temperature gave the carbon atoms the time they needed to react with each other and to link up in a highly ordered chain of single-file carbon tetrahedrons, forming these diamond-core nanothreads.” Nano Diamond 2 201409229914890

Badding’s team is the first to coax molecules containing carbon atoms to form the strong tetrahedron shape, then link each tetrahedron end to end to form a long, thin nanothread. He describes the thread’s width as phenomenally small, only a few atoms across, hundreds of thousands of times smaller than an optical fiber, enormously thinner that an average human hair. “Theory by our co-author Vin Crespi suggests that this is potentially the strongest, stiffest material possible, while also being light in weight,” he said.

The molecule they compressed is benzene — a flat ring containing six carbon atoms and six hydrogen atoms. The resulting diamond-core nanothread is surrounded by a halo of hydrogen atoms. During the compression process, the scientists report, the flat benzene molecules stack together, bend, and break apart. Then, as the researchers slowly release the pressure, the atoms reconnect in an entirely different yet very orderly way. The result is a structure that has carbon in the tetrahedral configuration of diamond with hydrogens hanging out to the side and each tetrahedron bonded with another to form a long, thin, nanothread.

“It really is surprising that this kind of organization happens,” Badding said. “That the atoms of the benzene molecules link themselves together at room temperature to make a thread is shocking to chemists and physicists. Considering earlier experiments, we think that, when the benzene molecule breaks under very high pressure, its atoms want to grab onto something else but they can’t move around because the pressure removes all the space between them. This benzene then becomes highly reactive so that, when we release the pressure very slowly, an orderly polymerization reaction happens that forms the diamond-core nanothread.”

The scientists confirmed the structure of their diamond nanothreads with a number of techniques at Penn State, Oak Ridge, Arizona State University, and the Carnegie Institution for Science, including X-ray diffraction, neutron diffraction, Raman spectroscopy, first-principle calculations, transmission electron microscopy, and solid-state nuclear magnetic resonance (NMR). Parts of these first diamond nanothreads appear to be somewhat less than perfect, so improving their structure is a continuing goal of Badding’s research program. He also wants to discover how to make more of them. “The high pressures that we used to make the first diamond nanothread material limit our production capacity to only a couple of cubic millimeters at a time, so we are not yet making enough of it to be useful on an industrial scale,” Badding said. “One of our science goals is to remove that limitation by figuring out the chemistry necessary to make these diamond nanothreads under more practical conditions.”

The nanothread also may be the first member of a new class of diamond-like nanomaterials based on a strong tetrahedral core. “Our discovery that we can use the natural alignment of the benzene molecules to guide the formation of this new diamond nanothread material is really interesting because it opens the possibility of making many other kinds of molecules based on carbon and hydrogen,” Badding said. “You can attach all kinds of other atoms around a core of carbon and hydrogen. The dream is to be able to add other atoms that would be incorporated into the resulting nanothread. By pressurizing whatever liquid we design, we may be able to make an enormous number of different materials.”

Potential applications that most interest Badding are those that would be vastly improved by having exceedingly strong, stiff, and light materials — especially those that could help to protect the atmosphere, including lighter, more fuel-efficient, and therefore less-polluting vehicles. “One of our wildest dreams for the nanomaterials we are developing is that they could be used to make the super-strong, lightweight cables that would make possible the construction of a “space elevator,” which so far has existed only as a science-fiction idea,” Badding said.

In addition to Badding at Penn State and Guthrie at the Carnegie Institution, other members of the research team include George D. Cody at the Carnegie Institution, Stephen K. Davidowski, at Arizona State, and Thomas C. Fitzgibbons, En-shi Xu, Vincent H. Crespi, and Nasim Alem at Penn State. Penn State affiliations include the Department of Chemistry, the Materials Research Institute, the Department of Physics, and the Department of Materials Science and Engineering. This research received financial support as part of the Energy Frontier Research in Extreme Environments (EFree) Center, and Energy Frontier Research Center funded by the U.S. Department of Energy (Office of Science award #DE-SC0001057).

Source: Penn State

Genesis Nanotech Headlines Are Out!


Organ on a chip organx250Genesis Nanotech Headlines Are Out! Read All About It!

https://paper.li/GenesisNanoTech/1354215819#!headlines

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SUBCOMMITTE EXAMINES BREAKTHROUGH NANOTECHNOLOGY OPPORTUNITIES FOR AMERICA

Chairman Terry: “Nanotech is a true science race between the nations, and we should be encouraging the transition from research breakthroughs to commercial development.”

WASHINGTON, DCThe Subcommittee on Commerce, Manufacturing, and Trade, chaired by Rep. Lee Terry (R-NE), today held a hearing on:

“Nanotechnology: Understanding How Small Solutions Drive Big Innovation.”

 

 

electron-tomography

“Great Things from Small Things!” … We Couldn’t Agree More!

 

NIST: Ultrasonically Propelled Nanorods Spin at Controlled High Speed: Applications Inside the Body and for Machining and Mixing


NIST Spin Rods 14CNST004_nanorod_LR_1Vibrate a solution of rod-shaped metal nanoparticles in water with ultrasound and they’ll spin around their long axes like tiny drill bits. Why? No one yet knows exactly. But researchers at the National Institute of Standards and Technology (NIST) have clocked their speed—and it’s fast. At up to 150,000 revolutions per minute, these nanomotors rotate 10 times faster than any nanoscale object submerged in liquid ever reported.

The discovery of this dizzying rate has opened up the possibility that they could be used not only for moving around inside the body—the impetus for the research—but also for high-speed machining and mixing.

Scientists have been studying how to make nanomotors move around in liquids for the past several years. A group at Penn State looking for a biologically friendly way to propel nanomotors first observed that metal nanorods were moving and rotating in response to ultrasound in 2012. Another group at the University of California San Diego then directed the metal rods’ forward motion using a magnetic field. The Penn State group then demonstrated that these nanomotors could be propelled inside of a cancer cell.

But no one knew why or how fast the nanomotors were spinning. The latter being a measurement problem, researchers at NIST worked with the Penn State group to solve it.

“If nanomotors are to be used in a biological environment, then it is important to understand how they interact with the liquid and objects around them,” says NIST project leader Samuel Stavis. “We used nanoparticles to trace the flow of water around the nanomotors, and we used that measurement to infer their rate of rotation. We found that the nanomotors were spinning surprisingly rapidly.”

14CNST004_nanorod_LR
Inference of nanorod rotation: A nanoparticle traces the microvortical flow around a nanorod rotating at up to 150,000 RPM propelled by ultrasound.
Credit: Balk/NIST
View hi-resolution image

The NIST team clocked the nanomotors’ rotation by mixing the 2-micrometer-long, 300-nanometer-wide gold rods with 400-nanometer-diameter polystyrene beads in water and putting them between glass and silicon plates with a speaker-type shaker beneath. They then vibrated the shaker at an ultrasonic tone of 3 megahertz—much too high for you or your dog to hear—and watched the motors and beads move.

As the motors rotate in water, they create a vortex around them. Beads that get close get swept up by the vortex and swirl around the rods. By measuring how far the beads are from the rods and how fast they move, the group was able to work out how quickly the motors were spinning—with an important caveat.

“The size of the nanorods is important in our measurements” says NIST physicist Andrew Balk. “We found that even small variations in the rod’s dimensions cause large measurement uncertainties, so they need to be fabricated as uniformly as possible for future studies and applications.”

According to the researchers, the speed of the nanomotors’ rotation seems to be independent of their forward motion. Being able to control the “speed and feed” of the nanomotors independently would open up the possibility that they could be used as rotary tools for machining and mixing.

Future avenues of research include trying to discover exactly why the motors rotate and how the vortex around the rods affects their interactions with each other.

*A.L. Balk, L.O. Mair, P.P. Mathai, P.N. Patrone, W.Wang, S. Ahmed, T.E. Mallouk, J.A. Liddle and S.M. Stavis. Kilohertz rotation of nanorods propelled by ultrasound, traced by microvortex advection of nanoparticles. ACS Nano, Articles ASAP (As Soon As Publishable) Publication Date (Web): July 14, 2014. DOI: 10.1021/nn502753x.

The Promise of Graphene


2-grapheneDraw a line with a pencil and it’s likely that somewhere along that black smudge is a material that earned two scientists the 2010 Nobel Prize in Physics. The graphite of that pencil tip is simply multiple layers of carbon atoms; where those layers are only one atom thick, it is known as graphene. The properties of a material change at the nanoscopic scale, making graphene the strongest and most conductive substance known.

Instead of marking mini-golf scores on paper, this form of carbon is suited for making faster and smaller electronic circuitry, flexible touchscreens, chemical sensors, diagnostic devices, and applications yet to be imagined. Graphene is not yet as ubiquitous as plastic or silicon, however, and producing the material in bulk remains a challenge. Because graphene’s properties rely on it being only one atom thick, until recently, it was only possible to make it in small patches or flakes. Physicists at Penn have discovered a way around these limitations, and have spun out their research into a company called Graphene Frontiers.

Graphene Frontiers’ technology was developed by A.T. Charlie Johnson, director of Penn’s Nano/Bio Interface Center and a professor in the Department of Physics and Astronomy in Penn Arts & Sciences, along with Zhengtang Luo, a former postdoctoral researcher in Johnson’s lab. They founded the company in 2011 through the Penn Center for Innovation’s UPstart program, which serves as a business incubator for technologies developed at the University. UPstart connected the researchers with Michael Patterson, then a member of the Wharton Executive MBA program, and now the company’s CEO.

 

 
Read more: Pushing the frontiers of a new material (w/video)

Flexible electronics could transform the way we make and use electronic devices


Flexible electronics open the door to foldaway smartphone displays, solar cells on a roll of plastic and advanced medical devices — if we can figure out how to make them.

QDOTS imagesCAKXSY1K 8Nearly everyone knows what the inside of a computer or a mobile phone looks like: A stiff circuit board, usually green, crammed with chips, resistors, capacitors and sockets, interconnected by a suburban sprawl of printed wiring.

But what if our printed circuit board was not stiff, but flexible enough to bend or even fold?

It may sound like an interesting laboratory curiosity, but not to Enrique Gomez, an assistant professor of chemical engineering at Penn State. “It could transform the way we make and use electronic devices,” he says.

Gomez is one of many scientists investigating flexible electronics at the University’s Materials Research Institute. Others are doing the same at universities and corporations around the world.

Flexible electronics are in vogue for two reasons.

First, they promise an entirely new design tool. Imagine, for example, tiny smartphones that wrap around our wrists, and flexible displays that fold out as large as a television. Or photovoltaic cells and reconfigurable antennas that conform to the roofs and trunks of our cars. Or flexible implants that can monitor and treat cancer or help paraplegics walk again.

Penn State’s interest in flexible and printed electronics is not just theoretical. In October 2011, the University began a multi-year research project with Dow Chemical Corporation. Learn more about the partnership.

Second, flexible electronics might cost less to make. Conventional semiconductors require complex processes and multi-billion dollar foundries. Researchers hope to print flexible electronics on plastic film the same way we print ink on newspapers.

“If we could make flexible electronics cheap enough, you could have throwaway electronics. You could wear your phone on your clothing, or run a bioassay to assess your health simply by wiping your nose with a tissue,” Gomez says.

Before any of this happens, though, researchers have to rethink what they know about electronics.

Victim of Success

That means understanding why conventional electronics are victims of their own success, says Tom Jackson, Kirby Chair Professor of Electrical Engineering. Jackson should know, because he helped make them successful. Before joining Penn State in 1992, he worked on IBM‘s industry-leading laptop displays. At Penn State, he pioneered the use of organic molecules to make transistors and electronic devices.

Modern silicon processors integrate billions of transistors, the semiconductor version of an electrical switch on tiny slivers of crystalline silicon.

Squeezing so many transistors in a common location enables them to handle complex problems. As they shrink in size, not only can we fit more transistors on a chip, but the chip gets less expensive to manufacture.

“It is hard to overstate how important this has been,” Jackson explains.

“Remember when we paid for long-distance phone calls by the minute? High-speed switching drove those costs way down. In some cases, we can think of computation as free. You can buy an inexpensive calculator at a store for $1, and the chip doesn’t even dominate the cost. The power you get is amazing.”

That, says Jackson, is the problem. Semiconductor processors are so good and so cheap, we fall into the trap of thinking they can solve every problem.

Sometimes, it takes more flexibility to succeed.

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Consider surgery to remove a tumor from a patient’s liver. Even after following up with radiation or chemotherapy, the surgeon is never sure if the treatment was successful.

“But suppose I could apply a flexible circuit to the liver and image the tissue. If we see a new malignancy, it could release a drug directly onto that spot, or heat up a section of the circuit to kill the malignant cells. And when we were done, the body would resorb the material,” Jackson says.

“What I want,” he says, “is something that matches the flexibility and thermal conductivity of the body.” Conventional silicon technology is too stiff and thermally conductive to work.

Similarly, large, flexible sensors could monitor vibrations on a bridge or windmill blade and warn when they needed maintenance.

“If you want to spread 100 or 1,000 sensors over a large area, you have to ask whether you want to place all the chips you need to do that, or use low-cost flexible electronics that I can apply as a single printed sheet,” Jackson says.

None of the flexible electronics now under development would match the billions of transistors that now fit on silicon chips, or their billions of on-off cycles per second. They would not have to. After all, even today’s fastest televisions refresh their displays only 240 times per second. That is more than fast enough to image cancer in the body, reconfigure an antenna, or assess the stability of a bridge.

So how, exactly, do we make flexible electronics, and what kind of materials do we make them from?

Printing

To explain what draws researchers to printing flexible electronics, Jackson walks through the production of flat panel displays in a $2-3 billion factory.

The process starts with a 100-square-foot plate of glass. To apply wires, the factory coats the entire plate with metal, then covers it with a photosensitive material called a resist. An extremely bright light flashes the pattern of the wires onto the coating, hardening the resist. In a series of steps, the factory removes the unhardened resist and metal under it. Then, in another series of steps, it removes the hardened resist, leaving behind the patterned metal wires.

Factories repeat some variant of this process four or five times as they add light-emitting diodes (LEDs), transistors and other components. With each step, they coat the entire plate and wash away unused materials. While the cost of a display is 70 percent that of a finished device, most of those materials get thrown away.

None of the flexible electronics now under development would match the billions of transistors that now fit on silicon chips, or their billions of on-off cycles per second. They would not have to.

“So it’s worth thinking about whether we can do this by putting materials where we need them, and reduce the cost of chemicals and disposal. It is a really simple idea and really hard to do,” Jackson says.

An ideal way to do that, most researchers agree, would be to print the electronics on long plastic sheets as they move through a factory. A printer would do this by applying different inks onto the film. As the inks dried, they would turn into wires, transistors, capacitors, LEDs and all the other things needed to make displays and circuits.

That, at least, is the theory. The problem, as anyone who ever looked at a blurry newspaper photograph knows, is that printing is not always precise. Poor alignment would scuttle any electronic device. Some workarounds include vaporizing or energetically blasting materials onto a flexible sheet, though this complicates processing.

And then, of course, there are the materials. Can we print them? How do we form the precise structures we need? And how do we do dry and process them at temperatures low enough to keep from melting the plastic film?

Material World

Fortunately, there are many possible materials from which to choose. These range from organic materials, like polymers and small carbon-based molecules, to metals and even ceramics.

At first glance, flexible ceramics seem like a stretch. Metals bend, and researchers can often apply them as zigzags so they deform more easily.

Try flexing a thick ceramic, though, and it cracks. Yet that has not deterred Susan Trolier-McKinstry, a professor of ceramic science and engineering and director of Penn State’s W.M. Keck Smart Materials Integration Laboratory.

Ceramics, she explains, are critical ingredients in capacitors, which can be used to regulate voltage in electronic circuits. In many applications, transistors use capacitors to provide instantaneous power rather than waiting for power from a distant source.

Industry makes capacitors from ultrafine powders. The tiniest layer thicknesses are 500 nanometers, 40 times smaller than a decade or two ago. Even so, there is scant room for them on today’s overcrowded circuit boards, especially in smartphones. Furthermore, there is a question about how long industry can continue to scale the thickness in multilayer ceramic capacitors.

Trolier-McKinstry thinks she can deposit smaller capacitors directly onto flexible sheets of plastic, and sandwich these in flexible circuit board. That way, the capacitors do not hog valuable surface area.

One approach is to deposit a precursor to the capacitor from a solution onto a plastic film and spot heat each capacitor with a laser to remove the organics and crystallize the ceramic into a capacitor. Another approach is to use a high-energy laser beam to sand blast molecules off a solid ceramic and onto a plastic substrate.

As long as she can keep capacitor thicknesses small, Trolier-McKinstry need not worry too much about capacitor flexibility. Previous researchers have demonstrated that it is possible to bend some electroceramic films around the radius of a Sharpie pen without damage.

Of course, not every element placed on a flexible substrate will be small. So what happens if your transistors need to bend?

One way to solve that problem is to make electronics from organic materials like plastics. These are the ultimate flexible materials. While most organics are insulators, a few are conductive.

“Organic molecules have tremendous chemical versatility,” Gomez explains. “My group’s goal is to turn these molecules into transistors and photovoltaic cells.” Easier said than done. The almost infinite number of possibilities available in organic chemistry, he says, make it challenging to find the right combination of structure, properties and function to create an effective device.

Molecules may not be picky about their neighbors, but they still need to form the right type of structures to act as switches or turn light into electricity. Gomez attacks the problem by using a technique called self-assembly. It starts with block copolymers, combinations of two molecules with different properties bound together in the middle.

Trolier-McKinstry thinks she can deposit smaller capacitors directly onto flexible sheets of plastic, and sandwich these in flexible circuit boards. That way, the capacitors do not hog valuable surface area.

“Think of them as a dog and a cat tied together by their tails,” Gomez explains. “Ordinarily, they want to run away from each other, but now they can’t. Then we throw them into a room with other tied dogs and cats. What happens is that all the cats wind up on one side of the room and the dogs on the other, so they don’t have to look at each other.”

Gomez believes this process could enable him to build molecules programmed to self-assemble into electronic structures at very low cost.

“The overarching problem,” Gomez continues, “is figuring out how to design the molecule and then tickle it with pressure, temperature and electrical fields to form useful structures. We don’t really understand enough to do that yet.”

Despite the challenge, flexible electronics promise changes that go beyond folding displays, inexpensive solar cells, antennas and sensors. They could veer off in some unexpected directions, such as helping paraplegics walk again.

Mimicking Jell-O

That is the goal of Bruce Gluckman, associate director of Penn State’s Center for Neural Engineering. To get there, he must learn how the brain’s neurons collaborate.

“Computations happen at the level of single neurons that connect to other neurons. Half the brain is made up of the wiring for these connections, and any cell can connect to a cell next to it or to a cell across the brain. It’s not local in any sense,” he explains.

Scientists measure the electrical activity of neurons by implanting silicon electrodes into the brain. Unfortunately, Gluckman says, the brain is as spongy as Jell-O and the electrode is as stiff as a knife.

Plunging the electrode into the brain causes damage immediately. Every time the subject moves its head, the brain pulls away from the electrode on one side and makes better contact on the other. It takes racks of electronics to separate the signal from the noise of such inconsistent output.

“This is why we need something other than silicon,” Gluckman says.

Despite the challenge, flexible electronics promise changes that go beyond folding displays, inexpensive solar cells, antennas and sensors. They could veer off in some unexpected directions, such as helping paraplegics walk again.

Flexible electronics would better match the brain’s springiness. While some researchers are looking at all-organic electrodes, Gluckman believes they are too large and too slow to achieve the resolution he needs. Instead, he has teamed with Jackson to develop a flexible electrode based on zinc oxide, a faster semiconductor that can be deposited on plastic at low temperatures.

The work is still in its early stages, but Gluckman believes they can develop a reliable electrode that lasts for years and produces stronger, clearer signals.

Researchers have already demonstrated that humans can control computer cursors, robotic arms and even artificial voice boxes with today’s problematic electrodes. Yet the results are often short-lived.

“No one is going to let you operate on their brain twice,” Gluckman says. “If you want to directly animate limbs with an implant, the implant has to last the life of the patient. If we can do that, we can enable paraplegics to get around on their own.”

As Jackson notes, computers and smartphones may have powered silicon’s development, but the results are visible in everything from cars and digital thermometers to toys and even greeting cards.

Displays and solar cells are likely to power the new generation of flexible electronics, but brain implants are just one of the many unexpected directions they may take.

Enrique Gomez is assistant professor of chemical engineering, edg12@psu.edu. Thomas N. Jackson is Kirby Chair Professor of Electrical Engineering, tnj1@psu.edu. Susan Trolier-McKinstry is professor of ceramic science and engineering and director of the W.M. Keck Smart Materials Integration Laboratory, STMcKinstry@psu.edu. Bruce Gluckman is associate director of Penn State’s Center for Neural Engineering, bjg18@psu.edu.