A new nanoparticle technique to make drugs more soluble

Before Ibuprofen can relieve your headache, it has to dissolve in your bloodstream. The problem is Ibuprofen, in its native form, isn’t particularly soluble. Its rigid, crystalline structures — the molecules are lined up like soldiers at roll call — make it hard to dissolve in the bloodstream. To overcome this, manufacturers use chemical additives to increase the solubility of Ibuprofen and many other drugs, but those additives also increase cost and complexity. The key to making drugs by themselves more soluble is not to give the molecular soldiers time to fall in to their crystalline structures, making the particle unstructured or amorphous. Researchers from Harvard John A. Paulson School of Engineering and Applied Science (SEAS) have developed a new system that can produce stable, amorphous nanoparticles in large quantities that dissolve quickly. But that’s not all. The system is so effective that it can produce amorphous nanoparticles from a wide range of materials, including for the first time, inorganic materials with a high propensity towards crystallization, such as table salt. These unstructured, inorganic nanoparticles have different electronic, magnetic and optical properties from their crystalized counterparts, which could lead to applications in fields ranging from materials engineering to optics. David A. Weitz, Mallinckrodt Professor of Physics and Applied Physics and an associate faculty member of the Wyss Institute for Biologically Inspired Engineering at Harvard, describes the research in a paper published today in ("Production of amorphous nanoparticles by supersonic spray-drying with a microfluidic nebulator"). “This is a surprisingly simple way to make amorphous nanoparticles from almost any material,” said Weitz. “It should allow us to quickly and easily explore the properties of these materials. In addition, it may provide a simple means to make many drugs much more useable.” The technique involves first dissolving the substances in good solvents, such as water or alcohol. The liquid is then pumped into a nebulizer, where compressed air moving twice the speed of sound sprays the liquid droplets out through very narrow channels. It’s like a spray can on steroids. The droplets are completely dried between one to three microseconds from the time they are sprayed, leaving behind the amorphous nanoparticle. At first, the amorphous structure of the nanoparticles was perplexing, said Esther Amstad, a former postdoctoral fellow in Weitz’ lab and current assistant professor at EPFL in Switzerland. Amstad is the paper’s first author. Then, the team realized that the nebulizer’s supersonic speed was making the droplets evaporate much faster than expected. “If you’re wet, the water is going to evaporate faster when you stand in the wind,” said Amstad. “The stronger the wind, the faster the liquid will evaporate. A similar principle is at work here. This fast evaporation rate also leads to accelerated cooling. Just like the evaporation of sweat cools the body, here the very high rate of evaporation causes the temperature to decrease very rapidly, which in turn slows down the movement of the molecules, delaying the formation of crystals.” These factors prevent crystallization in nanoparticles, even in materials that are highly prone to crystallization, such as table salt. The amorphous nanoparticles are exceptionally stable against crystallization, lasting at least seven months at room temperature. The next step, Amstad said, is to characterize the properties of these new inorganic amorphous nanoparticles and explore potential applications. “This system offers exceptionally good control over the composition, structure, and size of particles, enabling the formation of new materials,” said Amstad. “ It allows us to see and manipulate the very early stages of crystallization of materials with high spatial and temporal resolution, the lack of which had prevented the in-depth study of some of the most prevalent inorganic biomaterials. This systems opens the door to understanding and creating new materials.”
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Successful boron-doping of graphene nanoribbon

Physicists at the University of Basel succeed in synthesizing boron-doped graphene nanoribbons and characterizing their structural, electronic and chemical properties. The modified material could potentially be used as a sensor for the ecologically damaging nitrogen oxides, scientists report in the latest issue of ("Atomically controlled substitutional boron-doping of graphene nanoribbons"). Graphene nanoribbon Graphene nanoribbon under the microscope. (Image: University of Basel) Graphene is one of the most promising materials for improving electronic devices. The two-dimensional carbon sheet exhibits high electron mobility and accordingly has excellent conductivity. Other than usual semiconductors, the material lacks the so-called band gap, an energy range in a solid where no electron states can exist. Therefore, it avoids a situation in which the device is electronically switched off. However, in order to fabricate efficient electronic switches from graphene, it is necessary that the material can be switched ”on” and ”off”. The solution to this problem lies in trimming the graphene sheet to a ribbon-like shape, named graphene nanoribbon (GNR). Thereby it can be altered to have a band gap whose value is dependent on the width of the shape. Synthesis on Gold Surface To tune the band gap in order for the graphene nanoribbons to act like a well-established silicon semiconductor, the ribbons are being doped. To that end, the researchers intentionally introduce impurities into pure material for the purpose of modulating its electrical properties. While nitrogen doping has been realized, boron-doping has remained unexplored. Subsequently, the electronic and chemical properties have stayed unclear thus far. Prof. Dr. Ernst Meyer and Dr. Shigeki Kawai from the Department of Physics at the University of Basel, assisted by researchers from Japanese and Finnish Universities, have succeeded in synthesizing boron-doped graphene nanoribbons with various widths. They used an on-surface chemical reaction with a newly synthesized precursor molecule on an atomically clean gold surface. The chemical structures were directly resolved by state-of-the-art atomic force microscopy at low temperature. Towards a Nitrogen Oxide-Sensor The doped site of the boron atom was unambiguously confirmed and its doping ratio – the number of boron atoms relative to the total number of atoms within the nanoribbon – lay at 4.8 atomic percent. By dosing nitric oxide gas, the chemical property known as the Lewis acidity could also be confirmed. The doped nitric oxide gas was highly-selectively adsorbed on the boron site. This measurement indicates that the boron-doped graphene nanoribbon can be used for an ultra-high sensitive gas sensor for nitrogen oxides which are currently a hot topic in the industry as being highly damaging to the environment.
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With silicon pushed to its limits, what will power the next electronics revolution?

The semiconducting silicon chip launched the revolution of electronics and computerisation that has made life in the opening years of the 21st century scarcely recognisable from the start of the last. Silicon integrated circuits (IC) underpin practically everything we take for granted now in our interconnected, digital world: controlling the systems we use and allowing us to access and share information at will. The rate of progress since the first silicon transistor in 1947 has been enormous, with the number of transistors on a single chip growing from a few thousand in the earliest integrated circuits to more than two billion today. Moore’s law – that transistor density will double every two years – still holds true 50 years after it was proposed. Moore’s law still holds true after 50 years Moore’s law still holds true after 50 years. (Image: shigeru23, CC BY-SA) (click on image to enlarge) Nevertheless, silicon electronics faces a challenge: the latest circuits measure just 7nm wide – between a red blood cell (7,500nm) and a single strand of DNA (2.5nm). The size of individual silicon atoms (around 0.2nm) would be a hard physical limit (with circuits one atom wide), but its behaviour becomes unstable and difficult to control before then. Without the ability to shrink ICs further silicon cannot continue producing the gains it has so far. Meeting this challenge may require rethinking how we manufacture devices, or even whether we need an alternative to silicon itself. Speed, heat, and light To understand the challenge, we must look at why silicon became the material of choice for electronics. While it has many points in its favour – abundant, relatively easy to process, has good physical properties and possesses a stable native oxide (SiO2) which happens to be a good insulator – it also has several drawbacks. For example, a great advantage of combining more and more transistors into a single chip is that it enables an IC to process information faster. But this speed boost depends critically on how easily electrons are able to move within the semiconductor material. This is known as electron mobility, and while electrons in silicon are quite mobile, they are much more so in other semiconductor materials such as gallium arsenide, indium arsenide, and indium antimonide. The useful conductive properties of semiconductors don’t just concern the movement of electrons, however, but also the movement of what are called electron holes – the gaps left behind in the lattice of electrons circling around the nucleus after electrons have been pushed out. Modern ICs use a technique called complementary metal-oxide semiconductor (CMOS) which uses a pair of transistors, one using electrons and the other electron holes. But electron hole mobility in silicon is very poor, and this is a barrier to higher performance – so much so that for several years manufacturers have had to boost it by including germanium with the silicon. Silicon’s second problem is that performance degrades badly at high temperatures. Modern ICs with billions of transistors generate considerable heat, which is why a lot of effort goes into cooling them – think of the fans and heatsinks strapped to a typical desktop computer processor. Alternative semiconductors such as gallium nitride (GaN) and silicon carbide (SiC) cope much better at higher temperatures, which means they can be run faster and have begun to replace silicon in critical high-power applications such as amplifiers. Lastly, silicon is very poor at transmitting light. While lasers, LEDs and other photonic devices are commonplace today, they use alternative semiconductor compounds to silicon. As a result two distinct industries have evolved, silicon for electronics and compound semiconductors for photonics. This situation has existed for years, but now there is a big push to combine electronics and photonics on a single chip. For the manufacturers, that’s quite a problem. Semiconductor lasers Semiconductor lasers, where alternatives to silicon such as germanium have already found a role. (Image: CC BY-SA) New materials for future Of the many materials under investigation as partners for silicon to improve its electronic performance, perhaps three have promise in the short term. The first concerns silicon’s poor electron hole mobility. A small amount of germanium is already added to improve this, but using large amounts or even a move to all-germanium transistors would be better still. Germanium was the first material used for semiconductor devices, so really this is a “back to the future” move. But re-aligning the established industry around germanium would be quite a problem for manufacturers. The second concerns metal oxides. Silicon dioxide was used within transistors for many years, but with miniaturisation the layer of silicon dioxide has shrunk to be so thin that it has begun to lose its insulating properties, leading to unreliable transistors. Despite a move to using rare-earth hafnium dioxide (HfO2) as a replacement insulator, the search is on for alternatives with even better insulating properties. Most interesting, perhaps, is the use of so-called III-V compound semiconductors, particularly those containing indium such as indium arsenide and indium antimonide. These semiconductors have electron mobility up to 50 times higher than silicon. When combined with germanium-rich transistors, this approach could provide a major speed increase. Yet all is not as simple as it seems. Silicon, germanium, oxides and the III-V materials are crystalline structures that depend on the integrity of the crystal for their properties. We cannot simply throw them together with silicon and get the best of both. Dealing with this problem, crystal lattice mismatch, is the major ongoing technological challenge. Different flavours of silicon Despite its limitations, silicon electronics has proved adaptable, able to be fashioned into reliable, mass market devices available at minimal cost. So despite headlines about the “end of silicon” or the spectacular (and sometimes rather unrealistic) promise of alternative materials, silicon is still king and, backed by a huge and extremely well-developed global industry, will not be deposed in our lifetime. Instead progress in electronics will come from improving silicon by integrating other materials. Companies like IBM and Intel and university labs worldwide have poured time and effort into this challenge, and the results are promising: a hybrid approach that blends III-V materials, silicon and germanium could reach the market within a few years. Compound semiconductors have already found important uses in lasers, LED lighting/displays and solar panels where silicon simply cannot compete. More advanced compounds will be needed as electronic devices become progressively smaller and lower powered and also for high-power electronics where their characteristics are a significant improvement upon silicon’s capabilities. The future of electronics is bright, and it’s still going to be largely based on silicon – but now that silicon comes in many different flavours.
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New theory leads to radiationless revolution

Physicists have found a radical new way confine electromagnetic energy without it leaking away, akin to throwing a pebble into a pond with no splash. The theory could have broad ranging applications from explaining dark matter to combating energy losses in future technologies. However, it appears to contradict a fundamental tenet of electrodynamics, that accelerated charges create electromagnetic radiation, said lead researcher Dr Andrey Miroshnichenko from The Australian National University (ANU). "This problem has puzzled many people. It took us a year to get this concept clear in our heads," said Dr Miroshnichenko, from the ANU Research School of Physics and Engineering. Dr. Andrey Miroshnichenko Dr. Miroshnichenko with his visualization of anapoles as dark matter. The fundamental new theory could be used in quantum computers, lead to new laser technology and may even hold the key to understanding how matter itself hangs together. "Ever since the beginning of quantum mechanics people have been looking for a configuration which could explain the stability of atoms and why orbiting electrons do not radiate," Dr Miroshnichenko said. The absence of radiation is the result of the current being divided between two different components, a conventional electric dipole and a toroidal dipole (associated with poloidal current configuration), which produce identical fields at a distance. If these two configurations are out of phase then the radiation will be cancelled out, even though the electromagnetic fields are non-zero in the area close to the currents. Dr Miroshnichenko, in collaboration with colleagues from Germany and Singapore, successfully tested his new theory with a single silicon nanodiscs between 160 and 310 nanometres in diameter and 50 nanometres high, which he was able to make effectively invisible by cancelling the disc's scattering of visible light. This type of excitation is known as an anapole (from the Greek, 'without poles'). Dr Miroshnichenko's insight came while trying to reconcile differences between two different mathematical descriptions of radiation; one based on Cartesian multipoles and the other on vector spherical harmonics used in a Mie basis set. "The two gave different answers, and they shouldn't. Eventually we realised the Cartesian description was missing the toroidal components," Dr Miroshnichenko said. "We realised that these toroidal components were not just a correction, they could be a very significant factor." Dr Miroshnichenko said the confined energy of anapoles could be important in the development of tiny lasers on the surface of materials, called spasers, and also in the creation of efficient X-ray lasers by high-order harmonic generation.
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