2010/12/23

Ferrofluids help you see better

22 December 2010

US researchers have used ferrofluids as liquid pistons that could be used to make adjustable liquid lenses with nearly perfect spherical interfaces for applications such as an optometrist's phoropter. A phoropter measures the way light is focused in the eye and is used to determine prescriptions for glasses and contact lenses.

Ferrofluids are colloidal solutions of ferromagnetic nanoparticles suspended in a dispersing liquid. Ferrofluid droplets can be manipulated by a magnetic field, so they could be used in systems that need precise control, such as optics, drug delivery, and electronic devices.

Amir Hirsa and colleagues from Rensselaer Polytechnic Institute in Troy, New York, have made such a device by filling three of four holes in a substrate with ferrofluid; the ferrofluid's surface tension allows droplets to protrude from either side of the substrate. They filled the fourth hole with 1-methylnaphthalene, a compound used as a liquid lens. They sealed the system and filled it with water, producing two chambers, with the substrate as the separator and the ferrofluid and 1-methylnaphthalene being the only connections between them.

As a magnetic field was applied to the device, the ferrofluid moved further into one chamber, pushing the 1-methylnaphthalene liquid lens and changing its curvature

When the team applied a magnetic field, they were able to move the ferrofluid further into one chamber, which in turn pushed the 1-methylnaphthalene lens, changing its curvature. Capillarity - where liquid spontaneously rises in a tube because of an unbalanced molecular attraction at the boundary between the liquid and the tube - then restores the system to its original state, making a type of liquid switch. The system moves continuously like a piston and by controlling the movement of the ferrofluid, the curvature of the 1-methylnaphthalene liquid lens can be adjusted as desired.

'With the same basic elements, you could make many different things, from adaptive lenses to pumps to ways of controlling heat transfer,' says Hirsa who was inspired 'to find natural ways of moving a system with surface tension'.

Nicole Pamme, an expert in microfluidics from the University of Hull in the UK thought the work made a nice addition to the field and particularly liked the ability to control the system remotely. 'Without any moving parts inside the device, one can control a lens quite accurately and precisely just by moving something else in a different position,' she says.

Hirsa now hopes to optimise system integration and to adapt this technology to other materials to increase the range of applications.

Patricia Pantos

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22 December 2010

It was another tough year for the pharma industry, with downsizing, pricing concerns and the impending expiry of patents on many big-selling products all having an impact. But some of the biggest headlines were caused by eye-watering fines dished out in the US for, in most cases, violations of the False Claims Act through off-label marketing - promoting medicines for indications they haven't been approved for.

Scrutiny of the industry's commercial practices has increased in recent years, leading to a big rise in investigations for fraud and abuse in claims for reimbursement under government-funded health insurance programmes, such as Medicare. In 2009, Pfizer faced the largest ever corporate fine of $2.3 billion (£1.5 billion). Nothing in 2010 came close to that, but there was no shortage of big payouts. Allergan, for example, was fined $600 million for off-label promotion of Botox, AstraZeneca $520 million over antipsychotic Seroquel (quetiapine), and Novartis $422 million over antiepileptic Trileptal (oxcarbazepine).

Tactics companies were charged with included: ghost-writing scientific papers; promoting drugs to physicians working with patient groups the drugs weren't approved to treat; and even creating sham consultancies that enabled them to pay physicians to attend what were little more than marketing presentations. Meanwhile, GlaxoSmithKline (GSK) was fined $750 million for selling a range of substandard drugs manufactured in the early 2000s at its plant in Cidra, Puerto Rico.

This rise is in large part a result of the US whistleblower rules that protect those who bring corporate misbehaviour to the attention of the authorities. Not only do they gain protection from retaliation, they can also earn a slice of any resulting fines. In the GSK case, the quality control manager who reported the problem was awarded almost $100 million.

Howard Dorfman, counsel in the life sciences practice at US law firm Ropes & Gray, believes more cases are inevitable. 'There is a continuing interest in rooting out fraud and abuse within the healthcare industry,' he says. 'The Department of Justice has already signalled its intention to continue its vigorous investigation activities. When you consider the increasing focus on patient safety related to off-label drug use, I think these investigations will continue and even, perhaps, escalate.'


And more investigations could lead to stricter rules. Fines are more than just a financial burden - they have a negative effect on consumers who are already dubious about the industry's integrity. And this, Dorfman believes, could lead to companies facing increased legislation. 'Whether the industry has been successful in communicating its commitment to transparency, integrity and stopping inappropriate marketing practices is ultimately for the public to decide,' he says. 'But public image is definitely a concern, and both companies and trade organisations are spending considerable amounts of time and effort addressing it.'

There has been debate in the US about whether these fines are sufficiently large to 'send a message' to the industry, he says. 'I certainly think these amounts are extraordinary, and it's somewhat simplistic to suggest they don't have an impact on companies. They certainly get the attention of company executives. But because of the perception by some people outside the industry that the fines have not brought these practices to an end, there is increasing speculation that criminal prosecutions will be brought against employees in positions of authority.' Indeed, this is already happening. At the end of November, a former GSK in-house lawyer was charged with obstruction and making false statements. This is unlikely to be the last such prosecution.

And now the companies are facing scrutiny on another front - the US Securities and Exchange Commission (SEC), which oversees the financial markets, is working much more closely with the Food and Drug Administration (FDA) due to concerns that information about product development, adverse events and clinical trials is not being disclosed sufficiently quickly. 'The SEC wants to ensure information important to the investment community or the general public is provided in a timely and public way,' Dorfman says. The SEC has even been mandated by Congress to set up a whistleblower programme, expected to be put into effect in the spring, and it's likely that even more investigations and prosecutions will appear as a result.

Problems abound

The fallout from the 2009 swine flu pandemic was another source of critical headlines. After the World Health Organization (WHO), perhaps prematurely, declared H1N1 a pandemic, the pressure was on for pharma companies to develop and manufacture a preventative vaccine, and governments around the world put in huge orders. Yet the pandemic didn't lead to all that had been feared, leaving big stocks of unused vaccine. A report for the Council of Europe declared that public health priorities were distorted by the WHO, which vastly overestimated the seriousness of the pandemic. Meanwhile, scientists advising the WHO had done paid work for pharma companies standing to gain from vaccine sales, it asserted.


Due to a whistleblower action, GSK made the biggest payout this year

Safety issues remain a concern, and it's looking like the end of the line for one of the most controversial medicines of recent years, GSK's antidiabetic Avandia (rosiglitazone). The drug has been under a cloud because of its potential to cause cardiac side-effects: it has been withdrawn in Europe, and while it remains on the market in the US, the FDA has severely restricted its use. GSK has already settled in more than 10,000 patient lawsuits, and more are ongoing.

Mergers activity slows

In recent years, the pharma industry has engaged in a lot of mergers and acquisitions. In 2009, for example, Pfizer bought Wyeth, Merck & Co bought Schering-Plough and Roche bought Genentech. But 2010 brought us only small deals and the Sanofi-Aventis $18.5 billion hostile bid for Genzyme, which has yet to reach a conclusion. Is this an end to the pharma 'mega-merger'? Unlikely, says Kevin Bottomley, senior principal at consultancy PharmaVentures: 'Everyone has been hugely cautious, and there has been little access to debt financing in the current economic situation.'


The industry 'patent cliff' is coming up fast
Another trend he identifies is a growth in large pharma companies divesting chemistry assets, particularly in the manufacturing arena. 'Products are divested, and the manufacturing assets go with them,' he says. 'These tend to be products that the big companies see as non-core - those that have gone off patent, where they still own the brand name but generic competition means there is little marketing support.'

The patent 'cliff', where many big-selling products will be opened up to generic competition, is looming ever closer, and Bottomley believes this may lead to the divestiture of numerous products that were once big sellers. 'In the old days, once it had been made by big pharma they continued to make it, but now some companies are even going as far as viewing the whole concept of manufacturing as non-core.'

Those looming patent expiries are a big driver for companies to cut costs. The fallout from last year's mega-mergers is continuing to hurt, with Merck & Co, for example, intending to close several European research sites. Even those that haven't merged are seeing the falling axe as a way to increase their bottom line by reducing their outgoings. AstraZeneca, for example, announced it will close its research sites at Charnwood, UK, and Lund in Sweden.

The need to cut costs is also being fuelled by an ever-growing pressure on prices, particularly in the Eurozone, coupled with a weakness in research pipelines. 'I think we will see the large shake-outs continue,' Bottomley says. 'Roche, which we take as a bellwether for a company that is doing well at the moment, is cutting costs quite severely. And even Novartis, which has said it isn't making big cuts, is no longer making the major investments it was.'

He believes these trends will continue in 2011, along with a return to intense merger and acquisition activity. 'When they've gone through all this, what will the industry look like?' he asks. 'I think big pharma will be leaner and more focused. Clearly there is still a need for innovation and the medicinal chemists who are looking for new drugs, but companies will look to be more cost-efficient. I also think there will be more externalisation of manufacturing - a trend that has been going on for years and is certain to continue.'

However, the number of diseases and populations that remain in need of drug treatment gives hope for the industry's future, as Eddie Gray, president of pharmaceuticals at GSK, told the Financial Times Pharma & Biotech Conference in early December. 'I remain an optimist for the pharma industry, though not necessarily the one we have now,' he said. 'Whether it's in the developing world, or the demographics of ageing in the developed world, demand for unmet need will remain high.'

Sarah Houlton

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Cellulose catalyst rewrites rules of attraction

21 December 2010

Chinese researchers have developed a magnetic solid acid catalyst that raises the prospect of efficiently converting biomass cellulose into useful chemicals, such as sugars for biofuel production.

According to the researchers, the catalyst is better than conventional equivalents because it shows good hydrothermal stability and can be recycled - magnetic nanoparticles pull the acid away from the substrate when a magnetic field is applied.

Using biomass as a source of renewable fuel has attracted interest in recent years in response to global climate change and the search for alternatives to fossil fuels. The main component of biomass is cellulose - a polymer comprising many glucose units linked by beta-1,4-glycosidic bonds, with each chain then interconnected by hydrogen bonds. This structure makes cellulose a tough compound to break down. Enzymes or acid catalysts are needed to do the job. But then separating the catalyst from the reaction residue can be energy intensive and costly.

Now, Yao Fu, at the University of Science and Technology of China in Hefei, and colleagues have come up with an answer. Inspired by previous work that showed sulfonic acid functionalised mesoporous silica materials work well as acid catalysts,1 the team designed and synthesised their new sulfonic acid catalyst in the presence of magnetic Fe3O4 nanoparticles, triblock copolymers and hydrogen peroxide.2

The magnetic solid acid catalyst improves the hydrolysis of cellulose to form glucose
© ChemSusChem

'By using our new catalyst, we saved an energy-consuming process to separate the solid catalyst and concentrate the glucose solution,' says Fu. The team tested the catalyst by studying the hydrolysis under different conditions of various carbohydrates, including: cellobiose, starch, cellulose and lignocellulose from corn cobs. They found their sulfonic acid effectively hydrolysed 1,4-glycosidic bonds, producing glucose yields of up to 96 per cent from cellobiose, a disaccharide comprising two glucose molecules. However, only 50 per cent yields were obtained from amorphous cellulose. Importantly, the acid could be used repeatedly without deactivation.

'Developing a heterogeneous catalyst for cellulose hydrolysis has been a goal for many scientists,' says Joseph Binder, who researches biofuel chemistry at the University of California Berkeley, US. He thinks the enhanced separation and stability properties of the new catalyst are an encouraging contribution towards this goal. 'Still, the challenge of achieving high yields of glucose through the action of a solid catalyst on the insoluble cellulose substrate remains to be solved,' he adds.

Fu acknowledges that further work needs to be done to realise the industrial potential. 'The optimisation of hydrolysis conditions and low cost catalyst synthesis need to be overcome,' he says. But after modifications have been made to the process and reactor, Fu is optimistic that the process of hydrolysis of cellulose using a magnetic acid catalyst can be scaled up to industrial level.

James Urquhart

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Cutting edge chemistry in 2010

21 December 2010

What discoveries caused the biggest buzz in chemistry labs around the world in 2010? With the help of an expert panel of journal editors, Chemistry World reviews the ground breaking research and important trends in the year's chemical science papers.

Space

Many discoveries came from outer space in 2010. This included the work by Jan Cami of the University of Western Ontario, Canada, and colleagues, who used an infrared spectrograph to identify buckminsterfullerene (C60) and C70 in the planetary nebula Tc 1 (Chemistry World (CW) September, p21).1 This discovery helps back up theories about diffuse interstellar bands (DIBs), absorption lines in astronomical spectra. Investigating these DIBs is one reason why Harry Kroto and colleagues performed the experiments that made C60 in the first place.

Small cement-like companions indicated the posibility of ice on the large asteroid 24 Themis
In another part of the universe, an international team of researchers found water vapour close to a carbon-rich giant star, something previously thought impossible (CW October, p26)2. Investigating the circumstellar envelope around star IRC +10216 - the deep sooty outflow of dust and gas around the aging and expanding star - the researchers discovered dozens of spectroscopic lines, corresponding to water vapour at different temperatures and hence locations within the envelope. Scientists will now have to rethink their understanding of the chemistry that takes place as carbon-rich stars grow older and expand.

Earlier in the year, two teams of US astronomers found water ice on the surface of asteroid 24 Themis (CW June, p21).3 The teams independently concluded that the asteroid held water ice, again using infrared spectroscopy, and by combining their results the teams showed that a thin frost layer covers the whole surface of the asteroid. Because such a thin layer should sublime into space quite quickly, the scientists propose that the asteroid must contain a subsurface ice reservoir that replenishes the surface ice as it is lost. These findings support the theory that asteroids could have brought water to planet Earth, although proving it is another matter.

As well as bringing water to the planet, Nir Goldman and co-workers at the Lawrence Livermore National Laboratory and Stanford University in the US suggested that the early building blocks of life could survive hitching a ride to earth on a comet. Their computations found that the shock waves of a comet impact could promote short lived C-N bonded oligomers that then break up to form stable complexes containing glycine, an essential amino acid (CW October, p27).4

Life, but not as we know it

2010 also saw chemistry help investigate and explain biological phenomena. Craig Venter was back in the news again, this time for creating a synthetic bacterium by transplanting a chemically synthesised chromosome into an empty cell (CW July, p26).5 The man-made microbe was the work of a team led by Dan Gibson at Venter's institutes in Rockville, Maryland and San Diego, California, US and can grow and replicate just like its biological counterparts.

Meanwhile, John Parnell and colleagues at the University of Aberdeen, UK found discrepancies in the 34S to 32S ratio in Scottish rocks (CW December, p18).6 The rock samples, from the north-west highlands of Scotland, suggested that complex life could have existed on Earth 400 million years earlier than thought.

Enzymes were made into playmates (CW online, October 23) by a team led by Milan Stojanovic of Columbia University in New York, US.7 The scientists created a biological automaton that could be taught to play tit-for-tat, and never lose. The automaton comprised a solution of 16 enzymes that could recognise and respond to 'moves' from a human player, opening up a new avenue in molecular programming.

In the metallomics field, American scientists led by Michael Adams showed that scientists working in the field should shift their focus from classical protein-based purification to metal-based identification and purification. The team used Pyrococcus furiosus as an example and showed that of 343 metal peaks in chromatography fractions, 158 did not match any predicted metalloprotein. Purifying eight of these fractions gave four new metalloproteins, suggesting that metalloproteomes are larger and more diverse than first expected (Nature, DOI: 10.1038/nature09265).8

Light

Light based chemistry continued to fascinate. Xueming Yang and Alec Wodtke investigated why methanol helps generate hydrogen from water using titanium dioxide and sunlight. They found that the methanol gives up it's hydrogen to the bridge-bonded oxygen of the TiO2 (Chem. Sci., DOI: 10.1039/c0sc00316f).9

Gold particles in leaves induce bioluminescence

At the Photosynthesis Congress in Beijing, Jian-Ren Shen of Okayama University in Japan received a standing ovation after announcing that his group had managed to get the structure of Photosystem II at a resolution of 1.9A. The protein complex is the first protein in light dependant reactions and supplies all of the electrons needed for photosynthesis by oxidising water. The new understanding that this structure brings has huge importance for artificial photosynthesis and solar energy conversion.

In related work, Greg Scholes led a team based in Toronto and Sydney that investigated antenna proteins. These proteins absorb light and transmit the resultant excitation energy between molecules to a reaction centre where photosynthesis takes place.10 The team showed compelling evidence that the 5nm wide proteins share their electronic excitation in a quantum-coherent manner. The proteins exhibit this 'coherent wiring' even under biologically relevant conditions, suggesting that distant molecules within the photosynthetic proteins are 'wired' together for more efficient light-harvesting (Nature, DOI: 10.1038/nature08811).

And from using light in leaves, to making it. Taiwanese researchers diffused gold nanoparticles into plants to make chlorophyll to produce a red emission (CW December, p20). The idea is that these 'bio-LED' leaves could be used like street lights.11

The large nano field

Culminating in the awarding of the Nobel prize in physics to Andre Geim and Kostya Novoselov (CW November, p8), graphene perhaps unsurprisingly featured heavily in the headlines in 2010. Geim's group at the University of Manchester, UK themselves made a kind of 2D Teflon by completely fluorinating sheets of graphene without damaging the graphene sheet or its supports in the process. The resultant fluorographene is mechanically strong and chemically and thermally stable, and as well as being used like Teflon could be used as a thin insulator in organic electronics or find use in LEDs and displays (Small, DOI: 10.1002/smll.201001555).12

Speaking of displays, researchers in Korea and Japan made large graphene films that they then incorporated into touchscreen displays (CW August, p22).13 The graphene was doped with nitric acid to make it act like a large transparent electrode, ideal for touchscreen applications, and much stronger and more environmentally friendly than indium tin oxide, which is usually used for touchscreens.

As well as large sheets, several groups reported ways to make circuits using graphene. Graphene nanoribbons were built up using a new bottom up approach by European researchers (CW September, p33).14 The nanoribbons are about 1nm wide and built from a radical precursor on a metal surface, which allows the width and shape of the nanoribbons to be controlled. The identical shape of the nanoribbons means that the electronic properties are also controllable, ideal for nanoelectronics.

Graphene circuits were also made by a hot AFM tip that 'drew' onto graphene oxide.15 The heat of the AFM tip reduces the graphene oxide and leaves behind conductive lines of graphene, just like with a pen on paper (CW July, p36). The same tip can then read what it has written, which is useful for quality control.

Real time transmission electron microscopy (TEM), used by Andrei Khlobystov at the University of Nottingham, UK made graphene curl up to make fullerenes and allowed the process to be observed at the same time (CW June, p22).16 This contradicts current theories of how fullerenes are made, which assumes near atomic carbon is needed. TEM and quantum chemical calculations explain that when a carbon atom is removed from the edge of a graphene flake of 60-100 carbon atoms, the two carbons left bonded to only two neighbours pair up, creating a pentagon. This causes the sheet to curl and as more carbons are removed, the sheet becomes a bowl and then a ball. Although these fullerenes are made using the electron beam of the TEM, the heat used in fullerene production could do the same job.

TEM was also used by some of the same team in collaboration with Chinese researchers (CW January, p29). They filmed metal atoms caged inside fullerenes that were held inside a carbon nanotube. The movie showed the metal atoms chewing their way out of the fullerenes before clustering and attacking the nanotube itself, proving that the interior of carbon nanotubes is not always as chemically inert as thought.17


DNA walker moves along a fixed track on a surface

Molecular machines
There was some fun with molecular machines again this year. David Leigh and collegues in Edinburgh made a two legged molecular walker that could walk along a track in one direction (CW February, p26),18 while Ben Feringa finally managed to make his rotary motors go in both directions (CW December, p19).19 The direction of rotation was changed by base induced epimerisation. Earlier in the year, Feringa had also produced a rotary motor that could be locked by changing the pH of the solution (CW February, p26).20

In the US, two separate teams helped move the idea of nanorobots working on assembly lines closer (CW June, p26). Milan Stojanovic's team at Columbia University in New York made a 'molecular spider' that could move along a fixed track, while Ned Seeman's group at the University of New York, developed a nanoscale assembly line that can be programmed to 'manufacture' products as a DNA walker moves down the line.21

So that's 2010, let's hope 2011 is even more memorable.

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South Africa sends medical isotopes to US

20 December 2010

The first batch of imported molybdenum-99 (Mo-99) produced with low enriched uranium (LEU) and approved for patient use in the US arrived earlier this month. However, there is concern that the achievement is primarily political and does not address the US supply shortage.

Mo-99 is widely used to detect illnesses, including heart disease and cancer, through nuclear medicine scans. Approximately 20 million medical procedures involving nuclear medicine are performed in the US every year. But the US imports all of its Mo-99, which is manufactured at a handful of aging nuclear reactors in Europe, Canada, Russia and now South Africa.

Unplanned shutdowns of these reactors for maintenance or safety reasons have led to shortages of medical isotopes, with scarcity of the important medical isotope reaching crisis level last year.

The delivery to Lantheus Medical Imaging near Boston, Massachusetts, US, is the result of collaboration between the US National Nuclear Security Administration (NNSA) and the South Africa Nuclear Energy Corporation (Necsa), a state-owned company.


The decay product of Mo-99 - the metastable isotope Technetium-99 (Tc-99m) - is used for scans

The NNSA provided $25 million (£16 million) through its Global Threat Reduction Initiative (GTRI), which aims to reduce and protect vulnerable nuclear and radiological materials located at civilian sites worldwide.

'A fundamental part of the GTRI program is to achieve nuclear nonproliferation goals without negatively impacting the supply of Mo-99, which is used by tens of thousands of patients every day,' Parrish Staples, director of European and African threat reduction at the NNSA, tells Chemistry World.

South Africa converted highly enriched uranium (HEU) to LEU, while maintaining its Mo-99 capacity, demonstrating, he says, that the two objectives can be accomplished simultaneously.

'This is a landmark achievement - it is something that we have been pushing for 20 years, and the commercial producers said it was impossible,' says Alan Kuperman, a University of Texas nuclear proliferation expert. 'Now we see that the other major producers of Mo-99 also could convert from bomb-grade uranium to LEU.'

Dark clouds

Others, however, say that such short term efforts are shifting medical isotope capacity farther from the US.

'The [NNSA] announcement is all about nonproliferation,' says Robert Atcher, a radiochemist who manages the Department of Health and Human Services' programs with Los Alamos National Laboratory. 'It doesn't expand US production capabilities at all.' In fact, Atcher says there is some indication that the molybdenum yield from the process is lower with LEU than HEU.

The most recent shortage was caused by the volcanic eruption in Iceland earlier this year, which held up shipments. Each day a shipment is delayed translates to a loss of 25 per cent of the molybdenum to radioactive decay, according to Atcher. 'Mo-99 doesn't have much of a shelf life,' he says.

Domestic supply

Most observers agree that the US needs to start producing its own medical isotopes to protect against supply interruptions.

Covidien, a healthcare device and supply company based in Dublin, Ireland, with corporate functions at its Mansfield site in Massachusetts, US, began working with US engineering firm Babcock & Wilcox in January 2009 to develop technology to manufacture Mo-99. The ongoing collaboration is billed as an initial step toward establishing large-scale US supply of medical isotopes.

'We are all moving as rapidly as we can because it is clear that LEU will be the standard for the molybdenum production facilities,' says Covidien spokesman Stephen Littlejohn.

Meanwhile, the NNSA's goal is to ensure through its cooperative agreements that Mo-99 is produced domestically without the use of HEU by the end of 2013. New legislation - which passed the House of Representatives last year with an overwhelming 400-17 vote, but then stalled in the Senate - would phase out US exports of HEU for foreign production of medical isotopes within 7-13 years. It would also foster domestic production of Mo-99 without HEU and subsidise construction of production facilities by authorising government cost-sharing.

The bill will likely be reintroduced in the new Congress after it convenes in January. Its main opponent in the Senate - Republican Kit Bond from Missouri - is retiring and won't be returning to Capitol Hill.

Rebecca Trager, US correspondent for Research Europe

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Frozen assets in biobanks

20 December 2010

Scientists from Sweden have devised a technique that extracts both DNA and RNA from frozen tissue in a bid to improve large-scale extractions from samples stored in biobanks, which could aid cancer research.

Tobias Sjöblom and colleagues from Uppsala University used magnetic silica beads to target and extract DNA and RNA from tissue samples. Because DNA competes with RNA to attach to the beads, the DNA can be recovered first. 'The technology fulfils an unmet need, so has a huge potential impact on tissue biobanking,' says Lucy Mathot from Sjöblom's team.

High quality DNA and RNA preparations are necessary to study genes responsible for cancer and to identify which cancer medication to use. Researchers prefer to carry out analyses using tissues frozen from fresh because the fragments they can get from these samples are longer and better preserved than with alternative methods. Current column-based techniques for the serial extraction of DNA and RNA are labour-intensive so are not suitable for large scale applications and the automation needs of cancer biobanks.

Tissue samples are broken down, magnetic silica beads are added, the beads attach to DNA and RNA and are removed with a magnet

Sjöblom's team broke down the tissue samples by grinding them with a chaotropic salt solution, which helps to break down the DNA and RNA, and then added the magnetic silica beads. When the beads attached to the DNA, they were able to recover the samples with a magnet. Then they captured the remaining RNA in the same way.

Bert Vogelstein, a cancer researcher at the Johns Hopkins University School of Medicine in the US says: 'The technique looks like it will be quite useful for preparing precious samples for next-generation sequencing analysis.'

In the future, the team plans to implement the procedure on a robotic platform to enable parallel sample processing.

Jennifer Newton

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Atomic weights change to reflect natural variations

20 December 2010

The atomic weights for ten elements are to be expressed as intervals rather than single values, the International Union of Pure and Applied Chemistry (Iupac) has announced. The decision marks a move away from the commonly held view of atomic weight as a 'constant of nature' towards a more accurate interpretation based on naturally occurring variations in atomic weight.

Extract from the proposed isotopic periodic table
© Chemistry International

It has been known for many years that the atomic weight of an element can vary depending on its number of stable isotopes and their relative abundances. The idea that elements can be made up of more than one stable isotope goes back as far as the early 20th century and today these differences are exploited by labs all around the world in fields as diverse as food authentication and geology.

So, after all this time, why the change? According to Michael Berglund, a member of Iupac's Commission on Isotopic Abundances and Atomic Weights, which proposed the change, it is purely because more reliable and precise measurement data are now available. He points out that in its previous form, the standard atomic weight for an element like lithium was just an average value. 'It would actually be very difficult to find a material with this exact atomic weight,' he says.

'The truth', as Berglund puts it, can now be revealed: that atomic weights are not constants of nature. The first ten elements for which atomic weights will be stated as intervals in the Table of Standard Atomic Weights are: hydrogen, lithium, boron, carbon, nitrogen, oxygen, silicon, sulfur, chlorine and thallium. But more will inevitably follow. Those up for discussion at the next meeting of the commission, in 2011, include helium, copper and lead.

Tyler Coplen, director of the US Geological Survey's Stable Isotope Laboratory in Virginia, admits the change makes matters more complicated but thinks it's 'fantastic' for chemistry education. 'This is going to force teachers all over the world to learn about a thing called a stable isotope,' he says. Iupac is currently working on a new isotopic periodic table showing atomic weights as intervals, which it hopes will be the highlight of the International Year of Chemistry next year.

Hayley Birch

Novel route to key aromatics

19 December 2010

US chemists have found a new way to create aromatic compounds from straight chains of hydrocarbons by using an iridium-based catalyst. The reaction takes place at much lower temperatures than the conventional way of producing aromatic molecules from hydrocarbon chains and with a much higher degree of control over the end products, some of which are difficult or impossible to obtain by standard routes.

Aromatics are key building block molecules for the chemical industry. They are currently produced mainly by a process of catalytic reforming of petroleum feedstocks, which is carried out at temperatures of around 500°C, and produces a complex mixture of molecules that need to be subsequently separated.

Pincer-ligated iridium complex
© Nature Chem.

Now a team led by Alan Goldman of Rutgers University and Maurice Brookhart of the University of North Carolina at Chapel Hill has shown that it is possible to produce aromatic molecules from their straight-chain counterparts, n-alkanes, at temperatures several hundred degrees lower than other methods.

The key to the process is a so-called pincer-ligated iridium complex as a homogeneous catalyst. Here, iridium is clamped by three arms contained within a phosphine-based cage. 'This makes it very stable, allowing it to be heated to the temperatures we need, close to 200°C,' says Brookhart.

When an alkane is introduced to the catalyst, the iridium inserts itself between a C-H bond and prises the hydrogen away, presenting it to a hydrogen acceptor - in this case t-butylethylene. This results in the generation of a double bond within the carbon chain. The process is repeated twice more, creating a triene, which then undergoes cyclisation followed by loss of an additional equivalent of hydrogen to produce the aromatic product.

Different aromatics are produced depending on the number of carbons in the starting alkane. Many of the subsequent products are difficult or impossible to produce by other means says Goldman. 'For example if you start with decane, you end up with linear alkyl aromatics that are normally impossible to obtain with conventional routes, which combine olefins and lighter aromatics. Alternatively, if you tried to make these products from alkanes using current heterogenous routes you would get extensive bond breaking of the carbon chains, whereas we get mostly compounds with the same carbon number as our starting material.'

Anthony Haynes, an expert in homogeneous transition-metal catalysis at the University of Sheffield in the UK, is impressed by the study. 'The transformation of simple alkanes into valuable aromatic compounds is remarkable, and demonstrates the exquisite control of selectivity that is possible with an organometallic catalyst,' he says. Haynes adds that to make the concept practical 'it will probably be necessary to anchor the iridium catalyst to a solid support.'

Simon Hadlington

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2010/12/18

Lights, camera, action

17 December 2010


Martyn Poliakoff, CBE, FRS, is research professor of chemistry at the University of Nottingham in the UK. His main research interest is the application of supercritical fluids with a focus on green and sustainable chemistry. He is one of the narrators of 'The Periodic Table of Videos', which are popular on YouTube.

Can you tell us a little known fact about yourself?

I'm an Honorary Professor at Moscow State University, something I share with Fidel Castro and Bill Clinton.

Which of your academic achievements are you most proud of?

To me, academic work is rather like journalism - journalists get excited about the story they are working on, but when they move on to the next story, that one is more exciting than the one before. So I think that the only way you can operate as an academic is to be excited about whatever you are doing at a particular time. When I was younger, I did a lot of work on the reactive molecule iron tetracarbonyl, which is completely useless in the green chemistry context because it only exists at room temperature for a millionth of a second or less , but I am still quite proud of my experiments. As a professor, I am proud of the little contributions I can make to the design of an experiment by my research group. Experiments are almost always done by my students or postdocs. Sometimes, as a supervisor, the contributions to the design of the experiments are not as big as one would like. Occasionally, I have a really good idea , which makes the experiments work and that always give me pleasure.

You're keen to promote science on YouTube. Could you tell us more?

I began working with YouTube purely by accident. My university was collaborating with Brady Haran, a very talented video journalist, who wanted to make a periodic table of videos. I didn't think there was enough to say about some of the more obscure elements but as it turned out, there was plenty to say, at least enough to make short videos. We wanted to show that we enjoy chemistry and how much fun it can be.

We're in the process of making videos about different molecules and reactions. There are also other videos that are rather difficult to define, for example, we made a video of gold dissolving in Aqua Regia - a mixture of nitric acid and hydrochloric acid - it's not exactly a reaction or a molecule but we thought that people may be interested in seeing the gold dissolving.

Which video was the most fun to make?

They were all fun, but my favourite is about the element hassium. This is element 108 and I knew nothing about it. In fact, in the precredit sequence - the bit before the main title of the video - I was filmed saying 'I don't know anything about hassium, let's make something up'.

What is your favourite element?

I'm very fond of sodium. The chemical symbol for sodium is Na, which was my mother's nickname when she was a child. Each time I hear the word Na or see it written down, I get a warm feeling. I'm also fond of xenon, because it's been an important element in my research.

What excites you about chemistry and what does the future hold for green chemistry?

Objects we use in everyday life, such as most of the clothes we wear, are made from synthetic chemicals. The jacket I'm wearing is actually leather but the inside is made of polyester - a synthetic material. We couldn't enjoy any of these without the products of the chemical industry. Chemistry often has a bad image. People generally think about it polluting and destroying the planet but green chemistry allows young people to feel that they are helping both the planet and humanity at the same time. So it's doubly good!

With oil running out and the expanding world population leading to a greater demand for chemicals, we have got to do something. One of the greatest challenges is to get green chemistry to work. The future either holds success in delivering what people need or complete failure leading to society collapsing. We have to succeed. I hope that in the end the principles of green chemistry will be applied to most chemistry. You could argue that if green chemistry really succeeds, it will disappear because all chemistry will become green.

What advice do you have for young scientists?

Green chemistry offers terrific opportunities and there are different areas within the subject. It doesn't matter that some people are using ionic liquids, others using new catalysts, the important message is that green chemistry is not about one area being better than another. We need all those areas and many more to solve our current problems. One of the attractions of green chemistry is that there are huge opportunities for new ideas.

Which historical scientific figure would you most like to have dinner with and why?

I have been fortunate to have met many fascinating famous scientists. One of the exciting things is actually finding out what they are like as people and not just learning about what they have discovered. However, historical figures come from a very different age. Possibly, they would strike us as being pompous or very formal compared to nowadays, not because they were famous scientists but because they lived 100 or 200 years ago. From my point of view, there are two quite exciting events that happened in 1869. One was Mendeleev propounding the Periodic Table for the first time. The other was that Thomas Andrews, a physical chemist in Belfast, described the critical point of carbon dioxide for the first time. Supercritical fluids have played a very important part in my research. It's quite amusing that the two events took place in the same year. I would quite like to have dinner with Thomas Andrews and Mendeleev, though of course, they might not have been able to speak to each other because I am not sure whether Mendeleev could speak English. He definitely spoke German because he published some of his papers in German. It probably would be a rather strange triangular conversation.

How would your family and friends describe you?

Always doing chemistry.

When you got your CBE, how was your meeting with the Royal Family?

A CBE is a British Award, which stands for Commander of the Order of the British Empire. It is presented at Buckingham Palace by a member of the Royal Family. I met with Prince Charles and he was very interested in my work. We had a 45 second discussion about recycling plastics, which was quite unexpected. He really had done his homework!

You already have a number of fans; you even have a Martyn Poliakoff appreciation society on Facebook. How do you feel about being famous and how do you deal with fame?

I'm not sure that I'm particularly famous. My brother is a well known playwright in the UK and much better known than me. Ten years ago I was walking through Helsinki with a friend of mine, who is very well known in Finland. I was with him and my postdoc who asked, 'Have you noticed that everybody is looking at Neil?' I replied 'No', because I am used to people staring at my hair anyway. So I didn't notice anything different.

Drug delivery: from needles to nanorods?

17 December 2010

Gold nanorods warmed by beams of infrared light could be the ideal way to deliver drugs through the skin, researchers in Japan have discovered. Even the bulky proteins often used in vaccines can efficiently pass through the skin this way, the team has found.

Delivering drugs or vaccines through the skin can offer many advantages over pills or injections, say Dakrong Pissuwan, Takuro Niidome and colleagues at Kyushu University. Drugs delivered this way can avoid being quickly broken down by the liver, while vaccines can generate a stronger immune response because of the many antigen-recognising immune cells present in the skin.

However, large hydrophilic proteins tend to be poorly absorbed through the skin, being halted by the stratum corneum, the hydrophobic barrier layer of dead cells that make up the skin's outer surface. Pissuwan and Niidome have now shown how gold nanorods can help just such a protein, ovalbumin (OVA), to cross this barrier and enter the body.

The team exploited the fact that gold nanorods heat up when irradiated with near-infrared (NIR) light - a property known as the photothermal effect. The researchers mixed together OVA, the nanorods and a surfactant into an oil-based dispersion that could be applied to the skin. When hit by NIR light, the warmed nanorods erode the stratum corneum, allowing the protein to pass through. Tests using mice showed that the protein successfully triggered an immune response when delivered in this way.

Preparation of the surfactant/protein/gold nanorod complex
© Small

'We believe that the induced immune response is strong enough to be used as a vaccination technique,' Pissuwan says. The team is yet to study in detail whether the process damages the skin, but preliminary studies on the mice treated so far have not revealed any severe side effects, Pissuwan adds.

If it works as well in humans as it does in mice, the technique could offer a good way to deliver proteins through the skin, says Tom Robertson, who investigates transdermal drug delivery at the University of South Australia. 'Obviously this would be appealing to the consumer - the fear of needles has been side-stepped,' he says. 'If that leads to better compliance with vaccination programmes then that would be a big step.' The process could also be much cheaper than a competing vaccine delivery technology, microneedle patches, because of all the fabrication steps involved in making them, he adds.

Pissuwan and Niidome are currently investigating other types of drug that can be delivered through the skin using gold nanorods. 'The penetration of the gold nanorods through the skin also needs to be studied before we move to try it at the clinical level,' Pissuwan adds.

James Mitchell Crow

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2010/12/16

Measuring the strength of garlic

16 December 2010

A sensor to determine the strength of garlic for the food industry has been developed by UK scientists.

Richard Compton and his team from the University of Oxford have made an electrochemical sensor that detects the amount of diallylsulfides in garlic. Larger amounts of diallylsulfides indicate a stronger flavour.

'A couple of years ago, we developed a sensor to measure the heat of chilli peppers. In the course of discussions with the food industry, we learned of a similar need for garlic sensing,' explains Compton. Garlic is widely used to flavour food but varies in strength from species to species, crop to crop and source to source. 'The Moldovan Purple, for example, is much stronger than other varieties,' he says. Monitoring the strength of garlic purees for use in foods such as sauces and curries is done by human tasters but this is slow and neither reliable nor convenient, he adds.

The sensor works by suspending garlic puree samples in a solution containing bromide ions. The solution is analysed voltammetrically whereby electrogenerated bromine reacts with diallylsulfides to regenerate bromide. This results in an increase in peak current, which quantifies the response.


The sensor detects diallylsulfides in garlic - the more diallylsulfides, the stronger the flavour

'It's interesting that bromine is selective for just the sulfur-sulfur bonds rather than also adding to the abundant carbon-carbon double bonds present in alliin, allicin, diallyl polysulfides and analogous 1-propenyl compounds, all of which are found in garlic preparations,' says Eric Block, an expert in the chemistry of garlic from the University at Albany, US.

The selectivity arises since the timescale of voltammetric measurements is much shorter than that of conventional synthetic chemistry so that the bromine has time to react with the di-sulfide bonds but not enough to add to the carbon-carbon bonds, explains Compton.

'There is an increasing need for sensors for the environment, in medicine, health care and in industry,' says Compton. 'Electrochemical analysis is perfect for many analytical applications - for example, amperometric glucose sensor strips have transformed diabetics' quality of life. Electrochemistry has a major role to play, not least because of its sensitivity and potential for low-cost sensors.'

'Electrochemical techniques are easier to miniaturise and cheaper compared to techniques such as chromatography,' says Kenneth Ozoemena, who studies electrochemistry and photosensitised reactions at the University of Pretoria in South Africa. 'I am confident that this procedure will revolutionise the quality control of garlic and garlic-containing food.'

Elinor Richards

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New technique probes electron properties of individual atoms

15 December 2010

A new, low voltage electron microscopy technique allows scientists to discriminate not just between atoms of different elements but between atoms of the same element in different electronic states. The researchers who developed it say it could be broadly applied to analyse the fine structures of nanomaterials and important biological molecules.

The new technique can discriminate between carbon atoms with different numbers of bonds
© Masanori Koshino

Kazu Suenaga and Masanori Koshino at the National Institute of Advanced Industrial Science and Technology in Tsukuba, Japan, used a low voltage, scanning transmission electron microscope (Stem) to probe carbon atoms in graphene. By measuring the energy lost when electrons hit individual atoms, they were able to tell a carbon atom with one bond from others with two or three.

The team used a probe just 0.1nm in diameter to zone in on single atoms. 'In the past, if you were using some other technique, you could do spectroscopy for a local area of 1,000 atoms or a million atoms, something like that,' explains Suenaga. 'Now, with a very tiny probe, we can measure from single atoms.'

Achieving such high spatial resolution has traditionally required big, powerful electron microscopes operating at high accelerating voltages that blast atoms and can destroy specimens. But Suenaga and Koshino's low voltage (60kV) set-up produces the necessary short wavelength electrons for high resolution spectroscopy, whilst leaving samples intact.

Although there have been previous reports of identifying elements from a single atom using similar methods, this is the first time specific spectral peaks have been obtained from specific atoms, according to Stephen Pennycook, a Stem specialist at Oak Ridge National Laboratory, Tennessee, US. 'It's almost like seeing bonds one by one,' he says.

The achievements are impressive, says Pratibha Gai, chair of electron microscopy at the University of York's Jeol Nanocentre in the UK. 'The ability to record the reported data is a remarkable feat given the instabilities and inevitably very weak signal,' she adds.

Gai thinks the method should be applicable to other nanomaterials. And as Suenaga points out, exploring the atomic level structures of nanodevices will become increasingly important. But for now, he has other plans for the technique - for instance, in identifying the active atoms in individual molecules in order to predict how chemical reactions will occur. Previously this has only been possible through theoretical calculations, which would take too long in big molecules like proteins. Another idea is to use the technique to understand why, in solar cells, some silicon atoms perform less well than others.

Hayley Birch

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Biohydrogen produced in air

15 December 2010

A strain of nitrogen-fixing ocean microbe has been found to be the most efficient hydrogen-producing microbe to date, boosting the prospect of one day using hydrogen as an environmentally friendly fuel.

The US team behind the discovery says the naturally occurring cyanobacteria Cyanothece 51142 turns solar energy into hydrogen under aerobic conditions at rates several times higher than any other known photosynthetic microbe.

Normally, microbes that produce hydrogen do so under anaerobic conditions. This is because the enzymes they use for hydrogen production, namely nitrogenase and/or hydrogenase, are inhibited by oxygen. By understanding the way Cyanothece 51142 grows and fixes nitrogen, the team learned that nitrogenase was involved in its metabolism, raising suspicions of its hydrogen producing potential under unusually aerobic conditions.

'We expected high rates of hydrogen production, but we were very surprised to find such high rates "right out of the box,"' says co-author Louis Sherman, of Purdue University in West Layafette, Indiana, who collaborated with Himadri Pakrasi's lab at Washington University in Missouri, US. 'The strain has amazing capabilities and we think that there is still untapped potential.'

Cyanothece 51142 is able to produce hydrogen aerobically because it controls its metabolic processes by a circadian clock. It photosynthesises during the day and fixes carbon which it stores as glycogen, and at night it begins fixing nitrogen using the glycogen as an energy source and nitrogenase to convert N2 to NH3 with H2 as a byproduct. Although oxygen is present, high rates of respiration create an anaerobic environment in the cells which allows nitrogenase to function.

Biohydrogen production by Cyanothece 51142 cells using solar energy and atmospheric CO2 and/or glycerol. CO2 is fixed during the day to synthesise glycogen, which serves as an energy reserve and electron source for H2 production at night
© Nature Commun

The team experimented with various conditions to optimise the cyanobacteria's hydrogen production, and found that the microbes produced much more hydrogen if grown in the presence of additional carbon sources including glycerol, a waste product of industrial biodiesel production. The extra carbon is thought to boost the activity of nitrogenase.

By growing cells in glycerol-supplemented media and incubating under an argon atmosphere, the team obtained its highest yield of 467umol of hydrogen per mg of chlorophyll per hour, an order of magnitude higher than any other known hydrogen producing photosynthesising microbe.

'The nitrogenase system in general has been dismissed by many scientists as a sustainable route to photo-H2, in large part owing to the additional overhead paid for cellular energy in the form of ATP required by this pathway. The present work urges us to take a fresh look at this system,' says Charles Dismukes, who studies chemical methods for renewable solar-based fuel production at Rutgers, The State University of New Jersey, US. 'It is a superb example of what can be learned from mother nature and applied to biotechnological applications, though there is much to be studied before such a system could be utilised in the commercial sector,' he adds.

Sherman is aware of the challenges ahead but is hopeful that the work will boost research into hydrogen fuels. 'It will stimulate other biologists to keep studying photosynthetic microbes to find one with even better properties. And it will help policy makers realise that bio-hydrogen production is a possibility and enhance research into all of the other areas that need to be studied before a "hydrogen economy" is a reality,' he says.

James Urquhart

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2010/12/15

Vodka taste test tiff

15 December 2010

'Tis the season for the office drinks party, so perhaps an appropriate time for a row to have broken out over the science behind the taste of vodka.

Last May, Chemistry World reported on a paper published in the Journal of Agricultural and Food Chemistry in which a group led by Dale Schaefer of the University of Cincinnati in the US demonstrated that a particular hydrate of ethanol occurred in different concentrations in different vodka brands.1 This hydrate consists of around five molecules of water associated with one of ethanol. The relative amount of hydrate could give different vodka brands a different 'structurability', the authors suggested, and this in turn could account for people's preference for one brand over another.

Dirk Lachenmeier, head of the alcohol laboratory at the Chemical and Veterinary Investigation Laboratory in Karlsruhe, Germany, and colleagues Fotis Kanteres and Jürgen Rehm, however, remained far from convinced, and have published a comment on the original paper.2

Can you taste the difference between different vodkas?

The authors say that in their work as an 'alcohol control authority', which involves among other things authenticating brands, it has proved difficult to distinguish between one brand and another purely on taste. 'Even when using advanced approaches combining spectroscopy and chemometrics, it is not often possible to correctly assign the origin of vodka (e.g. between Russia and the rest of Europe),' they write.

'Probably there are differences in these structures but in my opinion this has nothing to do with the taste,' Lachenmeier tells Chemistry World. 'I do not think that very small difference would have an influence. I think there is more influence from labelling and branding.'

The team recently carried out tests to see if people could distinguish between vodkas of different alcoholic strength, ranging from 30 per cent to 60 per cent. Only 11 of 24 subjects could discriminate and rank the samples correctly. 'We do not believe there is currently sufficient significant evidence for a taste differentiation of vodka due to structurability or any other effect,' they conclude.

Schaefer and his coworkers Naiping Hu and Svetlana Patsaeva responded to the attack robustly in a rebuttal published in the journal.3 'First, we need to clarify our conclusions,' they say. 'We conclude that vodkas differ in structurability. We hypothesise that structurability is related to perception. Because this is a new idea, ipso facto there is no evidence for taste differentiation due to structurability.'

The blind tasting by Lachenmeier's group on the perception of alcohol content was 'ill conceived.' The rebuttal adds, 'To first approximation, structurability is independent of alcohol content, so alcohol-content perception is an inappropriate way to test whether subjects can distinguish structurability.The validity of this hypothesis is still an open question that should not be closed by preconceived ideas or ill-designed experiments.'

Simon Hadlington

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Speeding up electrons in solar cells

14 December 2010

Phillip Broadwith/Boston, US

Swiss and Chinese scientists have developed a new way of making the porous TiO2 electrode for solid state dye-sensitised solar cells (ss-DSSCs). The method could be more compatible with large scale manufacturing processes.

The team from the Federal Polytechnic School in Lausanne and the Changchun Institute of Applied Chemistry were trying to come up with an alternative to the titanium dioxide nanoparticle paste that has been used to make electrodes for DSSCs in various forms since their discovery by Michael Grätzel and Brian O'Regan in 1991.

There are several problems with nanoparticle-based electrodes, explains project leader Nicolas Tétreault, who spoke to Chemistry World during the recent Materials Research Society meeting in Boston, US. 'They are relatively poor electron conductors,' he says, 'which isn't such a problem in cells with liquid electrolytes.' But because these liquids tend to leak over time and are less suitable for mass production, there has been a move towards solid 'hole transport material' replacements.

However, this throws up problems of its own. Since electrons are not transported through the structure quickly enough, they tend to recombine with positively charged 'holes' in the hole transport material rather than making their way out of the electrode to generate an electrical current. 'So we need to speed up the electrons in the TiO2,' says Tétreault.

The nanowire electrode (right) transports electrons much faster than the nanoparticle equivalent (left) and has larger pores which are more easily filled with the hole transport material
© Nicolas Tétreault

To do this the team designed a new process using rod-shaped particles, which self assemble and join together into nanowires in 15 seconds from aqueous solution. 'We found that when the nanorods fuse together their crystal structures are aligned which helps fast transport,' says Tétreault.

Henry Snaith, who researches DSSCs at the University of Oxford, UK, agrees that improving charge transport should help improve the performance of the cells.
'Not having to burn out a polymer binder [as is required for the nanoparticle paste] opens up a few more possibilities in processing,' Snaith adds. However, he points out that the method still requires heating and treatment with titanium tetrachloride - in the same way the nanoparticle structures would - to get good conductivity between the individual wires. Tétreault acknowledges that this is a drawback, but hints that the team is working on a way to eliminate the heating step, which would open up the process to polymer backing materials to make flexible ss-DSSCs.

Snaith notes that the nanowire structure is more porous than the particle-based electrodes, which should make it easier for the hole transport materials to penetrate and fill the pores effectively. Better pore filling means the light-harvesting dye on the electrode surface shouldn't degrade so easily. However, he points out that to get a significant increase in power generation from ss-DSSCs will probably require a combination of more radical changes to the cell design.

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Lung implant is a breath of fresh air

14 December 2010

Artificial lung technology could reduce the death rate for patients awaiting a lung transplant, say US scientists.

Advanced lung disease is characterised by an inability to remove carbon dioxide from the blood and reduced oxygen uptake efficiency. A shortage of donors can mean long delays and high mortality rates for those awaiting a transplant. The only technology available to aid sufferers during this time is based in intensive care units, hindering quality of life.

Now, Joseph Vacanti and coworkers at Massachusetts General Hospital, Boston, have developed a device that achieves the CO2/O2 gas exchange that, when implanted in the body, could allow patients more freedom when awaiting a transplant. Their design is a microfluidic branched vascular network through which blood flows, separated from a gas-filled chamber by a silicone membrane less than 10um thick. The network is formed by casting polydimethylsiloxane, a biocompatible polymer, on a micro machined mould.

A device that achieves carbon dioxide/oxygen gas exchange could allow patients more freedom when awaiting a lung transplant

A major challenge faced by Vacanti's team was achieving a blood pressure within the device's channels similar to that in veins and arteries. They applied computational fluid dynamics to optimise the vascular network's structure to avoid clotting induced by excessive blood pressure. 'Fulfilment of these design criteria necessitated creating channels that had variable depth throughout the network and also had precise curvature,' says Vacanti's coworker, David Hoganson.

Vacanti's device could be scaled up for implantation. According to Hoganson, an implant-sized device could be fabricated by 'stacking the functional layers of the device to achieve the necessary surface area for gas exchange'.

Jaisree Moorthy, who specialises in using microfluidics in tissue engineering at the University of Pennsylvania, says that Vacanti's device provides a very elegant solution. Compared to existing devices, Moorthy comments that it 'is more efficient due to a thinner membrane, and mimics the biological CO2/O2 transfer rate'.

In the future, Vacanti hopes to develop the device further to incorporate engineered lung tissue.

Erica Wise

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2010/12/14

Nanotube probe for cellular studies

13 December 2010

A new way of peering inside biological cells using carbon nanotubes as tiny multifunctional endoscopes has been developed by US researchers. The team says its nanotube endoscopes allow many different cellular responses in a single cell to be studied in parallel without damaging the cell, and could be important for drug discovery and testing applications.

Existing methods for interrogating cells such as glass micropipettes or nanoneedles often cannot handle fluids well and run the risk of damaging cells. Fluorescent marker molecules are commonly used to probe cells, but cannot follow different cellular responses simultaneously.

Now, a team at Drexel University in Philadelphia, Pennsylvania, US, has come up with an all-in- one solution in the form of nano-sized endoscopes made from carbon nanotubes attached to standard glass micropipettes. 'In many ways it's similar to the kind of endoscopic tools physicians employ to probe the inside of a human body in a minimally invasive fashion. Ours is just many orders of magnitude smaller,' says Gary Friedman, a co-author of the study.

The team made the endoscopes by using a fluid flow technique to place multiwalled carbon nanotubes at the tip of a glass pipette which were then sealed with epoxy. By filling the CNT with magnetic magnetite (Fe3O4 nanoparticles, magnets could then be used to create tiny deflections in the CNT tip to precisely control it.

A multiwalled carbon nanotube is attached to the end of a glass pipette, which is coated with a non-conducting epoxy on the outside and a conducting epoxy on the inside. Inset: Scanning electron micrograph of an endoscope with 100nm carbon nanotube
© Nature Nano.

Experiments with the endoscopes revealed that optical signals observed via Surface Enhanced Raman Spectroscopy (SERS) from different regions within a cell matched existing observations on intracellular SERS. The team was also able to record electrochemical signals and transfer fluids and nanoparticles to and from a cell.

To determine if the endoscopes caused any damage the team looked at cellular calcium signals which increase when a cell becomes stressed. In addition, they made microscopic observations of cellular membranes and intracellular filamentary networks. They found minimal cell damage occurred compared to that caused by standard glass micropipettes.

'This presents an extremely powerful multifunctional intracellular probing technology that can penetrate deep into cells, manipulate intracellular components remotely with high resolution, and perform optical and electrochemical diagnosis at the single organelle level,' says Dejian Zhou, who develops functional nanomaterials at the University of Leeds, UK. 'Its main advantage over other cell interrogation technologies is the cylindrical shape of the probe, which allows for deep cell penetration without causing too much cell destruction,' he adds.

'The CNT endoscopes can be used whenever someone wants to follow in parallel different cellular responses to extracellular stimuli or injections of various agents through the endoscope,' says Friedman. 'This could be important in decoding various cellular signals, genetic and protein interaction networks useful for drug discovery.'

James Urquhart

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2010/12/13

Images show atom 'spinning top' control

12 December 2010

Previously unseen levels of control can be exerted over atomic orientation, movies recorded by researchers in the US, UK and Netherlands show. This is the first-ever imaging of an atomic angular momentum vector precessing in a magnetic field, a motion analogous to a spinning top spiralling about Earth's gravitational field as it slows.

Precession arises because angular momentum vectors, like nuclear spins, have an associated magnetic moment that can be made to align with a magnetic field. This phenomenon is exploited in NMR spectroscopy and magnetic resonance imaging. Having shown how to monitor precession changes as they apply a magnetic field, Claire Vallance of the University of Oxford, UK and her colleagues now hope to study how orbital positioning influences chemical reactions. 'In principle, we could take a p-orbital in an atom and see how its reactivity changes as it is rotated relative to a second reactant molecule,' Vallance told Chemistry World.

Together with David Parker at Radboud University Nijmegen, the Netherlands, and Richard Zare at Stanford University, US Vallance jointly led the effort to study precession using velocity map imaging (VMI). This technique is widely used to study gas-phase photochemical reactions, and Vallance and her colleagues used it to image molecular oxygen dissociated by a UV laser.

Three slices through a distribution of ionised oxygen atoms, with orbital angular momenta in alignment
© Claire Vallance/University of Oxford

The resulting oxygen atoms possess highly aligned orbital angular momenta, which the team then caused to precess by applying a magnetic field for a fixed time. They then ionised the atoms with a second, polarised, laser and used an electric field to accelerate the ions towards a detector that maps their positions in three dimensions. 'The movie shows three different slices through the 3D distribution,' Vallance explains.

An atom's ionisation probability, and therefore its detection probability, depends on a quantum mechanical interaction between its angular momentum distribution and the polarisation of the laser. Applying the magnetic field for different durations yields time-lapse movies of the precessional motion. 'As you make the distribution precess, the detection probability of the atoms changes, and that's what you're actually seeing,' Vallance says.

University of Leeds, UK VMI researcher Ben Whitaker called the work an 'elegant and carefully executed experiment'. He added that trying to control orbital alignments of reagents in bimolecular reactions would be 'an interesting endeavour'. 'For this reason it is an important contribution,' he says.

Andy Extance

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2010/12/10

Fees hike could focus the mind

10 December 2010

The UK government voted in favour of tripling the university fees cap to £9000 last night, although the vote was passed by a slim margin of just 21 votes. Science groups say this could improve higher education by focusing attention on how earning potential varies across the sciences.

Student protests in London turned violent as the results of the vote were announced, with 323 in favour and 302 votes against plans to increase the current cap of £3290.

Under the proposals, universities will be able to charge up to £9000 in 'graduate contributions', although those charging above £6000 will have to meet extra requirements on widening participation. Students will only begin to repay their tuition costs once they have graduated and are earning at least £21,000, repaying fees at a rate of 9 per cent of income above £21,000, with all repayments written off after 30 years.

Universities and science minister David Willetts said the higher education reform package was 'fair for students, fair for graduates and affordable for the nation', while business secretary Vince Cable said the coalition government had 'worked hard' to develop a 'fairer and progressive' graduate contribution scheme.

'There are quite a lot of unknowns at this stage,' says Diana Garnham, chief executive of the Science Council. 'We simply don't know yet how students are going to react to this - but what's important is to protect the ability for able students from any background to pursue Stem [science, technology, engineering and maths] subjects at university.'

Student protests in central London turned violent, with over 30 people arrested included a dozen for violent disorder and two for arson
© Associated Press

Garnham thinks the new system could bring some advantages as universities and students will have to adapt how courses are presented and selected. 'Universities will have to give much better information about the employability of the graduates on courses,' she says. 'We'll be putting much more information in the hands of the customer to choose the courses that will really equip them for well paid jobs.' This is particularly important in the sciences, she says, where she feels there has been some misrepresentation about earning potential for those studying Stem subjects: 'Although people have said you can earn £250,000 more over your lifetime if you study physics, for example, that's not true if you studied biological sciences.'

Another concern she has is the rigidity of the payment model. In other countries there is greater flexibility in how and when fees can be paid, which could lure students abroad. 'For example, in the US, if you get a combination of a cheap bank loan, some family funding and a bursary, it may actually turn out cheaper to go there and you won't come back with a debt for your lifetime.'

'I think we're going to see big changes in the way higher education is delivered,' Garnham says. 'Although the scaffolding's now in place, I'm not sure we know what the building's going to look like.'

Mixed reactions

Wendy Piatt, director general of the Russell Group of research intensive universities said she was 'relieved' by the vote: 'Given the far reaching cuts to university funding introduced by the current and previous governments, higher graduate contributions are the fairest and only viable way forward,' she said. While the group remains concerned about the shortfall in university funding, Piatt said the vote marked 'an important step in the right direction'.

Universities UK, which represents the UK's universities, reluctantly welcomed the news, with president Steve Smith making clear that the situation was far from ideal. 'From the outset, Universities UK has opposed the budget cuts, but we recognise that the government proposals are the best option in the current circumstances,' Smith said in a statement. 'A vote in favour was crucial to provide financial stability for our universities and it means that they can plan their future.' However, he said it was now a priority for the government to clarify the details of the proposed system, and that the organisation's support for the proposals was conditional upon a long term commitment to investment in higher education.

However, the University and College Union (UCU), which represents academic staff in higher and further education, shot down the results of the vote saying there were 'no winners' in the plans. 'Students will see the cost of their degrees rocket and universities will have to charge much higher fees just to recoup the money the government is taking away in budget cuts,' UCU general secretary Sally Hunt said in a statement. 'This battle is not over and we will continue to fight the cuts institution by institution.'

Anna Lewcock

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Breaking news for the CO bond

10 December 2010

UK scientists have pinpointed the moment that the CO bond, the strongest bond of any diatomic molecule, breaks when oxidised by a gold catalyst.

Carbon monoxide (CO) poisons the blood by binding to the oxygen-carrier haemoglobin, preventing oxygen transport in the body. Its oxidation to carbon dioxide is an essential process for life preservation applications such as in submarines, mining industries and for space travel. Gold catalysts can be used in the oxidation process at ambient temperature.

Until now, research has only focussed on the catalysts' active site and not on the reaction mechanisms. Graham Hutchings, Albert Carley and colleagues at the University of Cardiff have investigated the reaction mechanism occurring on a Au/Fe2O3 catalyst and found that CO dissociates at ambient temperature when co-adsorbed with O2.

Unravelling the mechanistic puzzle of CO dissociation on gold surfaces

'The oxidation of CO gives a surprising result on a gold catalyst as the CO bond being broken is counterintuitive since it is the strongest diatomic bond,' says Hutchings.

The team used a temporal analysis of products (TAP) reactor coupled with mass spectrometry to analyse the order in which products are made on the catalyst surface. 'A TAP reactor is a way of putting very controlled pulses of relatively small numbers of molecules onto a catalyst and rapidly analysing the products that are made,' explains Hutchings. Using the TAP reactor allows the initial aspects of the reaction to be explored, which were used to underpin the model surface science and theoretical studies.

'This is an elegant multi-technique study, combining both experiment and theoretical aspects that get to the heart of the catalytic mechanism,' says Richard Catlow, an expert in computational and structural studies of complex materials at University College London in the UK. 'The most significant finding here is that there is strong evidence for O2 dissociating at the interface of the gold particle and the support.'

The team now plans to see if this mechanism is present in other catalytic systems.

Carl Saxton

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Lithiation through the lens

09 December 2010

Scientists have generated high resolution images of lithium ions being deposited on a single nanowire anode, revealing how the material grows and flexes in response to charge. The US and Chinese researchers say the technique will help in the development of more advanced battery systems in the future.

Lithium ion batteries are widely used, but as they are charged and discharged the anode material inside the batteries undergoes large volume changes, which leads to strain in the material causing it to break up. Nanowire anode materials are able to charge and discharge without this breaking thus prolonging the battery's life, but the mechanisms involved were unknown until now.

An international team led by Jian Yu Huang from Sandia National Laboratories, in Albuquerque, US has now observed the lithiation and delithiation (charging and discharging) of a nanowire electrode in an electrochemical cell by placing it inside a transmission electron microscope (TEM) that produces images of the nanoscale process in real time, enabling the team to see the electrochemical reaction occurring at a single particle level.

The team's electrochemical cell consists of a tin oxide (SnO2) nanowire anode - a fairly common new material, lithium cobalt dioxide (LiCoO2) cathode and an ionic liquid containing a lithium ion salt as the electrolyte. Previous attempts to observe these reactions inside a TEM were prevented because traditional ethylene carbonate based liquid electrolytes would evaporate in the high vacuum conditions used. The very low vapour pressure of the ionic liquid means minimal evaporation occurs, solving this problem.

The electrochemical cell is set up inside the TEM to observe the processes on a single particle scale
© Science/AAAS

The SnO2 nanowire is attached to a scanning tunnel microscope (STM) tip, allowing the anode to be easily positioned in the ionic liquid, completing the electrochemical cell. A negative potential is then applied to start the electrochemical reaction. This draws the lithium from the cathode, through the electrolyte to the anode where it is deposited.

As the reaction takes place TEM images show that lithium enters the nanowire along defect channels and the anode becomes distorted, becoming significantly longer but only slightly wider, with the nanowire volume more than doubling.

John Sullivan, one of the research team, explains that even when the whole nanowire was totally immersed in the ionic liquid, lithiation primarily resulted in elongation with relatively little radial swelling. 'We speculate that the strain energy to lengthen the wire is less than the strain energy to expand it as the elongation is always moving away from the reaction [defect] site,' he says.

'The findings have implications on how material would behave as real electrodes in batteries,' says John Owen, a lithium ion battery expert at the University of Southampton in the UK. 'It would be very interesting if they could do the same thing with silicon nanowires as silicon is the material of greatest interest for batteries,' he adds.

Sullivan explains that in the future this new technique will indeed be used to observe the electrochemical reactions of other electrode materials like silicon, in order to develop more advanced high performance batteries.

Mike Brown

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Eco-friendly chromatography

09 December 2010

Spanish scientists have devised a greener form of liquid chromatography by using cyclodextrins as additives in the mobile phase. This results in more water being used in the chromatographic process.

Cyclodextrins are a natural, renewable compound made from starch and are totally biodegradable. They can be modified and tailor made, and as a result are used in a variety of fields including the pharmaceutical, food and cosmetic industries.

High performance liquid chromatography (HPLC) is a commonly used analytical technique that allows fast separation and quantification of compounds in complex mixtures. Owing to its high resolution and sensitivity, it is widely employed in academic and industrial settings.

Using cyclodextrins in chromatography could increase the amount of water being used

Antonia Martin and colleagues from the Complutense University of Madrid investigated ways of reducing the amount of acetonitrile and developing chromatographic methods that use an increasing amount of water and renewable solvents like ethanol. 'Due to the toxicity of acetonitrile, these mobile phases have to be treated as chemical waste, so we were interested in using non-toxic solvents, especially alcohols, as an alternative,' says Martin.

Being greener is only a benefit if the performance of the new system is comparable to current methods. To check this, Martin and her team tested for beta-carbolines, a naturally occurring alkaloid linked to neurological diseases, in human blood serum. The results were as good as non-cyclodextrin modified HPLC in terms of accuracy - in fact the cyclodextrins increased the detection sensitivity.

Peter Dunn, a leader in green chemistry at Pfizer, Sandwich, UK, found it interesting that Martin's team had used cyclodextrin-based mobile phases to replace the acetonitrile. 'There was a rapid increase in the price of acetonitrile during 2008 so these substitutions will lead to significant cost benefits as well as green chemistry benefits,' he adds.

Rebecca Brodie

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2010/12/09

Nanodiamond encrusted bones

08 December 2010

Phillip Broadwith/Boston,US

Using tiny diamonds to reinforce biodegradable polymers could make them strong enough to make surgical screws that simply dissolve once their purpose is served, say US scientists.

Speaking at the Materials Research Society conference in Boston, US, Ioannis Neitzel, part of a team led by Yury Gogotsi at Drexel University in Philadelphia, explained that nanodiamonds would be ideal for reinforcing polymers for biological use because they are completely biocompatible and don't interfere with cellular processes.

However, Neitzel points out that it is not as simple as just mixing the diamonds with your polymer of choice - the key is matching the surface chemistry of the diamonds to the properties of the polymer. Without any modification, nanodiamonds tend to clump together in the polymer, he says, 'so then when you pull on them you just break the agglomerates apart and you don't get the advantages of the diamond properties.'

The functionalised nanodiamonds have a hydrophobic surface, and can then be incorporated into polymers to be used in products such as surgical screws (inset)
© Biomaterials

To avoid this, the team took advantage of the fact that the surface of nanodiamonds is covered with functional handles like carboxylate groups. By converting these to amides with octadecylamine, the team produced nanodiamonds with a hydrophobic surface, to match the hydrophobic poly(l-lactic acid) (PLLA) they wanted to reinforce. PLLA has good biocompatibility and biodegradability characteristics, but on its own it doesn't have the mechanical strength to be used in biomedical applications like surgical screws or bone scaffolds.

'Because you have the hydrophobic chains on the nanodiamond and the hydrophobic polymer matrix, the chains mix together like spaghetti, which helps to disperse the diamonds,' explains Neitzel. 'It also gives a strong interaction with the polymer, which improves the mechanical properties.'

With 10 per cent added nanodiamonds, the team's composites are three times as stiff and nine times as hard as pure PLLA, which makes them much more suitable for making things like surgical screws to fix broken bones together.

'There is a lot of interest in nanodiamonds for composites because they are not only very hard but have interesting surface chemistry,' says Milos Nesladek, who researches nanodiamonds at Hasselt University in Belgium. He suggests the work could be combined with other research into loading drugs onto the surface of nanodiamonds to make medical implants that release drugs to aid healing or reduce inflammation as they degrade.

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