Industry 'disturbed' at Europe BPA ban

30 November 2010

The European Union says it will ban the controversial monomer bisphenol A (BPA) as a raw material in baby bottles due to concerns over its impact on human health. Companies in the EU will not be able to sell or import baby bottles made using BPA after 1 June 2011.

BPA has been under intense scrutiny in recent years due to evidence of links to a range of reproductive and developmental conditions. The compound is primarily used as a monomer in the production of the most common polycarbonate - usually called simply 'polycarbonate'. In the polymerisation, it reacts with another monomer, phosgene, which removes water and leads to repeating carbonate (-O-(C=O)-O-) groups.

No more BPA in baby bottles from 2011

Polycarbonate is used in a wide range of applications including electronics, construction materials and automotive components. But it can degrade in the presence of water and release BPA leading to human exposure. Those critical of the use of the compound have been particularly vocal about baby bottles, which are subject to high-temperature sterilisation processes.

Government agencies around the world have generally endorsed the industry view that materials made from BPA are safe in their intended uses. In September, for example, the European Food Safety Authority said that there was no reason to change its 2008 opinion that exposure to BPA from food containers was well below safe limits. But this has not stopped national governments, such as those of France, Denmark and Canada, taking preventative measures, including bans of certain products.

The EU move has drawn criticism from the plastics industry, which says there is no new evidence to support a change in policy. 'We are disturbed; we are astonished,' says Jasmin Bird from Plastics Europe, the European association for plastics manufacturers. 'This decision does not respect the processes we have in EU regulation for a material that has been approved for use in food contact,' she adds.

Polycarbonate remains popular with manufacturers due to its unique combination of properties. It is highly transparent thanks to its amorphous molecular structure, and its aromatic rings make it highly resistant to shattering. Polymethylmethacrylate can be used as an alternative but it is not as strong.

The polycarbonate for baby bottles market is only a very small part of the total polycarbonate market, which has exploded in the last 20 years, driven in part by the demand for CDs and DVDs. Producers were hit hard by the financial crisis, which had a particularly negative impact on the automotive industry. Sales of polycarbonate products at German chemical group Bayer, for example, fell 21 per cent to 1.9 billion (£1.6 billion) in 2009 from 2.4 billion in 2008. But the impact does not seem to have been permanent. The company made sales of polycarbonate products of 2.1 billion in the first nine months of 2010. It has said it is focusing on new applications for the materials - one is the use of polycarbonates as a lightweight material for car windows.

Whether new markets for polycarbonate will secure the future of the material remains to be seem. But for now one thing is certain: 'The market for baby bottles is gone,' says Bird.

Andrew Turley

30 November 2010

Finland may soon become a viable source of lithium minerals as new reserves are identified that could help ease Europe's reliance on countries such as China for supplies of the material.

Keliber, the Finnish subsidiary of Norwegian company Nordic Mining, has found promising additional resources of spodumene (LiAl(SiO3)2, a source of lithium used in batteries) inpegmatite rock in Ostrobothnia in western Finland.

Extracted spodumene cores
© Keliber

'It would appear that the quantity of ore is significantly larger than earlier thought and the impact of this on our lithium projects is significant,' said Ivar Fossum, managing director of Nordic Mining.

Demand for lithium minerals has grown in recent years driven by the importance placed on lithium-ion batteries as next-generation power sources for technologies such as hybrid electric vehicles. But manufacturers are largely dependent on sources in Chile, Argentina and China.

'We are still investigating and exploring the resource potential in the area, so we have not yet reached a level where we have a firm estimate of the available and minable resources,' Nordic Mining's chief financial officer Lars Grøndahl tells Chemistry World. There are very few lithium projects in Europe, says Grøndahl, adding that the endeavour should be considered 'strategically very interesting' from a European perspective.

If the lithium project goes ahead, 50 million (£42 million) would be needed to begin operations, which will commence two years after construction starts. Grøndahl suggests that a combination of loans from banks and state-owned funding institutions in the Nordic region, together with equity would be used to finance the project.

Lithium batteries are widely used in products from mobile phones to watches, laptops to cameras

Keliber plans to be the first lithium carbonate (Li2CO3) manufacturer in Europe, and has developed an environmentally friendly method of making Li2CO3from spodumene using biogas from biological waste as the energy and raw material for the process.

Although the economic downturn has had an impact on lithium supply, demand and prices, the outlook to 2013 is optimistic, particularly as lithium secondary batteries for automotive uses are now reaching commercialisation, according to market research from UK-based Roskill Information Services.

Not all mining consultants agree on the future of the many lithium projects springing up globally ahead of projected demand, however. Lithium mining consultant Edward Anderson, chief executive of Canada and US-based TRU Group, believes it is unlikely that spodumene-based projects will be able to compete with brine sources, trapped millions of years ago at the bottom of salt lakes. Some 90 per cent of lithium today comes from brine. These sources are 'very sustainable, low cost, highly competitive, and cannot be beaten,' Anderson suggests.

Helen Carmichael



Mystery of diamond polishing solved?

29 November 2010

Researchers in Germany believe they may have solved a riddle that has puzzled the gemstone industry for centuries: why diamond - the hardest known material - can be polished by bits of other diamond, and why only on certain surfaces and in particular directions. The finding could result in improved ways to polish diamond, and in particular new approaches to obtaining perfectly flat surfaces on artificial polycrystalline diamond, which could find important applications in areas such as electronics.

Diamond is typically polished using diamond grit embedded in a rapidly spinning cast iron wheel. Polishers have known for hundreds of years that some facets of the diamond appear 'softer' and more easily polished than others. It was known that this correlated with the fact that carbon atoms are packed in a variety of ways within the crystalline lattice, some more tightly than others, but the precise mechanism of how the surface is worn down remained a mystery.

Now a team led by Lars Pastewka and Michael Moseler at the Fraunhofer Insitute for Mechanics of Materials in Freiburg have used molecular dynamics simulations to come up with a plausible explanation of how polishing works.

A sharp-edged diamond particle (grey atoms, upper left) 'peels off' a dust particle from the glass-like phase (green atoms) at the surface of the diamond (grey atoms, bottom). At the same time, oxygen from the air (red atoms) reacts with the carbon chains (brown atoms) at the surface to form carbon dioxide
© Fraunhofer Institute for Mechanics of Materials IWM

The simulations suggest that as the polishing wheel comes into contact with the diamond, the impact causes atoms to be dislodged from the surface. 'This forms an amorphous layer, which slowly creeps across the surface of the underlying crystal,' says Moseler. Carbon atoms in this amorphous slug make bonds with those in the crystal lattice below. As the layer moves one of two things can happen to these bonds. If the underlying atom is relatively loose, it will be dragged from the crystal. If it is tightly packed, as in some planes within the lattice, it will remain in place and the bond will snap.

This accounts for some surfaces and directions being more amenable to polishing than others, says Moseler. The finding opens the way to modifying the amorphous layer to include atoms that bond more tightly to those of the underlying crystal so that even the 'hard' faces can be polished. This could be especially important in processing synthetic diamond which is polycrystalline with many random faces - hard and soft - at the surface, making it difficult to polish to the tolerances needed in many electronic applications.

Mike Ashfold, an expert on the chemistry of diamond at the University of Bristol in the UK, says, 'Polishers have long recognised that some diamond surfaces polish more easily, and more successfully, than others; this work offers the first detailed atomistic explanation for such behaviour. The rationale is persuasive and reproduces - qualitatively at least - the relative surface/direction wear rates observed experimentally.'

Simon Hadlington


DNA readers ratchet closer

29 November 2010

Rapid, cheap DNA sequencing has just edged a step closer, thanks to a new technique to control the motion of single DNA strands as they pass through a protein nanopore 'reader'. The advance, which was the work of Reza Ghadiri and his team at the Scripps Research Institute in La Jolla, US, cracks the fundamental problem that has been holding back nanopore-based DNA sequencing - how to get the DNA to travel slowly enough through the pore to read off the sequence base by base.1

The idea behind such protein pore-based readers - such as those recently developed by Hagan Bayley at Oxford University, UK2 - sounds simple in principle. An electrical potential is used to draw single DNA strands from one side of the pore to the other. As each strand enters the pore, the current flowing through the pore changes measurably - and the exact current is characteristic of the DNA base occupying the pore at the time.

In theory, the DNA sequence can then be read off by recording the changing current as the DNA strand traverses the pore. However, in practice, the voltage needed to thread the stand into the pore then sucks the DNA through the pore far too quickly for each individual base to be detected.

Ghadiri's solution is to attach a polymerase enzyme - the protein nature uses to turn single-stranded DNA into double-strands during cell replication - to the top of the DNA strand. As the enzyme works its way along the strand, adding bases one by one to form the second strand, it gradually draws it through the pore, base by base at a rate that would be slow enough for each base to be electrochemically identified.

The approach exploits the motor function of DNA polymerase to ratchet DNA strands through a nanopore slow enough for the bases to be identified
© Angew. Chem. Int. Ed.

'You can think of the polymerase as a motor protein,' says Ghadiri. 'It's not just slowing the speed of DNA going through the pore that is important - you have to go through the pore in this stepwise fashion.'

'This remarkable demonstration that DNA can be ratcheted through a nanopore by an enzyme, without the cyclic addition of reagents, complements recent successes in base identification,' says Bayley, who collaborates with Ghadiri on DNA readers but was not involved in this latest research. 'When the two are combined, a nanopore sequencing device will be complete.'

Ghadiri says he is already working on the next generation version of his system, which will combine his DNA polymerase approach with the kind of 'read-head' nanopore developed by Bayley that can identify each base as it passes through the pore. 'It is another challenge putting all these things together, but at least there is no fundamental issue that it cannot be done.'

James Mitchell Crow



Water and sunlight: a winning catalytic combination

28 November 2010

Researchers have incorporated a sunlight-activated trigger into an oxygenation process that uses water as the oxygen source. The combination approach is a step towards mimicking nature's photocatalytic processes and could help reduce carbon dioxide emissions and lead to further applications for solar energy.

Shunichi Fukuzumi and coworkers from Osaka University in Japan and Wonwoo Nam from Ewha Womans University in Seoul, Korea and colleagues have developed highly efficient photocatalytic oxygenations of organic substrates such as sodium p-styrene sulfonate, using sunlight as an initiator and water as an oxygen source.

The team developed a ruthenium (II) complex that absorbs light and uses the energy to reduce a cobalt complex. The ruthenium (III) complex then goes on to react with a manganese porphyrin oxygenation catalyst. This reaction causes the manganese porphyrin complex to give off a proton, and become the active species responsible for the oxidation of organic substrates. The catalyst can oxygenate substrates by using water in a phosphate buffer solution (pH 7.4) as an oxygen source.

'This is an important step for the general use of water as a clean and abundant reactant using solar energy,' say Fukuzumi. He goes onto explain that current industrial oxygenation processes are energy consuming, resulting in large amounts of CO2 emissions. 'Oxygenation reactions using water as an oxygen source under mild conditions using solar energy would contribute to cut down CO2 emissions,' he adds.

Richard Douthwaite, an expert in photocatalysis from the University of York in the UK, believes that the work is an interesting proof of principle. 'What they appear to have done is take two known reactions and stitch them together,' he says. 'But no-one has shown before that light can be used to mediate these oxidation processes with water,' he adds.

Fukuzumi acknowledges that there is still work to do to make the process truly environmentally benign. The team's aim is to replace the cobalt complex with molecular oxygen 'to develop oxygenation reactions with water as the oxygen source, oxygen as the oxidant, under mild conditions using solar energy.'

Mike Brown



Printing on bioactive paper

26 November 2010

An enzyme printing process that prints the product of an enzyme-catalysed reaction, but not the enzyme molecule itself, has been designed by scientists in Australia to produce bioactive paper.

Taking their inspiration from traditional printing methods such as ink jet and thermal contact printing, Wei Shen and colleagues from Monash University, Australia, have used relief and planographic printing methods to print the product of a reaction catalysed by an enzyme, in this case horseradish peroxidise (HRP).

Most current enzyme printing techniques use an 'ink' that contains the enzyme for biosensing. The problem with this method is that when the enzyme is transferred from the printer to the paper in the ink, it is difficult to recover the enzyme and reuse it. The enzyme may also interfere with any further reactions that occur on the paper.

A pattern of a cat's head was digitally generated and an ink jet printer was used to print a solution of horseradish peroxidase onto a nitrocellulose film

One technique developed by Shen to avoid the movement of the enzyme molecules involves the immobilisation of HRP on a nitrocellulose film to form the printing plate. They then coat paper with a liquid substrate that changes colour on contact with HRP. When the printing plate is pressed against the paper, the biochemical reaction makes the paper change colour at the point of contact.

Another technique investigated involves the use of an ink jet printer to make a digitally-generated enzyme pattern on a flat printing plate. When this plate is placed in contact with paper, the different surface chemistries of the plate generate an image.

By simply printing the reaction, and not the molecule, Shen has developed methods that can be reused for as long as the enzyme remains active.

Brian Derby, a specialist in biomaterials from the University of Manchester, UK, felt that the authors 'demonstrate the flexibility of their approach by using non-contact printing (ink jet) to pattern their printing plate' and comments, 'this is a very clever piece of lateral thinking'.

This kind of printing has many practical uses. 'It has potential applications in novel packaging materials, low-cost diagnostics, food safety, anti-counterfeiting, and pathogen detection using bioactive papers,' explains Shen. Research into developing these applications is currently underway.

Rebecca Brodie


Medicine gets smart

26 November 2010

Korean scientists have developed a fast and simple mobile phone-based device to test urine samples for common diseases in developing countries. This could provide a cheap, painless solution for detecting disease in remote areas.

Dae-Sik Lee at the Electronics and Telecommunications Research Institute and colleagues developed a pocket-sized urinalysis colorimetric reader capable of sending data wirelessly via a smart phone. To take urine samples, the team used a commercially available 10-parameter urinalysis paper strip that detects glucose, protein, bilirubin, urobilinogen, ketones, nitrite, pH, specific gravity, erythrocytes and leukocytes.

Lee's team tested the device on 1000 human urine samples and the results were comparable with those given by hospital equipment, demonstrating reliable glucose and protein analysis. It uses a colorimetric multidetection diode comprising LEDs, photodiodes and an optical splitter, which reads the colour intensity changes on the paper strips.

In remote areas of the developing world early detection and prevention of disease is rare. Portable lab on a chip devices have been developed to help combat this but many are not up to the standards required for use in such environments, as they are often expensive with high power consumption and take a long time to produce results, whereas Lee's device can produce readings within six seconds.

The simple and easy to use handheld device could prove vital for patients in remote areas of the developing world

'Disease prevention through early screenings or diagnosis in daily life is very important,' says Lee. 'We believe that miniaturised and functionalised devices can provide promising and practical approaches to accomplish this vision.'

'The work is exciting as it fits into the trend of decentralised healthcare. The idea of a simple handheld instrument to deliver diagnostic results in the developing world is logical and very feasible to implement,' says Samuel Sia, an expert in biomedical engineering, at Columbia University, New York, US. 'However, the authors should try to match their clinical test to a real clinical need, and demonstrate that their approach can work in the field,' he adds.

Lee's team hopes to develop technology to combine the reader with microfluidic biosensors and to provide more accurate measurements of analytes.

Carl Saxton


Fingerprinting red wine

26 November 2010

A sensor that can discriminate between different tannins and be used to fingerprint a wide variety of red wines to confirm their authenticity has been developed by US scientists.

Eric Anslyn and colleagues at the University of Texas at Austin and University of California Davis have developed a sensor made with colour-changing indicators. They used the sensor to test wine samples from different vintners and managed to distinguish between specific flavonoids - chemicals found in fruit and vegetables, tea and red wine - in particular looking at tannins, which are responsible for colour, aging ability and texture.

When wine is added to the sensor, the indicators are displaced, which results in a colour change that can be monitored and recorded. The team found that patterns emerged for different wine varietals. They tested Pinot Noir, Zinfandel, Beaujolais, Cabernet Sauvignon, Shiraz and Merlot and assigned signatures to each wine type. The team could also classify wines from the same varietal. They tested different brands of Shiraz (and Zinfandel in a separate study) and they were able to link the tannins to the genome of the specific grape.

The sensor can assign signatures to different wine types and to wines within types

'The ability to fingerprint mixtures of metabolic origin, without knowing their exact compositions, has huge potential for applications in medical diagnostics, environmental science and the food industry,' says Anslyn.

Kim Janda, a detection expert at the Scripps Research Institute in the US, has visions of the sensor being used for 'biodefense purposes where rapid and accurate identification is at a premium.' Janda adds: 'if Anslyn improved the method further he could put sommeliers out of business!'

'Product authenticity is an important issue with food and beverages, particularly with high value products such as wine,' says Bob Dambergs, a senior research scientist at the Australian Wine Research Institute, Glen Osmond. 'Flavonoid compounds define red wines and this study makes clever use of specific interactions of flavonoids with peptides to produce a sensor array with high discriminatory power. Most wine producing countries have strict label-integrity regulations to protect consumers - the availability of rapid analysis methods utilising chemical sensors will facilitate compliance monitoring.'

Emma Shiells


Enriching the origin of life theory

26 November 2010

An enantioenrichment of the amino acid valine, which could shed light on the origin of chirality on Earth, has been achieved by scientists in Spain.

Chirality is important as amino acids and sugars are present in one single enantiomer in all organisms, and enzymes and receptors are chiral too. As organisms don't have the same response to different enantiomers and many active components of medicines are chiral, understanding how pure enantiomers form can help us understand how we evolved and help develop the medicines of the future.

Cristóbal Viedma, from the Complutense University in Madrid, and colleagues have been able to amplify the purity of one enantiomer over another in valine, one of life's building blocks. They chose valine because it was found in meteorite samples in a non-racemic form and the enantiomeric excesses matched values obtained under simulated interstellar conditions.

Scientists observe the enantiomeric enrichment of amino acid valine in a sublimation experiment

Viedma's team sublimated a racemic mixture of valine. When the valine condensed, it formed a conglomerate. A conglomerate is a mixture of crystals formed by pure enantiomers - the pure crystals can be extracted from the mixture. The group found that when they continued to heat the flask, this amplified the initial enantiomeric excess. 'One can imagine similar processes occurring near volcanoes where temperature gradients are enormous and such scenarios would have been plausible on primitive Earth,' comments Viedma.

Up until now, enantioenrichment has been studied with solid-liquid systems, even though gas-solid transformations may have been plausible in both our primeval planet and star-forming regions. 'It is true that gas-solid transformations may not be as general as solid-liquid equilibria, but you never know what is going to turn out to be useful,' says Viedma. 'This is an interesting project in terms of the intriguing conundrum of the origin of biological chirality as well as extensions to the manufacture of chiral substances.'

'I have no doubt that it will change my understanding of how crystals grow in a profound way,' says Michael McBride, who studies chemical reactivity and physical properties of organic solids at Yale University, US. 'Understanding this behaviour might expand the range of what we can control in chemistry and materials science.'

Amaya Camara-Campos



Making plastics from plants

25 November 2010

Cheap bio-oil could soon compete with crude oil in plastic manufacture, thanks to work by US scientists.

Pyrolysis oil, made from biomass, is mainly used for heating or electricity production. However, scientists at the University of Massachusetts-Amherst have now shown that this cheap starting material can be converted into feedstock chemicals for the plastics industry, and at a competitive price.

Scientists have previously used zeolite catalysts to make feedstock materials like aromatic and olefinic hydrocarbons from pyrolysis oil, but the yields were quite low. The Massachusetts team, led by George Huber, and featuring visiting scientists from Southeast University in China and the University of Nottingham, UK, added a hydrogenation step prior to the zeolite conversion and in this way increased the amount of these valuable chemicals produced by up to three times.

The process uses standard catalysts - ruthenium and platinum for the hydrogenation, and then a commercial zeolite catalyst to convert the hydrogenated pyrolysis oil to the target molecules. By integrating these processes, only partial hydrogenation is required, avoiding high temperature hydrogenation and catalyst coking. The zeolite step at the end can then be done using a fluidised bed reactor that recycles any coked zeolite catalyst, and because the chemistry is well understood, the scientists can tweak the conditions to produce different products depending on what's required.

Portable biorefinery for pyrolytic oil production. The technique can produce high-volume chemical feedstocks including benzene, toluene, xylenes and olefins from pyrolytic bio-oils, the cheapest liquid fuels available today derived from biomass
© Phil Badger, Renewable Oil Internatiional

'There are mainly six major petrochemicals that provide the whole plastics industry with its feedstock,' explains Huber. 'We've worked out a way to make the same chemicals from biomass that you make from crude oil today,' he added, 'and we think we can be competitive with $60 per barrel oil using this technology'.

At the time of writing, crude oil was trading at around $80 (£50), so the technology certainly sounds competitive. Huber, in collaboration with Anellotech, a start-up he helped found, is currently scaling up the process to send litre amounts of their products to interested commercial partners.

Ultimately, Huber explains that the limiting factor in his technology will be the price of hydrogen, which will dictate the balance between hydrogenation and zeolite conversion. Chris Saffron, an expert in converting biomass into fuels and chemicals at Michigan State University agrees that the hydrogenation will be a limiting factor, but not just due to cost. 'One question I'd have is where are they going to get their hydrogen from?' Saffron says, explaining that pyrolysis oil is made in rural communities will and need hydrogenation before transport because pyrolysis oil itself is reactive.

Huber does suggest some solutions to this problem, splitting water using renewable electricity sources is one idea, or using hydrogen acquired from more biomass. Ultimately, Saffron does think that overall the science is promising: 'The fact that one can convert biomass to hydrocarbon fuels that could drop into existing infrastructure, is encouraging', he adds.

'We still think there are several improvements we need to make, from designing better catalysts to designing more efficient reactors and improving process innovation,' Huber concludes. But he says the paper provides 'a roadmap of what needs to happen.'

Laura Howes


Capping scientific migrants

25 November 2010

A new UK immigration cap could bias against researchers looking to come to the UK.

This week UK Home Secretary Theresa May announced plans to introduce an annual cap of 21,700 highly skilled and skilled non-European workers, such as researchers, entering the UK. The changes will come into force from April 2011.

One thousand of these visas will be available for 'highly skilled' migrants that display 'exceptional talent', such as scientists, academics and artists. The remaining 20,700 'skilled' migrants will be allowed entry if they have a graduate level job offer from a UK institution or company.

But there are concerns that the points based system (PBS) used to decide whether individuals qualify for a UK visa isn't set up to adequately recognise progression or success in a scientific career.

Scoring points

Migration into the UK falls into two categories - highly skilled workers (the so called Tier 1 route) and skilled workers (Tier 2). The existing Tier 1 route includes entrepreneurs and investors entering the country. This route will be reformed, but will not be subject to immigration limits in order to bring more money into the country. International transfers within businesses will not be limited, but will require employees to be earning a salary of over £40,000 to be able to stay in the UK for over 12 months, and their stay will be restricted to five years.

Prime Minister David Cameron and Home Secretary Theresa May visit UK Border Agency staff
© Steve Parsons/PA Wire

The new Tier 1 route for 'exceptional talent' will be open to migrants who have won international recognition in scientific and cultural fields - such as Nobel prize winners - or those who are likely to achieve such recognition in the future.

'We do not accept the premise of needing to cap exceptional talent, because the UK needs global scientists more than global scientists need the UK,' says Imran Khan, director of the Campaign for Science and Engineering (Case) in the UK. 'If they can't get into the UK, they will go somewhere else.'

But is it the points based system that Khan pinpoints as particularly problematic, especially for those hoping to enter the UK on a Tier 2 visa. 'The way the PBS has been set up does not reward scientific careers,' he says. 'If you have a PhD you get 45 points, compared to 80 points for an MBA - that's really skewed and is based on a very superficial judgement on the value of migrants to the UK,' he adds.

'I think [the immigration cap] could very well damage UK science, but there is an opportunity for the Home Office to prevent that happening by reforming the PBS in order to properly reward scientific careers,' states Khan.

'The government recognises that there is an important contribution made by scientists and researchers to the UK and the economy,' a spokesman from the UK department for Business, Innovation and Skills (BIS) told Chemistry World. 'The changes [to the Tier 1 route] actually give a greater weight to academic qualifications, so we can still attract the high quality researchers and scientists.'

The numbers game

Science-focused industries are also concerned by the new proposals. While the provision for intra-company transfers received a positive response, the Association of the British Pharmaceutical Industry (ABPI) said in a statement that it 'welcomes the creation of the exceptional scientists category, but questions if the number proposed is sufficient to meet the demands of academia, research charities and industry.The UK pharmaceutical industry alone currently employs over 27,000 people in R&D.'

The Home Secretary also announced that she would be launching a consultation on student visas, aiming to restrict entry only to those studying at degree level, though with some flexibility.

Students currently account for almost two-thirds of non-EU migrants entering the UK each year, said May, with nearly half of these studying for courses below degree level. Too many students at these lower levels are abusing the system by entering the UK with a view to living and working rather than studying, said May, a practice which must be curbed. 'The thing to emphasise is that legitimate and high quality higher education and further education will be protected,' a BIS spokesperson said.

Mike Brown


Designing safer stents for heart patients

25 November 2010

A study by UK researchers provides insights into how the body reacts to the metal stents used to wedge open blocked blood vessels in heart patients. The research could aid the creation of materials designed to reduce the risk of complications associated with stents.

In an angioplasty, a stent is inserted into a blood vessel to widen it, with the aim of improving blood flow. In around a quarter of cases, however, healing of the surrounding tissue leads to a new blockage - a complication known as in-stent restenosis (ISR). Although medicated stents reduce the risk of ISR, they are expensive and may increase the likelihood of a clot forming on the stent, and of heart attack.

An ideal alternative would be a material or stent coating that triggered a less vigorous healing response. But first scientists need to understand more about the complex processes that lead to ISR. Matteo Santin and colleagues at the University of Brighton studied the effects of stainless steel stents on human cells, comparing them to the effects of fibrin and collagen gels, which mimicked substrates in clots and damaged blood vessels respectively.

Smooth muscle cells adhering to tissue culture plastic, collagen gel and stainless steel
© J. R. Soc. Interface

'We tried to understand why stainless steel upsets this healing process and all our evidence shows that the interaction of the cells with the metal surface leads to excessive proliferation of the smooth muscle cells,' says Santin. Their work builds on previous studies indicating that the metal surface activates inflammatory cells to produce signals that stimulate cell growth.

'It has long been known that the phenotype of smooth muscle cells is much dependent on the underlying substrate and that the stent material has adverse effects during the healing response,' says Vicente Andrés, a vascular biologist at the Spanish National Centre for Cardiovascular Research in Madrid, Spain. 'The studies by Guildford et al are of obvious interest, however more work is needed to conclusively demonstrate effects on cell proliferation.'

Meanwhile, Santin's team has been working on making stent surfaces more biocompatible. They have already applied for a patent for a dendrimeric polymer that Santin describes like a 'nano-tree' - the root sticks to the metal surface, while the branches selectively interact with molecules involved in cell behaviour. An ultra-fine layer of the polymer shouldn't crack like existing coatings upon expansion of the stent, crucial because loose pieces are a potential cause of clots.

Hayley Birch


Mimicking nature's leaving group

24 November 2010

A synthetic leaving group to be used in DNA synthesis could lead to new antiviral drugs or an artificial rival to DNA, say European scientists.

DNA can be synthesised using enzymes to catalyse the polymerisation of nucleoside triphosphate building blocks. Nucleoside monophosphates are incorporated in a growing nucleic acid chain, while pyrophosphates are released as leaving groups. Replacing the pyrophosphate leaving groups with synthetic alternatives could open up a range of biotech opportunities.

Now, Piet Herdewijn from the Catholic University of Leuven, Belgium, and colleagues have designed a series of leaving groups that are compatible with HIV-1 reverse transcriptase (an enzyme that synthesises DNA from RNA). They found that the most efficient pyrophosphate mimic was 3-phosphono-L-alanine. Herdewijn explains that they have managed to improve the kinetics of incorporating the nucleotide into the chain compared to previous leaving groups. However, 3-phosphono-L-alanine has a lower efficiency than pyrophosphate, which can cause DNA synthesis to stall. But the team says that they hope to use the stalling effect to create new antiviral drugs that selectively stall the synthesis of viral DNA, preventing virus replication.

The most efficient pyrophosphate mimic was 3-phosphono-L-alanine

The implications of this research aren't limited to new drugs, says Herdewijn, and designing a replacement for the pyrophosphate group could be a step towards creating an artificial rival to DNA. 'The long term goal is to look at nucleic acid synthesis using alternative biochemistry and eventually make xeno-nucleic acids [artificial nucleic acids] as an alternative to natural nucleic acids in vivo,' explains Herdewijn.

David Jakeman, an expert in biosynthetic mechanisms at Dalhousie University, Canada, says that this could be an interesting avenue of research in the future. 'The study of non-canonical mimics of pyrophosphate provides insight into the role of the leaving group in DNA synthesis, by HIV-1 reverse transcriptase. These advances may provide new directions for biotechnological applications of in vitro, and ultimately in vivo, DNA synthesis and replication.'

Russell Johnson



Novel green separation system

23 November 2010

Researchers in Canada have stumbled across a new chromatographic separation method that could make an inexpensive and green contribution to the analytical chemist's toolbox.

Michael Fogwill and Kevin Thurbide at the University of Calgary were experimenting with water at high temperature and pressure (in its so-called subcritical form), saturated with CO2 as a mobile phase in a chromatography system. They used a conventional packed column as the stationary phase and stainless steel tubing either side of the column. When the experiment was finished they removed the column and flushed the remaining sample through the steel tubing. To their surprise they realised that separation was still occurring. 'It was a bit of a eureka moment,' says Thurbide. 'How were we getting separation?'

The team analysed the caffeine content of a cup of coffee
© Anal. Chem.

Further investigation revealed that water was coating the inner surface of the tubing and remaining stationary. The precise way in which the water is deposited and distributed is not yet clear, but the team calculated that a uniform film would be around 4 um deep and that the amount of water held by a given length of tubing was highly reproducible.
'So we are able to coat the stainless steel with water and pump in CO2 as the mobile phase and analytes will partition based upon their ability to dissolve in CO2 versus water,' says Thurbide.

To demonstrate the utility of the system the team analysed the caffeine content of a cup of coffee bought on the high street and the ethanol content of a biofuel. Because of the high differential solubility of caffeine and ethanol between the phases, sharp peaks were observed with no sample preparation needed.

The researchers point out that the technique is green - it does not use organic solvents or an organic stationary phase - and is inexpensive. Thurbide acknowledges that it is not yet as efficient as it might be, probably because of the relatively thick film of water as stationary phase. The researchers are looking to improve on this.

'It's great to read papers based on the exploitation of simple unexpected
experimental observations and strange anomalies, which end up resulting in a new research direction entirely,' says Brett Paull, an expert in separation chemistry at Dublin City University in Ireland. 'The work clearly has a way to go, but further developments and applications are sure to follow this first paper,' he adds.

Simon Hadlington



Irish drug industry fears bailout tax terms

22 November 2010

Any increase in Ireland's corporation tax rate as part of a financial bailout could hurt the country's rapidly expanding pharmaceutical industry, currently its largest contributor to corporation tax.

Ireland is in talks with the European Union and the International Monetary Fund regarding a potential rescue package to stabilise the Irish banking system and protect the euro. So far Irish leaders have ruled out any increase in its corporation tax rate as part of the deal. But media reports have suggested that member states may try to force an increase to guarantee a return on their investment.

Ireland's corporation tax rate of 12.5 per cent is amongst the lowest in Europe. A spokesperson for the Irish Pharmaceutical Healthcare Association (IPHA) says: 'Corporation tax is very important to the industry. It is one of the primary reasons why the industries came to Ireland and continue to invest in the Irish economy.' Indeed, 13 of the largest 15 pharma companies, including Bayer, Pfizer, GlaxoSmithKline, AstraZeneca and Roche have at least one manufacturing site there. This has helped Ireland become the second largest net exporter of medicines in the world.

The Irish pharma industry employs 24,500 people, according to IPHA figures

The pharma industry contributes 3 billion (£2.6 billion) in total tax receipts to the Irish economy. More recently, there have been signs that drugmakers are interested in the country for more than just manufacturing. Earlier this year, for example, Warner Chilcott moved its global headquarters from the US to Ardee in Ireland.

The European Commission representative for Ireland describes media reports as 'mere speculation', adding that 'the government has stated its intentions very clearly that it will not be looking to increase the corporation tax'.

Two weeks ago, Puerto Rico changed its taxation system so that from next year most multinational corporations will have to pay much higher taxes to compensate for lower taxes paid by individuals. 'In Puerto Rico, the governor's decision to increase taxes is negatively impacting the multinational corporations,' the IPHA spokesperson says. 'This is what will happen in Ireland if the corporation tax is increased. It will reduce our global competitiveness to attract foreign investors.'

Akshat Rathi


Nature's pipettes

22 November 2010

A pipetting method that mimics the way flowers protect themselves from water damage could find its way into restaurants, say US and French scientists.

Flowers in aquatic environments have a flood defence mechanism. When they are submerged in water, the petals fold over to form a capsule, trapping an air bubble within, protecting the genetic material. Pedro Reis and his colleagues at the Massachusetts Institute of Technology, Virginia Tech and Paris Tech recreated this phenomenon using a petal-shaped vinylpolysiloxane film that they cast and cut to achieve the required stiffness.

The team found that when the film was pulled out of water, it closed up to grab between 20 and 600 mm3 of water. The petals were then prevented from opening, much like how water will not flow from the open end of a straw if the other end is covered. They realised that the pipetting mechanism effect is mathematically opposite to that of the flower trapping an air bubble. 'It is the inverse of the natural problem only in that the hydrostatic pressure, resulting from gravity, is a source of suction that causes closure when the flower is pulled upwards,' explains Reis' colleague John Bush, who adds that the same phenomenon would occur in real flowers were it not for the stalk obstructing the closure.

Chef José Andrés is looking to use this phenomenon to introduce a new palate cleanser between courses

Bush is collaborating with chef José Andrés, who trained at the three Michelin-starred restaurant El Bulli in Spain and now owns a number of restaurants in Washington DC, US. Andrés is looking to use this phenomenon to introduce a new palate cleanser between courses. 'You could make the flower edible, perhaps out of gelatine,' explains Reis, 'and inside would be strong liquor. You could eat the whole thing.'

'I think it's nice in the sense that it's passive,' says Dominic Vella, an expert in fluid mechanics at the University of Cambridge, UK. 'All you have to do is touch the pipette down and then lift it up and it automatically captures a volume.'

Reis and his team are now looking to explore further uses for their pipettes, including using them to grab oil that's floating on water.

Yuandi Li



Rise of the micro machines

19 November 2010

Microjet engines called microbots that can transport cells within a fluid to any desired location have been developed by German scientists.

Manipulating nanomachines to transport biological matter in the body has been a challenge until now. Samuel Sanchez from the Institute for Integrative Nanosciences in Dresden and colleagues have shown that by using a magnet, it is possible to navigate a microbot towards a specific cell within the body, pick it up from point A and transport it to point B.

Taking their inspiration from Mother Nature, the team looked at existing biological motor proteins - flagellae, which are tail-like projections that protrude from certain cells to help them move independently, and kinesin, a more complex motor protein found in eukaryotic cells that aids cell movement during mitosis and meiosis. Both are powered by chemical fuel and produce mechanical energy.

By using a magnet, it's possible to navigate microbots towards specific cells, pick them up from point A and transport them to point B

Sanchez's team was able to transport multiple micro-objects in fluid, such as colloidal microparticles and metallic nanoplates. They had also reduced the toxicity of the peroxide fuel using the enzyme catalase, which breaks down the peroxide and releases oxygen bubbles that propel the microbots. 'The next step was to demonstrate that our microbots can transport biological material such as cells,' explains Sanchez.

To do this, the group made small machines made up of hollow tubes containing a thin layer of platinum on the inside. They found that the machines moved independently in a peroxide solution when controlled externally by a small magnet manipulated with a joystick. The microbots can be directed towards suspended cells in solution, where they suck them up through the tube and transport them to the desired location. They released the cells from the tube by rapidly turning the magnet.

'This groundbreaking discovery by the Sanchez group opens up new avenues for highly important biomedical and bioengineering applications,' comments Martin Pumera, an expert in nanotechnology and microfluidics at Nanyang Technological University, Singapore. 'It is truly a dream come true.'

Sanchez and his team hope that in the future their microbots could perform visionary tasks within the body. 'I would like to see our microbots swimming inside the bodies of animals, delivering drugs to required locations, for example, in the vicinity of cancer cells or replacing diseased cells with healthy ones.'

Philippa Ross


The medicine's in the (wine) bottle

19 November 2010

Some red wines contain such high levels of polyphenols that a single glass has equivalent bioactivity to several daily doses of an anti-diabetes drug, say Austrian scientists.

Polyphenols play a key role in the health benefits of wine by acting as antioxidants that prevent cell damage, but the other possible effects of these chemicals are not yet fully understood. Now, a group led by Alois Jungbauer from the University of Natural Resources and Life Sciences, Vienna, Austria, have shed light on this area by examining polyphenols in eight Austrian red wines. They assessed polyphenol activity towards a receptor called PPAR-gamma (peroxisome proliferator-activated receptor gamma). This receptor is present in many tissues in the body, and is primarily involved in the development of fat cells, in energy storage, and in modifying lipid and glucose levels in the blood, making it a key target for drugs for cardiovascular and metabolic diseases.

Red wines are rich in polyphenols, in particular epicatechin gallate, also found in green tea, and ellagic acid, which is found in many fruits

All of the wines were rich in polyphenols, in particular epicatechin gallate, also found in green tea,and ellagic acid, which is found in many fruits. When the team ran PPAR-gamma binding assays, they found that not only did these compounds bind to the receptor, but that the wines contained enough of them to rival the activity of the potent drug rosiglitazone, which is used to treat type 2 diabetes. One of the wines, a 2003 Blaufränkisch, contained particularly high polyphenol levels - just 100 mL contained levels equivalent to about four times the daily dose of rosiglitazone.

Jungbauer says that tannin-rich red wines contain more of the polyphenols, but that it is too early to come to any general conclusions about grape varieties. However, he suspects that environmental factors and wine technology have as much influence as the type of grape. He points out: 'grape tannin and oak tannin supplements are often used in wine technology as antioxidants, and are added to the mash or fermented must. These extracts are rich in polyphenols and may also be a potent source of PPAR-gamma ligands.'

Chi-Tang Ho, a food scientist at Rutgers School of Environmental and Biological Sciences, New Jersey, US, thinks that this is an 'extremely exciting' study, and that it provides 'good experimental evidence for the potential anti-diabetic effect of drinking red wine in moderation.' 'Grape skin extracts have great potential, and although the influence of ethanol is not yet fully understood, I am confident that it will be possible to replace some synthetic compounds by plant extracts,' concludes Jungbauer.

David Barden


A tattoo to monitor health

19 November 2010

A sensor to be injected into the skin just like a tattoo that measures sodium concentrations in the blood has been developed by US scientists. The sensor could be used to monitor diseases or warn against dangerously low sodium levels during exercise.

Heather Clark from Northeastern University, Boston, and coworkers made plastic nanobeads that fluoresce to different extents with changes in sodium levels. The beads are coated with a biocompatible polymer and are injected just under the skin to allow the fluorescence to be monitored easily.

Technology for determining the amount of sodium in the bloodstream has been available for some time. However, it requires a blood sample from the patient, which limits the measurements to isolated time points. This is a problem for understanding a condition called hyponatremia, where sodium concentrations in blood serum are lower than normal. Hyponatremia can occur after certain types of surgery, with brain trauma or tumours, and has been found in endurance athletes.

The team is developing a sensor to inject into the top layer of the skin that falls off after seven days, like a non-permanent tattoo

The team tested the sensor by injecting it into the skin of mice and analysing the fluorescent images produced. Clark says she hopes that the final product will be a safe and minimally invasive sensor. 'We are currently developing a more biodegradable sensor,' she explains, 'to inject into the epidermis (the top layer of the skin) that falls off after seven days, so it would be like a non-permanent tattoo.' Clark envisions the sensor beads could be placed into the fingertip and monitored in much the same way that blood oxygen concentrations are in hospitals - with a pulse oximeter clipped to the finger.

'The technique has potential, however there is still some way to go,' says Ibtisam Tothill, an expert in analytical biochemistry at Cranfield University, UK, who adds that it must be proven to be quantitative before it can be applied to humans. Clark agrees that this is the next step and the group hope that it will be relatively straightforward to demonstrate the applicability to real situations. In the future, Clark also hopes to develop a nanoclinical analyser capable of measuring more than one analyte.

Fran Burgoyne


Targeting tumours with graphene oxide

19 November 2010

A graphene oxide anticancer drug carrier that combines different targeting mechanisms has been designed by scientists from China.

Many anticancer drugs are toxic or cause harmful side effects because they target healthy cells as well as tumour cells. Yongsheng Chen from Nankai University, China, and colleagues have developed a delivery system using functionalised graphene oxide as the drug carrier. Graphene oxide has a very high surface area, enabling it to transport a large amount of the drug. As cancer cells are typically more acidic than normal cells, the team developed the system to increase drug release as pH decreases. This confines the drug to the tumour site and limits uptake by healthy cells. This could allow doctors to use higher doses and improve the effectiveness of treatments, or reduce side-effects for patients.

Chen's team attached superparamagnetic Fe3O4 nanoparticles to the graphene oxide. 'Using Fe3O4 nanoparticles linked to the graphene oxide allows the carrier to be targeted to the tumour site by an external magnetic field,' explains Chen. Many cancer cells have high numbers of folate receptors on their surface so the team attached folic acid to the nanoparticles as a second targeting mechanism. This makes it more likely that the drug carrier will enter tumour cells rather than healthy cells. The team then loaded doxorubicin, a potent anticancer drug, onto the graphene oxide via pi-pi stacking.

Preparation of the multi-functionalised graphene oxide anticancer drug carrier

They tested the carrier in cell uptake and toxicity studies in human breast cancer cells in vitro. These tests confirmed that the carrier can transport and release doxorubicin into tumour cells.

Michael Sailor, an expert in designing nanoparticles for biomedical applications at the University of California, San Diego, US, cautions that further work is needed to test the safety and biological life cycle of any graphene-based drug delivery system. 'One of the major challenges in nano-enabled drug delivery is degradability of the device once it has performed its function. Although many nanoparticles are safely excreted by the body, many others are not. Future patients will be concerned about a nanodevice sticking around after it has delivered its drug or performed its diagnostic test.'

'Nanomaterial-based targeting drug delivery systems are still at an early stage for commercial applications,' agrees Chen. 'Some reports suggest that modified graphene can be excreted safely from the body, but the digestion or downgrading of nano-delivery vehicles needs more research. This is the focus of our future studies.'

Russell Johnson


'Hunger hormone' activating enzyme holds promise as obesity target

18 November 2010

Blocking a key gut enzyme involved in the hunger response can reduce weight gain in mice, say US and Taiwanese researchers. The approach could eventually lead to treatments for obesity in humans that would work by damping down hunger pangs.

The market for obesity drugs is worth over $1 billion (£625 million) a year, with some 300 million potential patients. A current focus for drug developers is synthetic hormones that mimic the actions of gut hormones involved in controlling blood sugar levels. Some have already been approved for use in diabetes.

Philip Cole and colleagues at the Johns Hopkins University in Maryland, University of Cincinnati in Ohio and National Taiwan University in Taipei took a slightly different approach. They based their studies on the hormone ghrelin, also known as 'the hunger hormone'. Ghrelin is normally activated by the enzyme ghrelin O-acyltransferase (Goat), which attaches an eight-carbon fatty acid to one of the hormone's serine residues to produce acyl-ghrelin. Without Goat, ghrelin can't trigger hunger.

GO-CoA-Tat combines parts of ghrelin and octanyl-CoA to block the binding site in the activating Goat enzyme
© Science/AAAS

Cole's team designed a molecule to block Goat. Their compound, GO-CoA-Tat, contains ghrelin residues and octanyl-CoA - bearing the required 8C fatty acid - but the two are cemented together. 'The design of the agent was based on the idea that by linking together the two main substrates of the enzyme we could create a bivalent inhibitor that would bind specifically to this enzyme,' explains Cole. 'We believe it sits in the sites that the normal substrates would bind to.'

The synthetic molecule reduced weight gain in normal mice, but not in mice that were deficient in the hunger hormone, suggesting the effect was due to a lack of activated ghrelin.

John Wilding, an obesity expert at the University of Liverpool, UK, says the approach looks promising but is still a long way from producing a drug to treat obesity in people. Cole agrees the work is very early stage - his team have yet to refine their compound. But he also says that too little is known currently about the long-term effects of interfering with ghrelin, which is thought to influence growth and may even play a role in memory.

Wilding notes that the research also produced data that could throw further light on the hormone's function - by showing that insulin secretion is enhanced when GOAT is inactivated. 'This would be consistent with observations that ghrelin might suppress insulin secretion, however this effect is not particularly great,' says Wilding.

Hayley Birch



New drug pricing rules in Germany

18 November 2010

Ned Stafford/ Hamburg, Germany

German pharmaceutical companies are facing combined annual revenue losses of more than 2 billion (1.7 billion) under a new law approved by the Bundestag. Meanwhile, industry observers are warning that the revenue losses could weaken drug research and development in Germany's vibrant pharmaceutical industry.

The law was approved on 11 November and will take effect from 1 January as part of an effort to rein in exploding costs for Germany's massive public health insurance system. It will require pharma companies to negotiate prices for new drugs with health insurers, severely limiting their previous freedom to set prices.

Drug prices in Germany are among the highest in Europe and have come under increasing scrutiny in recent years. Public health insurers, who cover nearly 90 per cent of the population, last year spent around 32 billion on drugs, according to a report from AOK, Germany's largest public health insurer. This represented 19 per cent of their 170 billion total spend.

Some 'new' drugs are just repackaged versions of old drugs, says Jens Spahn

Furthermore, prices in Germany are used as a reference for prices in more than a dozen other countries. Therefore, if the new law succeeds in bringing them down, a ripple effect might be felt beyond Germany, which is the largest drug market in Europe and third largest globally behind the US and Japan.

Despite opposition to the new law, the Association of Research-based Pharmaceutical Manufacturers (VFA), which represents the industry in Germany, has been cautious in its criticism, adopting a wait-and-see attitude until details of the price negotiation process are finalised.

Rolf Ackermann, spokesman for Bayer, Germany's largest drug company, says the new law is a continuation of the 'government intervention' drug price policies of recent years. But the industry is not yet certain what the end effect of the new law will be because 'many details of its implementation are still open'. However, he adds: 'In the long term there is a danger that the new pricing regulations will have a negative effect on investment in Germany's pharmaceutical sector and on research and development.'

Jens Spahn, a Bundestag member who sits on the health committee, says that the move is a 'big step towards more appropriate reimbursement prices for drugs in Germany. The new law will make it very difficult to bring new drugs to market without additional impacts'. He adds: 'There will now be a strong incentive to focus research on new pharmaceuticals having a measurable impact on patient's health and to put less effort into marketing strategies. In the long term, this will strengthen Germany's ability to compete globally in pharma research.


Cellulose used to make smart window materials

18 November 2010

Using nanocrystalline cellulose (NCC) from wood pulp, Canadian researchers have for the first time prepared mesoporous chiral nematic structured silica materials that may have potential as tuneable reflective filters in smart windows, chiral catalysts in synthesis and even as optical sensing devices.

A team led by Mark MacLachlan at the University of British Columbia in Vancouver, used an aqueous solution of NCC with silica precursors and found that in a narrow pH range they formed chiral structures with pore diameters in the range of 4 to 5nm and which are organised in a helical thread-like form.1

Mesoporous silica materials have been prepared before but attaining chirality has been a difficult task. 'Others tried it before but it turns out that the pH range over which these structures are formed without any disruption is very narrow,' says MacLachlan. These structures are chiral because of the sugar chains of cellulose that form the pores.

Tuning the pores gives different coloured films, but adding a drop of water turns them transparent
© Nature/K Shopsowitz

Viveka Alfredsson is based at Lund University in Sweden and works on the formation of mesoporous silica materials and its functional derivatives. She says, 'It is good to see cheap and widely available cellulose being used to make chiral mesoporous silica. Other chiral mesoporous silica structures have been made - for example by Shunai Che from Shanghai Jiao Tong University in China - but by using quite expensive chiral surfactants.'2

The material is also porous, and filling up the pores with water makes the structure completely transparent. This happens because the refractive index of water is very close to that of SiO2 and the differences are invisible to the naked eye.

The materials also possess impressive photonic properties. 'The origin of colour in the material is really interesting,' says MacLachlan. 'The material selectively reflects the wavelength of light that matches the helical pitch of the pore.' So by varying how steeply the pore spirals in the material, it can be made to reflect different colours.

This means that materials can be made that they are transparent to visible light but reflect infrared light, which could be used to coat windows and help stop heat leaking out of buildings.

The team is now looking at ways to use the silica template for building chiral nematic semiconductors and chiral catalysts.

Akshat Rathi


Probing stomach cancer

18 November 2010

A technique that could be used to distinguish between benign and malignant ulcers in the stomach has been developed by scientists from Singapore.

Gastric cancer is one of the leading causes of cancer-associated death in the world and the success of treatment is highly dependent on how quickly the cancer is detected. Currently there is no efficient detection method and patients must undergo repeated endoscopy tests where ulcerous regions are analysed visually and random biopsies are taken. Benign areas look similar to malignant areas and often the cancer can only be diagnosed at an advanced stage.

Now, Zhiwei Huang and colleagues at the National University of Singapore and National University Hospital have developed an endoscopy probe that analyses tissue using Raman spectroscopy. Raman is a non-destructive technique that measures the wavelength of light scattered from a sample. Huang says 'the development of a non-invasive optical diagnostic technique to complement current endoscopic imaging techniques would represent a significant advance, improving early diagnosis of gastric cancer and precancer'.

An endoscopy Raman probe can detect malignant ulcers in vivo

The team tested the probe on a number of patients and found that significant Raman spectral differences between benign and malignant tissue can be delivered. 'This work demonstrates the technical feasibility and clinical potential of using an endoscopy Raman probe for in vivo detection of malignant ulcers,' says Haishan Zeng, an expert in analysing tissue samples at the British Columbia Cancer Research Center, Canada.

Huang hopes that the technique can provide diagnostic information that will give new insights into the biochemical and architectural changes of benign and malignant gastric ulcers, improving in vivo differentiation. The team now aim to develop the technique to look at other internal organs.

Harriet Brewerton



DNA origami meets low-cost lithography

17 November 2010

Chemists in the US have developed an easy way to integrate the 'bottom up' assembly of DNA origami with the 'top down' patterning of low cost lithography. The method, which involves sticking pieces of DNA to prepositioned gold islands, might help researchers in their bid to use DNA origami for nanoelectronics.

DNA origami is a means of folding DNA strands into something like a pegboard, onto which different molecules can be attached. In principle the origami can self-assemble into circuits with features just a few nanometres in size, but so far researchers have had difficulty controlling them because the origami are made in solution, so when deposited on a surface they can go everywhere.

The distance between components in electronics such as flash memory devices has shrunk to just tens of nanometres in recent years, and could drop even further, explains Hongbin Yu, a member of the research team at Arizona State University. One way to position components such as DNA origami that could be used in nanoelectronics is to go over the surface with highly precise lithography, but lithography at this scale requires expensive equipment. 'The cost of the tool to produce such features is so high only a handful of companies can afford them,' says Yu. 'Using DNA self-assembled structures on a patterned surface is an exciting way to reach such small dimensions with relatively low cost.'

Structures formed by connecting gold islands with DNA origami tubes (all scale bars are 300nm)
© Nano Letters

In the new technique the researchers, led by Yu's colleague Hao Yan, modify the ends of DNA origami tubes with sulfur-containing 'thiol' groups, which can bind to gold. Using low-cost lithography, they then position two gold islands, just tens of nanometres in diameter, where they want the origami to go. When they deposit the origami, the ends of a single tube attach to the two islands, thereby forming a link in the right location.

'This work is important in that it is difficult to fabricate devices whose salient features span sub-nanometre to millimetre scales in length,' says William Shih, an expert in DNA nanotechnology at Harvard University, Cambridge, US. 'Success will lead to more sophisticated and powerful electronic devices than are possible today.'

'Yan's group seems to have struck a pretty good compromise, and they have come up with a good solution that will find application when we want to arrange 1D structures, like tubes, on a surface,' says Paul Rothemund at the California Institute of Technology, US, who invented DNA origami.

The researchers now plan to attach molecules such as carbon nanotubes, semiconducting nanoparticles or nanowires to the DNA origami to create functional networks with their gold islands.

Jon Cartwright


Safer sunscreens

17 November 2010

Coating titania nanoparticles with carbon could result in a safer UV filter to be used in sunscreen, say Italian scientists.

Long-term exposure to UVA and UVB radiation from sunlight can cause wrinkles, damaged skin and, in some cases, skin cancer. Titania (TiO2), one of the main components in sunscreens, can absorb and scatter UVA and UVB radiation. However, titania can also become reactive under UV rays and in contact with water, generating free radicals that cause skin damage.

Now, Ivana Fenoglio and Stefano Livraghi's teams from the University of Torino in collaboration with the Institute for Health and Consumer Protection, Ispra, have modified the surface of titania nanoparticles to decrease their reactivity under UV. The groups coated the nanoparticles with ethylene glycol and heated the resulting compound to 300ºC to carbonise it. They found that this reduced the nanoparticles' oxidative power and consequently decreased free radical formation. 'It was very surprising to find out that by using ethylene glycol as a precursor, the formation of free radicals is reduced. This differs from the results of other studies done with titania nanoparticles modified with carbon,' says Fenoglio.

Long-term exposure to UV radiation from sunlight can cause wrinkles, damaged skin and, in some cases, skin cancer

'To use titania particles for skin care, a delicate balance is needed to prevent formation of reactive oxygen species, which have been suspected to cause skin damage, without affecting the desirable optical properties,' says Sefik Suzer, an expert in inorganic nanoparticles at Bilkent University in Ankara, Turkey. 'This research will undoubtedly help in developing a new generation of cosmetic products as well as leading to formulation of new routes for special applications of titania.'

'This research may be a starting point for setting up protocols to produce UV filters that may find applications in different fields including the cosmetics industry,' says Fenoglio.

Lorena Tomas Laudo


Temperature breakthrough for hydrogen storage

17 November 2010

A compound first made in 1923 releases hydrogen at a lower temperature than ammonia borane, one of the most studied materials for hydrogen storage.

Efficient hydrogen storage is an important step in developing a hydrogen economy. One way of storing hydrogen is in chemical compounds that reversibly release hydrogen when they are heated. Diammoniate of diborane (DADB, [(NH3)2BH2]+[BH4]-) as a hydrogen-containing species has the potential to be a storage material, but the crystal structure of the compound that would give valuable information about its properties has not been resolved until now.

Using a combination of X-ray and neutron powder diffraction patterns, Mark Bowden and Tom Autrey at the Pacific Northwest National Laboratory, Richland, and the Los Alamos National Laboratory, and coworkers resolved the crystal structure. 'DADB is an interesting compound because it contains a high weight fraction of hydrogen, one of the highest for a stable material at room temperature,' says Bowden.

Diammoniate of diborane contains a high weight fraction of hydrogen, one of the highest for a stable material at room temperature

When Bowden and the team heated DADB, they found that it behaved in a similar way to ammonia borane, but DADB releases hydrogen at 85°C, whereas ammonia borane releases hydrogen at 110°C.

Hydrogen release at this temperature is very interesting since it is in this temperature range that a practical hydrogen storage system must operate, says Stewart Parker of the Rutherford Appleton Laboratory, Didcot, UK, but it is important to have better knowledge of the system's reversibility.

Jon Counsell



Water takes forbidden form

16 November 2010

With at least fifteen different crystal forms, two different disordered solid phases (glasses), and perhaps two different liquid states, water is a prodigious shape-shifter. But Valeria Molinero and colleagues at the University of Utah, US now claim that water has still more tricks up its sleeve. They say that, when water is confined between two flat plates just 8.5 Angstroms apart - room enough for just two molecular layers - it can adopt a quasicrystalline state which appears to have a 'forbidden' twelve-fold symmetry.

Although there have been speculations that water might adopt such a solid form, there has previously been no firm evidence that it might exist. What's more, all earlier quasicrystals have been mixtures of two or more components, making this the first to be composed of just one. So far, however, it's just a prediction based on computer simulations - the Utah group hasn't observed quasicrystalline water experimentally.

Quasicrystals were first discovered in 1984 in an alloy of manganese and aluminium. Like crystals, they generate x-ray diffraction patterns with symmetrically arranged bright spots, but with symmetries - five-, ten- and twelve-fold - that can't be produced by any regular, orderly packing of constituent particles. Instead, quasicrystals are not perfectly periodic: they contain local atomic arrangements with these forbidden symmetries, but which do not repeat exactly.

The hydrogen-bonded network (left) and the full simulations (right) of quasicrystalline water films
© J. Chem. Phys

Water seems a good candidate for making an ice-like quasicrystal, because hydrogen bonding between the molecules favours the formation of pentagonal rings.

Molinero and colleagues simulated water between the two plates at pressures of up to 5000 atmospheres: the pressure promotes pentagonal rings rather than the hexagonal rings of regular ice, because they are more compact. The researchers found one crystal phase made up of pentagons linked with four-fold symmetry, and another phase composed of both pentagons and hexagons, with twelvefold quasi-symmetry. Hideki Tanaka of Okayama University in Japan, a specialist in simulations of water and ice, says that the findings are 'of significant interest', although he adds that he's not convinced it will prove possible to observe it experimentally

Molinero admits that the conditions of the simulations are hard to create experimentally, but adds the researchers have also found that the quasicrystal state can be stabilised without applying pressure, by tuning the strength of the water-surface interaction. So it might conceivably be made by depositing a thin film of water onto a single flat surface. 'Our holy grail is vapour deposition of the quasicrystal,' she says. 'But I expect it will take us a while, or a stroke of good luck, to be able to predict the surfaces and temperatures needed for that.'

Philip Ball


pH prompts protein structure

15 November 2010

US researchers studying the naturally-occurring amyloid protein Pmel17 have discovered that pH plays an important role in its structure, helping the body control its aggregation.

Misfolded fibrous proteins, called amyloids, are commonly associated with diseases such as Alzheimer's and Parkinson's. However not all amyloids are disease related - they can also fulfill useful roles. To determine what marks this difference, Jennifer Lee and colleagues at the National Institutes of Health in Bethseda, US, studied the structure of Pmel17; an amyloid which acts as a scaffold for melanin formation.

'Melanin is formed in an organelle called a melanosome,' says Lee. 'We were interested how pH solution would affect [Pmel17] amyloid formation because the organelle's pH changes as it matures.'

Lee analysed the structure of the repeat domain of Pmel17 in vitro. She found that beta-sheet aggregates formed around pH4 and these elongated into fibrous scaffolds at pH5. However at pH values above 6, the amyloid completely dissolved.

Amyloid structures at pH 5.5 (left), 5 (middle) and 4 (right)
© Proc. Natl. Acad. Sci. USA

'Pmel17 has a lot of carboxylic acid side chains which are critical in aiding the formation of amyloid structure,' says Lee. 'It's very different from disease related amyloids which are quite robust. At physiological pHs Pmel17 fibres would not form so maybe that's why they're benign.'

'The striking thing is that the pH range is so narrow,' says Filip Meersman who researches protein folding and amyloids at the Catholic University of Leuven, Belgium. However he says the work does not appear to have any direct implications for understanding disease-related amyloids.

'What we're trying to understand is whether it is on the molecular level that the functional and disease related amyloids are different, or is it the way amyloid formation is controlled by the cell?', says Lee. 'For example if the amyloid formed in these organelles were to leak then they're not stable under normal cellular conditions. This is the beginning in trying to understand and compare and see if that's the case.'

Manisha Lalloo



Using host-guest chemistry as molecular velcro

14 November 2010

Molecular recognition, a microscopic process, has been used by Japanese researchers to assemble gels into macroscopic structures. The result is a bit like molecular velcro, the molecules catch each other and hold the gel cubes together.

Akira Harada, and colleagues at Osaka University, took doughnut shaped cyclodextrin (CD) 'hosts' and 'guests' that like to sit inside the CDs and bound each to separate polymer chains. When cubes of the different polymers mix in water, they find each other and stick together. They do this because the guest molecules at the surface of one gel cube find and sit inside the host molecules of the other gel cube.

This kind of host-guest interaction is well known in solution chemistry, but hasn't been applied on a macroscopic scale before. Phil Gale of Southampton University, UK, points out that the idea is one of those that is so simple and elegant that it seems obvious as soon as you've seen it. 'Why didn't anyone think of this earlier?' he asks.

Cubes of polymers incorporating either a cyclodextrin host or a molecular guest stick together on contact
© Nature Chemistry

Biological systems use molecular recognition to assemble themselves, and this inspired Harada to use the same process to 'make use of our knowledge of host-guest chemistry in the real world'.

The host-guest interactions the team used are selective - different guests prefer to sit in the differently sized cyclodextrins. The team bound both alpha-CD and the larger beta-CD to polyacrylamide chains, and did the same with adamantyl, n-butyl or tert-butyl groups. Even when all the different gels are mixed in the same container, the adamantyl and tert-butyl gels only stick to beta-CD gels and n-butyl gels only stick to alpha-CD gels.

Harada's gels also show how strong host-guest interactions can be, even though the host and guests are not actually covalently bonded together. When beta-CD and adamantyl gels stick together, the host-guest interactions are so strong that the gel cubes will break before the join can be pulled apart. However, the other gels stick less strongly and can be joined and pulled apart intact.

'I think this is a beautiful demonstration of how interactions between molecules can lead to macroscopic attraction between objects on the real life scale' adds Gale, who works on supramolecular chemistry and molecular recognition himself.

Harada plans to investigate using different intermolecular interactions including using biological molecules and would like to use his system to bind to the surfaces of cells, perhaps to immobilise the cells on surfaces. He also suggests other medical uses for his technology, like sticking together wounds with a polymer that selectively interacts with skin cells to hold them together. After all, as he says, 'all you have to do is just mix the parts in water.'

Laura Howes



12 November 2010

Fragranced household products, even those labelled as 'green', can emit large numbers of hazardous chemicals that aren't listed on their labels, US researchers have confirmed. The research raises questions about the risks associated with these products and regulating the claims on their labels.

A team led by Anne Steinemann at the University of Washington in Seattle, US, used gas chromatography to analyse the volatile organic compounds (VOCs) released from 25 of the top-selling US products such as detergents, hand sanitisers and air fresheners, and found that they emit many hazardous compounds.

Among the most toxic of these were carcinogens such as acetaldehyde, formaldehyde, 1,4-dioxane and dichloromethane. According to Steinemann, the US Environmental Protection Agency states that there is no safe threshold for exposure to these chemicals. Other hazardous compounds found included methanol, cumene, hexane and chloromethane.

Household products claiming to be 'green' gave off the same VOCs as other products

Under US regulations, companies are not required to disclose ingredients in a fragrance mixture. There is also no regulation over the use of terms such as 'green', 'organic', 'non-toxic' or 'natural'. These claims appeared on 19 of the 25 tested products' packaging or advertising, but the team found that they emitted toxic compounds as much as 'non-green' products did.

'No one really knows the definitions of these words,' says Ian Colbeck, an air quality specialist from the University of Essex, UK. 'I think it would help if the manufacturers agreed, in some way, to use these terms based on certain conditions.'

Colbeck is concerned by the lack of exposure studies on human beings. But Steinemann responds that, 'even if we had done exposure analysis, we cannot say based on that whether these products are safe or not. There are so many factors involved in the ultimate effect on the health of the subjects.'

Research into the toxicity of these products is challenging because the same air freshener may cause an asthma attack in one person, but a seizure in someone else, and have no effect at all on most people, says Steinemann. The analysis is made more difficult as 'it may not be that a single VOC causes one effect and another VOC causes a different effect, but it may be that it is a mixture of VOCs that cause the harmful effect.'

However, Colbeck remains skeptical, 'I don't think that householders should be particularly concerned about these products,' he says. 'But it would be interesting to study the occupational hazards of these compounds in people who work, for example, at launderettes.'

Steinemann reiterates the gravity of the situation and urges researchers to investigate further and raise these questions to the regulatory authorities, 'Some people are known to react to much lower concentrations of these chemicals than we can even detect.'

Akshat Rathi


Trapping and stretching DNA

12 November 2010

Microfluidics can be used to trap a single DNA-enzyme complex in its native state for real-time analysis without having to immobilise the DNA or the enzyme, claim US researchers.

Enzymes called restriction enzymes are used to chop up DNA at specific points called recogition sites, making them useful tools in biochemistry. To anayse how they recognise and cleave DNA, the enzyme or DNA needs to be immobilised on a glass slide, but this can modify their properties, and make it difficult to analyse the products. To combat this, Susan Muller and Weilin Xu at the University of California, Berkeley, pre-bound a restriction enzyme to DNA, and fed it through a microfluidic system. This trapped the complex, and then stretched it out. Adding Mg2+ then activated the enzyme, cleaving the DNA, and permitting analysis of the products.

Ron Larson, a chemical engineering expert at the University of Michigan, Ann Arbor, US, says: 'this work represents a novel and elegant use of fluidics to trap and stretch single DNA molecules without interference by surfaces.' He adds that 'the "look Ma, no hands" approach pursued by Xu and Muller has a number of advantages, not least of which is the ability to recover cleavage products for further study.'

Molecular configuration image showing the trapping, stretching and subsequent cleavage of DNA

The technique can give information about how restriction enzymes act to determine their mechanism of action, which holds promise for a broad range of DNA-protein interaction studies, says Muller. This has been difficult in the past, but is being addressed by single-molecule studies, which avoid the problem of properties being averaged over a range of DNA molecules.

The main benefit of the current work, says Muller, is that the complex does not need to be tethered or modified, making it simpler than previous methods that used labelled enzymes. 'We were able to follow the cleavage process in real time at the single-molecule level,' she adds. The accuracy in determining the location of the recognition site on the DNA, she says, is comparable to or better than other single-molecule techniques. Ultimately, she concludes, 'one may be able to extract subtle differences in binding and cleavage frequencies among multiple recognition sites on a single DNA substrate'.

David Barden