SAFE HEATING OF LARGER SCALE REACTIONS
Asynt - a leading provider of heating block technology to organisations worldwide has announced new versions of its DrySyn Maxi and DrySyn Super Maxi for labs tasked with larger scale reactions (2000-5000ml). Constructed in solid anodised aluminium - both the DrySyn Maxi and DrySyn Super Maxi deliver outstanding thermal and magnetic transfer efficiency and the durability suitable for use in any laboratory environment. Design improvements in the latest generation of these products has resulted in improved heat transfer characteristics up to 300°C, faster heating and cooling, and a smaller footprint. Affordably priced the DrySyn Maxi single position heating block system is designed to accommodate 2000ml or 3000ml flasks. For 4000ml and 5000ml flasks the DrySyn Super Maxi is the heating block of choice. Used in combination with a standard hotplate stirrer, DrySyn Maxi and Super Maxi units are proven to outperform the heat-conducting properties of oil baths. They pose a far lower fire risk and their use makes the clean-up of glassware far easier as there is no residual oil contamination on the outside of the flasks. In addition to accelerating your chemical reactions - DrySyn Maxi and Super Maxi heating blocks ensure a safer, cleaner, healthier working environment. The DrySyn Maxi and Super Maxi also provide a superior alternative to heating mantles. Designed by chemists for chemists, these DrySyn heating blocks provide full unhindered visibility of your reaction. In addition heat resistant handles allow fast, easy and safe lifting of your reaction flask from the heater/stirrer.
MIXER-REACTOR CHIP IMPROVES CONTROL OF RAPID HIGHLY EXOTHERMIC REACTIONS
Uniqsis Ltd. has demonstrated how its proprietary glass static mixer-reactor chip technology can be used to perform highly exothermic reactions more conveniently at higher temperatures with useful throughputs under continuous flow-through conditions. To achieve high reproducibility and facilitate scale up, it is important to control both mixing and temperature, particularly for highly exothermic or rapid mixing-dependent reactions (‘Type A’ reactions). Where the diffusional mixing provided by simple ‘T’-piece mixers is too slow to afford good control and reproducible reaction outcomes, Uniqsis has introduced a range of ingenious glass static mixer blocks ('chips') that incorporate channels with active mixing geometries to provide efficient turbulent mixing throughout the reaction vessel whilst also functioning as very efficient heat exchangers. Uniqsis offers both conventional 2 input 1 output static glass mixer/reactor chips for combining 2 reagent streams, useful in nitration chemistry for example, and a 3 input 1 output chip which is particularly useful for reactions requiring a ‘quench’ input. The chips are easy to incorporate into the reaction flow path and use conventional threaded connectors that require no tools to attach and achieve leak-free seals over a wide temperature range. Precision machined from chemically inert borosilicate glass, these chip are tested to operate efficiently at up to 40 bar pressure and from -80°C to +150°C.
NOTTINGHAM FURTHER INVEST IN GREEN CHEMISTRY LABORATORY
The School of Chemistry at the University of Nottingham (UK) has placed a sizeable order with Asynt to upgrade their undergraduate teaching facilities with DrySyn Scholar Plus heating block systems. The School of Chemistry at the University of Nottingham (www.nottingham.ac.uk/chemistry/index.aspx) is one of the leading Chemistry departments in the UK and is recognised internationally for its world leading research portfolio, excellence in teaching and extensive engagement with Industry. Its expertise spans the spectrum of modern chemical technology including synthesis, analysis and characterisation, ranging from the core chemistry disciplines to areas at the interface with biological sciences and engineering (sustainable chemical processing). In 2012 GlaxoSmithKline (GSK) and The University of Nottingham formalised a collaboration to establish a new laboratory to accommodate a Centre of Excellence for sustainable chemistry, and to construct an innovative carbon neutral sustainable chemistry facility. David Chambers-Asman, Director of Operations & Administration at the School of Chemistry commented: “In line with Nottingham's commitment to develop ‘green and sustainable’ chemistry methodologies, we wanted to find a safe, more environmentally friendly alternative to heated oil baths for our undergraduates to learn about organic synthesis […] After reviewing the market we elected to invest in Asynt DrySyn Scholar heating block systems because of their robustness, enhanced operator safety features and ease-of-use - making them the ideal for our organic synthesis”.
FULLY AUTOMATED DRYING OR CONCENTRATION OF VERY LARGE VOLUMES
Genevac has announced the launch of the ROCKET 4D – a fully automated system for automatic drying or concentration of very large volumes (a few to 100 litres) in one operation with no user interaction. Simply load your sample, select a method, press start, and walk away – the system will do the rest. Compact in size the ROCKET 4D allows you to dry or concentrate your samples with complete confidence as it uses proprietary vacuum technology to suppress solvent bumping and foaming – problems associated with sample loss when using large scale rotary evaporators. Rocket 4D comes as standard with a single, 5 litre 316 stainless steel vessel for drying or concentrating product. This has detachable handles and is easily lifted into and out of the evaporator. Access to the dried or concentrated product in the vessel is very easy. Dried products can be scooped out, or where enhanced user protection is needed, re-dissolved while the vessel is still in the system. Liquid products can be easily drained via a drain port in the side of the rotor, using a dedicated pouring stand. Users wishing to dry volumes larger than five litres require the ‘Autofeed’ option, which enables the Rocket 4D to draw in product from the user’s own external supply. The Rocket 4D controls product feed, drying and the discharge of condensed waste solvent without any external intervention. The autofeed system has an integrated rinse circuit which enables dried products to be automatically re-dissolved in a small volume of solvent at the end of the process. Alternatively, the same circuit can be used under manual control for solvent exchange, by selecting a different solvent for re-dissolve.
AUTOMATED DIRECT-TO-VIAL CONCENTRATION SYSTEM
A series of technical papers are available from Genevac that demonstrate the advantages and benefits that their proprietary SampleGenie technology offers to chemical, environmental and food labs tasked with pooling and concentrating GC and HPLC fractions. Traditional protocols for concentration of GC or HPLC fractions has involved drying multiple fractions in an evaporator, re-suspending pooled fractions into a single vial and then re-drying before storage and analysis. Even with modern centrifugal evaporators such processes typically take 2-3 days to complete. The development of SampleGenie™ technology enables samples in Genevac evaporators to be concentrated, without loss of volatile components, directly into a single GC or HPLC vial eliminating the need for reformatting of samples after drying. This, and the automation offered by Genevac evaporators simplifies the protocol to a single overnight drying step before storage and analysis. Not only does SampleGenie remove time consuming manual steps – it lowers labour costs and improves data reliability.
SAFE AND HIGH YIELDING FLOW NITRATION METHODOLOGY
Uniqsis has published details of a mild nitration method using its FlowSyn flow chemistry system that enables short reaction times and high conversion to be achieved whilst minimising the amount of corrosive (and potentially explosive) hot nitrating mixture present in the reactor at any one time. Nitration is an important synthetic procedure that is often difficult to control. Under continuous flow-through conditions, however, exotherms are typically well controlled and nitration can be safely performed on a large scale. Using Uniqsis’s proprietary glass static mixer/reactor chip technology - nitration can be safely performed under accelerated conditions at elevated temperature and pressure without the associated problems typically encountered in batch reactors of controlling latency periods or controlling thermal run away. Application Note 22 describes how the Uniqsis FlowSyn™ flow chemistry system fitted with a glass static mixer/reactor chip can be used to undertake rapid, high yield nitration of methyl 3-methoxy, 4-ethoxybenzoate using nitric acid and acetic acid by the method described above. The product was conveniently isolated in high yield and purity by precipitation from water.
HIGH TEMPERATURE ULTRASONIC FLOW METER
Titan Enterprises has announced a new high temperature version of its low cost Atrato ultrasonic flowmeter. Capable of operating up to 110°C, the new Atrato is purpose designed for applications involving high temperature cooling water and oils. The Atrato from Titan Enterprise is true inline non-invasive flow meter without the contorted flow path and disadvantages of alternative ultrasonic designs. It can handle flows from laminar to turbulent and is therefore largely immune from viscosity. It also offers excellent turndown, linearity and repeatability. Atrato flowmeters use patented 'time-of-flight' ultrasonic technology that enables them to operate over very wide flow ranges (250:1) with excellent accuracy (better than ±1.5%) over the whole span. Ruggedly constructed with PEEK pipe connections and either a glass or 317 Stainless Steel flow tube the compact Atrato is compliant to IP54 standards. Its clean bore construction makes it ideal for a wide range of flow applications. Titan's proprietary signal processing system permits flow measurement over the whole Reynolds number range allowing both viscous and non-viscous products to be metered accurately. An integral USB interface makes it extremely easy to install and enables users to directly monitor flow volume and rate on an external PC as well as altering operating conditions.
SARTOCHECK 4 PLUS BAG TESTER
Sartorius Stedim Biotech has launched the new Sartocheck 4 plus Bag tester, the latest addition to its well-established Sartocheck line. The new system is the first device allowing reliable pre-use testing of single-use bioreactors after installation, based on the proven pressure decay measurement method. The Sartocheck 4 plus Bag tester directly responds to the market needs for increased security and quality assurance when single-use components are used. The Sartocheck 4 plus Bag tester performs a pre-use test of the entire bioreactor, including tubing. This device is capable of detecting typical leaks that might have been caused by operator handling errors upon installation of a bioreactor. Therefore, the bag tester is ideal for eliminating the risk of filling a defective single-use bioreactor with expensive cell cultures.
KEMIRA & GENERAL ELECTRIC
Kemira and General Electric (GE) are excited to announce that, effective immediately, Kemira’s Paper Segment will furnish GE Water & Process Technologies’ boiler and cooling water chemical product technologies to the pulp and paper industry. Kemira customers will benefit from the addition of GE’s advanced boiler and cooling water treatment products. In addition, they will be able to utilize the GE Water & Process Technologies Service Reliability Centre which provides monitoring of customer’s key process variables.
DRÄGER FLAME 3000
Draeger Safety UK introduces its latest safety solution. The new Dräger Flame 3000 is a highly advanced explosion-proof image processing flame detector. It has been designed for standalone operation and can also be integrated with a control system or fire panel, offering a reliable solution to flame detection, as well as a high level of false alarm immunity. The state-of-the-art Flame 3000 and existing Flame 5000 are suitable for use in hazardous environments such as refineries, chemical and pharmaceutical plants since the sensitivity is not affected by reflections.
Moving liquids with sound helps identify drug candidates that traditional lab techniques miss
How do researchers know whether new molecules will have a positive or negative effect? How much does the technique for moving a liquid affect the results? What about testing compounds for their environmental or health impacts: is one liquid handling process better than another when it comes to accuracy of the data?
A paper published by the journal PLOS ONE, May 1, 2013, demonstrates that the technique used to transfer compound solutions does indeed matter. The three researchers who wrote “Dispensing Processes Impact Apparent Biological Activity as Determined by Computational and Statistical Analyses”, (http://dx.plos.org/10.1371/journal.pone.0062325) conclude that if traditional techniques introduce errors early in the scientific process, the implications are vast.
“Biologists, chemists, and computational modellers who help design compounds—all types of scientists should be aware of this issue,” said study co-author Sean Ekins, senior consultant with Collaborations in Chemistry. “From our early training, every biologist learns to use pipettes, devices like eye-droppers, to move liquids.”
Traditional testing by drug companies uses pipettes to create serial dilutions before assessing biological activity. A newer method uses sound to transfer liquids in microscopic volumes without pipettes. This “acoustic” method minimizes significant errors in the resulting data, according to the new study.
“Among other problems, compounds can stick to pipettes and not get transferred,” said Ekins. “Hardly anyone questions the technique, but those doing drug discovery may see issues with their data and not know why.”
To improve drug efficacy and time-to-patient, researchers need the process to be effective and accurate. Scientists worldwide depend on shared databases for their research, yet they rarely know how the underlying data was produced. The study concluded that it is critical to consider that a key technique, moving liquid via pipettes, may be introducing significant errors.
“All data from the past and much of the data generated today is based on experiments done with traditional pipetting and serial dilutions,” said Ekins. “Errors in this first stage are carried forward into computational models that are used to guide drug discovery. Scientists who are trying to design effective compounds might be doing so on false models. Our findings suggest that moving liquids with sound could improve screening results and prevent the development of misleading models.”
The authors developed their analyses, in part, using data published by AstraZeneca in US Patent 7,718,653. The researchers measured the potency of a class of several anti-cancer drugs, which always measured higher when the compounds were transferred with acoustic dispensing compared to pipette transfer.
“The paper shows that compounds yield different results depending on whether they were transferred by sound or pipette,” said Joe Olechno co-author of the paper and senior research fellow at Labcyte Inc. “Other researchers have seen similar results and have adopted acoustic dispensing. It became even more exciting when we found that the acoustic computational modelling correctly predicted which compounds would be the most potent while the serial dilution model could not.”
A method that allows researchers to more accurately predict the best compound to treat a disease could have a major impact on the industry and society. By comparing the models created from pipette-dispensing results with the crystal structures of molecules in AstraZeneca’s protein target, the team showed that the acoustic technique was most consistent with biological structures.
“This work highlights that data generated with traditional technologies like pipettes may be suspect. More investigation of the observations is required,” said Antony Williams, of the Royal Society of Chemistry and the third co-author of the paper. “But clearly, how we move liquids has a dramatic impact on the biological activities measured and much caution when using pipettes is advised.”
“Incorrect processes have the potential to significantly affect chemical testing in many areas,” Ekins said. He urges scientists to ask questions about the data they use. How much of a database is generated using pipette methods? How much is erroneous? How does it affect all subsequent science and conclusions?
Beta-blockers may boost chemo effect in childhood cancer
Beta-blockers, normally used for high blood pressure, could enhance the effectiveness of chemotherapies in treating neuroblastoma, a type of children’s cancer, according to a new study published in the British Journal of Cancer.
Researchers from the Children’s Cancer Institute Australia (CCIA) found that three beta-blockers (carvedilol, nebivolol and propranolol) were able to slow the growth of neuroblastoma cancer cells grown in the lab, and when combined with chemotherapy these anti-cancer effects were increased. When the chemotherapy drug vincristine was added together with beta-blockers, survival was greatly improved in mice.
Study lead author Dr Eddy Pasquier, Senior Research Officer in the Tumour Biology and Targeting Program at CCIA, said: “Three of the seven different beta-blockers tested in the lab all slowed tumour growth. When combined with these beta-blockers, vincristine was four times more effective than when used alone.”
Neuroblastoma is a cancer that develops from nerve cells left over from a baby’s development in the womb. Around 100 children are diagnosed with neuroblastoma each year in the UK, most of whom are under the age of 5. Despite the number of children surviving neuroblastoma rising from 17 per cent in 1971 to 64 per cent today, the aggressive form of the disease is still very hard to treat successfully.
Dr Julie Sharp, senior science information manager at Cancer Research UK, said: "We urgently need more effective treatments for children with neuroblastoma, and this research opens up a new avenue to explore. But this approach has only been tested in mice, and may not have the same effect in children, so more work needs to be done to show whether this might work in the clinic."
Scientists map process by which brain cells form long-term memories
Scientists at the Gladstone Institutes have deciphered how a protein called Arc regulates the activity of neurons – providing much-needed clues into the brain’s ability to form long-lasting memories.
These findings, reported in Nature Neuroscience, also offer newfound understanding as to what goes on at the molecular level when this process becomes disrupted.
Led by Gladstone senior investigator Steve Finkbeiner, MD, PhD, this research delved deep into the inner workings of synapses. Synapses are the highly specialized junctions that process and transmit information between neurons. Most of the synapses our brain will ever have are formed during early brain development, but throughout our lifetimes these synapses can be made, broken and strengthened. Synapses that are more active become stronger, a process that is essential for forming new memories.
However, this process is also dangerous, as it can overstimulate the neurons and lead to epileptic seizures. It must therefore be kept in check.
Neuroscientists recently discovered one important mechanism that the brain uses to maintain this important balance: a process called “homeostatic scaling.” Homeostatic scaling allows individual neurons to strengthen the new synaptic connections they’ve made to form memories, while at the same time protecting the neurons from becoming overly excited. Exactly how the neurons pull this off has eluded researchers, but they suspected that the Arc protein played a key role.
“Scientists knew that Arc was involved in long-term memory, because mice lacking the Arc protein could learn new tasks, but failed to remember them the next day,” said Finkbeiner, who is also a professor of neurology and physiology at UC San Francisco, with which Gladstone is affiliated. “Because initial observations showed Arc accumulating at the synapses during learning, researchers thought that Arc’s presence at these synapses was driving the formation of long-lasting memories.”
But Finkbeiner and his team thought there was something else in play.
The role of arc in homeostatic scaling
In laboratory experiments, first in animal models and then in greater detail in the petri dish, the researchers tracked Arc’s movements. And what they found was surprising.
“When individual neurons are stimulated during learning, Arc begins to accumulate at the synapses – but what we discovered was that soon after, the majority of Arc gets shuttled into the nucleus,” said Erica Korb, PhD, the paper’s lead author who completed her graduate work at Gladstone and UCSF.
“A closer look revealed three regions within the Arc protein itself that direct its movements: one exports Arc from the nucleus, a second transports it into the nucleus, and a third keeps it there," she said. "The presence of this complex and tightly regulated system is strong evidence that this process is biologically important.”
In fact, the team’s experiments revealed that Arc acted as a master regulator of the entire homeostatic scaling process. During memory formation, certain genes must be switched on and off at very specific times in order to generate proteins that help neurons lay down new memories. From inside the nucleus, the authors found that it was Arc that directed this process required for homeostatic scaling to occur. This strengthened the synaptic connections without overstimulating them – thus translating learning into long-term memories.
Implications for a Variety of Neurological Diseases
“This discovery is important not only because it solves a long-standing mystery on the role of Arc in long-term memory formation, but also gives new insight into the homeostatic scaling process itself – disruptions in which have already been implicated in a whole host of neurological diseases,” said Finkbeiner. “For example, scientists recently discovered that Arc is depleted in the hippocampus, the brain’s memory center, in Alzheimer’s disease patients. It’s possible that disruptions to the homeostatic scaling process may contribute to the learning and memory deficits seen in Alzheimer’s.” Dysfunctions in Arc production and transport may also be a vital player in autism. For example, the genetic disorder Fragile X syndrome – a common cause of both mental retardation and autism, directly affects the production of Arc in neurons.
“In the future,” added Dr. Korb, “we hope further research into Arc’s role in human health and disease can provide even deeper insight into these and other disorders, and also lay the groundwork for new therapeutic strategies to fight them.” Support for this research was provided by a Ruth L. Kirschstein Fellowship, the National Institute of Neurological Disease and Stroke, the National Institute on Aging and the Keck Foundation.
Too green to be true? Researchers develop highly effective method for converting CO2 into methanol
Université Laval researchers have developed a highly effective method for converting CO2 into methanol, which can be used as a low-emissions fuel for vehicles. The team led by Professor Frédéric-Georges Fontaine presents the details of this discovery in the latest issue of the Journal of the American Chemical Society.
Researchers have been looking for a way to convert carbon dioxide into methanol in a single step using energy-efficient processes for years. "In the presence of oxygen, methanol combustion produces CO2 and water," explained Professor Fontaine. "Chemists are looking for catalysts that would yield the opposite reaction. That would allow us to slash greenhouse gas emissions by synthesizing a fuel that would reduce our dependence on fossil fuels."
The catalyst developed by Frédéric-Georges Fontaine and his team is made of two chemical groups. The first is borane, a compound of boron, carbon, and hydrogen. The second, phosphine, is made up of phosphorus, carbon, and hydrogen. "Unlike most catalysts developed thus far to convert CO2 into methanol, ours contains no metal, which reduces both the costs and toxic hazard of the catalyst," added the chemistry professor at the Faculty of Science and Engineering.
CO2 to methanol catalysis requires a source of hydrogen and chemical energy. The researchers had the idea of using a compound called hydroborane (BH3), and the results have been spectacular. The reaction achieved is two times more effective than the best catalyst known—and it produces little waste. What makes the discovery even more compelling is the fact that the chemical reaction does not damage the catalyst, which can be reactivated by adding new substrate.
The only downside of the operation is the price tag. "Our approach to creating methanol is highly effective from a chemistry standpoint, but for now the process is expensive," explained Professor Fontaine. "It takes a lot of energy to synthesize hydroborane, which makes it more expensive than methanol. We are working on ways to make the process more profitable by optimizing the reaction and exploring other hydrogen sources."