Microreactors: Improving manufacturing by going small

When perfumes, creams, shampoos and other similar products are manufactured, the chemical reactions involved typically take place in big, agitated containers called reactors. The various ingredients are mixed in the container, often along with catalysts that increase the reaction speed, while temperature, pressure and a variety of other parameters are carefully controlled. These reactors are usually quite large (several cubic meters in volume) in order to be able to produce large quantities of a product. They operate in discontinuous cycles, which means they must be stopped, emptied and cleaned before each new use.

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The GGRC team worked with the company Givaudan Suisse SA to rethink this process, and ended up taking a diametrically different approach – dividing up the substance into small volumes in order to produce it more efficiently. With their invention, the chemical reaction doesn’t take place in big containers, but in micro-channels, each with a diameter of a few hundred microns. Several thousand of these channels can be assembled together.

Continuous production

“The primary advantage is a much higher level of safety,” explains GGRC director Lioubov Kiwi. “Any problem or risk of explosion remains confined within a tiny volume. It’s also much easier to control the temperature and, in fact, the entire process. In addition, they function continuously, with reactants entering on one side of the micro-tubes and the final product continuously generated at the exit.”

In terms of efficiency, the new machine is advantageous because it reduces the loss of raw materials. “About 20% of raw materials, up to now wasted, can now be recuperated,” the professor explains. In addition, the size of installations can be reduced by a factor of ten. Finally, the procedure improves product quality, because there are fewer impurities and waste products produced in the procedure.

Provided by Ecole Polytechnique Federale de Lausanne

Small things, big thinking

From molecules to jungles, biological systems grow themselves. This natural hierarchical self-assembly process, which operates simultaneously on many scales, fascinates Dr Chris Forman, an Associate Researcher at Cambridge University’s Institute for Manufacturing. Having trained as a theoretical physicist and worked in satellite communications, he decided to concentrate his research efforts on sustainability and to look at how academic disciplines could work together to unlock some of the mysteries that lie behind the staggeringly complex processes in biology.

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Forman is one of the contributors to a new series of online videos titled Under the Microscope produced by the University of Cambridge.  These one-minute videos capture glimpses of the natural and man-made world seen in stunning close-up and convey the excitement of cutting-edge science in areas that range from beetle eyes to killer T-cells, from nano-wires to fish skeletons. Each one is accompanied by an explanatory voiceover from the scientist involved, who talks about his or her research and how it might impact on society. The series will appear twice a week on the Cambridge University website.

In choosing to focus on images of fruit flies and beetle antenna Forman draws attention to the extraordinary structures found in the ordinary organisms – and encourages us to look deep into their structure and function to see how they are fine tuned to tasks that help them to thrive and survive. “I wanted something with a big yuck factor to show the remarkable level of integration that exists in the natural world,” he says.  “On a nano-scale the beetle’s eye and the fly’s foot reveal a stunning complexity that simply eludes current manufacturing.  And close-up images of bugs grab the attention of children and adults marvellously.”

Forman works mostly at the level of individual molecules – his PhD focused on the prospect of transporting electrons along self-assembled protein fibres, not unlike spider silk – but he also keeps a close eye on the big picture of larger scale structures and processes to guide his work.  Perhaps the best example of this interplay between processes at very different length scales concerns the natural levels of carbon dioxide in the atmosphere.  The natural balance of CO2 arises to a large extent from repeating the same chemical reactions trillions upon trillions of times around the planet in living cells, and the precise details of those chemical reactions are determined mostly by the sequence of information in genes.

His vision is that, by understanding molecular self-assembly and mixing this with the ability to perform arbitrary chemistry, we could make radically diverse structures for many purposes from the same restricted set of materials as natural systems. This would make it easier for each local community to be in balance with its immediate environment while achieving its economic goals, and sharing the knowledge of how to do this around the world could allow a global harmony to emerge naturally, one molecule at a time.  Such visionary holistic ideas are just one aspect of the fast-developing field known as biomimetics.

While some of Forman’s work is based on making connections between existing fields of science, much of it could be described as leaps of the imagination. By thinking a stage beyond what we already know, he is working on ideas that may not see fruition for 20 years – or may indeed evolve into unforeseen directions.  “As university researchers we have the freedom to think about such blue sky prospects without some of the restrictions that apply when you are working in the commercial or public sector. In particular, at Cambridge we are also able to move more easily between sectors by virtue of the collegiate system,” he says. “The more I study the natural world, the more impressed I am by what it can teach us about molecular organisation. I want to inspire the thinkers and leaders of the future who will take the knowledge discovered in universities and apply it in the commercial and political worlds.”

The world’s resources are under huge pressure from an expanding human population. Transport is a big user of energy and manufacturing processes rely heavily on transport.  As Forman puts it: “Industry depends on large lumps of materials being moved from process to process – often across the planet.” He asked himself a simple question: what would happen if we eliminated all methods of transport? “If you can’t travel, you have to do everything in one place: raw material extraction, manufacturing, assembly, consumption and recycling. Is there anything that can do this already? Yes – it’s called a tree! A tree gets it nutrients, it grows and dies. As it decays it releases its nutrients thereby nurturing the myriad of creatures that use it as an environment.  A tree does all this without moving from where it takes root -and it’s solar powered. While we can’t make everything from trees we can get construction materials, textiles and food which represent the bulk of our basic needs.  Perhaps in the future we will be able to extract even more than this from artificial static systems designed to emulate and fit in with the local natural ecology.”

All organisms are made from the same basic materials – carbon, hydrogen, oxygen and so on. What drives them to grow, and what makes them so amazingly diverse, is the information stored in their genes and the compartmentalisation that provides a context to that information.  “Take a mushroom, a tree and a pig. They appear completely different but they all use DNA, proteins, lipids etc. All have the ability to grow but they grow in markedly different ways, which depends strongly on their local environment.  In looking at how these fundamental forces interact at all length scales we are looking both at global environmental factors and the quantum processes in individual molecular interactions that we are only just beginning to grasp. It is a global system with quantum resolution and each of us is part of that system,” says Forman.

“A living biological cell is basically a complex network of chemical reactions contained inside a little bag. Can we emulate this process and replicate it? Maybe by compressing our processes into small packages and distributing them all over we can do all our recycling and manufacturing in our houses, rather than in factories with lorries moving large lumps of stuff about?  In this way we get more control as individuals over what we want and how it’s made. This could be better for both the environment and the economy – as it gives all seven billion of us the same chance to add value to our lives locally, which is considerably more value than currently exists in the world.”

Forman believes that science might one day enable us to create products as complex as IPods and computers in our living rooms – designed for our own immediate needs and made from local material.  Currently, industrial sectors such as energy, textiles, food and high-tech electronics are all looking at how to copy or exploit nature in many ways.  In the energy sector viruses and enzymes are being used to organise batteries or capture solar energy. Sectors such as food and textiles are already biologically-based. In hi-tech electronics people are looking at using organic molecular-based electronics to create next generation flexible displays. “Perhaps these radically different sectors should consider joining forces to learn how they can benefit In terms of optimal use of resources at the molecular scale.  Imagine a cake that displayed an edible temporary video screen? Imagine being able to make such a cake in your own kitchen? It’s conceivable that the commercial battles of the future will take place inside artificial cells in the walls of our houses rather than on the shelves of the supermarkets.”

The ultimate goal is to achieve a closed loop economy – a system that is self-sustaining with respect to material, in which the same material loops around and around the economy and is endlessly powered by sunlight alone. On each cycle the precise form and function of the material is determined solely by the individual for whatever purpose they have need of there and then, and the job of industry and regulation is to enable them to do it harmlessly.   One way of achieving such a closed loop is to create what is known as an industrial ecology, in which companies trade waste for mutual benefit. The best known example is the city of Kalundborg in Denmark, in which industries as diverse as energy, plaster-board manufacturing, road construction and pig-farming have collaborated to achieve economic and ecological efficiency.

By shrinking a city-wide industrial ecology into a volume the size of a cell, the need to transport raw materials and products over long distances is removed, and the energy required to process the material is reduced to the point where sunlight can be used directly. We know the range of species that can be produced with biological cells; if we are able to harness similar processes we may open up a huge array of possibilities.  But how far can we take this idea technologically?  Forman is keen to communicate these ideas to the public to acquire their input before it is fully explored scientifically and has devised a talk called “Can iPods grow on trees?”  He says: “The idea behind it isn’t as nuts as it sounds.  Every component in an iPod has a biological analogue.   To give one example: just as you can upload a tune to play on your IPod, so the lyre bird has learned to reproduce any sound it hears perfectly. Nature is an inspiring teacher.”

Provided by University of Cambridge (news : web)

Particle-free silver ink prints small, high-performance electronics

 University of Illinois materials scientists have developed a new reactive silver ink for printing high-performance electronics on ubiquitous, low-cost materials such as flexible plastic, paper or fabric substrates.

Jennifer Lewis, the Hans Thurnauer Professor of Materials Science and Engineering, and graduate student S. Brett Walker described the new ink in the Journal of the American Chemical Society.

"We are really excited about the wide applicability and excellent electrical properties of this new silver ink," said Lewis, the director of the Frederick Seitz Materials Research Laboratory at the U. of I.

Electronics printed on low-cost, flexible materials hold promise for antennas, batteries, sensors, solar energy, wearable devices and more. Most conductive inks rely on tiny metal particles suspended in the ink. The new ink is a transparent solution of silver acetate and ammonia. The silver remains dissolved in the solution until it is printed, and the liquid evaporates, yielding conductive features.

"It dries and reacts quickly, which allows us to immediately deposit silver as we print," Walker said.

The reactive ink has several advantages over particle-based inks. It is much faster to make: A batch takes minutes to mix, according to Walker, whereas particle-based inks take several hours and multiple steps to prepare. The ink also is stable for several weeks.

The reactive silver ink also can print through 100-nanometer nozzles, an order of magnitude smaller than particle-based inks, an important feature for printed microelectronics. Moreover, the ink's low viscosity makes it suitable for inkjet printing, direct ink writing or airbrush spraying over large, conformal areas.

"For printed electronics applications, you need to be able to store the ink for several months because silver is expensive," Walker said. "Since silver particles don't actually form until the ink exits the nozzle and the ammonia evaporates, our ink remains stable for very long periods. For fine-scale nozzle printing, that's a rarity."

The reactive silver ink boasts yet one more key advantage: a low processing temperature. Metallic inks typically need to be heated to achieve bulk conductivity through a process called annealing. The annealing temperatures for many particle-based inks are too high for many inexpensive plastics or paper. By contrast, the reactive silver ink exhibits an electrical conductivity approaching that of pure silver upon annealing at 90 degrees Celsius.

"We are now focused on patterning large-area transparent conductive surfaces using this reactive ink," said Lewis, who also is affiliated with the

Beckman Institute for Advanced Science and Technology, the Micro and Nanotechnology Lab and the department of chemical and biomolecular engineering at the U. of I.

The U.S. Department of Energy and the National Science Foundation supported this work.

Story Source:

The above story is reprinted from materials provided by University of Illinois at Urbana-Champaign.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

S. Brett Walker, Jennifer A. Lewis. Reactive Silver Inks for Patterning High-Conductivity Features at Mild Temperatures. Journal of the American Chemical Society, 2012; 120105082029000 DOI: 10.1021/ja209267c

Note: If no author is given, the source is cited instead.

Disclaimer: Views expressed in this article do not necessarily reflect those of ScienceDaily or its staff.

Graphene quantum dots: The next big small thing

 A Rice University laboratory has found a way to turn common carbon fiber into graphene quantum dots, tiny specks of matter with properties expected to prove useful in electronic, optical and biomedical applications.

The Rice lab of materials scientist Pulickel Ajayan, in collaboration with colleagues in China, India, Japan and the Texas Medical Center, discovered a one-step chemical process that is markedly simpler than established techniques for making graphene quantum dots. The results were published online this month in the American Chemical Society's journal Nano Letters.

"There have been several attempts to make graphene-based quantum dots with specific electronic and luminescent properties using chemical breakdown or e-beam lithography of graphene layers," said Ajayan, Rice's Benjamin M. and Mary Greenwood Anderson Professor of Mechanical Engineering and Materials Science and of chemistry. "We thought that as these nanodomains of graphitized carbons already exist in carbon fibers, which are cheap and plenty, why not use them as the precursor?"

Quantum dots, discovered in the 1980s, are semiconductors that contain a size- and shape-dependent band gap. These have been promising structures for applications that range from computers, LEDs, solar cells and lasers to medical imaging devices. The sub-5 nanometer carbon-based quantum dots produced in bulk through the wet chemical process discovered at Rice are highly soluble, and their size can be controlled via the temperature at which they're created.

The Rice researchers were attempting another experiment when they came across the technique. "We tried to selectively oxidize carbon fiber, and we found that was really hard," said Wei Gao, a Rice graduate student who worked on the project with lead author Juan Peng, a visiting student from Nanjing University who studied in Ajayan's lab last year. "We ended up with a solution and decided to look at a few drops with a transmission electron microscope."

The specks they saw were bits of graphene or, more precisely, oxidized nanodomains of graphene extracted via chemical treatment of carbon fiber. "That was a complete surprise," Gao said. "We call them quantum dots, but they're two-dimensional, so what we really have here are graphene quantum discs." Gao said other techniques are expensive and take weeks to make small batches of graphene quantum dots. "Our starting material is cheap, commercially available carbon fiber. In a one-step treatment, we get a large amount of quantum dots. I think that's the biggest advantage of our work," she said.

Further experimentation revealed interesting bits of information: The size of the dots, and thus their photoluminescent properties, could be controlled through processing at relatively low temperatures, from 80 to 120 degrees Celsius. "At 120, 100 and 80 degrees, we got blue, green and yellow luminescing dots," she said.

They also found the dots' edges tended to prefer the form known as zigzag. The edge of a sheet of graphene -- the single-atom-thick form of carbon -- determines its electrical characteristics, and zigzags are semiconducting.

Their luminescent properties give graphene quantum dots potential for imaging, protein analysis, cell tracking and other biomedical applications, Gao said. Tests at Houston's MD Anderson Cancer Center and Baylor College of Medicine on two human breast cancer lines showed the dots easily found their way into the cytoplasm and did not interfere with the cells' proliferation.

"The green quantum dots yielded a very good image," said co-author Rebeca Romero Aburto, a graduate student in the Ajayan lab who also studies at MD Anderson. "The advantage of graphene dots over fluorophores is that their fluorescence is more stable and they don't photobleach. They don't lose their fluorescence as easily. They have a depth limit, so they may be good for in vitro and in vivo (small animal) studies, but perhaps not optimal for deep tissues in humans.

"But everything has to start in the lab, and these could be an interesting approach to further explore for bioimaging," Romero Alburto said. "In the future, these graphene quantum dots could have high impact because they can be conjugated with other entities for sensing applications, too."

Co-authors include Angel Marti, aprofessor of chemistry and bioengineering, postdoctoral research associates Zheng Liu and Liehui Ge, senior research scientist Lawrence Alemany and graduate student Xiaobo Zhan, all of Rice; Rice alumnus Li Song of Shinshu University, Japan; Bipin Kumar Gupta of the National Physical Laboratory, New Delhi, who worked at the Ajayan lab on an Indo-US Science and Technology Forum fellowship; Guanhui Gao of the Ocean University of China; research technician Sajna Antony Vithayathil of Baylor College of Medicine; Benny Abraham Kaipparettu, a postdoctoral researcher at Baylor College of Medicine; Takuya Hayashi, an associate professor of engineering at Shinshu University, Japan; and Jun-Jie Zhu, a professor of chemistry at Nanjing University.

The research was supported by Nanoholdings, the Office of Naval Research MURI program on graphene, the Natural Science Foundation of China, the National Basic Research Program of China, the Indo-US Science and Technology Forum and the Welch Foundation.

Story Source:

The above story is reprinted from materials provided by Rice University.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

Juan Peng, Wei Gao, Bipin Kumar Gupta, Zheng Liu, Rebeca Romero-Aburto, Liehui Ge, Li Song, Lawrence B. Alemany, Xiaobo Zhan, Guanhui Gao, Sajna Antony Vithayathil, Benny Abraham Kaipparettu, Angel A. Marti, Takuya Hayashi, Jun-Jie Zhu, Pulickel M. Ajayan. Graphene Quantum Dots Derived from Carbon Fibers. Nano Letters, 2012; : 120106121847009 DOI: 10.1021/nl2038979

Note: If no author is given, the source is cited instead.

Disclaimer: Views expressed in this article do not necessarily reflect those of ScienceDaily or its staff.

Scientists develop new class of small molecules through innovative chemistry

Combining the power of synthetic chemistry with some advanced screening technologies, the new approach could eventually expand by millions the number of provocative synthetic compounds available to explore as potential drug candidates. This approach overcomes substantial molecular limitations associated with state-of-the-art approaches in small molecule synthesis and screening, which often serve as the foundation of current drug discovery efforts.

The study, led by Scripps Research Associate Professor Glenn Micalizio, was published Nov. 20, 2011, in an advanced online edition of the journal Nature Chemistry.

To frame the significance of this advance, Micalizio explains that high-throughput screening is an important component of modern drug discovery. In high-throughput screening, diverse collections of molecules are evaluated en masse for potential function in a biological area of interest. In this process, success is critically dependent on the composition of the molecular collections under evaluation. Modern screening centers maintain a relatively static collection of molecules, the majority of which are commercially available materials that have structures unrelated to natural products -- molecules that are appreciated as validated leads for drug development.

"This divergence in structure between natural products and commercially available synthetics lies at the heart of our inquiry," said Micalizio. "Why should we limit discovery of therapeutic leads to compound collections that are influenced by concerns relating to commercial availability and compatibility with an artificial set of constraints associated with the structure of modern screening centers?"

To expand the compounds available for investigation, the scientists embraced an approach to structural diversity that mimics nature's engine for the discovery of molecules with biological function. This process, termed "oligomerization," is a modular means of assembling structures (akin to the way that letters are used in a sequence to provide words with meaning) where a small collection of monomeric units can deliver a vast collection of oligomeric products of varying length, structure, and function (like the diversity of words presented in a dictionary).

Coupling this technique with a synthetic design aimed at generating molecules that boast molecular features inspired by the structures of bioactive natural products (specifically, polyketide-derived natural products, which include erythromycin, FK-506, and epothilone), the scientists established a new chemical platform for the discovery of potential therapeutics.

Micalizio points out: "The importance of oligomerization to drive discovery is well appreciated in chemistry and biology, yet a means to realize this process as an entry to small molecule natural product-inspired structures has remained elusive. The crux of the problem is related to challenges associated with the control of shape for each member of a complex oligomer collection -- the central molecular feature that defines biological function."

"It is the stability associated with the shape of these new compounds that lies at the heart of the practical advance," he continued. "The unique features of this science now make possible the ability to synthesize large collections of diverse natural product-inspired structures that have predictable and stable three-dimensional shapes."

Micalizio said that the science described represents a first step toward revolutionizing discovery at the interface of chemistry, biology, and medicine by embracing nature's strategy for molecular discovery. Coupling this type of advance with modern screening technology that can handle the evaluation of large compound collections at low cost (such as work by Scripps Florida Professor Thomas Kodadek, a co-author of the new study), can dramatically enhance the future of pharmaceutically relevant science.

The potential of this vision was highlighted in the new study, in which a 160,000-member compound collection was employed to discover the first non-covalent small molecule ligand to the DNA binding domain of p53 -- an important transcription factor that regulates a variety of genes involved in cell cycle control and cell death.

More information: "A Biomimetic Polyketide-Inspired Approach to Small-Molecule Ligand Discovery," Nature Chemistry.

Provided by The Scripps Research Institute (news : web)

Small molecule receptor detects lipid's telltale sign of cell death

Researchers from Boston College have developed a new class of small molecule receptors capable of detecting a lipid molecule that reveals the telltale signs of cellular death, particularly cancer cells targeted by anti-cancer drugs, the team reports in the current electronic edition of the Journal of the American Chemical Society.

Researchers led by Assistant Professor of Chemistry Jianmin Gao successfully grafted the key residues of the milk protein lactadherin onto the molecular scaffolding of a short but sturdy circular chain of amino acids to create cyclic lactadherin (cLac) mimics capable of binding to apoptotic, or dying, cells.

Gao said his team spent a year and a half focused on a finding a new method of measuring cell death. The team wanted to create an alternative to traditional tests that measure whether or not a tumor has shrunk in size after several weeks of treatment. The team's focus was on finding a way to measure the presence of dead cells, not the absence of tumor cells.

"We started by looking for a method to detect dying cells," said Gao. "The sensitivity of scientific and medical imaging is better if you look for the appearance of something, rather than the disappearance. What we wanted to look for is that in the initial stages of treatment the therapy's molecules are beginning to trigger the death of cancer cells. That can give you an idea a drug is working much sooner than the current methods of evaluation."

The newly engineered cLac molecules could prove useful as a prognostic tool which could enable oncologists to determine the effectiveness of anti-cancer drugs in a matter of days rather than several weeks, said Gao, who added that further research and testing will need to be conducted.

"Given the small size and ease of synthesis and labeling, cLacs hold great promise for noninvasive imaging of cell death in living animals and, ultimately, in human patients," Gao said.

The cLac molecule is relatively small, built upon on a cyclic peptide scaffold of approximately a dozen amino acids, yet Gao's laboratory tests show it is capable of capturing the lipid molecule phosphatidylserine (PS) – a function nature accomplishes by using proteins of several hundred amino acids, Gao said. In apoptotic cells PS flows to the surface where cLac is able to latch onto the dying cells while bypassing living cells. In the current report, researchers colored cLac with a fluorescent dye in order to highlight apoptotic cells for fluorescence microscopy. By using appropriate tracing agents, cLac should be detectable through commonly used imaging technology, including MRI and PET.

The cLac molecule could offer a cost-effective, more stable and cleaner alternative to natural PS-binding proteins used for similar purposes, Gao said. Those proteins are bulky and relatively unstable, contain metal cofactors that make results difficult to interpret and show poor ability to penetrate tissue because of their size.

Gao said cLac could also serve as a useful tool for researchers who use protein as a cell death indicator to screen for millions of compounds. The use of the small, peptide-binding molecule could substantially reduce costs for researchers, Gao said.

Provided by Boston College (news : web)

Large or small, platinum clusters provide new insights

Using Environmental Molecular Sciences Laboratory's high-performance supercomputing capabilities, scientists helped resolve longstanding controversies about the effect of platinum cluster size on some emissions-reducing reactions in automobile catalysts.

The research team included scientists from the University of California, Nanostellar, Inc., the University of Virginia and Lawrence Berkeley National Laboratory.

Carbon monoxide (CO) removal from combustion exhaust, typically carried out by oxidation on three-way catalysts containing platinum, is critically important for cleaner-burning engines.

The researchers used EMSL’s Chinook supercomputer to carry out detailed ab initio quantum mechanical calculations on very large (201-atom) platinum clusters to model the environment of platinum nanoparticles fully covered with CO.

The team integrated rigorous kinetic, isotopic, and in-situ spectroscopy studies of platinum clusters with theoretical simulations of CO oxidation catalysis at conditions prevalent in many industrial applications to gain a better understanding of catalytic activity on platinum clusters.

When a platinum catalyst covered with CO is at low temperatures, the size of the platinum cluster makes little difference in the rate of oxidation.

For other reactions catalyzed by platinum clusters in automobile exhaust, larger clusters will oxidize nitric oxide or dimethyl ether much faster.

CO oxidation is also a critical step in the production of pure hydrogen streams for use in fuels cells and in many chemical processes.

More information: Allian AD, et al. 2011. "Chemisorption of CO and Mechanism of CO Oxidation on Supported Platinum Nanoclusters." J. Am. Chem. Soc., 2011, 133 (12), pp 4498–4517 DOI: 10.1021/ja110073u

Provided by Environmental Molecular Sciences Laboratory

Small scale chemistry could lead to big improvements for biodegradable polymers

Using a small block of aluminum with a tiny groove carved in it, a team of researchers from the National Institute of Standards and Technology and the Polytechnic Institute of New York University is developing an improved “green chemistry” method for making biodegradable polymers. Their recently published work is a prime example of the value of microfluidics, a technology more commonly associated with inkjet printers and medical diagnostics, to process modeling and development for industrial chemistry.

“We basically developed a microreactor that lets us monitor continuous polymerization using enzymes,” explains NIST materials scientist Kathryn Beers. “These enzymes are an alternate green technology for making these types of polymers—we looked at a polyester—but the processes aren’t really industrially competitive yet,” she says. Data from the microreactor, a sort of zig-zag channel about a millimeter deep crammed with hundreds of tiny beads, shows how the process could be made much more efficient. The team believes it to be the first example of the observation of polymerization with a solid-supported enzyme in a microreactor.

The group studied the synthesis of PCL (Polycaprolactone), a biodegradable polyester used in applications ranging from medical devices to disposable tableware. PCL, Beers explains, most commonly is synthesized using an organic tin-based catalyst to stitch the base chemical rings together into the long polymer chains. The catalyst is highly toxic, however, and has to be disposed of.

Modern biochemistry has found a more environmentally friendly substitute in an enzyme produced by the yeast strain Candida antartica, Beers says, but standard batch processes—in which the raw material is dumped into a vat, along with tiny beads that carry the enzyme, and stirred—is too inefficient to be commercially competitive. It also has problems with enzyme residue contaminating and degrading the product.

By contrast, Beers explains, the microreactor is a continuous flow process. The feedstock chemical flows through the narrow channel, around the enzyme-coated beads, and, polymerized, out the other end. The arrangement allows precise control of temperature and reaction time, so that detailed data on the chemical kinetics of the process can be recorded to develop an accurate model to scale the process.

“The small-scale flow reactor allows us to monitor polymerization and look at the performance recyclability and recovery of these enzymes,” Beers says. “With this process engineering approach, we’ve shown that continuous flow really benefits these reactors. Not only does it dramatically accelerate the rate of reaction, but it improves your ability to recover the enzyme and reduce contamination of the product.” A forthcoming follow-up paper, she says, will present a full kinetic model of the reaction that could serve as the basis for designing an industrial scale process.

While this study focused on a specific type of enzyme-assisted polymer reactions, the authors observe, “it is evident that similar microreactor-based platforms can readily be extended to other systems; for example, high-throughput screening of new enzymes and to processes where continuous flow mode is preferred.”

More information: S. Kundu, et al. Continuous flow enzyme-catalyzed polymerization in a microreactor. J. Am. Chem. Soc. DOI:10.1021/ja111346c

Provided by National Institute of Standards and Technology (news : web)

Microreactors: Small scale chemistry could lead to big improvements for biodegradable polymers

 Using a small block of aluminum with a tiny groove carved in it, a team of researchers from the National Institute of Standards and Technology (NIST) and the Polytechnic Institute of New York University is developing an improved "green chemistry" method for making biodegradable polymers. Their recently published work is a prime example of the value of microfluidics, a technology more commonly associated with inkjet printers and medical diagnostics, to process modeling and development for industrial chemistry.

"We basically developed a microreactor that lets us monitor continuous polymerization using enzymes," explains NIST materials scientist Kathryn Beers. "These enzymes are an alternate green technology for making these types of polymers -- we looked at a polyester -- but the processes aren't really industrially competitive yet," she says. Data from the microreactor, a sort of zig-zag channel about a millimeter deep crammed with hundreds of tiny beads, shows how the process could be made much more efficient. The team believes it to be the first example of the observation of polymerization with a solid-supported enzyme in a microreactor.

The group studied the synthesis of PCL,* a biodegradable polyester used in applications ranging from medical devices to disposable tableware. PCL, Beers explains, most commonly is synthesized using an organic tin-based catalyst to stitch the base chemical rings together into the long polymer chains. The catalyst is highly toxic, however, and has to be disposed of.

Modern biochemistry has found a more environmentally friendly substitute in an enzyme produced by the yeast strain Candida antartica, Beers says, but standard batch processes -- in which the raw material is dumped into a vat, along with tiny beads that carry the enzyme, and stirred -- is too inefficient to be commercially competitive. It also has problems with enzyme residue contaminating and degrading the product.

By contrast, Beers explains, the microreactor is a continuous flow process. The feedstock chemical flows through the narrow channel, around the enzyme-coated beads, and, polymerized, out the other end. The arrangement allows precise control of temperature and reaction time, so that detailed data on the chemical kinetics of the process can be recorded to develop an accurate model to scale the process.

"The small-scale flow reactor allows us to monitor polymerization and look at the performance recyclability and recovery of these enzymes," Beers says. "With this process engineering approach, we've shown that continuous flow really benefits these reactors. Not only does it dramatically accelerate the rate of reaction, but it improves your ability to recover the enzyme and reduce contamination of the product." A forthcoming follow-up paper, she says, will present a full kinetic model of the reaction that could serve as the basis for designing an industrial scale process.

While this study focused on a specific type of enzyme-assisted polymer reactions, the authors observe, "it is evident that similar microreactor-based platforms can readily be extended to other systems; for example, high-throughput screening of new enzymes and to processes where continuous flow mode is preferred."

* Polycaprolactone

Story Source:

The above story is reprinted (with editorial adaptations  from materials provided by National Institute of Standards and Technology (NIST).

Journal Reference:

Santanu Kundu, Atul S. Bhangale, William E. Wallace, Kathleen M. Flynn, Charles M. Guttman, Richard A. Gross, Kathryn L. Beers. Continuous Flow Enzyme-Catalyzed Polymerization in a Microreactor. Journal of the American Chemical Society, 2011; : 110325123921095 DOI: 10.1021/ja111346c

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Molecular muscle: Small parts of a big protein play key roles in building tissues

 

We all know the adage: A little bit of a good thing can go a long way. Now researchers in London are reporting that might also be true for a large protein associated with wound healing.

The team at the Kennedy Institute of Rheumatology at Imperial College reports in the Journal of Biological Chemistry that a protein generated when the body is under stress, such as in cases of physical trauma or disease, can affect how the protective housing that surrounds each cell develops. What's more, they say, tiny pieces of that protein may one day prove useful in preventing the spread of tumors or fibrosis.

At just 174 nanometers in diameter, tenascin-C is pretty big in the world of proteins, and it looks a lot like a spider with six legs, which are about 10 times longer than its body. Thanks to those long legs, tenascin-C can do real heavy lifting when it comes to wound healing.

"Tenascin-C plays many roles in the response to tissue injury, including, first of all, initiating an immune response and, later, ensuring proper tissue rebuilding," explains Kim Midwood, who oversaw the project.

When the injury alarm is rung, tenascin-C shows up on the scene and attaches to another protein, fibronectin. Together, tenascin-C and fibronectin help to construct the housing, or extracellular matrix, that surrounds each cell.

"The extracellular matrix is the home in which the cells of your body reside: It provides shelter and nutrients and also sends signals to the cell to tell it how to behave," says Midwood. "To make a finished tissue, the matrix must be carefully built."

Tenascin-C's job is a temporary one. When your hand is cut, for example, it appears at the edges of the wound and then goes away when scar tissue develops, says postdoctoral research associate Wing To: "Tenascin-C is thought to play a major role during the rebuilding phase of tissue injury by promoting regeneration of tissue that has been damaged."

If the extracellular matrix were a construction site, tenascin-C could be seen as the scaffold upon which the weaving of fibronectin threads, or fibrils, is done. "Tenascin-C has multiple arms, and we have shown that it has multiple binding sites for fibronectin," Midwood says. "In this way, it can bind to many fibronectin fibrils at once and help to form the whole tissue by linking the fibrils together. Then, when the repair is done, the scaffolding is taken down."

Midwood and To systematically determined where tenascin-C and fibronectin bind together. They also identified small parts of tenascin-C, known as domains, that can bind to only one fibronectin fibril apiece.

"The small domains act as caps of the scaffold. No more fibronectin fibrils can bind once these caps are in place," Midwood says. So, in essence, they found that certain pieces of tenascin-C determine when fibril building should stop once enough, but not too much, tissue is made.

The findings could be especially useful for creating therapies for conditions in which there is aberrant extracellular matrix deposition, such as in cancers, fibrotic conditions or chronic non-healing wounds, adds To.

In abnormal conditions, such as in the case of a tumor cell, "the home that's made of fibronectin helps it to survive, shelters it and provides signals that enable it to proliferate," says Midwood. "As the tumor thrives, the home keeps on growing, expanding to destroy the existing neighborhood."

Similarly, in fibrotic diseases, tissue rebuilding rages out of control – with too much fibronectin assembly – so that it takes over the whole affected organ, Midwood says.

"In the end, we found that tenascin-C has both stop and go functions cleverly concealed in the same molecule," Midwood says. "The large spiderlike protein may provide a scaffold for building, and the small domains of the protein block excess building. Small domains may be therapeutically useful in situations where too much fibronectin drives disease."

If certain domains can stop uncontrolled matrix deposition in conditions where there is an increase in unwanted extracellular matrix, such as in fibrosis, then they could be useful tools for controlling such diseases.

Meanwhile, To says, in conditions with high levels of tenascin-C degradation by enzymes, for example in nonhealing chronic wounds, that may expose active tenascin-C domains, "if we can stop the production of these domains during disease progression with specific inhibitors, maybe we could help ameliorate the condition.

Similarly we could try and get the cells to make tenascin-C variants that are not as easily broken down by enzymes to help facilitate wound healing."

More information: Midwood and To's paper was named a "Paper of the Week" by the Journal of Biological Chemistry.

Provided by American Society for Biochemistry and Molecular Biology

Residual dipolar couplings unveil structure of small molecules

 German chemists at the Technische Universitaet Muenchen and the Karlsruhe Institute of Technology introduced a new method for identifying chemical compounds. The approach they used is an improvement on nuclear magnetic resonance measurements -- for decades one of the most successful methods for determining the chemical structure of organic molecules. The results now published in the scientific journal Angewandte Chemie show a handy approach to structural data when classical methods of analysis fail.

The team of Professor Burkhard Luy from KIT and Junior Professor Stefan F. Kirsch from the TUM has now shown for the first time that certain NMR parameters, the so-called residual dipolar couplings (RDCs), can make a significant contribution towards determining the constitution of chemical compounds when traditional methods fail. To do this they embedded molecules of the compound in a gel which slightly constricts their mobility. By stretching the gel, the molecules can be aligned along a preferred orientation. While residual dipolar couplings average out in solution, they become measurable in such partially aligned samples and provide valuable structural information that can be used to build a model of the molecule.

To test this new approach to chemical structure determination the scientists examined a molecule whose atomic composition was known, but not the precise connectivities of the individual atoms in the molecule. The molecule was obtained using a unique reaction, so there were no precedents for its structure. Classical methods of analysis failed because of the compactness of the molecule. In this particular case it was only possible to determine the structure by means of residual dipolar couplings, so that the newly acquired knowledge could be used to draw conclusions about the formation of the molecule – something that in the past could only be speculated about.

"This type of analysis will not be suitable for all structures in the future," said scientists Luy and Kirsch. "There will still be molecules whose structures will defy all attempts at unraveling, in spite of tremendous efforts and cutting-edge technologies. But this new method provides us with one further tool to help us unravel the structural mysteries of nature."

More information: Grit Kummerlöwe, Benedikt Crone; Manuel Kretschmer, Stefan F. Kirsch und Burkhard Luy: Residual Dipolar Couplings as a Powerful Tool for Constitutional Analysis: The Unexpected Formation of Tricyclic Compounds. Angewandte Chemie International Edition, scheduled to go online 17 or 18 February 2011. DOI:10.1002/anie.2010007305

Provided by Technische Universitaet Muenchen

Small molecule may deactivate enemy of cancer-fighting p53

Scientists are conducting a pioneering clinical trial to test the effectiveness in leukemia of a small molecule that shuts down MDM2, a protein that can disable the well-known tumor suppressor p53.

The clinical trial is under way at MD Anderson and five other sites in the United States and United Kingdom.

The first-in-class drug has shown clinical activity in some patients and been well-tolerated, Michael Andreeff, at The University of Texas MD Anderson Cancer Center said.

“P53 can be activated by chemotherapy or radiation, but both of these therapies carry risks of causing secondary tumors,” Andreeff said.

“If we can activate this tumor-suppressor with a method that is non-genotoxic and does not cause damage to a patient”s DNA, we may be able to help avoid secondary tumors caused by other treatments,” he added.

Normally, p53 halts the division of defective cells and forces them to commit suicide or lose the ability to reproduce. However, the tumor suppressor is disabled in many types of cancer, often because of gene mutations or defective signaling.

While mutations of the TP53 gene are rare in cancers of the blood, the p53 protein may be degraded by other factors, including high levels of MDM2, which binds to p53 and orchestrates its degradation.

In preclinical studies, small-molecule MDM2 antagonists called Nutlins were found to be effective in solid tumors, leukemia and lymphoma.

The drug used in this study, RG7112, a novel small molecule being developed by Roche, is a member of the Nutlin family.

Patients with relapsed or refractory acute or chronic leukemia were given RG7112 orally each day for 10 days, followed by 18 days of rest. Forty-seven patients, including 27 with acute myeloid leukemia (AML), have been treated to date.

There has been evidence of clinical activity, and one patient with AML has been leukemia-free for nine months. Reductions in lymph node and spleen size, as well as in circulating leukemia cells, were seen in chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).

The preliminary results of this ongoing Phase I study were presented at the 52nd Annual Meeting of the American Society of Hematology. (ANI)

Disclaimer: Bioscholar is not intended to provide medical advice, diagnosis or treatment. The articles are based on peer reviewed research, and discoveries/products mentioned in the articles may not be approved by the regulatory bodies.