science/technology
First ACHEMA Of The New Century Germany's triennial exhibition and congress provides largest ever stage for chemical technology of the future Michael Freemantle C&EN London
T
he scale and scope of ACHEMA, held in Frankfurt every three years, are immense. The event, a combination of exhibitions and congress focusing on the chemical process industry, provides a unique stage for displaying the latest developments in chemical technology, environmental technology, and biotechnology. And although these three technologies provide the central themes of the fair, technology in other areas linked to chemical processing—including information, safety, materials, microreactors, food, and pharmaceuticals, as well as nanotechnology—also feature prominently. ACHEMA, a German acronym for chemical engineering exhibition and congress, is subtitled International Meeting on Chemical Engineering, Environmental Protection & Biotechnology. It is organized by DECHEMA, the Frankfurt-based German Society for Chemical Engineering & Biotechnology. Last month's ACHEMA 2000 was the 26th exhibition and congress in the triennial series. "At ACHEMA, all the equipment sectors of the chemical process industry, from research and the laboratory to entire plants, are represented in the exhibition," noted DECHEMAs chief executive, Gerhard Kreysa, at a press briefing. 'The primary objective of ACHEMA is to foster the exchange of ideas and experiences between manufacturers and users of plants, equipment, components, and apparatus. Special emphasis is placed on the presentation of innovations and new developments." The first-time visitor to ACHEMA is easily overwhelmed by the sheer physical magnitude of the exhibition and the Frankfurt Exhibition Grounds. There are 10 exhibition halls, most of which have two or three floors. The distance 4 8 JUNE 19, 2000 C&EN
between Hall 1, near the city entrance, and Hall 9, at the furthermost Galleria entrance, is about 1 mile. The walk between the two takes about 20 minutes— even longer if you do not use the moving walkways that link the various halls. The grounds has its own railway station, congress center, and hotel, and it is served by a dozen or so restaurants as well as numerous cafes, bars, and hot dog stands. "ACHEMA is a giant," observed DECHEMA's public relations manager, Christina Hirche. The giant takes over much of the center of Frankfurt for a week in May. The prices of hotel rooms more than double during the week, and some of the 220,000 or so participants from around 100 countries who do not book accommodations early enough are obliged to stay out of town and commute to Frankfurt by a halfhour or more train journey each day. This year's fair consisted of more than 4,100 exhibits and almost 1,000 lectures on a wide range of topics. "ACHEMA 2000 is once again set to break all previous records," Kreysa told journalists at the start of the event He pointed out that the number of exhibitors increased by a record 12.1% compared with the ACHEMA in 1997. "The exhibition groups devoted to re-
search and innovation; pharmaceutical, packaging, and storage techniques; thermal processes; pumps, compressors, valves, andfittings;and materials technology and testing all registered double-digit percentage growth rates," Kreysa added. "In addition, the number of lecture contributions at the congress increased by around 28% compared with 1997." These increases are significant, according to Wolfgang Habig, a member of the DECHEMA board, chairman of the ACHEMA committee, and former member of the supervisory board of Westfalia Separator, Oelde, Germany. "Measured by numerous important indicators, ACHEMA 2000 far outstrips past ACHEMA events," he said at the press briefing. "How could it be otherwise? We find ourselves in a situation where the global economy is looking rosier than it has for quite some time. And virtually every sector of the chemical process industry is benefiting from the positive economic climate. Among a broad cross-section of ACHEMA exhibitors
According to Hirche, about 1,000 journalists from the trade press, the daily press, radio, and television registered to cover ACHEMA 2000. "When reporters from the daily press come up to me and ask me what are the highlights of ACHEMA, I tell them it is impossible to single out just one or two highlights because there are so many in each exhibition hall and in the congress," she told C&EN. Each ACHEMA has its own distinctive features, and certain technological trends can be discerned from the exhibitions and the congress. For example, ACHEMA 2000 featured the first-ever International Symposium on
high-speed laboratory technologies. It consisted of plenary lectures and four parallel sessions on high-throughput chemistry, automation and miniaturization in synthesis and screening, DNA sequencing and biochips, and ultra-high-throughput screening and effective assay methods. The symposium was accompanied by a special exhibition in which more than 40 companies presented the latest developments in combinatorial synthesis, miniaturization of reactors, biochip technology, computer-aided design of active s u b s t a n c e s , and database applications. The opening plenary lecture, titled "Industrialization of Drug Discovery," was presented by Christof Fattinger, head of measuring techniques and automation in the pharmaceutical research division of Hoffmann-La Roche, Basel, Switzerland. Addressing a standing-room-only audience, Fattinger pointed out that the host of new discoveries deriving from genome research programs is having a pronounced impact on m e drug discovery and development process. "It seems probable that the causes of the 100 most important diseases are Hall to be found in some 5,000 to Hall; 10,000 genes and their proteins, the new drug targets," he suggested. Medicinal chemists workAus ing in the pharmaceutical inCity dustry are exploiting combinaExit Sort torial chemistry, using simultaneous multiple synthesis processes, in order to create new organic compounds that will considerably expand their existing compound libraries," Fattinger continued. He pointed out that the effectiveness of the drug discovery process depends on a number of factors, including the validity and suitability of the drug target and the nature of the compound library—its diversity and purity, for example. 'The quality of the information derived from screening assays is especially crucial," he said. "The ultimate goal is to lower the attrition rates of potential new medicines in the advanced clinical phases of the drug development process." Fattinger described a new automated compound-handling technology known as the Smart Roche Compound Deposi-
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there is now an unmistakabk feeling of optimism." The growing international ization of the industry and o ACHEMA is especially notewor thy, according to Habig. 'This time three years ago, the fac that 33.6% of ACHEMA exhibi tors were from overseas led me to talk about globalization as the key element that was radically transforming the environment within which ACHEMA operates," he said. 'This process has now become part of everyday reality—close to 38% of ACHEMA exhibitors now come from abroad, and 48 different countries are represented at the exhibition." ACHEMAs international dimension has been reinforced by a new DECHEMA concept known as ACHEMA Worldwide, which consists of a three-year cycle of three exhibition-congresses on three continents, starting with ACHEMA 2000. ACHEMASIA will be held in Beijing in May of next year; ACHEMAMERICA will take place in Mexico City in March 2002.
Synthesis, Screening & Sequencing. Other ACHEMA firsts included a congress session on chemical nanotechnology and an exhibition group devoted exclusively to biotechnology. "For the first time young, research-oriented biotechnology start-up companies, organized in Germany within DECHEMA as the Association of German Biotechnology Companies, have their own new biotechnology exhibition group," Kreysa explained. High-throughput c h e m i s t r y The 1st International Symposium on Synthesis, Screening & Sequencing focused on the latest developments in
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science/technology tory. 'The system enables Roche's medicinal chemists to search for candidate compounds in Roche's global compound library based on substructural concepts, submit the hit list of the computer search electronically to the compound handling system, and get the plates with the selected compounds the next day," he told C&EN. "The plates are properly customized for testing in biological assays or for measurements of biophysicochemical compound properties." Access to miniaturized aliquots of compounds from the library is fully computerized and robot-assisted. The daily capacity of the system is around 6,000 sample retrievals and placements into customized delivery plates, according to Fattinger. Roche and optical engineering company Carl Zeiss in Jena, Germany, have recently developed in a joint project an ultra-high-throughput screening system that can test around 200,000 samples per day, performing up to 10 measurements on each sample. "Miniaturization of test volumes, using microplates with 1,536 wells, translates into a dramatic reduction in the amounts of bioreagents and chemical samples required for primary screening assays," Fattinger said. Plate handling in the system is based on a robotic turntable concept and therefore avoids single-armed robots. All liquid-handling and optical detection operations are processed in parallel. With its 96-channel optics, the system's microplate reader can perform | high-precision analysis on 1,536 | samples in 16 steps in a matter of £ seconds, Fattinger noted. 1 "Combination of these automat- | ed systems results in a powerful re- £ search platform for target profiling, | combinatorial synthesis, primary £ screening, secondary screening, and compound subset screening," Fattinger added. In the symposium session on high-throughput chemistry, Ralf God, director of separation technologies at AnalytiCon, Potsdam, Germany, and Heike Stump, research scientist at Aventis Pharma Deutschland, Frankfurt, described the use of a technique known as multiparallel high-performance liquid chromatography (MP-HPLC) for high-throughput natural product drug discovery. "Nature has proven over thousands of years to be an inexhaust5 0 JUNE 19, 2000 C&EN
ible source of potent drugs," Stump observed. "Secondary metabolites from animals, plants, and microorganisms exhibit considerable structural diversity, which is complementary to that of synthetic compounds." She pointed out, however, that natural product extracts are complex mixtures often containing thousands of components. 'The challenge is to isolate and identify an active ingredient from an extract," she said. "In such complex mixtures, some compounds can interfere with the bioassay, leading to false-positive results. In addition, when interfering ingredients occur in large excess, biological effects can be hidden. It is therefore preferred to avoid screening crude extracts." According to God, sample quality can be dramatically improved by using prefractionated samples in the assays. "HPLC is a valuable tool for prefractionating crude natural product extracts," he said. "MP-HPLC is a new prefractionation technique with a very high throughput. Patents are pending on the technology." An MP-HPLC instrument designed in cooperation with Aventis and manufactured by AnalytiCon is now being used in Aventis' natural product laboratories in Frankfurt.
"The instrument is the first really parallel operating preparative HPLC system in the world," God said. "It is a fully automated system which is able to prepare prefractionated products for high-throughput screening from about 100 natural product extracts in less than one day. "A sophisticated injection system allows sequential loading and parallel injection of eight extract samples," he explained. 'The extracts are then separated on HPLC columns operated in parallel, generating multiple fractions of each natural product extract. A specially developed ultraviolet-absorbance detector based on fiber optics is used for recording eight chromatograms in parallel." The eluted fractions from the eight separation columns are then trapped on solid-phase extraction columns. The
trap columns are rinsed with water and then flushed with an organic desorbent to yield samples for screening, which are collected by a robot in deep-well plates. "This high-throughput prefractionation HPLC system was designed for running 24 hours a day in an unattended mode, and the whole process is controlled by easy-to-handle software," Stump remarked. "Incoming and outgoing samples are identified by bar-code reader, and data are directly transferred to a database." In the same symposium, Stefan Lamotte, division manager of columns and stationary phases at Bischoff Chromatography, Leonberg, Germany, asked, "What is the speed limit?" in a lecture on the use
of fast HPLC separations as a tool for high sample throughput. Bischoff Chromatography was one of the exhibitors in the special show associated with the symposium. "High sample throughput is a must in, for example, process monitoring, environmental analysis, food analysis, quality control in the pharmaceutical industry, and combinatorial chemistry," Lamotte said. "Ultrafast HPLC separations, with only insignificant loss of separation performance, can be achieved by using high flow rates in short columns packed with small particles." Lamotte reported that it is now possible to separate and detect six model compounds—uracil and five phenylalkanes—in nine seconds. The system uses a UV-absorbance detector and a 14mm column packed with ultrapure nonporous silica spheres, manufactured by MICRA Scientific, Northbrook, 111., that are 1.5 \xm in diameter. 'The instrument still has to be optimized," Lamotte said. "But even so, routine analysis in 30-second runs is now possible. The key to the efficient use of HPLC in high-throughput screening is the combination of modern packings and some modifications of commercial HPLC instruments." Speed of analysis is also a key factor in high-throughput catalyst research, according to Ferdi Schuth, director of the Max Planck Institut fur Kohlenforschung (Max Planck Institute for Coal Research), Mulheim, Germany. In the session on high-throughput chemistry, Schuth pointed out that there are many highly attractive chemical processes for which no suitable catalyst has been developed so far. That makes high-throughput techniques to identify catalysts highly desirable. However, the performance of a catalyst in an industrial process results from a delicate interplay between catalyst, reaction conditions, and catalytic reactor. It's difficult to optimize all these factors simultaneously in a highthroughput approach. "Although massively parallelized techniques for the discovery of novel catalysts are interesting, the scale-up of the findings is a serious problem," Schuth said. "These techniques are being used under conditions very different from those present in the technical catalytic reactor. It is therefore important to also have less parallelized tools which give data of similar quality to conventional testing.
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science/technology "We have developed techniques for the automated preparation and testing of heterogeneous catalysts on a scale of 10 to 100 mg in a parallelized fashion," he continued. 'The synthesis system is based on an automated dispenser equipped with automated precipitation and filtering devices built in-house. This system allows preparation of catalysts by impregnation, precipitation, or coprecipitation." Schiith's group has used the system to prepare various gold-based catalysts on different transition-metal supports for the catalysis of room-temperature carbon monoxide oxidation. However, the bottleneck in the catalyst-development process is the testing rather than the synthesis of the catalysts, he pointed out. To speed this process up, the group has developed a 16-pass parallel reactor in which a common feed is passed over all 16 catalysts. The stream coming off of each catalyst is passed separately for analysis by gas chromatography, mass spectrometry, or infrared spectroscopy. The analyses | | are not fully parallel, however. 11 Even so, when the separate streams are switched sequen- | | tially to the analyzer, the speed of the test procedure is increased by a factor of 15. The group has used the setup £| to identify several active catalysts for room-temperature CO oxidation. 'The 16-pass parallel reactor is now in routine use in our laboratory," Schiith said. 'We have also developed a 49-pass parallel reactor which enables a full array of 49 catalysts to be analyzed within three hours." The group is developing these tools in cooperation with a start-up company based in Heidelberg, Germany, known as High-Throughput Experimentation Co. "One should bear in mind that increasing the throughput by only a factor of 50, as is possible with moderately parallelized systems like ours, without losing substantial data quality, corresponds to enormous cost savings and much more rapid catalyst development," Schiith told C&EN. "We now have three types of parallelized reactors in use in our laboratory, and students and postdoctoral researchers in my group are increasingly relying on these reactors to find the optimum preparation conditions for specific catalysts and to search for novel catalysts." 5 2 JUNE 19, 2000 C&EN
Schiith remarked that software support for the design of large libraries of potential catalysts is often neglected. "Library design is an extremely difficult task since suitable descriptors for solids are still lacking," he said. "We are working on the development of such descriptors and on the implementation of design software modules. Intelligent library design will be one of the most important factors to discriminate between successful and less successful research groups in this field." Simon Collard, development :"" manager in the Catalyst & Chemicals Division of Johnson Matthey, Royston, England, pointed out that selection of the optimum catalyst for a particular reaction is often a time-consuming process because small changes in catalyst structure can result in dramatic differences in activity and/or selectivity. Collard's group has developed
methods that allow simultaneous screening of large numbers of preciousmetal catalysts in a range of reactions of industrial interest. The group is particularly interested in the platinum group metals: palladium, platinum, rhodium, iridium, and ruthenium. These metals are used to catalyze Heck, Suzuki, and other coupling reactions; reductions using hydrogen gas or hydrogen transfer reagents; dehydrogenations; carbonylations; oxidations; and other types of chemical reactions. The optimum performance of this type of catalyst depends on a number of factors, including the nature of the ligands bound to the metal, the solvent used, the temperature, and the pressure, Collard noted.
"Rather than supplying standard catalysts to our customers, we can now screen for the catalyst that is most suited for their specific reactions," he said. "Automation of the catalyst screening stage enables us to challenge some of the conventions of traditional catalysis. We are now able to explore whole areas of diversity that were previously barred to us due to lack of time or resources." Collard cited a homogeneous hydrogenation catalyst known as Crabtree's
catalyst as an example of catalyst diversity. The catalyst consists of a noncomplexing anion, such as hexafluorophosphate, and an iridium (I) center bound to three types of ligand: a diene, a tertiary amine, and a phosphine or similar ligand. "A screen of 400 catalysts is possible using two variants of the anion, two variants of the diene, and ten variants of each of the amine and phosphine," he explained. "A screen of this size would not have been considered in the days of serial processing." To carry out screening, Collard's group uses a system known as the Myriad Personal Synthesizer that automatically screens up to 24 reactions at a time and allows precise control over the duration and conditions of the reaction. Samples taken from the reactors during or after the reaction are analyzed by gas chromatography or HPLC.
Chemical nanotechnology Another first at the ACHEMA 2000 congress was a session on chemical nanotechnology. It opened with a lecture by Roland Wiirschum, senior research
associate at the Institute for Nanotechnology, Karlsruhe Research Center, Germany. Wurschum described the synthesis and material transport properties of nanocrystalline materials. He pointed out that the processing of ceramic powders for a variety of applications is commonly carried out using particles with very small sizes. Solid materials with nanoscale crystallite sizes are particularly attractive for potential applications because of the high number of interfaces in these materials. For example, work over recent years has shown that the sintering behavior of ultrafine grained ceramics such as zirconia (Zr02) and titanium dioxide (Ti02) with initial crystallite sizes in the 10-nm region exhibit improved sintering behavior compared with conventional microcrystalline powders. "Nanocrystalline solids can be synthesized by chemical methods, inert-gas condensation, and a variety of other routes," Wiirschum pointed out. "A particularly versatile and attractive route is gas-phase cluster synthesis." This method can be used to prepare not only nanocrystalline ceramics but
also highly dense nanocrystalline samples of metals such as palladium and iron, he explained. The method involves evaporating or sputtering the pure metal in an inert gas atmosphere followed by condensation of the resulting metal nanocrystallites, which can, if necessary, be oxidized in an oxygen atmosphere. A specimen of the nanocrystalline metal or its oxide is then obtained by compacting the powder in situ under high pressure. One key to understanding the hightemperature properties of ultrafine grained materials is the diffusion of atoms along and across the grain boundaries between the nanocrystallites. But diffusion data, particularly on nanocrystalline ceramics, are scarce, according to Wiirschum. "The transport of atoms in nanocrystalline materials is an important issue since it controls both the physical properties, such as plasticity, and the structural stability of these materials," he said. Last year, Wiirschum and coworkers reported data on the diffusion of oxygen in ultrafine-grained Zr0 2 . The group used a secondary ion mass spectrome-
ter to measure diffusion profiles of an 18 0 tracer in the material. 'The measurement of oxygen diffusivity in nanocrystalline Zr0 2 is relevant for the assessment of whether or not a high number of interfaces can improve the performance of solid-state oxide electrolytes," Wiirschum told C&EN. Reinhard Schomacker, chemistry professor at the Institute of Technical Chemistry, Technical University of Berlin, described recent developments in the preparation of nanoparticles by precipitation from water-in-oil microemulsions containing a nonionic surfactant. "Microemulsions are used in pharmaceutical preparations, cosmetics, and other applications," he said. 'The use of water-in-oil microemulsions for the synthesis of inorganic nanoparticles is not only relatively new, but also a simple, inexpensive, and versatile method of preparing nanoparticles." The method involves dissolving reactants in the water droplets of two similar microemulsions. The precipitation reaction is started by mixing the two microemulsions. The precipitated nuclei do
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science/technology not aggregate because surfactant molecules are adsorbed on the surface of the nuclei. "A high concentration of nuclei is therefore formed in the microemulsion, yielding particles of nanometer size," Schomacker explained. Until now, the synthesis of nanoparticles in microemulsions has only been carried out on a laboratory scale, according to Schomacker. "Since nanotechnology is regarded as a major future technology, methods for scaling up nanoparticle synthesis are needed," he said. "For industrial-scale production of nanoparticles, we need detailed knowledge of the particle formation mechanism so that the precipitation process can be controlled effectively." Schomacker's group has been investigating the influence of stirring rate, feed rate, and different ways of concentration control on the formation of palladium nanoparticles in a small semibatch reactor. The experiments involved mixing two microemulsions containing sodium tetrachloropalladate (Na2PdCl4-2NaCl) and the reduc-
ing agent sodium hypophosphite from their commercial use in cosmetic (NaH2P02-H20) in their aqueous phas- products and in medicine, liposomes es. Both microemulsions contained cy- are gaining more attention for their poclohexane as the continuous oil phase tential nonmedical applications, as miand an alkyl polyethyleneglycol ether- croreactors, for example," Walde said. type surfactant. The group showed "They are also protocell models for that nearly monodisperse nanoparti- questions on how life may have develcles of 5 to 10 nm in diameter can be oped on Earth some 4 billion years ago." obtained by precharging the reactor The liposomes studied by the ETH with the microemulsion containing the group are unilamellar vesicles prepared reducing agent and then adding the from l-palmitoyl-2-oleoyl-5w-glycero-3microemulsion containing the palladi- phosphocholine, a commercially availum salt at a constant feed rate. able, naturally occurring phospholipid. The group investigated the catalytic In the same congress session, Peter Walde, a professor in the Department of activity of bovine pancreas oc-chymoMaterials, Swiss Federal Institute of trypsin entrapped in the aqueous comTechnology (ETH), Zurich, reported re- partments of the liposomes. a-Chymosearch on the use of lipid vesicles with trypsin is a water-soluble proteolytic endiameters of around 100 nm as zyme. The researchers examined the selectivity of the entrapped enzyme for nanoreactors. "The aim of our work is to under- externally added peptide nitroanilide stand the catalytic behavior of enzymes substrates. They showed that the entrapped within the aqueous space of lip- trapped enzyme hydrolyzes benzoyl-Ltyrosine-^-nitroanilide, a small substrate id vesicles," Walde said. Lipid vesicles, or liposomes, are uni- that can migrate from the bulk aqueous lamellar or multilamellar spherical ag- medium across the phospholipid bilayer gregates consisting of one or more con- shell into the vesicle's aqueous interior. centric phospholipid bilayers. "Apart A larger ^-nitroanilide substrate con-
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taining four amino acids was not hydrolyzed because it could not permeate the bilayer from the external aqueous phase. Walde's team also determined the enzyme-catalyzed rates of hydrolysis for both substrates in the presence and absence of vesicles and developed a general mathematical model for the kinetic behavior of the enzyme. Using the model and the experimental data, the group was able to obtain the permeability coefficient of the smaller ^-nitroanilide substrate. 'To the best of my knowledge, it is the first time that an enzymatic reaction occurring inside a sub-micrometersized vesicle compartment has been investigated in detail experimentally and at the same time modeled by dynamic simulation, yielding directly the permeability coefficient of the externally added substrate," Walde told C&EN. Johannes G. Vos, chemistry professor at Dublin City University, Ireland, pointed out that nanocrystalline materials are potentially useful in the field of molecular electronics, for example, in the development of solar cells that use dye-sensitized nanocrystalline semiconductors for the efficient conversion of solar energy. In a lecture titled "Toward Photochemically Driven Supramolecular Devices," Vos outlined the findings of a recent research project on heterosupramolecular chemistry supported by a European Union (EU) program known as the Training & Mobility of Researchers (TMR) Programme. The TMR network, which Vos coordinated, involved about 50 researchers in six European research groups located in four EU countries. A heterosupramolecular system consists of a supramolecular system covalently bound to a nanoparticle— nanocrystalline Ti0 2 , for example. Heterosupramolecular systems are potentially useful because photoactive components that are capable of electron- or energy-transfer processes can be addressed at the macroscopic level through the solid, nanocrystalline phase. 'The aim of our project was to investigate the specific interaction between molecular components such as ruthenium complexes and a nanostructured surface and to design surfaces modified with multinuclear molecular components," Vos noted. 'The final aim of the project was to produce prototype devic-
es for consideration in potential applications such as electrochromic devices and solar cells." The researchers demonstrated that dinuclear molecular species, such as mixed-metal ruthenium-rhodium and ruthenium-osmium polypyridyl complexes, exhibit well-defined electronand energy-transfer processes and that long-lived charge-separated states can be achieved upon binding such dinuclear species to nanocrystalline Ti0 2 . Carboxy, pyridine, and thiol linkages were particularly good for anchoring the complexes to the metal oxide or metal surfaces. Vos also reported that a company known as Nanomat, based in University College Dublin, has been set up to commercialize the use of nanocrystalline surfaces developed in the TMR project. Jiirgen Ruhe, professor of chemistry and physics of interfaces at the Institute for Microsystem Technology, University of Freiburg, Germany, described recent work on the generation and characterization of ultrathin polymer films on solid surfaces.
"An important issue for the generation of stable micro- or nanopatterns is the strength of adhesion between the functional polymer molecules and the solid support," he noted. "Strong adhesion and good long-term stability can be obtained if the polymer chains carrying the functional groups are covalently linked to the substrate." Ruhe and coworkers have developed several new pathways for the synthesis of polymer monolayers that are covalently attached to solid surfaces. The new pathways allow the production of materials with tailor-made surfaces. Much of the work was carried out while Riihe's group was at the Max Planck Institute for Polymer Research, Mainz, Germany. The group has only recently moved to Freiburg. One pathway employs what Ruhe calls a "grafting-from" approach to generate monolayers of a polymer covalently attached to a solid surface. A selfassembled monolayer of a polymerization initiator is first covalently attached to the surface of the substrate. The polymer chains carrying the functional
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science/technology groups are then generated in situ by radical chain polymerization. Ruhe's group has, for example, synthesized a monolayer of the cationic polyelectrolyte poly[4-vinyl-iV-fl-butylpyridinium] bromide, covalently attached to a planar silicon dioxide surface. A neutral poly(vinylpyridine) monolayer is first grown on the surface by using a self-assembled monolayer of an azo initiator. This layer is then converted into the positively charged monolayer by a quaternization reaction. 'The thickness of the resulting cationic monolayer can be controlled over a wide range—from 2 nm to more than 1,000 nm in the solvent-free state—by varying reaction parameters such as polymerization time and temperature, and monomer concentration," Rlihe noted. Working with a group at Stanford University led by chemical engineering professor Curtis W. Frank, Riihe has also photochemically attached thin films of poly(styrene) and poly(ethyloxazoline) with a thickness of up to 16 nm on Si02 surfaces. Thefirststep in this process is to immobilize a photocoupling agent, such as benzophenone silane, on the surface. The silane moiety covalently anchors the benzophenone moiety to the substrate. The polymer is then spin-cast over the benzophenone derivative, and the two layers are illuminated with UV light. 'The thicknesses of the benzophenone silane and polymer layers are not important so long as both layers remain transparent," Riihe explained. "Alternatively, if a transparent substrate is used, the layers can be illuminated from the side that is not coated. During the illumination process, photochemical reactions between the polymer and the benzophenone moiety are induced, and the polymer coating becomes photolinked to the surface."
now integrated with information technology (IT). "Even previously 'unintelligent' components such as pumps and valves are increasingly being upgraded with IT components," he said. A typical example of this trend was provided by pump manufacturer Hermetic, based in Gundelfingen, Germany. The company points out that leakage-free, hermetic, submersible pumps are required in chemical and nuclear plants in which hazardous, toxic, or explosive fluids have to be moved in pipes. Such pumps have to be provided with the best possible safety and monitoring devices, the company stresses. Hermetic's new Axial Rotations Monitor (ARM-2000) contains sensor coils
and an electronic evaluation system that monitors the operation of the pump. A peripheral microprocessor-controlled unit can store data on the operation of the pump over a period of 370 days. Stored data can be retrieved for display, printed out, or transferred to a computTechnological trends er. The device not only monitors and DECHEMA board member Habig documents the rotation of the pump but identified a number of key technological also stops its operation and sounds an trends emerging from the ACHEMA alarm if warranted. 2000 exhibition. They included the inPumps, compressors, valves, and fitcreased use of combinatorial synthesis tings formed the largest exhibition methods for catalytic converter re- group at ACHEMA 2000, with over 800 search and the development of microre- exhibitors. DECHEMA, which devoted action technology. three of its 19 ACHEMA 2000 trend reHabig also pointed out that virtually ports to the topic, observed that these every type of product at the exhibition is components are now becoming inte5 6 JUNE 19,2000 C&EN
grated into fluid management systems that meet the specific requirements of customers. As an example, DECHEMA noted in one of these reports that embedded microprocessors in valve positioners provide improved positioning accuracy, diagnostics and data-logging facilities, digital communications, and, in some cases, direct control of flow rate and pressure drop. "Especially in the past year, several major manufacturers have extended this functionality to allow users to interrogate their valves from a Web browser across a company intranet or the Internet," the society's report pointed out. "Measuring devices and sensors are the unsung stars of the plant," DECHEMA suggested in another trend report. 'They are becoming more and more intelligent because the trend is toward integrating as many control functions as possible from the process control system into these devices." Field devices and instruments that can provide online diagnosis and preventative maintenance are also becoming an integral part of chemical processing, DECHEMA noted. Another trend identified by DECHEMA is the drive toward process intensification (PI), which the society defines as a radical design approach that makes production plants smaller, cheaper, and safer. 'The concept was born from the recognition that much of the capital cost for a chemical plant is related to the civil engineering structure," the society explained. "Significant reductions in capital cost can be achieved by reducing chemical plant size, and environmental benefits also arise from reduction in raw materials consumption, waste, and energy demands." One example of PI that DECHEMA cited was compact heat exchangers, which have much greater heat-transfer surface areas than conventional heat exchangers. This allows them to achieve much smaller temperature differences between process and cooling streams. As a result, compact heat exchangers can reduce fouling and lower energy requirements, DECHEMA noted. The development of microreactor technology also fits under the PI umbrella. "A traditional chemical plant is said to be equivalent to main-frame com-
puters that occupied whole buildings 20 years ago, while micro devices are equivalent to the lab-on-a-chip," according to DECHEMA. Gotthard Grass, managing director of the German Electrical & Electronic Manufacturers' Association, told journalists that electrical engineering and electronics are two of the common denominators of the technological developments on display at ACHEMA. "Laboratory and analytical techniques; pumps, compressors, valves, and fit- Grass (left) and Habig. tings; pharmaceutical, packaging, and storage techniques; and, of creasingly refined analyses allowing pocourse, engineering are some of the ex- tential new risks to be discovered early," hibition groups where electrical engi- he said. 'The central theme, however, is neering and electronics have become increasingly becoming product- and prothe key technologies," he said. duction-integrated environmental proGrass pointed out that electrical and tection using, for example, electronic electronic systems are important compo- control systems, which, by means of nents in safety and environmental protec- elegant process controls, prevent envition. "Electronic measuring and analysis ronmental risks from occurring in systems can, for example, conduct in- products and processes."
Habig also pointed to the change in emphasis in methods of environmental protection. "End-of-pipe environmental protection is being unmistakably nudged into the background by productionintegrated environmental protection," he said. 'The number of ACHEMA exhibitors that offer ecological system solutions has risen by 50% to more than 1,500." DECHEMA noted in another of its trend reports that sustainable production-integrated environmental protection requires changes to the process and different technical components. For example, the incorporation of filters, membrane systems, centrifuges, and evaporation units into a plant can ensure that wastewater or solvents are cleaned and fed back into the system. Biotechnology can also make a significant contribution to environmental protection, DECHEMA observed. "Bio-
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The Fourth International Conference on Some of the speakers that vfill^l6^iini^rite?|^l^MK^MWP JWtiSraj^:
The Scale-Up of Chemical Processes Hotel de France, St. Helier Jersey, Channel Islands
Since the first conference in 1994, this event has become established as the major international forum for the discussion of all aspects of Chemical Scale-Up and Optimisation. Speakers with unique expertise in their particular field will present a variety of topics including: Wide-ranging detailed Case Studies of Chemistry Engineering 0 Safety and Environmental Issues • Quality Assurance and Legislative Concerns Q Commercial, Educational and Theoretical topics
Mike Butters, Pfizer Central Research UK Voriconazole - Process Development of a Novel Broad Spectrum Triazole Antifungal Boy Cornils, Former Hoechst AG Germany From Nil to 500,000 Tons per Year: The first Scale-Up of Homogeneously Catalysed Biphasic Oxo Process
25th - 28th September 2000
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Joseph Brennan, SmithKline Beecham (Mfg) Ltd. Ireland FamVir - Development and Scale-Up of a Safer Process
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The conference attracts an international audience of over two hundred delegates, and is intended for senior Chemists, Chemical Engineers and Technical Managers from the Pharmaceutical, Fine and Speciality Chemical, Agrochemical, Flavour, Fragrance and Colour Chemical Industries. A detailed, high-quality publication including all presentations is provided, and there will be ample opportunity for questions and stimulating discussion during the conference.
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RogerJDavey, UMIST, UK Polymorphism in Molecular Crystals: The Scale-Up Rules Thorn van der Does, DSM Anti-Infectives The Netherlands Enzymatic Production of 6-APA, 7ADCA, Amoxillin and Cephalexin
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David am Ende, Pfizer Central Research USA Scale-Up of Grignard Reactions: A Chemical Engineering Perspective
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Ian Grayson, Laporte Fine Chemicals UK Development and Scale-Up in Thiazole Synthesis HgmSR
Wilfried Hoffman, Parke Davis Pharm Research Germany Use of RCl/ReactIR in Chemical Development Tom Hoppe, Ciba Speciality Chemicals USA Practical Considerations for the Safe Processing of Diazonium Salts
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Axel Kleeman, CPC-Cellular Process Chemistry GmbH, Germany Microreactors - Novel Tools to Improve and Optimise a Wide Range of Organic Reactions Mike Pollard, AgrEvo UK Ltd UK Scale-Up Issues in the Production of PCMF by Photochemical Chlorination
www.laporte.co.uk
John Smith, Raylo Chemicals Inc. Canada A Multipurpose GMP Production Facility. Some aspects of Design, Construction, Commissioning and Validation
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Jacques Wiss, Novartis Pharma Inc. Switzerland Use of On-Line Spectroscopic Tools (FTIR/RAMAN) for the Development and Monitoring of Chemical Processes
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