News amount of template released translates to a higher affinity. "The instant screening is a kind of washing step," says Takeuchi. "After the instant screening, we can deterSo many variables affect the affinity and mine whether or not the regular screenselectivity of molecularly imprinted polying should be mers (MIPs) that performed." finding the best reaction condiThe "regular tions can be a screening" is condrawn-out producted by washing cess. To speed each MIP10 times that process, Towith a methanolshifumi Takeuchi acetic acid-water and co-workers at solution and 3 Hiroshima City times with chloroUniversity Jaform to remove the pan) are tackling bound template. the problem with The polymers are techniques borthen incubated with The high-throughput preparation and rowed from ametryn for 24 h. binatorial chemis- screening of MIPs by a batch-type in situ The amount bound protocol using liquid-handling equipment. try They dewas obtained by scribed their work in the Tanuarv 15 issue subtracting the free ametryn from the origof Analytical Chemistry(p.285) inal amount The selectivity of polymers They made a combinatorial library of 49 that had been imprinted with ametryn was evaluated by incubating the MIPs with MIPs as artificial receptors for die triazine structurally related atrazine herbicides ametryn and atrazine by mixing various amounts of two functional monoAlthough the regular screening of mers—methacrylic acid (MAA) and 2-(triMAA-based library members provided fluoromethyl) acrylic acid (TFMAA). A positive results, the instant screenings fixed amount of template (ametryn or were inconclusive. Takeuchi attributes atrazine) is added to mixtures of MAA the discrepancy partially to the acetoniand/or TFMAA ethylene glycol dimethac- trile used in the initial screening. Acetonirylate (acrosslinker), 2,2'-azobisisobutyrotrile is not a favorable solvent for the nitrile (the initiator), and chloroform (to MIPs, but chloroform can not be used form pores). The members of the library before the MIPs are washed because rediffer only in their ratio of the functional versed-phase HPLC is required to sepamonomers. rate the template from other unreacted starting materials. After washing, the reg"In previous work, we found that methacrylic acid and its derivatives are suitable for triazine herbicides," says GOVERNMENT AND SOCIETY Takeuchi. "We developed the combinatorial molecular imprinting because we want to know which functional monomer would Big small-scale be the best for herbicide imprinting." funds The evaluation of the MIPs is twotiered. In the "instant first screening", a A major injection of funds into a U.K. confixed amount of acetonitrile is added to sortium of academic researchers and the MIPs immediately after the polymercompanies that hopes to create a miization is completed. Because acetonitrile croscale lab-on-a-chip has just been anis more polar than the chloroform used in nounced by the government's Departthe reaction, the template, which is bound ment of Trade and Industry. The funding to the polymer by hydrogen bonding, is amounts to £1.33 million (more than $2 released to the solution. The amount remillion), which is being matched by inleased varies with the affinity. The acetodustry backers. nitrile solution for each of the MIPs is The lab-on-a-chip consortium is coordianalyzed by HPLC after a 24-h incubation nated by Steve Haswell, a chemist at the period. The affinity is estimated by subUniversity of Hull, who first became intertracting the amount of template released ested in the design and construction of mifrom the original amount. A smaller croscale chemical equipment in 1987 after
Combinatorial MIPs
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Analytical Chemistry News & Features, February 1, 1999
ular screening does not require the separation step, so faster flow-injection analysis is used. In addition, Takeuchi says, "The instant screening only checks the rough affinity because it evaluates the dissociation of the template immediately after the polymer preparation." In contrast, the regular screening provides more detailed information. Both screenings use automated liquidhandling equipment and are performed in the vial used for preparation. This strategy for preparing and evaluating MIPs is much faster than previous methods. "A batch preparation of MIPs usually takes one week," says Takeuchi. "In contrast, the proposed combinatorial molecular imprinting currently provides 49 polymers within one day, followed by an automated evaluation." Although this work focuses on herbicides, Takeuchi suggests that the most important application should be a MIPbased assay for biologically active compounds. "If synthetic predetermined specific sorbents for particular compounds can be prepared in parallel in the same trap, plate, or chip, it will be of great interest in combinatorial chemistry, clinical analysis, and other fields," he says. The next step is to verify that the screening methods work for other MIPs. In addition, Takeuchi plans to construct a database on the effects of reactants and reaction conditions on the performance of MIP preparation. Takeuchi and his co-workers are also interested in constructing an integrated multiple assay system and a miniaturized assay system. Celia Henry
reading about what he describes as "the now legendary chip-based micro-GC" developed by Steve Terry and colleagues in California. Until very recently, it was difficult to obtain funding in the United Kingdom for research in this fast-growing area. "I don't wish it to sound like sour grapes, but I have constantly, in over fifteen applications, hit a wall of disbelief from reviewers that microscale chemistry can be done," says Haswell. "I have been doing it anyway, though," he adds. Over the past decade or so, many U.K scientists have worked hard to change this attitude so that the United Kingdom could establish an international presence in the field. The result was the establishment of a
group that could lobby for funds from the government and other sources. The recently announced injection of cash into microscale chemistry is the culmination of this effort. Several leading analytical research groups will benefit, including HaswelTs at Hull, Zeneca/SmithMne Beecham Centre for Analytical Sciences at Imperial College London (headed by Andreas Manz), chemical engineer Ron Pethig's group at Bangor University, the Bioelectronics Research Centre at the University of Glasgow (headed by Jonathan Cooper), and teams at Cardiff and Newcastle Universities, the University of Manchester Institute of Science and Technology, and the University of East Anglia in Norwich. On the industrial side are groups at Unilever, GlaxoWellcome Epigem, Kodak, Faraday Foresight NW, Optokem, Windsor Scientific, Kalibrant MSTB and LGC (formerly the Laboratory of the Government Chemist) The award forms part of a broader U.K government initiative known as Foresight. When he announced the award, Peter Mandelson, Secretary of State for Trade and Industry, said, "The projects combine the visionary thinking and creative partnership approach that is central to Foresight. All are underpinned by substantial support from industry." Foresight was established to improve decisionmaking today and develop visions for the future. The so-called LINK scheme is the main way in which the government provides support for research partnerships between U.K industry and scientists. The laboratory-on-a-chip project will involve a large multidisciplinary team, which will drive the science into a number of demonstrator systems—such as integrated analytical measurement and control systems—which Haswell says will have "clear commercial importance". "The funds have been hard to get and a long time coming," he says. "We don't intend using them to follow the pack but will develop truly innovative applications offered by the unique world of miniaturized chemical systems." LGC manages the consortium and is actively recruiting researchers from a wide range of scientific disciplines. First contact point for more information is LGC's Derek Craston (Queens Road, Teddington, U.K. TW11OLY, Telephone: +44 181 943 7365, Fax: +44 181 943 2767, E-mail:
[email protected]). David Bradley
Regulating new drinking water contaminants
mends that the first phase—reviewing health effects and exposure data, analytical methods, and treatment options—be completed within one year of publishing a CCL. Following the review, a preliminary risk The National Research Council's (NRC's) assessment should be conducted based on Committee on Drinking Water Contamidata obtained in phase one. After the risk nants released a report in December to assessment is complete, the committee assist the U.S. Environmental Protection Agency (EPA) in deciding which contami- recommends that EPA decide whether to drop each contaminant on the CCL benants on the current and future Drinking cause it poses no risk, consider it for reguWater Contaminant Candidate Lists (CCLs) to regulate, which need additional lation, or subject it to further research. The committee also recommends that a health occurrence data, and which need further advisory be issued for all contaminants not research (e.g., health effects/exposure dropped from the CCL. data, analytical methods, treatment options) . The report, entitled Setttng PrioriIn their deliberations, the committee ties for Drinking Water Contaminants, ad- considered 10 schemes for prioritizing dresses the first of three topics under chemicals on the basis of exposure and consideration by the committee. Future toxicity data. No comparable schemes are reports are expected about emerging available for microorganisms. The report drinking water contaminants and develop- concludes that a ranking scheme for priing CCLs. oritizing contaminants is not appropriate EPA has a long history of controlling for determining which contaminants on environmental contaminants based on the CCL should be regulated in drinking fixed lists of chemicals. Such lists need to water because sufficient data on occurbe updated periodically to ensure that rence and public health effects are not available for many of the contaminants on public health is not in danger from new the current CCL. In addition, the report and emerging contaminants. The Safe Drinking Water Act (SDWA) amendstates that "simple quantitative ranking ments of 1996 require EPA to formulate a processes cannot substitute for policy CCL—a list of unregulated ("not subjudgments by EPA". jected to any proposed or promulgated Britt Erickson national primary drinking water regulation") contaminants that constitute a poRaman effect tential risk in drinking water. EPA must develop a new CCL everyfiveyears and declared landmark decide whether to regulate at least five of At a ceremony in Calcutta, India, in Decemthe contaminants on each CCL. ber 1998, the American Chemical Society In addition, SDWA requires EPA to es(ACS) and the Indian Association for the tablish a National Drinking Water Contami- Cultivation of Science designated the Ranant Occurrence Database, which will con- man effect an International Historic Chemitain occurrence data for regulated and cal Landmark. unregulated contaminants, and an UnreguThe Raman effect—named for its dislated Contaminant Monitoring Regulation coverer, C. V. Raman of Calcutta Universi(UCMR) by August 1999 and every five ty—is a phenomenon in which a small fracyears thereafter. The UCMR will require tion of the llght scattered by a molecule is monitoring of no more than 30 unregulated of a different wavelength than the incident contaminants from the CCL that need addi- light. The frequency difference in wavetional occurrence data. numbers (cm-1) between the incident and scattered light depends on the frequency of The first CCL, containing 50 chemical molecular vibrations. Raman discovered and 10 microbiological groups/contamithe effect in 1928 and received the Nobel nants, was published on March 2,1998 Prize in physics in 1930. Raman spectros(Fed. Regist. 1998,63,10274-87). EPA has until August 2001 to decide whether to copy is now used in numerous applications, including materials characterization, proregulate specific contaminants on the list. cess monitoring, and biomedical diagnosis. The next CCL is due in February 2003. The NRC report recommends that EPA The International Historic Chemical use a phased approach for deciding which Landmark program is an extension of the contaminants from current and future National Historic Chemical Landmark proCCLs to regulate. The committee recomgram, which ACS began in 1992. Analytical Chemistry News & Features, February 1, 1999 8 7 A
