support, says Michael Duff, executive director of the Analytical Instrument Association, is reason for optimism. According to Richard Reding of EPA's Office of Water, Hansen's memo doesn't affect any of the work that has already gone on but rather "lays down the gauntlet" In fact, the Office of Water has taken the approach of introducing "flexibility" in its methods rather than a complete PBMS approach, and Reding doesn't see anything in the memo that conflicts with that philosophy. He also warns that any changes must still conform to each program's legislative mandates, and thus full implementation could occur after the 1998 deadline. In his memo, Hansen also calls for an integrated agencywide approach to environmental monitoring and a blueprint for investment in new and innovative technologies Alan Newman
PEOPLE
Graduate fellowship awards Eleven analytical chemistry graduate students have been selected by the ACS Division of Analytical Chemistry to receive fellowships for either the academic year ($14,000 paid over nine months) or for th< summer ($4650 paid over three months). The program encourages basic research in analytical chemistry and recognizes its future leaders.
Emily Niemeyer of the State University of New YorkBuffalo (Frank V. Bright). Niemeyer's research focuses on molecular-scale interactions and solute solvation in supercritical fluids and the enect of gas sorption on polymer dynamics. Her fellowship is sponsored by duPont. Stephen Sum of the University of Delaware (Steven D. Brown). Sum is developing a signal correction method that removes instrument and physical sample effects from analytical measurements, allowing for the transfer of multivariate calibration between instruments. His fellowship is sponsored by Perkin Elmer. Kami Thoen of Purdue University (Hilkka Kenttamaa).Thoen's research focuses on organic tandem mass spectrometry. Her fellowship is sponsored by Eli Lilly. Summer fellowships
Full-year fellowships
Craig Aspinwall of the University of Florida (Robert T. Kennedy). Aspinwall is working on developing and characterizing analytical methods for studying insulin secretion from single pancreatic beta cells. His fellowship is sponsored by Eastman Chemical. Kai Hu of the University of Texas (Allen J. Bard). Hu is using atomic force microscopy for characterizing surface charges of semiconductor nanoparticles. His fellowship is sponsored by Procter & Gamble.
Guodong Chen of Purdue University (R. Graham Cooks). Chen's research includes the kinetics of dissociation of cluster ions in mass spectrometry. His fellowship is sponsored by Dow Chemical. Peng Chen of the University of Indiana (MilosV. Novotny). Chen is working on glycoconjugate analysis and isolating and characterizing the fluorescent pigment associated with oxidative stress and aging using various techniques. His fellowship is sponsored by the Society of Analytical Chemists of Pittsburgh (SACP).
Rebecca Garden of the University of Illinois Gonathan V. Sweedler). Garden uses mass spectrometry to profile peptides within individual cells. Her fellowship is sponsored by the R. W. Johnson Pharmaceutical Research Institute. Paul Schnier of the University of California-Berkeley (Evan R. Williams). Schnier's research includes mechanistic studies of ionization and dissociation of large ions with the goal of developing mass spectrometry methods to rapidly characterize large biomolecules. His fellowship is sponsored by SACP. Irina Serebrennikova of the University of Calgary (Canada) (V. I. Birss). Serebrennikova is studying the electrocatalytical and nanostructural properties of Ni-Co oxide films. Her fellowship is sponsored by SACP. Mark Vitha of the University of Minnesota (Peter Carr). Vitha's research includes understanding the fundamental chemical forces governing the interactions of small molecules using surfactant micelles and thermodynamic and spectroscopic methods. His fellowship is sponsored by SACP. Honorable mentions are Susan L R. Barker of the University of Michigan (Raoul Kopelman), Indu Kheterpal of the University of California-Berkeley (Richard A. Mathies), and Lei Liu of the University of Pittsburgh (Sanford A Asher). Nominations
Applications are being accepted for the 1998-99 Division of Analytical Chemistry Graduate Fellowships. Five full-year and six summer fellowships are expected to be awarded.
Analytical Chemistry News & Features, September 1, 1997 5 2 5 A
News
cence, the intensity of which is proportional to concentration. The laser wavelength, tuned to 282 nm, excites only the fluorescence ffom the eydroxyl lOH) )adical, the most important oxidizing species in the atmosphere. The key, says Heard, is the expansion of the sample as it enters the FAGE chamber, which extends the OHfluorescencelifetime to several hunLABORATORY dred nanoseconds and allows scattered laser light to be discriminated against by a PROFILE gated photomultiplier detector. The redshifted fluorescence is measured at 307315 nm. High winds, light The system is being used to gather rain, and radicals information about the condition of the atmosphere. "The atmosphere contains later many trace gases, such as methane and Dwayne Heard is a scientist who likes other hydrocarbons, CO, NOx and to travel. Recently he and his team HCFCs. Unless some natural cleansing took a portable lab packed with equipprocess takes place, these gases would ment, which they call the "HOxBOx", build up and cause problems," explains to the barren westerly shores of Eire, Heard. "The ability of the atmosphere to 50 miles west of Galway. What poscontrol the levels of these gases—its oxisessed Heard—an atmospheric chemdizing capacity—is controlled by the conist at the University of Leeds in the centration of hydroxyl radicals." Undernorth of England—to take his crew to standing this cleansing process depends such a wild place? on knowing just how many radicals are The answer is literally blowing in present in "clean" air, found at remote the wind. Heard and his team speciallocations such as the Atlantic coast. "Our ize in sampling and analyzing trace atmospheric materials and their effects experiments seek through local measurements of OH to allow a thorough underon pollutant levels. To avoid complicastanding of the basic photochemical cytions from too many pollutants, the cles which can then be used by modelers best place to do this has to be remote. to predict the future behavior of the planSo the Atlantic coast it is. et's atmosphere " "Mace Head was chosen as a good The Ireland trip tested the validity of spot to assess the atmosphere, because the air usually comes straight off current atmospheric models. The chemistry of OH and its chemical cousin, the the Atlantic and has not passed over land for more than five days," explains H02 radical, which are also measured using FAGE, are inextricably linked to Heard. The prevailing westerlies are virtually every tropospheric species. Their almost as pure as is possible in the concentrations are very dependent on lonorthern hemisphere. cal conditions. If an atmospheric model So what is in the HOxBOx? "The predicts these concentrations accurately, essential items," says Heard, "a shipthe underlying chemistry is likely to be ping container, an expensive laser, a correct, and our understanding of tropobig pump, lots of optics and electronspheric oxidation processes is validated. ics, and an electronic lab book—an Until now few experimental outdated 486 PC," he confesses, ments of OH or H02 have been made in "which comprise the FAGE (fluoresthe marine boundary layer cence assay by gas expansion) system to measure atmospheric radicals." In their initial experiments last year, B In the FAGE system, the air sample the team reached a sensitivity of 2 x 10 3 molecules/cm for OH. "Atmospheric is sucked into a detection chamber pressure is 2.5 x 1019 molecules per cubic from 18 ft above ground. The sample centimeter at 298 K," Heard says, "so expands to about 0.7 torr, forming a supersonic molecular beam expansion, we're looking at a very low fraction." For 7 and is then subjected to UV laser light. H02 the sensitivity was ~10 molecules under the same conditions. The team The excitation of free radicals in the sample produces a measurable fluores- measures H02 by chemically converting it
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Analytical Chemistry News & Features, September 1, 1997
Analyzing clean air. HOxBOx measures OH radicals.
to OH with added NO and then detecting the OH using the same fluorescence technique. For their latest venture, Heard's team boosted laser power and finetuned their homegrown software and, despite rather muddy conditions, which gave the HOxBOx a distinct tilt at the site, achieved much better sensitivities of 3 x 105 molecules/cm3 for OH and about 106 for HOz. With these improvements, they measured typical daytime maxima for these species of a few million and 108 molecules, respectively, allowing them to collect daily profiles. "In almost every instance, some new feature of atmospheric science has emerged from a comparison of field and theoretical data," says Heard, so the work is well justified. "Accurate predictive models are vital to assessing the impact on the atmosphere caused by changes in anthropogenic emissions, for example, from motor cars or from industry. A reduction may cause the problems associated with urban pollution, global warming, and acid rain to be alleviated," says Heard. "Clearly it is important to validate these models to ensure their output is accurate, and our field measurements are the key." "Future campaigns are planned in various places, including clean background, semirural, and urban sites," adds Heard, depending on funding of course and whether his team can put up with the wind. David Bradley
The fellowships are open to full-time graduate students working toward a Ph.D. in analytical chemistry who will have completed their second year of graduate studies by the time their fellowship begins. The applicant's graduate advisor must be a member of the Division, and only one nomination per advisor will be accepted. Applicants from previous years should reapply. In addition to the application forms, nominees must submit three letters of recommendation and undergraduate and graduate transcripts. Applications available from Robert A Libby, Division of Science Truman State University 100 East Normal Kirksville MO 635014221 (816-785-7499- fax 816-785-4045; libby@truman edu) RESEARCH UPDATE
The art of arranging receptors on a surface The drug industry is constantly seeking new therapeutic agents that can bind to a receptor and thus influence central biological signaling reactions. Combinatorial chemistry has multiplied the number of compounds that can be synthesized, increasing the need for rapid (and cheap) methods of screening for biological activity. Nevertheless, many of the functional tests of promising molecules are still done with animal experiments. A different approach is being explored at the Swiss Federal Institute of Technology in Lausanne. Horst Vogel and his coworkers—30 graduate students and postdocs—are incorporating biological receptor molecules into artificial membranes on solid sensor surfaces. The ultimate goal is to build sensors with fully active membrane receptor proteins that could be used for drug screening. "Once you know how to do it, such a device can be built easily, and it will be cheap and rugged," Vogel predicts. The young scientists in Vogel's group
Total internal reflection fluorescence monitors jellyfish protein.
combine their knowledge of chemistry, biology, physics, surface technology, and electronics to create devices that can be used for drug screening. In the June 1 issue of Analytical Chemistry (p. 1979)7 they used their techniques to immobilize green fluorescent protein from the jellyfish Aequorea victoria on a quartz surface. To control the molecular orientation, the protein was modified by genetic engineering: The mutant protein carries a continuous sequence of several histidines (a "Histag"). The histidines bind specifically to nitrilotriacetic acid—which is covalently bound to the quartz surface and loaded with divalent cations such as Ni2+ and immobilize the protein The kinetics and binding constant of the process and the fluorescence properties of the protein are Drobed by a laser beam that enters the auartz slide and the layer of bonded molecules at an anrie suitable for internal reflection The ODtical properties of the protein investigated by total internal reflection fluorescence prove that it is still stnictiir 11v intact after the h'nrTn r cess This
means that functionally active receptor mol1
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ecules can be bound in an ordered and directed manner on a surface. Although this setup is not yet a drug screening device, Vogel's group is moving closer to this goal. The researchers were successful in immobilizing Histagged neuroreceptors by the same technique and subsequently were able to screen different agonist and antagonist ligands for receptor binding by fluorescence measurements. Fast drug screening will require an array of sensors, each carrying an artificial membrane with a different receptor protein. The various compounds synthesized by combinatorial chemistry would flow over individual sensors. Molecules that interact with the protein would give rise to a change in conformation and eventually to an ion current, features that can be detected by a multitude of analytical methods such as the above-mentioned fluorescence spectroscopy (and related techniques), IR spectroscopy on thin laysurface plasmon resonance, or electrochemistry. Depending on the equilibrium constant between protein and ligand as few as 1000 molecules of a potential new drug could be sufficient to give a detectable signal A bilayer with incorporated proteins can be built auicklv and easilv then used for several hours Because'the sensor's properties can change over time the researchers recommend makino- afresh one each day
Vogel seeks cheap and rugged devices.
The group is now concentrating on several methods to create membranelike, self-assembled mono- or bilayers on various surfaces (gold, quartz, optical waveguides). Recently the Lausanne group incorporated the photoreceptor rhodopsin, a member of the class of G-proteincoupled receptors, into an artificial membrane immobilized on a gold surface. The rhodopsin molecules are transmembrane proteins that receive extracellular signals and transmit them across the cellular membrane into the cell. The interaction of the activated receptor with its G proteins and the subsequent signal amplification steps were investigated by surface plasmon "We expect to observe similar biologically important cascade reactions with other G-protein-coupled receptor proteins embedded within artificial membranes on solid surfaces This would be the ultimate breakthrough for using- functional assavs in novel drug screening devices "
Collaborations with the pharmaceutical industry and the financial support of new funding sources for applied research (so-called priority programs) of the Swiss National Science Foundation help drive these projects. Another factor is the proximity of the laboratory to the industry and research centers in microtechnology in the western part of Switzerland: in Lausanne at the Swiss Federal Institute of Technology and in Neuchatel at both the University and the Center for Electronics and Microtechnology. Vogel says that his research group is an example of how interdisciplinary research can help answer a seemingly simple question: How can one identify a promising molecule from a multitude of compounds synthesized by a machine? Veronika R. Meyer
Analytical Chemistry News & Features, September 1, 1997 5 2 7 A
