Focus
THE BARNETT INSTITUTE AT 25
I
ts offices are tucked away in a corner of the third floor of the life sciences building on the Northeastern University campus. Its out-of-the-way location belies the research conducted by its members, who are at the forefront of their respective fields. This month, the Barnett Institute for Chemical Analysis and Materials Science celebrates its 25th anniversary, offering an opportunity to look at where it's been, what its scientists are doing now, and where it will go in the future.
The Barnett Institute has established a world-class reputation and positioned itself well for the future.
each year with the Rosenblatt Memorial Lecture, which was established in 1992 and It was born in 1973 as the Institute of Chemi- named for Norman Rosenblatt, a former cal Analysis, Appllcations, and Forensic Sci- dean of Northeastern's College of Criminal Justice. ence—the result of a grant by the U.S. Department of Justice to establish centers of Even though the forensics emphasis excellence in criminal justice. The focus on has gone, the institute has lived on— forensics lasted only a short time, partially renamed the Barnett Institute of Chemical because of a lack of funding for graduateAnalysis and Materials Science in 1983 in student stipends, which forced the students recognition of the generous gift from Louis to be financially self-supporting. The roots in H. Barnett—with a focus on bioanalytical forensic science have not been completely chemistry and materials science. What has abandoned, however. They are celebrated given the Barnett Institute its staying Redefining themselves
power? "We try to redefine ourselves," says Barry L. Karger, the founding and current director of the Barnett Institute. "It's important to be doing new things and developing new technologies." Karger uses his own career as an example. "I got a Ph.D. in gas chromatography—that was the hot thing then. I was involved for nearly a quarter of a century in HPLC. Then CE came along. We're still ln CE a little bit, but we've moved on to coupling separations with MS." The Barnett Institute's financial situation can also be credited in part for its longevity. "Many of the other institutes have core funding from the government," says Karger. "We don't have a core grant, but we do have ea endowment That's unusual. We may be the only endowed analytical institute." The endowment currently stands at a little more than $4 million, and the institute is in the midst of a Silver Anniversary Campaign that is hoped will bring the endowment to $6 million and increase funding for equipment personnel and space.
Analytical Chemistry News & Features, May 1, 1998 329 A
Focus Karger credits the institute's advisory board for its guidance. The board, chaired by Louis Barnett himself, is populated by prominent members of the analytical instrumentation community, including Dieter Hoehn (retired vice-president of Hewlett Packard), Robert Finnigan (formerpresident of Finnigan Instruments), John Leeman (president of Leeman Labs), James Little (vice-president of Zymark Corporation), and James Waters (president of Waters Business Systems) Real problems The Barnett Institute cultivates close ties to industry. Part of that tight-knit relationship can be attributed to Northeastern University's deep roots in cooperative education or "co-op" programs, in which undergraduate students alternate between the classroom environment and the workplace. The major reason for the institute's excellent relationship with industry, however, is that the researchers look for "real problems". "We had the view that analytical chemistry doesn't live in a fishbowl," says Karger. "We develop tools to solve problems. Other people have the problems, so we have to work with them. That means that you have to be very strong in the analytical technology, but that's insufficient. You also have to be knowledgeable about the areas where the problems are." This attitude has meant that students who work in the institute, and even some of the postdocs (if they don't already have the background), take courses in modern biochemistry including protein chemistry genetics and immunology
Barry Karger has been with the institute from the very beginning. 330 A
Roger Kautz, a staff scientist in Karger's group, describes a large part of his role as "cruising the field for applications to connect the techniques, completed and nascent, of the Barnett Institute to problems in medicine and biology." He sees the applications focus as an important aspect of the Barnett Institute. "One of the attractions here is the more industrial perspective of let's solve some problems and invent technologies for doing that'." For example, the Karger group has been developing tools for enhancing the power of mass spectrometry by interfacing chemical cleanup and separation steps online. In one case, using affinity CE, they have developed an on-line combinatorial library screening tool to identify ligands, which bind to a target (1). In another program, they are working on enhancing analytical MS throughput using microfabricated devices. Recent work involves onchip separation followed online by MS and automated multichannel high-throughput infusion MS analysis Their goal is to reach at least an order of magnitude increase in on-line MS throughput using these devices DNA analysis has been a major focus of research efforts at the Barnett Institute— by individual research groups and by groups in collaboration. Karger's group has been involved in DNA sequencing by electrophoresis for many years, and it continues to be an area of interest. They recently developed a cleanup procedure for DNA samples that improves the sensitivity and robustness of analysis by CE (2). Also, they have achieved sequence reads of more than 1000 bases with high accuracy in less than hour. Roger Giese, one of the holders of the Bradstreet Chair in analytical chemistry, emphasizes the trace analysis of DNA and DNA adducts by GC/MS (3). Unllke sequencing applications, which are aided by DNA amplification methods such as PCR the analysis of DNA adducts must overcome the sensitivity challenge of "what you have is what you get". Giese comments, "With PCR, you can amplify the DNA per se, but you cannot amplify the adduct. If you've got a benzopyrene metabolite on some nucleobase of DNA you can't replicate that 'dirt'" The amounts of adducts on the DNA that might initiate
Analytical Chemistry News & Features, May 1, 1998
tentially miniscule. "Partly because the samples themselves may be tiny, there is no limit to how much sensitivity is needed," he says. Giese detects Roger Giese DNA adducts by derivatizing them with an electrophore and then analyzing the resulting products by electron capture (EC) (shorthand for electron capture negative ion chemical ionization) MS with quadrupole or FT-ion cyclotron resonance (FT-ICR) analyzers The GC aooroach requires that the electrophore be volatile and thermally stable He views the quadrupole as the instrument for mutine analysis and method staff Huang the group's coupling of GC with FT TCRMS is rather unusual "Some neonle might sav whyfnru
Program, which supports the development of technology that is considered too risky for industry to fund by itself. The lead company on the grant is Bruker, which is producing the mass spectrometer. George Church of Harvard Medical School is working on the CE and cycle sequencing. Giese's group tests the instrumentation and synthesizes the electrophoric tags. Ultimately, Genome Therapeutics will put the process into production as a diagnostic tool. Giese says the application goal is 100 spots per second multiplexed at a level of 400 electrophore tags (100 simultaneous sequencing reactions for the four nucleobases) a detection speed that would zip through the human genome in about five weeks Giese acknowledges that such claims are just arm-waving right now and that this does not include the steps before savs "We've shown some feasibility for everv'sten in the method " Paul Vouros who iointly holds the Bradstreet Chair with Ciese is also in volved in the application of mass spectrometric methods to bioanalytical problems. Vouros can claim much of the credit for the development of the MS capabilities of the institute. When I came here, we had basiii
i
ir
"i
cally half a mass spectrometer, he says. We had the shell but no GC and no direct insertion probe. Vouros's research shares with Giese's the characterization of DNA adducts as a driving force—in fact, they've done much of the work in collaboration. Vouros's work has gradually evolved into coupling capillary techniques, most recently capillary electrochromatography, with MS. His group looks at modified nucleic acids and tries to improve the detectability of the markers of damaged DNA so that the markers can be used with in vivo materials (4,5). They are also trying to discover why carcinogens attack particular nucleobases. Additional research areas for Vouros's group include analyses of combinatorial libraries (6 7) )ad vitamin D "Over the I've bppn attracted tr\ v i t a m i n T)
Paul Vouros
It's turning out to be an extremely impor tantcompound be-
cause analogues of vitamin D are supposed to inhibit the progression of leukemic cells." Much of the vitamin D work has been performed in collaboraThomas Gilbert tion with Satya Reddy, a pediatrician at Brown University Medical School. The researchers of the Baraett Institute are often approached to help solve problems. "That stimulates research that is problem-driven," says Vouros. "We put our heads together and think about what would be the best way to take advantage of the techniques. Having this problem-driven philosophy helps us become more ingenious and creative in the way we tackle problems." In addition, Vouros says, it keeps the research "relevant". The research of one faculty fellow in the analytical division doesn't quite fit the mold of the rest of the Barnett Institute. Thomas Gilbert focuses primarily on curriculum development in bioanalytical chemistry. Giibert is redesigning the undergraduate analytical course to reflect modern analytical chemistry and its strong biological underpinnings. "We're trying to develop a series of learning modules that are large-scale, project-length activities that integrate analytical principles, including topics not often covered in the traditional quant course." The students ot*f* i r i _
volved in designing their own experiments and developing trying and validating their own methods Yes, there is a materials science division Its smaller size would make the materials science division easy to overlook if the researchers weren't doing such interesting work. Geoffrey Davies, who also serves as the Institute's Associate Director for Operations, is by training an inorganic physical chemist. Over the past five years or so, his group has turned its attention to the study of humic substances (the brown polymers in soil). In recent research, they explored whether the humic acids isolated from soils in different parts of the world are very similar. They compared the metal-binding properties of humic acids isolated from Irish
peat, German peat, and New Hampshire soil. Using Langmuir isotherms, they found the capacity and the binding constant of the material for a given metal. The two humic acids they studied most extensively had the same first binding sites for copper, iron, and manganese, the same second binding site for iron and copper, and even a third site for copper (8). "It seems that on this basis these humic acids have the same binding sites. That's the first time anybody's come out and said that" Davies The group is trying to discover the actual structure of the humic acids They think the molecules are oxidized glycoproteins "That's my guiding light" says Davies "and I'm going to try to get to that light if it's the true light" The other faculty fellows in the materials science division include associate director Bill Giessen, the only person other than Karger who has been affiliated with the institute from its very beginnings, and Robert Markiewicz, a professor of physics. Their research efforts have focused on the development of high-temperature superconductors. For a number of years, Northeastern held the record for the material with the second highest T Current research includes enhancing currents in high-temperature superconductors by biaxial alignment. "When you try to make a wire of the high-temperature superconductors, [the wire] really won't work well because the current has difficulty flowing across the grain boundary," says Markiewicz. "The only way known to get the current to flow is to eliminate the grain boundaries." They do this by aligning the b and c axes of every grain in a powder to make a material simulating a single crystal. Markiewicz calls it the "Humpty-Dumpty" technique of growing crystals Another research area in Giessen's group, primarily performed by staff scientist Krassimir Marchev, is plasma-surface engineering, particularly plasma nitriding. The goal is to improve surface properties such as hardness. They use a lower temperature than commercial nitriding, so the Geoffrey Davies
Analytical Chemistry News & Features, May 1, 1998 331 A
Focus
bulk properties are unaffected—they form a layer thinner than 30 um. "We have achieved a new kind of crystalline phase that incorporates nitrogen and has superior corrosion resistance," says Marchev. What's coming? The Barnett Institute still has its founding director and associate director. Other members of the institute, including Vouros and Davies, have been there almost as long. "I have to start thinking about a future without the people who are here now," says Karger. "That doesn't mean tomorrow, but it means some time in the future. One of the things is die structure of the institute in the context of Northeastern University to make sure that it's part of the university so that it's easy for the next individual." Space is a precious commodity in any academic environment, and it's no different for the Barnett. "One of our dreams would
be to ultimately have our own building," says Karger, "I'm not sure how long that would take. Space is always one of the big issues at universities. Nevertheless, we have good facilities, and we're very strong in equipment." Karger describes institutes as "beyond academics". Members of the Barnett Institute have their primary appointments within other academic departments. (Current affiliations of faculty fellows and faculty affiliates include chemistry, mechanical engineering, pharmacy, and health sciences; physics; electrical and computer engineering; and biology.) "It's hard to see [primary appointments ever being made within the Barnett Institute]," says Karger "^^e're lucky in that we have not been part of the academic structure. I report to the provost's office which has allowed us to have a certain amount of nimbleness and an ability to moveflexibly" Celia Henry
References (1) Chu, Y.-H.; Dunayevskiy, Y. M.; Kirby, D. P.; Vouros, P.; Karger, B. LJ. Am. Chem. Soc, 1996,118, 7827-35. (2) Ruiz-Martinez, M. C; Salas-Solano, 0.; Carrilho, E.; Kotler, L.; Karger, B. L. Anal. Chem. 1998, 70,1516-27. (3) Giese, R. W. Chem. Res. Toxicol. 1997,10, 255-70. (4) Wolf, S. M.; Vouros, P. Chem. Res. Toxicoll 1994, 7, 82-88. (5) Szeliga, J.; Page, J. E.; Hilton, B. D.; Kisellyov, A. S.; Harvey, R. G.; Dunayevskiy, Y. M.; Vouros, P.; Dipple, A. Chem. Res. Toxicol. 1995,8,1014-19. (6) Dunayevskiy, Y. M.; Vouros, P.; Wintner, E. A.; Shipps, G. W.; Carell, T.; Rebek, J., Jr. Proc. Natl. Acad. Sci. USA 1996, 93, 6152-57. (7) Dunayevskiy, Y. M.; Lai, J.-J.; Quinn, C; Talley, F; Vouros, P. Rapid Commun. Mass Spectrom. 1997,11,1178-84. (8) Davies, G; Fataftah, A; Cherkasskiy, A.; Ghabbour, E. A; Radwan, A; Jansen, S. A; Kolla, S.; Paciolla, M. D.; Sein, L T., Jr.; Buermann, W.; Balasubramanian, M.; Budnick, J.; Xing, B.J. Chem. Soc, Dalton Trans., 1997,4047-60.
articles You can't get information any faster unless you're the author. Articles ASAPSM is an
will post journal articles on the
exciting advance in scholarly
Web 'As Soon As Publishable"
publishing that allows scientists,
— meaning 2 to I I weeks
only to ACS Web Edition
research institutions, industry,
earlier than they are avaiiable
subscribers, so if you're not
ACS research journals. This service is offered
government, and the public
in print. These are complete,
already one, now is the time
access to the results of scientific
peer-reviewed, fully edited
to sign up. For more details,
research in "real-time."
articles — not abstracts, not
visit the ACS Pubs Home Page:
Beginning in January 1998, the American Chemical Society
ACS 332 A
pre-prints — and they are available for all 26 prestigious
http://pubs.acs.org
PUBLICATIONS
Analytical Chemistry News & Features, May 1, 1199
Web Editions
