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And scientists had learned how to generate large diverse collections, or libraries, of organic and biological molecules and screen them quickly for biological activity or other functions. These libraries were generated by the parallel synthesis of many similar compounds, or by reacting large numbers of precursors in many different combinations at once—the so-called combinatorial approach. One of the key players in this field— chemistry professor Peter G. Schultz, who has a joint appointment at the UniRon Dagani netic recording materials, and amor- versity of California, Berkeley, and Lawphous silicon semiconductors for solar rence Berkeley National Laboratory C&EN Washington cells. Using this route, he was able to (LBNL)—wondered whether combinaoseph J. Hanak was close to spark- find new materials much faster—up to torial chemistry could also be used to ing a revolution in materials re- several hundred times faster—than by discover nonbiological or inorganic compounds. He got his colleague Xiaosearch some three decades ago, but using the conventional route. the world wasn't ready for it yet. RCA Labs, however, decided not to Dong Xiang, a solid-state physicist, inHanak, a Ph.D. chemist then work- expand this research effort. And despite terested in pursuing the idea with him ing at RCA Laboratories in Princeton, the publication of a series of papers and at LBNL. The result was a paper in SciN.J., was searching for new low- U.S. patents by Hanak and coworkers, ence [268, 1738 (1995)] in which they demonstrated, for the first time, temperature superconductors. that the combinatorial approach But he became increasingly imcould indeed be used to discover patient with the traditional, solid-state materials with novel time-consuming approach of properties. making one composition, testing its properties, then making a In that study, according to different composition, testing it, Xiang, the Berkeley researchers and so on. Why not make many sought to determine whether a different compositions at the combinatorial approach could unsame time, he wondered, and cover two of the most important then rapidly measure the relehigh-temperature cuprate supervant properties in a single conductors that had been found experiment? using the conventional one-at-atime synthesis method. Hanak's idea was the forerunner of a concept that is now takTo answer this question, the reing materials science by storm: searchers devised a method for the application of the combinatoforming thin-film arrays of solidrial approach, which the pharmastate compounds from multiple ceutical industry uses for the raplayers of precursors using sputterid synthesis and screening of ing. But unlike Hanak's approach, large collections of new drug canthe precursors are deposited ondidates, to the discovery of useful to the substrate sequentially rathnew materials. A 1,024-member library of X-ray phosphors as It appears er than simultaneously. "Each section of the substrate is exHanak's approach, which he under UV Illumination. posed to a different combination called the "multiple-sample concept," involved using sputtering to code- he tells C&EN, the approach "never be- of precursors by depositing each layer posit two or three elements or com- came popular" with researchers be- through a different mask," Xiang expounds on a substrate to create a contin- cause of the general lack of computers. plains. The masks direct the precursors uum of compositions [/. Mater. ScL, 5, 'Without a computer, you could not do to individual sample sites that are less 964 (1970)]. The compositions were the compositional analysis, automated than 1 mm across. This study involved the use of seven then determined by measuring the film testing of properties, and data processthickness in two or three spots and plug- ing, all of which are crucial for the meth- precursors: oxides or carbonates of the elements that make up known superging the numbers into equations that od to work," he explains. were solved using a mainframe computIn retrospect, "we were a little bit too conductive cuprates. After a series of er at a remote site. In the course of early," says Hanak, who is now a con- depositions, the library array was therscreening such "multicomponent sys- sultant on thin-film materials and renew- mally processed—a necessary step tems," Hanak uncovered a variety of able energy and is based in Ames, Iowa. leading to the production of crystalline new compositions, including superconFlash forward to 1995. Computers cuprates. Then the resistance at each ductors, light-emitting materials, mag- had become commonplace in the lab. site in the array was measured as a func-
A FASTER ROUTE TO NEW MATERIALS
Comhinatonal synthesis and rapid screening methods promise to make materials discovery more efficient and less wasteful
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tion of temperature. Sure enough, the sites containing the known supercon ductors showed large resistance drops indicative of superconductivity. The Xiang/Schultz paper was a reve lation for many materials researchers because it showed that relatively com plex materials such as high-tempera ture superconductors could be made and found in a parallel fashion. Before long, oth er papers began appear ing in the literature, de scribing efforts at using combinatorial methods to search for a wide vari ety of materials, includ ing magnetoresistive ma terials, phosphors, di electrics, ferroelectrics, polymers and polymer composites, semicon ductors, catalysts, and zeolites. Solid-state chemist Xlang Robert C. Haushalter even changed jobs as a result of the Xiang/Schultz paper: He moved to Symyx Technologies, a high-tech compa ny in Santa Clara, Calif., so that he could be part of the new wave that was begin ning to sweep through materials re search. Symyx was founded in 1995 by Schultz and biotechnology entrepre neur Alejandro C. Zaffaroni specifically tofindnew materials using combinatori al and high-throughput screening meth ods. When Haushalter joined Symyx two years ago, he tells C&EN, it was "the only show in town." Since then, oth er companies have started their own combinatorial materials efforts. Haushalter sees the combinatorial approach as "a tool that you can use to accelerate the discovery process." Xiang says the discovery process could be accelerated "by a factor of thousands, possibly millions." And because materi als libraries can be created with very small amounts of material, the combina torial route promises to be less wasteful than traditional approaches and possi bly also less expensive. In a recent review article, Schultz and coauthor David R. Liu point out that the properties of many functional mate rials arise from complex interactions that depend on their composition and processing. In general, scientists don't know how to predict a material's proper ties from its structure, so they have to search for structures that have desir able properties. "Given approximately 52
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60 elements in the periodic table that tances had been found only in certain can be used to make compositions con manganese oxides, according to Xiang. sisting of three, four,five,or even six el ements," Schultz and Liu write, "the uni Phosphors Using materials libraries, the Berke verse of possible new compounds with interesting physical and chemical prop ley team also has discovered new red, green, and blue light-emitting phos erties remains largely uncharted." And "once you get to four orfiveele phors that mayfinduse in luminescent ments," Haushalter says, the number of displays. One of the red phosphors, a possible compositions gadolinium zinc oxide doped with eu that can be made is so ropium [(GdL54Zno.46)03_6:Eu ο .06-1» IS large that, if you make them one at a time, you reported to have a purer red color than red phosphor can only scratch the sur the commercial 3+ Y 0 :Eu , an industry standard whose 2 3 face. In that situation, he emission peak is actually in the orangecomments, you have to red region [Appl. Phys. Lett, 72, 525 use the combinatorial ap proach—it's the only (1998)]. Although the new red phos sensible, efficient way to phor has a slightly lower quantum effi ciency than the commercial phosphor, it survey the possibilities. Combinatorial dis may be a better candidate for projection covery of materials is TVs,field-emissiondisplays, and X-ray still a very young field— imaging applications, according to one that has no proven Xiang and coworker Xiao-Dong Sun. The Berkeley group hasn't been the commercial successes sole player in the combinatorial phos (C&EN, Dec. 8, 1997, phor sweepstakes, however. Symyx re page 24). And its practitioners face searchers have discovered and opti many technical problems and other mized new luminescent compounds by hurdles on the road to developing mar preparing and screening combinatorial ketable products. Yet scientists pursu libraries containing some 25,000 sam ing the combinatorial approach are up ples on a 3-inch wafer. One of their finds beat about its potential, believing that is a red phosphor—an yttrium alumi it will most likely lead to a revolution in num lanthanum europium vanadate— materials research. that is redder than Y203:Eu3+ and offers Already, there have been some suc a comparable quantum efficiency [Na cesses, many from the LBNL group. ture, 389,9M (1997)]. Four months after their groundbreak ing paper on combinatorially produced superconductors, Xiang, Schultz, and their Berkeley co workers announced the discovery—us ing solid-state librar ies—of a new class of magnetoresistive materials based on cobalt oxide [Sci ence, 2 7 0 , 273 (1995)]. The resis tance of these mate rials undergoes a large change in a magneticfield,mak ing them potentially useful, for instance, for magnetic read/ write heads in com A "mixing head" Is used to Intimately mix small quantities of puter disk drives. diverse materials prior to depositing them as thln-fllm libraries Prior to this study, on an electrode array to test for catalytic properties In a large magnetoresis- methanol fuel cell.
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C0 2 + V2N2). This is a more com plex and challenging reaction, in part because incomplete reduction of NO to N20 is possible. Using 15NO in the feed gas, the researchers were able to distin 60
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chemistry guish the N2 product from the unreacted CO, and the N20 from C02. A num ber of interesting trends in reaction se lectivity were observed, all "in complete agreement with the more limited data set reported previously in the litera ture," they write. Even when combinatorial and fast screening methods pinpoint a promis ing new catalyst composition, there's no guarantee that it will become a commer cial product, Senkan points out. Not only would bulk samples of the material have to be synthesized using conven tional methods, but the material would have to pass numerous real-world per formance tests. 'There are lots of hur dles down the road," Senkan says.
Zeolites During the past year, researchers have begun reporting efforts to apply the combinatorial approach to the
Bein (left) and Senkan
synthesis of zeolites under hydrother mal conditions. Zeolites are microporous inorganic crystals such as aluminosilicates, which are widely used as ad sorbents, ion exchangers, and catalysts. They are also being investigated as ad vanced materials for a host of additional applications. Their synthesis requires demanding conditions: temperatures above the normal boiling point of the solvent, high pressures, and high pH. Duncan E. Akporiaye and coworkers at Sintef Applied Chemistry in Oslo, Norway, used a special multisample au toclave made out of Teflon (DuPont's polytetrafluoroethylene polymer) to car ry out 100 zeolite crystallizations in par allel at temperatures up to 200 °C [Angew. Chem. Int. Ed., 37, 609 (1998)]. The products had to be manually re moved from the reactors and were ana lyzed by conventional X-ray diffraction techniques.
Maier and coworkers at the Max Planck Institute advanced the state of the art by reducing the hydrothermal reaction volumes to 2 μι (from the 500 μι used by the Sintef group) and by au tomating the analysis. After carrying out 37 parallel syntheses in a microautoclave, they heat the product crystals to make them adhere to the silicon wafer forming the bottom of the autoclave. This wafer is removed, and the attached crys tals are automatically identified by X-ray microdiffraction, with the X-ray beam fo cused to a spot 500 μιη across [Angew. Chem. Int. Ed., 37,3369 (1998)]. As Purdue's Bein explained at the San Jose conference, his group has de veloped a somewhat different automat ed system for preparing and identifying zeolites. In his system, reagents are dis pensed automatically into Teflon auto clave blocks having eight or 19 reaction chambers with volumes of either 150 or 300 \iL· Six blocks have |â been processed at the same time. The products are recovered almost quantitatively using a centrifuge technique, and the resulting library can be analyzed automatically by X-ray diffraction or by scanning electron microscopy. The Purdue group has used this system to study, for example, the influence of different amounts of organometallic and organic structure-directing agents (templates) on the resulting zeolite phases. 'There are an enormous number of parameters" in zeolite syntheses that can be varied, Bein says, and dramatic effects sometimes are observed in the resulting structures. No one so far has reported the synthesis of any new zeolite structures using parallel synthesis, but that's something Bein would like to attempt in the near future. One thing is clear: Bein, like many materials researchers, is enthused with the combinatorial approach. "It's very convenient," he says, ticking off the advantages: fast library preparation, smaller reaction volumes, lower consumption of chemicals, and more data. And according to LBNL's Xiang, 'There are clear opportunities out there" for certain types of new materials. What's unclear is the impact that combinatorial methods will have on the materials industries, Xiang says. For that, we'll have to wait at least a few years.^4
