Back to the Future
Schultz is betting that for materials science, the present is like the late 1980s all over again. In 1995, Schultz-a Berkeley chemist who holds a joint position at the Lawrence Berkeley National Laboratory (LBNL)-teamed up with LBNL physicist Xiao Dong Xiang and others to create a combinatorial library of materials rather than drug candiates. The group first made arrays of 128 different compounds, each a potential high-temperature superconductor, and each a tiny speck just 200 millionths of a meter across. The Berkeley team and others went on to create libraries of phosphors, data storage materials, polymers, catalysts, and even electronic devices.
For all these diverse materials, the basic strategy is the same: Make a lot of compounds at once, then scan them simultaneously to see which works best. To make the superconductor array, for instance, the Berkeley team sprayed seven different inorganic oxides one at a time through a mask. By using a series of different masks to control the deposition of each oxide, the researchers created a checkerboard of compounds in which each 200-micron square on the board contained a different combination of elements. The entire chip was then processed and screened for activity.
But making such arrays turns out to be the easy part; it’s much harder to pick winners. “It doesn’t make a lot of difference if you can make 100,000 compounds at once if you still have to test them one by one,” says Brandeis University chemist Gregory Petsko, who is also a scientific adviser to ArQule. Rapid screening methods are widely available in drug discovery research to detect desired biological activity. But equivalent screens for measuring most physical properties, such as flexibility and electrical conductivity, simply don’t exist yet.
“How do you measure the strength of a nanogram of material?” asks Luke Schneider, who heads the combinatorial effort at SRI International, a consulting and research firm in Menlo Park, Calif. “Nobody has developed that technology yet.” Further, combinatorial approaches require measurements of thousands of compounds at once. “There’s a whole new technology that has to be built,” says Schneider.
Several groups are trying to develop convenient methods for rapidly testing the properties of huge batches of different materials. Symyx found its new blue phosphor earlier this year by simply shining ultraviolet light on an array of candidate phosphors to see which glowed the brightest. Other high-speed screens are in the works. Last year, Xiang and his LBNL colleagues invented a new high-speed scanning microscope that they use to screen arrays for electronic properties. Richard Wilson and his colleagues at the University of Houston have been experimenting with an infrared sensor for tracking the activity of arrays of catalysts by looking at the heat given off during reactions.
Although the hunt is on for new screens, most of the success in developing combinatorial materials has come in designing libraries of interesting new compounds. Recently, the Berkeley team staked out more new territory by reporting the first combinatorial array of electronic devices. In this case, the researchers made simple devices called ferroelectric capacitors, used to store information as packets of electrical charge on DRAM (dynamic random access memory) computer chips. Computer companies hope to shrink DRAM chips to even smaller dimensions. But the materials currently used to confine the electrical charge fail when they’re layered too thin, causing current to seep out like water from a leaky bucket.
To find new “buckets” that don’t leak as much, Xiang and co-workers built an array of several thousand capacitors, each with a charge-confining layer made of a slightly different ceramic alloy. The group found that a particular combination of barium, strontium, and titanium, spiked with a touch of tungsten, was the best yet at stopping the leak. The new material is not likely to find its way into devices immediately because it still must prove itself on other grounds, such as fitting in with current chip-making practices. But it offers a promising new lead.
Though capacitors and phosphors are tempting targets for these revolutionary combinatorial methods, the big payoff could prove to be catalysts. Catalysts are key to a myriad of commercial processes, ranging from plastic manufacturing to the production of high-volume chemicals to emission-control devices in cars. Come up with a catalyst to make a better-or cheaper-commodity plastic, and you stand to win big. “You can warp markets with those things,” says Hogan.
Despite the economic incentives, researchers have a tough time designing catalysts. Catalysis is a notoriously complex process, and catalysts are finicky creatures; each works best under its own set of conditions, such as temperature, pressure, and concentrations of reactants. Figuring out how these variables affect the catalyst is extraordinarily difficult. As a result, polymer chemistry has long been part science and part art, with chemists relying heavily on intuition-and sheer luck-to find new catalysts. “Nobody knows how to design the ideal catalyst from scratch,” says Petsko.
The complexity of the materials makes discovering new catalysts a prime testing ground for combinatorial chemists. In 1996, researchers led by Amir Hoyveda and Marc Snapper at Boston College turned in one of the first reports on creating libraries of different catalysts. And now just about everybody else, including Symyx, ArQule, SRI, and DuPont are trying to do the same thing.