Combinatorial chemistry allows a large number of drug candidates--nucleic acids, peptides and small organic molecules--to be screened simultaneously. Affymax Research Institute, a biotechnology company located in Palo Alto, Calif., has been a leader in the development of the combinatorial technique. Last year, Affymax was purchased by Glaxo, the world's largest drug maker. A few of the founders of Affymax recently embarked on an effort to apply combinatorial methods to the rest of the material world. Instead of working with biological molecules, these researchers are demonstrating how to use the combinatorial technique to screen thousands of both organic and inorganic compounds at a time.
Two articles that appeared last year in the journal Science outlined the potential of that approach for both speeding and broadening the cumbersome process of looking for novel materials. And a new company Symyx, (derived from the Greek word that means "to commingle substances to form something new"), has licensed the technology to develop it into a marketable product.
One of the papers described the use of combinatorial techniques to synthesize an array of high-temperature superconducting materials, quickly and easily. A team of researchers from the University of California at Berkeley and the Department of Energy's Lawrence Berkeley National Laboratory (LBNL) deployed an ion gun that sputters, or sprays, oxides through stencil-like masks onto a metal surface. "It's like a sophisticated spray paint can," explains Peter Schultz, a chemistry professor at the Howard Hughes Medical Institute at the University of California at Berkeley, who co-led the research effort with Xiao-Dong Xiang of LBNL. The technique is also similar to that used in the semiconductor industry to create circuit patterns on a chip by exposing selected sections to ultraviolet light.
In Schultz's experiment, the ion gun sprayed seven metal oxides--one at a time--through a mask having 128 rectangular openings, each of which measures just one by two millimeters. The entire grid covered a surface no larger than a single square on a checkerboard. To vary the composition within each of the 128 thin-film rectangles, a set of additional masks were placed atop the one that defined the grid elements. Each overlay mask blocked an oxide from reaching certain rows or columns of the grid. Researchers changed the overlay mask as each of the seven oxides was laid down separately. The various mask geometries insured that each rectangle in the array received a different combination of the seven oxides. The resulting mixtures were then sintered (baked) to produce finished ceramics.
The researchers then used an electrical probe to measure the resistance of the compounds at different temperatures. A number of the small rectangular thin-film elements were designed to replicate the properties of two known high-temperature superconductors--and, as hoped, the materials in those rectangles conducted electricity without resistance at 80 to 90 kelvins (degrees Celsius above absolute zero). That temperature is high enough that the coolant can be liquid nitrogen--a preferable alternative to the far more costly and short-lived liquid helium that is needed to supercool classical superconductors down to four kelvins.
Schultz and Xiang believe that these techniques will dramatically reduce the time consumed in testing new materials, because thousands of assays can be performed in a matter of hours. Current materials characterization methods typically require an entire work day just to test a single compound.
Moreover, combinatorial methods may apply across a broad range of materials. In a subsequent paper in Science, the experimenters successfully utilized the same methods to characterize the properties of a class of crystalline ceramics known as perovskites--specifically, cobalt oxide perovskites. These perovskites display what is called colossal magnetoresistance: their electrical resistance changes dramatically when exposed to a magnetic field, which makes them ideal for high-capacity data storage.
Combinatorial technology is now headed to market. Symyx, which was started by Schultz and Affymax's founder and chief executive, Alejandro Zaffaroni, is focusing on development of more practical hardware for creating and testing new materials. The company is considering, for instance, how to facilitate development of improved versions of the phosphors that light up computer or television displays. Combinatorial techniques could create a kind of display screen in which each picture element, or pixel, is illuminated by a phosphor having a different composition than the surrounding ones. The phosphors could be deposited through masks directly onto a base of conductive materials, which in turn would serve as an interface to the electrodes that send a current to the pixels. When the display is turned on, the phosphors that glow brightest or that show the most vivid colors could readily be singled out for further examination in the laboratory.
A similar approach might assist in the never-ending quest for better batteries. In this case, one would start with an array of miniature electrodes built on an insulating surface. Again employing a series of masks, workers could then fabricate thin layers of polymers that would serve as solid electrolytes between the grid of tiny anodes and cathodes. The polymers having the most desirable electrical properties would stand out.
Combinatorial materials science seems poised to change the way chemists work. "Instead of designing one experiment, you can design 10,000," Schultz says. Trial-and-error may become a lot more trial and a lot less error.