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science/technology IX gene and a promoter sequence taken from mice that will direct only the pig's mammary tissue to read and transcribe the gene. Several hundred copies of the hybrid gene are microinjected into a onecelled pig embryo, which is then transferred into a surrogate mother pig. The sows from this litter produce milk that contains the human protein. Plants, too, are showing potential as transgenic sources for therapeutic proteins. At Agracetus, a unit of Monsanto located in Middleton, Wis., staff scientist Vikram M. Paradkar and his colleagues are making and expressing a monoclonal antibody in transgenic corn seed. Such antibodies are being developed as targeting agents for delivering toxins to cancer cells, among other uses, he explained in Las Vegas. The Agracetus team plans to begin Phase I clinical trials of its antibody for cancer treatment by the end of the year. The antibody-bearing corn plants are made by bombarding immature corn embryos with gold beads carrying DNA plasmids that contain foreign genes engineered to express in the seed. The transgenic plants produced in this way are then screened to select the ones that have the highest level of antibody expression in their seeds. The plants are self-pollinated and used to grow a pure strain of antibody-producing corn. Cost is an important factor in commercializing such monoclonal antibody therapeutics because they generally need to be given in high doses. Several hundred milligrams per patient per treatment is a typical dose, Paradkar explained. Agracetus' transgenic corn can produce 2 kg of antibody per acre of corn planted. The researchers have extracted, recovered, and purified the antibody from the corn kernels at a process scale to yield therapeutic-quality antibody very similar to the antibody produced in cultured mammalian cells. Transgenic plants provide several other advantages besides lower cost, he noted. Viruses that infect plants don't harm humans, and no mammalian viruses are known to propagate in plant cells, making transgenic plants potentially safer sources of mammalian proteins than cultured mammalian cells. And production scale-up is very simple with plants—just plant more acreage. The typical market for a monoclonal antibody is about 100 kg per year, Paradkar says. "This can be managed easily in a few small farms to provide a high level of control," he noted. Rebecca Rawls 34 OCTOBER 6, 1997 C&EN
New method makes patterned polymer films From the ACS meeting Ultrathin multilayer polymer films with potentially useful electronic and optical properties have moved a big step closer to practical applications thanks to a new procedure that makes the molecules form ordered patterns on selected areas of a surface. Previously, thin films of polyions— polymers with ionic repeating u n i t s have been constructed in a number of laboratories by sequentially adsorbing layers of polyanions and polycations. But that so-called layer-by-layer technique leads to substrates with uniformly coated surfaces. The new method also uses alternating sheets of positively and negatively charged polymers. But now, by pretreating certain regions of a surface with one substance and the remaining areas with another, polyion films can be coaxed to form intricate patterns. Paula T. Hammond, assistant professor of chemical engineering at Massachusetts Institute of Technology, demonstrated the agility of her research group's film-growth procedure by coating gold surfaces with numerous parallel columns of polyion films. In one sample, strips of film a few hundred nanometers thick form 3.5-um-wide lines that are separated from each other by 2.5 urn. Hammond described the work in separate presentations to the Division of Polymeric Materials: Science & Engineering and to the Macromolecular Secretariat. "There's no question in my mind the additional feature of lateral resolution brings these materials much closer to application," commented Sanat K. Kumar, professor of materials science and engineering at Pennsylvania State University, University Park. "Others have also built
Hammond: self-assembling film patterns
up polymer films layer-by-layer," Kumar said, but by controlling the adsorption process horizontally and vertically, Hammond has come up with "another way of creating supramolecular structures." "I really believe this can be turned into a technique for device fabrication in the near future," Hammond noted. "The appeal is its simplicity." The procedure's fine control over molecular adsorption, she emphasized, may be used to prepare materials with customized refractive indexes or unique emittance, fluorescence, or electron-transfer properties. In the short term, electroluminescent instruments and sensors that diffract light of certain wavelengths under controllable conditions could result from the research, Hammond predicted. Other applications—such as waveguides used for fiber optics—will require more work. Working with graduate student Sarah L. Clark and undergraduate Martha M. Montague, Hammond prepares substrates using the microcontact printing technique developed by Harvard University chemistry professor George M. ~ — — — — - Whitesides. In his procedure, a silicon block is coated with a polymer into which a relief pattern is impressed by photolithography. Silicone rubber is polymerized on the relief pattern—transferring the pattern to the Optical micrograph (left) depicts large-scale order directed silicone sheet. The result by a templating procedure. Higher resolution atomic force is a rubber stamp whose micrograph (right) reveals topographic details. Nanometerpattern may contain mithick polyion films (green) can be made to adsorb almost crometer-sized features. exclusively on carboxyllc acid regions. Hammond's group
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inks the stamp with 16-mercaptohexadecanoic acid, then presses it onto a gold-coated silicon substrate. The stamping process imprints the gold substrate with lines of the carboxylic acid that are 3.5 um wide and separated from one another by 2.5 um. The imprinted substrate is then immersed in a solution of oligo(ethylene glycol>terminated alkanethiol to cover the gold regions left exposed. The gold surface, patterned with regions of alternating chemical functionality, serves as a molecular template for polyions, Hammond explained. It causes adsorption of polyion layers to proceed with lateral selectivity. By adjusting parameters—such as polyion molecular weight and electrolyte concentration— the researchers can choose whether layers of polycations and polyanions preferentially assemble on the carboxylic acid regions or on the oligo(ethylene glycol) regions. "Generally, the adsorption properties of polymers are difficult to control," Hammond noted. "But here, because chemical functionality is directly programmed into the surface, adsorbed polyions form microstructures by self-assembly." In one experiment, the patterned substrate was exposed to a solution of poly(diallyldimethylammonium chloride)— the polycation—rinsed, then treated with a sulfonated-polystyrene solution— the polyanion. The cycle was repeated several times, building an alternating polycation-polyanion stack almost exclusively on the carboxylic acid strips. "Before the process can be commer-
cialized, several issues must be studied," Kumar pointed out. For example, the ease of production, the reproducibility, and the size of the devices that can be made, he said. Electronic gadgets with nanometer-sized features will likely be more versatile than those built on the micrometer scale on which Hammond has demonstrated lateral resolution, he explained. "Nonetheless," Kumar added, "the method certainly appears to have a great deal of promise." Mitchjacoby
Modified flame retardant stays at surface
A
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Polymer
Fullerene with perfluoroalkyl chains
Making polymers take the heat
with clays on a microscopic level, Emmanuel P. Giannelis, associate professor of materials science and engineering at Cornell University, converts ordinary From the ACS meeting plastics into higher performance materiThe enormous growth of plastics use in als. The modified substances exhibit inrecent years has driven researchers to creased heat and flame resistance, imlook for ways of making the materials proved structural properties, and heightmore resistant to fire. One strategy that's ened resistance to gas diffusion. Gary W. Beall, vice president of Nanoemerged is to modify existing polymers cor—an Arlington Heights, Ill.-based so they resist burning. Polymer modifications generally use company that provides chemically modifire-retardant additives such as alumina tri- fied clays to the plastics industry—noted hydrate and compounds containing bro- that manufacturers have long tried to immine or phosphorus. Two papers present- prove polymer properties by blending ed to the Macromolecular Secretariat ad- the materials with inorganic compounds. dressed recent advances based on the way This has resulted mainly in "filled polythe additive interacts with the materials it mers" in which improvement in one atseeks to protect. In one, additives improve tribute has come at the expense of anmaterials by modifying the structure of other—for example, stiffer and stronger their bulk. In the other, the changes are polymers, but with much added weight. By contrast, the modern performance made almost exclusively at the surface. By causing organic polymers to mix materials are stronger and less flammable
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