Tiny polymer patterns might act as glue in 'biochips'
WEST LAFAYETTE, Ind. Engineers have developed a technique that might be used to glue cells or DNA to the surfaces of computer "biochips," a technology aimed at making diagnostic devices to be implanted in the body or used to quickly analyze food and laboratory samples.
The microfabrication technique, normally used for etching electronic circuits, is instead used to fashion "micropatterns" out of a material made primarily from a polymer, or plastic, called polyethylene glycol.
"The patterns' smallest features were 5 micrometers, or about one-twentieth as wide as a human hair, which makes them as small as some cells," says Rashid Bashir, an assistant professor of electrical and computer engineering at Purdue University.
Purdue engineers previously had announced that they had made the first protein biochips, in which a protein mated to a silicon computer chip might be used to detect chemicals, microbes and disease. However, researchers say they hope to attach many other types of biological entities, such as cells and DNA, capable of quickly detecting a wider range of substances, either in the body or in laboratory samples.
The polymer micropatterning development represents a possible means of gluing these proteins, cells or DNA to a computer chip.
"This polymer layer could be the intermediate layer between the biological entities and the chip," Bashir says. "The protein would go on top of the polymer."
Unlike many synthetic materials, polyethylene glycol is not attacked by the body's immune system, making it suitable for implantation. The polymer also is ideal for microfabrication because of its unusual optical properties that allow it to be formed into patterns by using ultraviolet light in a process called photolithography, which is used in the electronics industry to etch microcircuits. The plastic is applied to the surface of silicon chips as a film and covered with a patterned, stencil-like "photomask," which is opaque in some places but see-through in others. The UV light is shined on the mask, dissolving the polymer wherever it is exposed to the radiation. When the mask is removed, a plastic pattern remains.
"These polymer films can be patterned on surfaces in cellular dimensions or smaller," says Nicholas A. Peppas, Purdue's Showalter Distinguished Professor of Chemical and Biomedical Engineering, who worked with Bashir to co-direct the research of former chemical engineering graduate student Jennifer Ward. The work was done primarily by Ward, who received a doctoral degree in chemical engineering in August and presented her work in July, during a meeting of the International Society for Optical Engineering in San Diego, Calif.
The technique might be used, for example, to form precise polymer patterns containing certain regions that attract water and others that repel water. Depending on the design of such patterns, specific cells or molecules would stick to the polymer. Then, the glued biological materials on a biochip's surface would precisely fit specific cells, molecules and strands of DNA in a sample being analyzed, enabling a lock-and-key sort of attachment. When a targeted substance passed by the chip, it would become attached to the surface and the chip would signal that the substance had been detected. Such a technology might be used in the laboratory for speedy chemical and genetic screening of blood and other biological materials; to instantly analyze food products for contamination; and in future implantable medical devices that continuously monitor glucose in a diabetic person's blood and then automatically administer insulin.
The biochips are in a class of microscopic devices called MEMS, or microelectromechanical systems. Although they don't have moving parts like gears and levers, as is the popular perception of MEMS, they use micro-fabrication technology to achieve a biological function, namely interactions with cells and genes. MEMS used in biological applications are called bioMEMS.
So far, the smallest features within the patterns, while achieving cellular scale, are still more than 30 times larger than the features in today's microelectronic circuits, says Bashir, adding that future attempts will be made to reduce the size of pattern features.
"I think this is actually a first step," Bashir says. "We will be working on trying to make it smaller. But it's important to note that, for some biological applications, the 5-micron-size we have achieved is actually small enough" because cells range in size from 1 to 10 microns across.
Ward is now a chemical engineer at ExxonMobil Chemical Co., in Baytown, Texas. The three researchers developed their collaboration in a National Science Foundation program on Therapeutic and Diagnostic Devices, a cross-disciplinary training ground for engineers specializing in the field of biomedical devices, including artificial organs, biomaterials and controlled-release devices. The graduate program, which brings together students in biomedical, chemical, industrial, electrical and computer engineering, as well as pharmacy, was established at Purdue in 1999 under Peppas's direction. It is the only program of its kind in the United States, says Peppas, who, along with Bashir has a dual appointment in Purdue's Department of Biomedical Engineering.
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Rashid Bashir, (765) 496-6229, firstname.lastname@example.org
Writer: Emil Venere, (765) 494-4709, email@example.com
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UV free-radical polymerization for micropatterning
Jennifer H. Ward, Rafael Gomez,
We have developed novel techniques for the preparation of micropatterned structures from thin films prepared by the block copolymerization of monomers using UV free-radical polymerizations. The process involves polymerizing the first monomer layer in the presence of an iniferter (initiator-transfer agent-terminator) with a dithiocarbamate group to make a photosensitive polymer. Upon application of a second monomer layer on the first polymer layer and irradiation, a copolymer is formed between the two layers. Patterns are created on the films by applying a mask and selectively irradiating the surface. We have successfully polymerized poly(ethylene glycol) (PEG) onto a highly crosslinked material of poly(ethylene glycol) dimethacrylate. Various patterns have been created to determine the precision that can be achieved with this method. Preliminary results show that the patterns in the second monomer layer can be from 5mm to 100 mm thick, with feature size as small as 5 mm, allowing the use of this material to high aspect ratio structures for micro-fluidics. In addition, applications of this type of material are also in bioMEMS, biomaterials, and biosensors for the selective adhesion of cells and proteins.