Producing sensors with light and plastic
Technique may enable mass production of disposable microchips
A team from Virginia Commonwealth University in Richmond has taken the path less traveled and, as in the poem, that may have made all the difference. The group developed a way to produce biomolecule microarrays inside the channels of a chip made of cyclic olefin copolymer (COC), a commodity thermoplastic that has not been the target of much research for microarrays. The technique could enable mass production of disposable microfluidic sensors that can detect specific problems, such as particular pesticides in the environment or biological markers for a given disease.
The microfluidic sensor (on the bottom) consists of polyacrylate films (in blue on top) photografted to the plastic COC in specific locations by UV radiation shining through a photomask. The films then are functionalized to create a sensor by adding a targeting unit, such as DNA, a protein or another molecule. Courtesy of Julio C. Alverez, Virginia Commonwealth University.
COC has a number of advantages. It provides a vapor barrier, easy microprocessability, resistance to chemicals, low background optical fluorescence and considerable stiffness while offering significant UV transparency. It has been used in a number of commodity applications, including optical plastic components such as the lenses found in cameras and elsewhere. However, polymethyl methacrylate and polycarbonate have been the main plastics used for microchips and microfluidics.
According to Julio C. Alvarez, an assistant professor of chemistry and team leader, one reason for this may be the nature of COC. It is sold as a powdery resin, which must be melted in an injection molding process to produce a desired shape. In contrast, the alternatives are commercially available as plates, which are easier for researchers to work with.
However, COC, unlike its competitors, which have carbonyl bonds sensitive to short wavelengths, tolerates UV radiation well. The researchers used this characteristic to photograft acryl monomers to a COC surface.
They assembled microfluidic chips out of COC plates into which they had replica-molded microchannels. For a photo-polymerization light source, they employed a UV lamp from Lesco Corp. of Torrance, Calif., calibrated with an intensity meter from the same company. They then created a pattern on a quartz mask using gold or another metal.
The apparatus, noted Alvarez, was not groundbreaking or even very complicated. “The photonic equipment was simple, a UV lamp of known power and the use of photomasks that block the UV light in selected areas to provide a desired pattern.”
In the next step, the researchers dissolved acryl monomers in water and, in the case of the microchips, flowed this solution through the microchannels. They then illuminated the plastics by shining the UV lamp through the photomasks. The light broke chemical bonds and formed new ones. The result was the buildup of polyacrylic films in the exposed areas, with the thickness of the films ranging from 0.01 to 6 μm. The ability to adjust the thickness was important, because it affects the diffusion of chemicals into and out of the film.
The polyacrylic served as a substrate during subsequent processing, with proteins, DNA and biotinylated conjugates adhering to the films. The investigators characterized the modified COC surfaces through the use of such techniques as attenuated total reflection Fourier transform infrared spectroscopy, using a spectrometer and associated accessories from Thermo Fisher Scientific of Newington, N.H., for the measurements. To verify their films, they used fluorescence microscopy and various dyes, capturing the images with a microscope from Microscopes Inc. of St. Louis and a digital camera from Nikon Inc. of Melville, N.Y.
Building a sensor from films on plastic, researchers created DNA patterns on a sheet (A) and inside a microchannel (B) made of the plastic cyclic olefin copolymer (COC). They hybridized the patterns with a complementary DNA sequence labeled with a fluorescent tag, creating these images. Reprinted with permission of Langmuir.
The results showed that functional biochemicals could be immobilized in patterns inside microchannels. For example, the researchers demonstrated <100 μm DNA patterns inside a microchannel, verifying them through hybridization with a fluorescently labeled complementary sequence. The work was reported in the Dec. 29, 2006, online edition of Langmuir.
Part of this proof of concept involved optimizing the thickness, charge and number of biomolecules immobilized in the film. With that work done, the researchers are now moving to create sensors. That may take a year or two, and Alvarez noted that it will involve development of sensing principles to detect different bioprobes. “This research is currently under way in our lab, and we will report on this soon.”
He added that mass production will require further optimization of the technique. Such advances may require the replacement of the simple photonic setup with something more expensive and capable. For example, an illumination source with a collimated beam, such as a mask aligner, would increase the resolution and sharpness of the patterned features. It is not known, however, whether such changes will be needed.
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