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POROUS SILICON BIOSENSOR Exquisitely sensitive portable sensor promises to have many uses
A
simple, general-purpose sensor based on a novel signal transduction scheme promises to be able to detect virtually any molecule that binds tightly to another. The portable biosensor could be used for research, combinatorial chemistry screening, and diagnosing diseases. "We're taking advantage of the world of biology and host-guest chemistry," said M. Reza Ghadiri, associate professor of chemistry at Scripps Research Institute and Skaggs Institute for Chemical Biology, La Jolla, Calif. "If there's any molecule that can recognize another, we can exploit it." The chemists at Scripps and the University of California, San Diego, who created the system believe it will become the first practical, affordable biosensor with multiple applications. In medicine, for example, it could be configured to search simultaneously for hundreds of conditions or diseases—without even having to send samples to a lab. Scripps postdoctoral researcher Victor
S-Y. Lin described the porous silicon-based sensor to the Division of Organic Chemistry at the American Chemical Society's national meeting, held last week in Las Vegas. Ghadiri, Lin, and Scripps postdoctoral fellow Kianoush Motesharei collaborated with UCSD chemistry professor Michael J. Sailor and graduate student Keikipua S. Dancil to develop the device with funding from the Office of Naval Research. The biosensor not only can detect tiny concentrations of specific DNA sequences, Lin said, it also can recognize small organic molecules. The recognition elements can be based on nucleotide hybridization, enzyme-substrate binding, lectincarbohydrate interactions, antibody-antigen binding, host-guest complexation— essentially any of the supramolecular interactions that have been the focus of intense research in recent years. The design of the sensor capitalizes on the Sailor group's work with porous silicon semiconductors. Etching silicon wa-
Porous silicon biosensor tracks molecular interactions
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Charge-coupled device detector
Fiber-optic probe
Interferogram
Porous silicon layer
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fers increases their surface area tremendously, leaving tiny pillars of silicon oxide. Shining light on that porous material creates an interference pattern whose position shifts when the refractive index of the surrounding medium changes. Using well-established chemistry, the research team can attach various molecular recognition elements to the porous silicon surface. When the probing element tied to the surface binds its target molecule, the resulting change in refractive index causes a shift in the interference pattern that's picked up by a chargecoupled device (CCD) detector. For example, the chemists anchored a 16-nucleotide DNA strand to the porous silicon surface. In the presence of the complementary DNA sequence, they observed a pronounced shift in the wavelength of the silicon film's interference pattern. With DNA strands that didn't match, however, there was no significant change. The biosensor is sensitive enough to detect even femtomolar concentrations of DNA—a much smaller amount of analyte than current systems can pick up. "We think that the large surface area of the porous silicon allows us to pack more of the probing molecules onto the surface," Lin said. But the researchers suspect the silicon itself also plays a role. "The surprising sensitivity may be the result of a surface-enhanced phenomenon brought about by the semiconductor properties of the silicon matrix," Ghadiri said. The biosensor even can recognize multiple layers of biomolecular interactions, a feature the researchers call "cascade sensing." For example, Motesharei linked the small molecule biotin to the porous silicon, which allowed detection of the biotin-binding protein streptavidin. The biotin-streptavidin layer then was used to detect a specific antibody, which in turn was able to detect another antibody, which itself was used as a probe to detect the steroid digoxigenin. Having built their sensor out of economical silicon chips, an ordinary white light source, a simple fiber-optic probe, and the kind of inexpensive CCD detector found in home video cameras, the chemists predict it will be affordable enough to find widespread use. The researchers have filed a patent application for the device, which is small enough to fit in the palm of the hand. "It's so simple and it works so well, it's hard to imagine why somebody else hasn't come up with this before," Ghadiri said. Pamela Zurer SEPTEMBER 15, 1997 C&EN 7
