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CombiMatrix Publishes Article Validating Semiconductor Biowarfare Detection Arrays


Combimatrix, a maker of semiconductor-based microarrays, has recently become the latest in a series of biochip companies to marshal their technological resources in the service of biowarfare detection.

The company, which is midway through its second Defense Department SBIR grant to develop biowarfare detection applications for its biochips, has just published an article validating its technology for detection of a variety of biological agents in the journal Analytica Chimica Acta. The article “Antigen detection using microelectrode array microchips,” describes the company’s mechanism for securing antibody probes on its chips capable of detecting protein antigens.

This ability to use antibodies rather than DNA or RNA probes, said Bret Undem, Combimatrix’s director of business development, is “a key difference” between the company and other microarray makers that have defense contracts for biowarfare detection. “The better approach is to use antibodies, which bind to certain pathogens directly,” Undem said.

CombiMatrix, a wholly owned subsidiary of Squolamie, Wash.-based Acacia Research, uses complimentary metal oxide semiconductor technology to create chips with 1,024 test sites, or what the company calls “virtual flasks.” The sites are covered with a thick porous layer of material, in which the test sample is contained, and each site is attached to an electode. A fluidics unit delivers the test sample to each virtual flask.

In this new Analytica Chimica Acta article, company scientist Killian Dill and colleagues immobilized biotin moieties within the porous layer of their biochips, then applied a layer of streptavidin, which conjugates with the biotin. This streptavidin complex can then attach to other biotin, which is attached to the target antibody as a label.

The scientists received antibodies for Bacillus globigii spores from the US Army’s Aberdeen proving grounds. They attached these antibodies to the biotinylated chip surfaces. The actual Bacillus globigii spores were then hybridized to the array, and the specific patterns of spore presence were recorded after washing steps.

The researchers used the protein toxin saxitoxin as another test case, binding saxitoxin antibodies to the array’s electrodes and then successfully seeking out the presence of this toxin.

In another assay described in the journal article, the researchers used one antibody for capturing the protein, and another for labeling purposes.

CombiMatrix has been testing its arrays as antigen detection devices as a first step toward use of the chips outside the lab.

“Our goal is to develop a prototype that is portable and could be used in a military situation to detect airborne agents,” Undem said.

The company is applying for a third grant to further develop these antibody arrays, the demand for which has peaked lately. “We are putting more resources on this application given what’s going on,” Undem said. “We’ve been talking to a number of major companies about collaborations. I think that this may be a sustained long-term market for us, working for civilian and government agencies.”


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