Speeding Up SARS Research

Speeding Up SARS Research CombiMatrix develops a series of microarrays for severe acute respiratory syndrome Courtesy of CombiMatrix Following closely on the heels of the publication of the SARS (severe acute respiratory syndrome) coronavirus genome, Mukilteo, Wash.-based CombiMatrix recently announced the release of the first SARS microarray. The array will be made available at no cost to a limited number of government and academic research centers, says Ali Arjomand, senior scientist at CombiMatrix. The company plans to launch three types of chips: for detection and screening; for genome-wide detection of viral mutations; and for the study of viral and/or host gene expression. The array for mutation typing, which compares the hybridization pattern of a previously sequenced viral genome with a sample from a patient, is designed to identify new viral variants and the regions of the genomes in which the two versions differ. But Arjomand says that, as a drug screening and development tool, the gene expression array will have the greatest long-term impact. "This [array] is more for the long-term development of therapy, monitoring the progression of infection, and then testing the specificity of several potential drugs that affect the virus at the molecular level by altering its gene expression," he explains. CombiMatrix's proprietary array-manufacturing technology allows the company to create custom chips on-demand,1 making it highly suited to learn-as-you-go applications such as SARS research. Arjomand notes, "Because it is customizable, any new information that's learned about the virus can always be added in real time," thus keeping the chip designs up to date. The manufacturing process is fast: "We can make it tonight and use it tomorrow," he adds. Arjomand concedes that PCR-based methods for SARS detection, currently in development by other companies, ultimately may be faster and less expensive than microarray-based methods. "This is an area ideally suited for PCR," he says. "The problem is, what do you use as your markers? What portions of the genome do you want to amplify to indicate the presence or absence of the virus?" Llelwyn Grant, spokesperson for the Centers for Disease Control and Prevention in Atlanta, emphasizes that SARS research is at such an early stage that it is difficult to tell at this point which technology will be most valuable for studying and detecting the virus. --Aileen Constans 1. A. Constans, "Chips in Space," The Scientist, 15[19]:24, Oct. 1, 2001. *** Xeotron unites photochemistry and microfluidics in 3-D SARS microarray Courtesy of Xeotron Houston-based Xeotron has also released a SARS array, containing several replicates of 460 different 45-mer probes from the viral genome, on a 2,000-element array. Based on Xeotron's XeoChip™ technology, this microarray differs from traditional glass slide-based biochips in that it employs microfluidic channels for reagent flow and contains "a microfabricated substrate containing hundreds to thousands of three-dimensional nanochambers in an area the size of a dime," according to Xeotron's Web site. Like microarray giant Affymetrix, Xeotron makes its XeoChip arrays using a photolithographic process to synthesize probes on-chip and in parallel. But whereas Affymetrix uses physical photomasks, Xeotron uses computer-generated photopatterns and proprietary Photo-Generated Reagent chemistry. Deprotection is initiated by directing light at selected nanometer-scale chambers using digital projection photolithography. Computer-generated light patterns control a device that projects the appropriate light patterns onto the chip at each reaction cycle, selectively deprotecting illuminated regions and making them available for coupling with the next added nucleotide building block. According to Xeotron, this approach efficiently generates oligonucleotide arrays of high sequence fidelity, with stepwise yields of greater than 98.5%. "Not only is the combination of the chemistry and digital photolithography considerably less expensive and faster than the photomask methodology used in conventional photolithographic processes, but it also enables unprecedented flexibility," says David Sun, Xeotron's vice president of business development, marketing, and sales. "A wide range of chemistries can be used to generate microarrays bearing virtually any type of molecule," he adds, including DNA, RNA, peptides, peptide analogs, and small organic molecules. In addition to a small selection of off-the-shelf chips, Xeotron can also make custom arrays. Clients supply either a list of gene-specific probes or select from among the many predefined sequences in Xeotron's online Virtual Probe Library. Proprietary software automatically plans the chip design and programs the requisite light patterns for each synthesis cycle. The chips can be produced within a day, and customers can expect delivery of custom arrays for routine, nonemergent use within two weeks. For hybridization and chip-processing steps, users need Xeotron's M-2 Microfluidic Station, capable of handling two chips simultaneously. The chips are compatible, however, with most commercially available scanners and imagers for detection. --Deborah A. 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Speeding Up SARS Research

Speeding Up SARS Research

CombiMatrix develops a series of microarrays for severe acute respiratory syndrome

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