In the pond of DNA microarray providers relying on in situ synthesis, Affymetrix is still the biggest fish. But some smaller fry believe they will be able to snatch away a few juicy bites from their big brother: Xeotron, with a unique combination of photo-generated reagents, digital photolithography, and microfluidics, is poised to enter the market for custom-made DNA arrays, and is already thinking about testing new waters with its peptide arrays. This week, the Houston-based company published a paper online in Nature Biotechnology describing its technology for individually addressable parallel peptide synthesis on microchips.
Xeotron’s patent-pending microarray technology relies on a silicon-based microfluidics chip manufactured by Applied MEMS that contains either 4,000 or 8,000 tiny chambers on an area of little more than one square centimeter. Each chamber serves as an independent reaction vial to synthesize a specific type of oligonucleotide or peptide. But in contrast to the photoprotected monomers used by Affymetrix and others, Xeotron employs conventional building blocks and starts the reaction with a photo-generated reagent such as an acid. This chemistry does not only allow it to make any type of peptide — whereas only eight different directly activated amino acids have been published so far, according to co-founder Xiaolian Gao — but also allows it, at least in principle, to synthesize other polymers, such as carbohydrates.
“We should be able to make this a more general chemistry platform, going into the broader area of chemical genomics,” said Gao. Besides using a different chemistry, Xeotron also does not use photomasks, like Affy, but creates the light pattern that determines which reaction gets started with a digital micromirror device.
This microarray platform is a far cry from what Xeotron was founded to develop: flat-panel display technology. In 1995 Xiaochuan Zhou, former associate director of the Nano-Material Fabrication and Technology Center at the Texas A&M University; Gao, a chemistry, biology, and biochemistry professor at the University of Houston and Zhou’s wife; and Erdogan Gulari, a professor of chemical engineering and macromolecular science at the University of Michigan, got together to develop flat-panel display technology that involved a digital micromirror device. But they quickly decided that producing micorarrays by using the device for photolithography and combining it with Gao’s photo-generated reagent chemistry was going to be a better business plan.
Initially funded by various government and research foundation grants, Xeotron secured $9 million in venture capital in a series A round last summer that included Vanguard Venture Partners, Fremont Ventures, and others. Earlier this year, it announced that it had won a $3 million DARPA grant to develop an array-based oligonucleotide synthesis system to assemble up to 10,000 base pairs of DNA within 24 hours. The grant was recently increased by another $800,000 according to David Sun, Xeotron’s vice president of development and marketing. Within the next few months, the company, which has grown to 34 employees, is hoping to increase its cash by another $18 million to $20 million in a series B round.
Within that same timeframe, the company is planning to bring its first products to market: custom-made DNA arrays for expression profiling as well as a generic DNA cancer chip. Moreover, its peptide chips will be ready for early testing by the end of this year.
But rather than trying to compete with its big brother’s high-density genome chips, Xeotron is going after a more focused clientele, “people who have already looked at a larger set and nailed it down to a few thousand or a few hundred” genes, said Gao. Customers can choose their probe sets from any sequenced genome, and the oligo size is variable. The turnaround time for the chips can be as little as a few days, said Sun, depending on whether the customer provides all the probe sequences or only a list of genes. The chips do not require a hybridization station, although Xeotron will offer one, and only consume 10 µl of sample, according to Sun. They are compatible with several types of scanners.
But Xeotron is not alone in the arena for custom-designed in situ synthesis DNA chips: Madison, Wis.-based NimbleGen has already been offering high-density custom arrays with 195,000 features since April and is planning to come out with a chip synthesizer next year, while Mannheim, Germany-based Febit currently is planning to bring its integrated DNA chip synthesis and analysis station to market in early 2003.