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Seeing Cheap Chips by the Millions, Taiwan Enters Microarray Fab Venture

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The Taiwan Ministry of Economic affairs has created a joint venture, the Phalanx Biotech Group, which plans to bring high-density microarrays to the global marketplace within two months.

Using its experience with semiconductors as a model, Taiwan, and a set of Taiwan-based businesses and North American research entities, will enter the emerging microarray marketplace seeking to attack established competitors by manufacturing high-density chips at price-points of tens rather than hundreds of dollars.

Taiwanese officials were not available for comment. However, BioArray News has obtained detailed information on the alliance, first reported in the Taiwan newspaper, China Post.

The first product available will be the Phalanx Human Liver2000 microarray. The chip will contain oligonucleotide probes for 1,964 liver-associated genes and 36 controls classified into seven categories based on their tissue source — adult/normal; fetal/developmental; and disease associated. The probes are taken from NCBI Unigene clusters. The chips are expected to be available in March.

The next product from the Taipei assembly line will be a single human genome chip, containing probes for 30,000 human genes derived from NCBI Unigene clusters, and targeted for availability in December. Phalanx will also offer services including array design, DNA hybridization, scanning, and database management.

“They have the nanotechnology and the silicon chip history,” said Ron Woznow, chief executive officer of the Canadian Genetics Discovery Network, a partner in Phalanx. “We have the biology.”

According to Woznow, the initial product, the liver array, will be offered because of the prevalence of liver disease in Asian populations.

Woznow said CGDN, a Canadian government and private business-funded entity created to promote scientific cooperation among scientists, entered a collaborative agreement with Phalanx for one reason.

“We want to make sure our researchers have leading-edge tools,” he said. “Our involvement is to give our scientists the first opportunities to use these chips. We are not interested in sharing in the profitability of Phalanx. If we keep at the leading edge, other commercial opportunities are going to fall out of things such as finding an interesting gene.”

Mass Production in Silicon

Taiwan is one the world’s largest manufacturer of semiconductors and is a leader in the foundry concept of semiconductor manufacturing -- mass-producing wafers of silicon chips that others slice and sell. Taiwan’s products can be found in cell phones, hand-held computers, and toys, and soon, on a glass microarray chip.

Phalanx is a spin-off of a four-year development project started by the Ministry of Economic Affairs in 1999 and managed by the Industrial Technology Research Institute, a 6,000-employee government sponsored organization launched in 1973 to create core technology and transfer it to the private sector. The institute incubated Taiwan Semiconductor Manufacturing Corp., and United Microelectronics, now global manufacturing giants in chips. The ITRI R&D entity licenses some 600 technologies annually.

Phalanx enters the field with 16 patents licensed from ITRI — although it is not clear whether they are US patents — an ink-jet based microarray manufacturing technology, a war chest the equivalent of $14 million (US) in funding, and a list of stakeholders that includes: CGDN, which is headquartered in Vancouver, Canada; The Information Systems for Biotechnology agricultural genomics information organization of Virginia Tech, and Taiwan companies: China Steel, Ylon Group, Taiwan Fertilizer, and Fubon Group. Andrew Wang is the chairman of Phalanx.

Taking aim at Diagnostics

According to ITRI literature, the biochip program it has developed is aimed at the diagnostics market and includes microarrays paired with air-driven microfluidics devices for sample preparation and DNA amplification. A DNA chip has been prototyped to identify 25 pathogenic bacteria strains.

Phalanx is the name under which the manufacturing system was developed. It uses technology developed in ITRI laboratories to create the injection-based micro-dispensing ink-jet device at the center of the process.

ITRI has also developed bioinformatics tools, including a novel algorithm called FLAG (Fast Local Alignment for Gigabase), for DNA sequence alignment.

The Manufacturing Process

Phalanx is targeting a production line that, at full speed, creates a new slide every second, and some 50,000 a day. The Phalanx system relies on an ink-jet technology that comes from technology developed at ITRI’s Opto-Electronics and Systems Laboratories. It can deliver 200 reagents simultaneously to produce spots of 50 to 100 micrometers at a density of 3,500 per square centimeter. The arraying technology is enabled by using individual jets with channels and pumps that deliver a drop a second from high-capacity reservoirs holding enough oligos for production runs of one million slides.

Oligos are presynthesized and undergo MALDI-TOF mass spectrometry analysis for quality control after loading in reservoirs. During the dispensing process, industrial cameras monitor the production as another quality control system.

The slides have a hydrophobic surface coating with highly-active 2D/3D functional groups, which is produced using a technology that evolved out of methods used in compact disc manufacturing.

In the Lab

For Steven Scherer, senior scientist, genetics and genomic biology director, The Center for Applied Genomics at the Hospital for Sick Children in Toronto, the chips mean savings. His facilities will use the microarrays as part of the Canadian Genetic Disease Network.

“I run an Affymetrix core lab and it’s a wonderful technology,” he said.

“But for some of the experiments we do, it’s just too expensive,” he said. “We want to test dozens or hundreds of clinical samples; so, if we can use a more targeted and cheaper chip, it means we can do more experiments and get more data, so that’s an added advantage for us.

— MOK

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