After announcing a microarray-based collaboration with France’s Genopole Public Interest Research Group last week, Taiwan’s Industrial Technology Research Institute revved its engines for a race to reach the array industry’s holy grail: production of a one-chip array containing the entire human genome.
“We plan on having them available by the end of the year,” Chungcheng Liu, director of the molecular biomedical technology division of ITRI, told BioArray News.
The high-density arrays are to be mass-produced by the Phalanx Group, a spinoff of ITRI. This group, Taiwan’s attempt to reproduce in genomics its ability to mass-manufacture semiconductors at highly competitive prices, has a $30 million war chest to fuel its efforts and a method to use ink-jet technology to manufacture the arrays, and a plan to provide gene expression profiling services along with them.
An industrially produced single-chip human genome microarray appears within the grasp of the industry but the two largest microarray manufacturers, Affymetrix and Agilent Technologies, have yet to project when they will package the known genes of the human genome onto one chip. But others, such as Nimblegen of Madison, Wisc., say they already have a technology that is capable of producing this longed-for tool. However, spotting 30,000 probes on a singlechip is just part of a process that requires rigorous testing and quality assurance, as well as a market that would buy it.
Phalanx is targeting a production line that, at full speed, will create a new slide every second, and some 50,000 a day. The Phalanx system relies on an ink-jet technology that was 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 every second from high-capacity reservoirs that hold 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 60-to 70-mer oligonucleotide probes on the arrays are taken from NCBI UniGene clusters.
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.
The research collaboration with Genopole Public Interest Research Group, or GPI, will focus on testing the arrays produced through this process, said Liu. The partnership will initially revolve around the Phalanx Human Liver 2000 microarray, a chip that contains oligonucleotide probes for 1,964 liver-associated genes and 36 controls, and classified into categories based on their tissue source — adult/normal; fetal/developmental; and disease-associated.
GPI is an association of 21 research laboratories and 42 biotechnology companies created in 1998 in the region surrounding Paris as a geographic center for genomic research and biotechnology development. Executives of the government-funded agency were unavailable for comment.
Genopole joins the Canadian Genetics Discovery Network, (http://www.bioarraynews.com/articles/ view-article.asp?Article=200326132736) Phalanx’s other research partner, in being the first to beta-test the Liver 2K microarray, and then the 30,000-probe human genome array, Liu said. The target date for releasing data from the Liver 2K gene research is in October, Liu said.
The collaboration is part of an ongoing effort by ITRI to collect research partners globally, with “expensive” microarray-based experiments to conduct, Liu said.
ITRI is a 6,000-employee government-sponsored organization launched in 1973 to create core technology and transfer it to the private sector. In addition to startups like Phalanx, the institute has incubated global semiconductor manufacturing giants Taiwan Semiconductor Manufacturing Corp., and United Microelectronics.
Phalanx enters the field with 16 microarray-manufacturing patents licensed from ITRI, including an ink-jet based microarray manufacturing technology and a novel algorithm called FLAG (fast local alignment for gigabase) for DNA sequence alignment.
ITRI is the controlling investor in Phalanx, with a list of stakeholders including: CGDN, which is headquartered in Vancouver, Canada; and Taiwan companies China Steel, Ylon Group, Taiwan Fertilizer, and Fubon Group. Andrew Wang is the chairman of Phalanx.
Phalanx is also planning to engage in a large-scale gene-expression mapping project using its high-density arrays, said Liu.
“[Taiwan] doesn’t have the money that the US spends in this area,” Liu said. “But, we have some very unique technology that gives us leverage. So far, the quality control and everything looks fantastic.”
But, like many other microarray researchers, the Taiwanese team of 70 scientists and technicians involved in the single-chip human genome project, are up against the same hurdle that others face: sample acquisition and preparation.
“Sample preparation is as expensive as the chip,” said Liu.
Phalanx plans to manufacture 100,000 high-density arrays for its human genome-mapping project.
“It’s a big project, one that we think will stimulate the biotech development of Taiwan,” Liu said.