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At BioChips 2003 Meet, Innovation Blooms In a Time of Deeply Constrained Funding

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Michael Kane, one of the speakers at last week’s three-day Biochips 2003 conference in Boston, talked for more than a half hour about Spanscript, Trivera’s product for creating non-redundant cDNA libraries for use in microarray analysis.

After taking questions from the audience, he said he would be glad to speak one-on-one with those interested in the technology, since the three-employee company had folded.

“The technology is still viable,” he said.

Spanscript is aimed at researchers investigating non-typical organisms, such as a scientist developing cDNA libraries for studying the 13-stripe ground squirrel, Kane said. The process provides 3-prime cDNAs from any eukaryotic organism, taken from RNA samples, and then amplified by PCR.

Kane created and managed Pfizer’s core DNA microarray facility before joining Ann Arbor, Mich.-based Genomic Solutions as vice president of research and development. Then, after co-inventing Spanscript, he took the top executive position with start-up Trivera when it was spun off after Genomic Solutions reorganized.

Kane said he is hopeful of finding financing to further commercialize it through a $2 million fund that the state of Michigan just announced to support startup efforts from former Pfizer scientists who were laid off after the merger with Pharmacia.

With a novel technology in hand, but facing a dire funding environment, Kane illustrates well the challenges facing those attempting to commercialize microarray technologies.

He is not alone. Allen Northrup, president and CEO of Microfluidic Systems of Pleasanton, Calif., introduced RAIDDS (Rapid Integrated DNA/RNA Detection System), an integrated air collection, sample processing, and PCR detection system in a microfluidic platform that, apart from its lengthy name, looks very much like an office water cooler.

RAIDDS is seen as a system for the air monitoring of buildings and hotels, and will contain disposable microfluidics systems.

In the middle of his presentation, Northrup flashed a slide that described the product roadmap for his company, describing the path that the company is developing for biodefense applications that will help fund research into diagnostics products. Inserted into a corner of the image, a box: “Next generation microfluidics systems beyond pathogen detection — Proteomics.”

“To raise money these days, you have to have a proteomics slide; so there it is. We’ll do it when we have nothing left to do,” said Northrup, who knows well the challenges of fund-raising. He co-founded Cepheid in Sunnyvale, Calif., and there raised some $12 million in funding and grants for developing microfluidics bioassay sample processing and analysis systems.

Innovation

Following is a roundup of some of the other technologies presented at the conference:

Droplet-Based Bio Lab-on-a-Chip. Richard Fair, professor of electrical and computer engineering at Duke University, presented a novel system that utilizes electricity for dispensing, mixing, and transporting as small as 1 nanoliter droplets of fluids such as serum, plasma, and saliva. The system is based on an array of electrodes imbedded in an integrated circuit that moves liquids independently without using valves or pumps by leveraging the Electrowetting effect — the electrical control of surface tension.

Plastic Microarray Slides. Developed by STEAG microParts of Dortmund, Germany, in collaboration with Exiqon, Euray is a plastic DNA-array slide. The company says this polymer platform has low fluorescence, homogeneous spots, and has the capability for a greater number of integrated design features when compared to glass slides.

Carbon Nanotube Nanoelectrode Array for Ultrasensitive DNA Detection. Jun Li, senior research scientist in the Center for Nanotechnology, NASA Ames Research Center, presented research that concludes that vertically aligned carbon nanotubes can be used to create nanoelectrode arrays, which can be used to detect and measure DNA/RNA, protein antibodies/antigens, and whole cells. The process, developed at Ames, and funded in part by the National Cancer Institute, grows nanotubes by using microelectrodes, and then creates a silicon-based nanoscale array that is used in conjunction with electrochemical detectors for pathogens.

Whitehead Database V.3

The Whitehead Institute has a multidisciplinary team developing what Tom Volkert, the director of its microarray core facility, hopes will set new standards for microarray databases, ChipDB3.

Created on an Oracle platform, the web-accessible database will be based on the ArrayExpress scheme of EBI and will be MIAME compliant, including MAGE-ML compatibility, but with “a lot” of modifications in the database architecture, Volkert told BioArray News.

The driving force for the database is for publishing microarray-related data, he said.

“The data must be accessible for publication,” he said. “If [the database] isn’t available, it will be difficult to publish.”

It is already operational for in-house upload and download and will be available for public use in eight months, Volkert said.

The database allows the input of data from Affymetrix microarrays, something that the previous versions did not enable, and will satisfy a growing need at the core facility, which now processes as many GeneChip arrays as spotted arrays, he said. The database will also hold location analysis data (see Lab Report, page 6).

It will also integrate data derived from desktop PC software like Excel, OmniGrid, and GenePix; and will have the capability to track arrays by barcodes through an integrated LIMS system that automates data acquisition and storage layered on top of its previous ability to monitor array manufacturing and sample processing.

The Whitehead core has two GeneChip systems and runs eight chips at a time through fluidics for a throughput of 24 arrays a day. Volkert said the facility’s three workers manufacture as many as 15,000 arrays in a six-month period, using a Cartesian PixSys 5500 robot that can process 50 slides with up to 15,000 spots on each slide.

“Generating data is not hard,” said Volkert, “But sharing it, and using it is. For the technology, getting standards for databases and formats, and developing a consensus on how to analyze this data is the most important frontier we face.”

Considering CDNA or Oligos

Ernest Kawasaki, head of the microarray facility of the National Cancer Institute’s Advanced Technology Center, has spent almost half of his 18 months at the facility preparing the agency’s user base for a possible switch from cDNA-based arrays to 50- to 70-mer long-oligo microarrays. Much of the time has been spent comparing platforms, and plotting the statistical comparisons between Incyte cDNA, and Compugen/Operon platform long-oligo arrays of 70 mers.

Kawasaki said preliminary results indicate that the data from the oligo arrays are “as good or better” than that derived from cDNA arrays. The center is continuing its research.

— MOK

 

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