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ViaLogy Releases a Second Validation Test For Affymetrix Platform; Other Chips to Follow

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ViaLogy has the results in hand of a second validation study of its technology, conducted for Affymetrix, and the results are encouraging, an executive of the company told BioArray News this week.

The study results, presented to Affymetrix in early June, show improved results in reproducibility, higher sensitivity, and lower false negatives with the same or better false positive rate in analyzing data derived from Affymetrix’s GeneChip platform and its software.

“We call it software PCR,” said Bud Bromley, who is vice president for business development for ViaLogy, a 14-employee Pasadena, Calif.-based company spun off from ViaSpace Technologies, a technology commercialization company operated by the NASA/Caltech Jet Propulsion Laboratory.

“PCR doesn’t go away,” Bromley said. “You still have to do RT-PCR to validate the genes, but PCR shifts from [doing] every sample to validating genes that look interesting.”

ViaLogy’s technology is based on stochastic resonance and quantum interferometric computing techniques — developed in aerospace research —which amplify signals to enable the detection and quantification of hybridization events that other technologies might not detect due to background noise.

Public release of the study was approved by Affymetrix but with the qualification that it is not to be considered an endorsement of ViaLogy’s platform by the company.

Services Offering

ViaLogy is early into commercializing its technology, which it offers on a services-only basis, available online or by mail. Users pay $5,000 for a set-up fee for a new format or for user-spotted arrays, but for catalog arrays already registered in the software, it’s $250 for each file analyzed through the VMAxS service. Raw files are uploaded to ViaLogy’s server, re-processed to enhance the signal-to-noise ratio, analyzed, and then returned to the user, formatted for the next step in informatics.

In the Affymetrix study, Via-Logy applied its analysis to a set of blinded results from Affymetrix.

The data came from 30 U133A GeneChip experiments, from 21 spike-in experiments, and also nine endogenous tissue experiments.

“There were large numbers of present calls that were not called present or even seen on the Affymetrix analysis,” said Bromley of the experiment. “Put it this way, there was a very large improvement in false negative performance and relatively no difference in false-positive performance versus the Affymetrix standard software. And, a 70-percent improvement in precision CVs.”

The technology will be tested on the standard BioConductor GeneLogic solution series and the Affymetrix Latin Square test suite, Bromley said.

Other Platforms

ViaLogy is not limiting its analysis to the Affymetrix platform. The company is also collaborating with Witterswill, Switzerland-based Zeptosens. Qiagen has been working to optimize the mRNA extraction, purification, and labeling protocols for Zeptosens’ SensiChip DNA microarrays, which are available only in Europe, while Zeptosens has been working on optimizing sensitivity of the chips themselves. The companies have reported that the combination of technologies enables them to detect mRNA levels from as few as 1,000 cells with reproducible results.

The Zeptosens SensiChip array is based on planar waveguide technology, which creates a thin layer of light above the chip surface to excite only fluorophores bound to the surface of the chip, while leaving those in solution dark — thus decreasing background fluorescence, and in doing so enabling users to skip enzymatic amplification steps.

Bromley said that analysis of data from the Zeptosens platform, processed through ViaLogy, has detected signal from 10 nanograms of total RNA from a sample of 1,000 cells without amplification, a limit of quantitation, but can detect at 20 picograms from that same sample, he said.

The company is also planning to apply its technology to Agilent’s microarray platform, but is waiting on the No. 2 player to release a new format for its files. That application is expected to be available by late July.

The technology’s limitation is in the spot-finding software, which must be able to zero-in on a spot in order to function automatically.

Spots on pre-printed arrays are easy to find, while home-brews are more abstract in spot location.

“We use the noise to find and quantitate the signal,” said Bromley. “We are looking for disturbances in the noise to tell us where the signal is and how much is there. It’s an event detector.”

Bromley, who sold the first spotted microarray technology to SmithKline Beecham, when he was vice president of sales and marketing for Molecular Dynamics, said that overall, the preprinted microarray industry has created a tool that is good at capturing hybridization.

“We have gone back and looked at archived files, and the reproducibility is very good,” he said. “The [hybridization] events are being captured by Affymetrix and almost all the other chips, but the event is not being captured by the software out there.”

And while the ViaLogy application is showing things that other applications haven’t, he said the proof is in RT-PCR validations, such as those done in the Affymetrix study, which is available on the ViaLogy website at http://www.vialogy.com/press/corp_prarch.html.

—MOK

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