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Ciphergen s Phenomics Chip and Software Tech: New Biomarker Discovery Standard

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PALO ALTO, Calif.--Ciphergen Biosystems here coined the term phenomics to describe the combination of proteomics and phenotype analysis encompassed by two methods for finding novel markers for diseases using protein profiles rather than genetics. One approach focuses on standard 2-dimensional gels, while a new technology applies DNA-chips to proteomics. Ciphergen recently introduced protein chip technology, including database software and additional visualization software for mining protein data. From a small sample, Ciphergen's product isolates proteins, measures molecular weight, compares abundance, and feeds this data into a database on an NT workstation. Accompanying software allows researchers to compare protein profiles of diseased and healthy tissue to find novel markers.

According to Lars Barfod, the company's vice-president of sales and marketing, this technology could save researchers days of work, and has the advantage of being able to detect proteins from samples as small as 50-100 cells. "Our protein chip technology will eventually become the industry standard in biomarker discovery," Barfod contended.

Researchers can apply tissue directly to one of up to 24 one-millimeter spots on a protein chip array. Each chip is coated with a chemical surface or with receptors, antibodies, or enzymes for a specific protein type. After four wash steps, the chip goes into a mass reader about the size of a two-drawer file cabinet. A laser strikes the chip, breaking noncovalent bonds, and an electric field accelerates the freed proteins through the detector of a mass spectrometer. The smaller proteins are first to enter the spectrometer, which separates proteins by molecular weight.

This process, called surface enhanced laser desorption/ionization (SELDI), produces a spectrum of protein weight and abundance that is fed into a database on the NT workstation. Using bioinformatics software that Ciphergen provides with the product, researchers can analyze the database for differences between samples, such as normal or disease tissue, or for the series of wash steps that best separates a protein of interest from its cellular neighbors. When the wash steps are optimized to detect a specific protein, Barfod said, "it produces highly reproducible differences between samples."

Each array takes 20 minutes to process, though sifting through the data takes much longer. Ciphergen provides some visualization software which converts the SELDI data into the familiar gel form, but currently leaves it to customers' IT experts to develop more elaborate tools. Ciphergen is also looking for partners to help create additional software tools to mine protein databases for identifying markers.

Ed Galvin, head of Ciphergen's IT group, said protein data storage is now local, but that there are plans to store the data in a server. Although Ciphergen only provides phenomics database and software tools, Galvin said he sees a role for the technology in confirming mRNA studies. "mRNA systems tell researchers what to expect, then they can examine proteinchip data for peaks of that mass in appropriate cell types," he said.

Galvin said the company wrote demonstration software that allowed researchers to conduct queries across protein and mRNA databases. The problem, he said, is that the mRNA database is unique to the experiment, so the software does not work in all systems. The next set of tools, beyond better visualization, will pull out significant phenomic data and make it understandable, Galvin said.

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