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While Protein Chips Not Quite Ready to Roll, Innovators Still Attracted to the Marketplace

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Opening the proteomics arrays session at the Lab Automation conference in Palm Springs, Calif., this week, session chair Douglas Gurevitch of UC San Diego warned presenters not to lean on the podiums — “they’re on wheels.”

He might have added that the warning does not apply to protein arrays themselves: the technology is not yet rolling into full-scale commercial use despite years of promise as tomorrow’s DNA array.

This may all change if Zyomyx is successful with the protein profiling biochip system that it officially launched this week. The system includes biochips, an automated workstation, a biochip reader, and data analysis software. The Hayward, Calif., company also has debuted a 30-cytokine profiling array.

But the experience of PerkinElmer, which debuted its ProteinArray workstation last September, may forecast a long adoption cycle for any company’s protein chip system. The ProteinArray workstation includes an automated reaction chamber that allows up to 48 protein array experiments to be conducted with the touch of a button. The company has also become a major provider of hydrogel substrates for do-it-yourself protein microarrays, and an arrayer tailored to spot proteins. “We have a full suite of products for running protein arrays,” Robert Cavallo of PerkinElmer Life Sciences said in his presentation to the conference.

While Cavallo told BioArray News that the ProteinArray Workstation has found a number of customers — especially in German, and in the UK — most of the customers are ones “who are developing their own assays,” he said. In other words, the market is still at an early-adopter phase.

PerkinElmer believes it will see the market for its system grow as some of these assay developers begin to market their assays, said Cavallo. The company is also working on its own assays, including a 43-spot cytokine profiling chip. The array, which PerkinElmer scientists are developing jointly with Ruo-Pan Huang of the Emory School of Medicine, uses a biotin-streptavidin sandwich assay to capture target cytokines, and can currently detect cytokines at concentrations down to 2-3 pg/ml, Cavallo said in his talk. The team, he added, is also working on a larger array that would include chemokines and other proteins as well.

The infant protein array market is not all bad news. For small-scale innovators, like Dhavi Gosalia, a doctoral student at the University of Pennsylvania’s Institute for Medical Engineering, it means there is still room, and time, to develop a breakthrough in protein arrays.

Gosalia described in his conference presentation enzyme microarrays that he has developed using no-frills technology. The arrays involve spotting libraries of up to 4,000 proteins, plus a glycerol buffer, onto a glass slide using a GeneMachines pin arrayer, then later spraying the sample that is being interrogated onto the chip, along with a fluorescent dye, with a piezoelectric aerosol. This aerosol technique, Gosalia said, results in no cross-contamination of the reaction sites on the chip, and less than a 15 percent CV between slides. Gosalia demonstrated one application of this technique, in which he first spotted thrombin and a number of other proteins onto the chip with the arrayer, then applied whole blood samples to see which proteins on the chip reacted with the blood. Gosalia said this assay could be adapted for various types of disease screening. Gosalia said he plans to publish a paper on it soon.

On the other end of the organizational size spectrum, Applied Biosystems is also getting into the protein array game before the market’s sewed up. Jaime Arenas of ABI spoke about a joint venture with HTS Biosystems of Hopkinton, Mass., to develop a protein array, the Applied Biosystems 8500 Affinity Array System.

The chip, which the companies have been jointly developing under a licensing agreement announced in April, uses a form of surface plasmon resonance (SPR) for high-throughput analysis of binding kinetics, Arenas said. SPR involves shining a laser onto a gold or similar chip substrate at the spot where the binding pairs will meet, then measuring the diffraction curve. A change in this curve indicates that two molecules have bound at the site.

While SPR has been in the protein array universe since Biacore introduced its four-spot SPR chip in the early 1990s, Arenas said this array is different: It has up to 400 different protein targets on its square-centimeter surface area. Also, unlike a traditional SPR, which takes place on a smooth surface, this array uses HTS’s grating-coupled SPR, a toothed surface, that couples the light to the gold substrate and substitutes for the prism.

The array is contained within a square-inch gold chip, which is assembled with a gasket to create a self-load chamber with an inlet and outlet, then is mounted onto a 1 x 3 inch slide, Arenas said.

ABI and HTS have also developed spotfinding software that compares the data from spots to reference points, and generates a table of binding constants for the various proteins being tested. ABI and HTS are still experimenting with various surface chemistries, including streptavidin coatings, and are working with collaborators from Dyax and the University of Utah.

This new array joins a crowded field of both SPR and traditional technologies that are in development.

While none of these has yet become the Affymetrix of protein chips, there is however, some indication that the technology is moving forward into biopharma.

— MMJ

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