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Metrigenix Goes with the Flow: Develops Microfluidic Protein Chips, Universal Array


Gene Logic spinoff MetriGenix is spinning its novel microfluidic flow-through chip technology in two new directions: as a speedy, low-cost protein capture chip, and a universal nucleic acid array.

The first application comes out of a collaboration the company announced last week with Temple University in Philadelphia, using flow-through chips as parallel assays for calcium regulatory proteins involved in heart disease.

The second application is a straightforward licensing deal with Tm Biosciences of Toronto, in which Tm’s is non-exclusively licensing its universal array technology to MetriGenix in exchange for an undisclosed percentage of royalties on MetriGenix’s sales of universal array products.

These partnerships exemplify the Gaithersburg, Md., company’s strategy of finding collaborators to commercialize its second-generation microarray technology in areas not completely dominated by market-leader Affymetrix and a handful of others.

“We are looking at trying to find a number of partners with different expertises, so we can fully exploit the platform,” said MetriGenix CEO Drew O’Beirne. “We won’t be able to do it [alone] as a startup,” he added.

Even though the company raised $15 million in financing, it faces a reality common to many post-boom startups, that of having to reach the product stage without cash infusions from the public market.

MetriGenix core technology, its flow-through chip, involves a honeycomb surface of vertical microchannels. Probe molecules are attached to the inner walls of the microchannels, and sample is flowed through them. Infineon, a semiconductor spinoff of German electronics giant Siemens, is supplying the substrate, which is so dense that a million channels fit on a square centimeter, O’Beirne said. MetriGenix has developed the cartridge, the microfluidic engineering, and the surrounding instrumentation, in order to make the chip system, which it calls the 4D assay, as automated as a household appliance on “The Jetsons” cartoon. “All the user has to do is put the sample on the cartridge, push a button, and go have coffee,” O’Beirne said.

Also, in keeping with this Jetsonesque efficiency, the action of flowing the sample through the channels vastly speeds up hybridization or binding times. An assay can take less than an hour, according to O’Beirne.


Antibody Channels


The flow-through chip’s acceleration of the assay is potentially useful not only with DNA probes, but also with proteins, said Kenneth Margulies, the Temple researcher who is leading the project to develop the heart disease assays. The flow-through aspect “gives the array accelerated kinetics and advantages in sensitivity,” Margulies said.

Margulies, who is co-director of Temple’s cardiovascular research group, has selected monoclonal antibodies that he has previously isolated, as well as ones known to be implicated in heart disease, for the protein chips. The antibodies will be attached to the chips covalently using attachment chemistry that MetriGenix has patented, and binding will be detected using chemiluminescence. Margulies is planning to test out assays on 350 archived human myocardial samples to see if the array-based test has clinical utility.

“If the test does prove to be of clinical use, then we can make it commercially available,” said O’Beirne.

While MetriGenix has conducted internal proof-of-principle protein chip studies, Margulies still faces current technological obstacles that are not present with DNA applications of the technology, such as the fact that antibody-antigen binding conditions are not uniform

“One chip won’t be able to do 200 targets,” said Margulies. “Maybe we will have sets of fives that run under five conditions. Part of the development work is to find out what the wiggle room is and how many can be done in parallel.”

MetriGenix is supplying partial funding for the study. The rest comes from a supplement to an RO1 grant from the National Institute on Aging that called for researchers to use new technology in their existing research, Margulies said.


Universal Appeal?


For the universal nucleic acid array project, MetriGenix is planning to develop chips by the third quarter of this year.

These universal arrays involve 100 separate complementary linear pairs of tag and anti-tag primers. The anti-tags are attached to the insides of the microchannels, and the tags are attached to the target molecule during amplification.

Tm is also developing a system with 1,000 tag/anti-tag pairs, which MetriGenix also has committed to validating on its flow-through chip.

MetriGenix chose to partner with Tm because it saw an opportunity to produce “flexible, economical arrays that can be optimized for any gene sequence, O’Beirne said.


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