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     May 12, 2008

      
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2008 May / June
praxis

Liver chips? Pass the dip!


Liver spots: To test new drugs and compounds, researchers use two slides: one dotted with liver enzymes, the other with cells from a particular organ. Safety is gauged by how the cells react with the liver metabolites. Live cells are green, dead ones red.

In less than a year, all cosmetics sold in Europe will have to be "cruelty-free—that is, developed without the use of animal testing. As the industry sweats over the new regulations, chemical engineering professor Douglas Clark, together with Jonathan Dordick of Rensselaer Polytechnic Institute and the team at Solidus Biosciences, the company Clark co-founded, are busy developing a solution.

The technology comes in two parts, which Clark and Dordick call the MetaChip and the DataChip, though the "chips" in this case are actually indistinguishable from the glass slides used in high school biology classes. Why DataChip then, instead of DataSlide? "Well, because that sounds better," says Clark.

The liver metabolizes drugs and, Clark says, is "essentially the body's first line of defense for clearing toxic compounds." The MetaChip is basically a "liver on a chip." To assemble this artificial liver, Clark's lab uses a machine called an arrayer to print about 3,000 dots of liver enzymes on a slide. The dots are evenly arrayed, like cookies on a baking sheet, and the chemicals to be tested are then layered upon the slide in the same pattern—one chemical or combination of chemicals for each dot. As in the human liver, chemical reactions ensue and new compounds, called metabolites, are created that, in turn, can inhibit or activate other enzymes.

That's where the DataChip comes in. It is designed to "approximate, as closely as we can, the response of the body to the compounds produced in the MetaChip," Clark explains. "Unfortunately, we sort of have to do this one organ at a time." The DataChip is stamped with human organ cells to be tested—the kidney, say—then sandwiched together with the MetaChip (the faux liver), so that the metabolites and the kidney cells can interact.

Toxicity is then measured by comparing the concentration of the chemicals to the percentage of cells that die. More specialized tests could measure signs of irritation or allergy. In addition to the immediate applications for drug development, Clark sees his chips eventually having a role in medicine. Physicians may one day use personalized MetaChips to tailor prescriptions to individual patients.

Clark admits that what happens in the body is more complicated than what transpires on his slides. But if he and his team can't replicate the entire system, he says, "hopefully we can replicate what's most important."




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