Toxicology-on-a-Chip Improves Drug Safety

A new biochip can detect drug compounds that may cause toxic reactions in users, which will help keep them from being placed on the market, thereby improving drug safety at an early step in the drug discovery process.

The MetaChip (metabolizing enzyme toxicology assay chip) mimics the effects of metabolism in the human liver where enzymes break down, neutralize, and excrete chemicals from food and pharmaceuticals. In many cases, the metabolized chemicals, called metabolites, are harmless or even beneficial. However, some are toxic, and this toxicity can be hard to predict or find at early stages of drug discovery with current testing methods.

In the new process, drug candidates are added to a chip containing about 2,000 combinations of eight enzymes used in human liver metabolism and then sandwiched with a slide of human organ cells in order to detect toxic reactions to the compound. When toxic reactions are detected, the toxic drug compounds are eliminated as potential candidates for further development as new drugs. To quickly analyze the results, the researchers are working on an automated MetaReader device.

The MetaChip was developed by researchers at Rensselaer Polytechnic Institute (Troy, NY, USA), the University of California-Berkeley (USA), and Solidus Biosciences, Inc. (Troy, NY, USA). The work of the collaborators was reported in the January 25, 2005, issue of Proceedings of the [U.S.] National Academy of Sciences.

Solidus Bioscieces has received a U.S.$1.7 million award from the U.S. National Institutes of Health (Bethesda, MD, USA) to optimize the MetaChip for market. Rensselaer will receive about $500,000 as a sub-contractor of the award. The technology has been patented by Rensselaer Polytechnic Institute and the University of California-Berkeley and licensed exclusively to Solidus Biosciences.

"Compounds can be screened early, quickly, and effectively by the MetaChip to prevent toxic drugs from getting through the discovery process, being put on the market, and then getting recalled, such as we've seen with several high-profile cases recently,” said Jonathan Dordick, professor of chemical and biological engineering at Rensselaer and a co-founder of Solidus Biosciences.




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Rensselaer Polytechnic
Univ. of California-Berkeley
Solidus Biosciences