This slide includes approximately 2,000 combinations of eight enzymes used in human liver metabolism. To detect toxic drug compound reactions, the slide is “stamped” with a second slide of human organ cells. A microarray scan image of human cells in collagen-gel drops shows the determination of toxic drug reactions by the MetaChip. Green dots represent live cells and black dots (4th and 8th row) represent dead cells due to toxic drug metabolites. Photos by RPI/Moo-Yeal Lee and Jonathan Dordick

Recalls of popular prescription drugs are raising public concern about the general safety of new pharmaceuticals. A collaborative group of Rensselaer and other researchers says that identifying which drug candidates are toxic early in the discovery process can help prevent harmful pharmaceuticals from being placed on the market in the first place, and they have developed a tool to do it.

Researchers at Rensselaer, University of California-Berkeley, and Solidus Biosciences Inc. have developed a biochip, called the MetaChip, which can analyze drug candidates for toxicity and eliminate harmful ones before they advance to pre-clinical stages. Now beginning the second phase of funding for the National Institutes of Health (NIH)-supported project, researchers are working to optimize the technology for the end user: pharmaceutical and biotechnology companies. The researchers are working to bring the MetaChip to market within a year.

“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,” says Jonathan Dordick, the Howard P. Isermann ’42 Professor of Chemical and Biological Engineering at Rensselaer and co-founder of Solidus Biosciences. 

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. But some metabolites are toxic, and this toxicity can be difficult to predict or find at early stages of drug discovery with current testing methods.

Solidus Biosciences, a biotech company located at the Rensselaer Incubator for start-up businesses, recently received a $1.7 million, three-year award from NIH through its Small Business Technology Transfer Program to optimize the MetaChip for market. Rensselaer will receive approximately $500,000 as a sub-contractor of the award. The technology has been patented by Rensselaer and UC-Berkeley and licensed exclusively to Solidus Biosciences.

Dordick, UC-Berkeley partner Douglas Clark, and other collaborators published findings on the MetaChip in the Jan. 25, 2005 issue of Proceedings of the National Academy of Sciences in a paper titled “Metabolizing Enzyme Toxicology Assay Chip (MetaChip) for High-Throughput Microscale Toxicity Analyses.” The peer-reviewed publication defines the technology and results of testing in more detail.

Development of the MetaChip technology is part of several NIH-funded research projects at Rensselaer seeking more efficient ways to synthesize and identify compounds that merit further development as possible new drugs.

Read the press release.

Published December 12, 2005