Researchers at Rensselaer Polytechnic Institute, University of California-Berkeley, and Solidus Biosciences Inc., have developed a biochip called the MetaChip, laden with approximately 2,000 combinations of eight human liver enzymes. The chip is essentially a micro toxicology lab to “analyze drug candidates for toxicity and eliminate harmful ones before they advance to pre-clinical stages”:
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.
“The relatively slow pace of technology development in toxicology and clinical safety evaluation that could be used in early phases of drug development continues to hinder the progression of lead compounds to pharmaceuticals,” Dordick says. “In addition to safety concerns, drug discovery is an extremely costly process with more than $1 billion invested in each approved drug. For the first time, the MetaChip can enable the initial and high-throughput analysis of metabolism-induced toxicology to be performed before significant resources are invested in the drug’s development.”
The MetaChip uses a culturing method by combining enzyme catalysis with cell-based screening on a single microscale chip. The drug candidates are added to a chip containing approximately 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 pharmaceuticals. The researchers are also working to develop an automated MetaReader device to quickly analyze the results.
Dordick, Clark, and 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.”
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