Startup biotech Solidus Biosciences has been awarded a three-year Phase II Small Business Technology Transfer grant worth approximately $1.8 million from the National Institutes of Health to support the commercialization of MetaChip, its so-called toxicology-on-a-chip tool, a company official said last week.
In addition, the company will use the money to develop a full toxicology/drug-discovery platform, complete with incubation and imaging components, to use with MetaChip, Solidus co-founder Jonathan Dordick told CBA News last week. There is no timeline yet, however, for the full commercial release of the MetaChip or for the development of a chip reader, tentatively dubbed MetaReader.
Rensselaer Polytechnic Institute, which will receive approximately $500,000 as a sub-contractor of the award, announced the grant earlier this month. Dordick is a professor of chemical and biological engineering at RPI.
Solidus won Phase I of the grant — worth $500,000 — in 2004 under a special NIH program on innovative toxicology models. That grant supported Solidus' founding and the initial development of a prototype version of MetaChip.
MetaChip essentially mimics the human liver in an in vitro setting for conducting relatively high-throughput toxicity testing. It is an alternative to animal toxicity testing, gene microarrays, or toxicity assays using human hepatocytes, which is the most similar type of test because it uses live cells.
"We could either partner with an instrument manufacturer or bring expertise in house. It's not a huge endeavor because device development is a pretty mature industry."
The chip consists of a sol-gel microarray containing one or more human P450 isoforms that generate biologically active metabolites of a candidate compound. The volume of the sol-gel spots can be varied from five to 100 nanoliters and arrayed in various ways.
Researchers can add a compound to the sol-gel spots, then "sandwich" a slide with a cell monolayer onto the array. After incubating the cells and allowing them to react with P450 metabolites, researchers could then remove the cell slide, stain the cells, and determine the percentage of dead cells using essentially any type of commercial scanner or microscope.
Currently, the product only consists of the chip and embedded enzymes. However, Solidus anticipates offering a full instrumentation system with the chip at least as an option.
"We envision providing the P450 chip and the cell chip," Dordick said. "The researchers would use this device to array their molecules on the entire chip, incubate them with the cells, do a quick staining, image the cells, and then, of course, there would be some software component involved."
The device, Dordick said, would encompass many of the things that get done in individual steps in toxicity screening.
"Given the number of steps that are needed, a typical 96-well or 384-well format is not really conducive to this type of study," he said. "However, pharma will use something like a 384-well format to introduce the compounds to the cells," which would be compatible with something like MetaReader.
Dordick added that Solidus' initial talks with potential pharma beta-testers of the MetaChip have netted mixed feedback about whether scientists would prefer a full turn-key system, or just a chip — although Dordick said that signs are pointing toward a full system.
"We could put the parts of it together — but whether we build it or not, we don't know yet," Dordick said, the 'we' referring to his partner and Solidus co-founder Douglas Clark, a professor of chemical engineering at the University of California, Berkeley. "We could either partner with an instrument manufacturer or bring expertise in house. It's not a huge endeavor because device development is a pretty mature industry."
The next important step for Solidus in getting the MetaChip to market is validating that results obtained with the tool are compatible with the types of results researchers would get using in vivo studies.
"Ultimately, in vitro-in vivo correlations are going to be crucial," Dordick said.
Earlier this year, Dordick and Clark published their first major validation of MetaChip in the Proceedings of the National Academy of Sciences. In that proof-of-principle paper, Solidus demonstrated how the MetaChip prototype could be used in combination with a breast cancer cell line to accurately mimic the activation of the anticancer drugs Cytoxan and Tegafur, as well as generate cytotoxic metabolites from acetaminophen (see CBA News, 3/1/2005).
Now, Solidus is turning its attention to providing more physiologically relevant models. Dordick said that the company is currently preparing another paper for publication that will show how the efficacy of MetaChip can be enhanced by using 3D cellular models.
In this case, Dordick said, the cell culture volumes would be reduced down to between 10 and 30 nanoliters, and arrayed in a 3D format in some sort of commercially available gel medium.
"This is likely to be more representative of how the cells would interact with the enzyme and other cells in an in vivo system," Dordick said. "I'm not saying that 2D systems aren't useful — in some cases they correlate very well with in vivo systems — but in this case the 3D system may be a better choice."
In fact, Dordick said, Solidus would continue to work with 2D systems, and the first product would likely be such a configuration.
Solidus has also initiated talks with pharmaceutical companies about beta-testing, which Dordick said will likely begin to pick up steam in the summer of the coming year. This will also aid in the validation process, he said, because pharmas may be able to pull out compounds that were clearly failures in later stages for toxicity reasons, and then bring them back for testing on MetaChip to verify the reasons for failure.
— Ben Butkus ([email protected])