Start-up biotech Cellasic recently pocketed $240,000 in two Phase I Small Business Innovation Research grants from the National Cancer Institute to further develop its core microfluidics-based cellular analysis chip for in vitro cancer drug toxicity screening, CBA News learned this week.
The company will use the cash to fund proof-of-concept studies for the technology and to develop a prototype chip it hopes to begin selling to the academic research market by the end of this year, co-founder Philip Lee told CBA News.
In addition, if Cellasic successfully completes the phase I SBIR grants, it hopes to use the potential Phase II SBIR funding to build a higher-throughput version of the system that may have application in pharmaceutical screening, tissue engineering, stem cell research, and clinical diagnostics.
“With the toxicity screening application, you have to start changing the way the whole industry works, and that’s going to take years.”
Cellasic was founded last year by Lee and Paul Hung, former graduate students in the laboratory of Luke Lee (no relation), director of the Nanotechnology Center and associate professor of bioengineering at the University of California, Berkeley.
Under Luke Lee’s supervision, Philip Lee and Hung used proprietary high-aspect ratio soft lithography techniques to develop a 10-by-10-chambered microfluidic cell culture chip (see CBA News, 1/18/2005).
The microfluidic channels are interfaced with an industrial pneumatic device that continuously feeds nutrients to the cells growing on the chip while providing a gradient of chemical concentrations for dose-response testing. The cells are grown on the chip in such a way that their interactions closely mimic human tissue.
All of this is done in an effort to provide more relevant toxicity testing than can be achieved using isolated cells in culture dishes or well plates – which is generally how it is done in pharmaceutical companies.
“Toxicity screening is something that is generally believed to be inadequate at pharmaceutical companies,” he told CBA News. “Liver cells are a common toxicity screening cell line, and you want to have the cells behaving as they would in a human, ideally.
“The problem is that with current screening methods – even if you take primary cells from humans and put them in a dish – the cell behavior is not predictive,” Lee added. “That’s known because you can look at gene expression, and you can look at the cells’ activity. So you have to go to animal models and clinical trials, and these things are very costly.”
Cellasic was awarded a pair of Phase I SBIR grants from the NCI. One, entitled “Microfluidic system for automated cell toxicity screening,” is worth $105,000 over a six-month period; while the other, called “Continuous perfusion cell microarray for in vitro toxicity screening,” is worth $135,000 over five months.
Lee said that the projects are both based on the same core microfluidics technology. However, one is geared more toward general high-content cell-based research and screening applications while the other uses human hepatocytes in cell-based toxicity screens of cancer drugs.
“The first application we’re targeting is what we believe to be a more immediately addressable market,” Lee said. “With the toxicity screening application, you have to start changing the way the whole industry works, and that’s going to take years. General high-content screening applications [involve] less change in terms of the science.
Lee said that HCS technology currently boasts advanced optics and robotics, “but if you come down to the biological component, the cells are still sitting in these plastic dishes which, to me, is still pretty primitive. So the idea is to develop a better system to put the cells in to control their environment, and hopefully improve their behavior.”
He also said that both applications use a “pretty similar set of microfluidics technologies,” but that the hepatocyte toxicity screening chip has higher throughput and kinetic flow control.
“We believe that this perfusion environment – the way nutrients are delivered to cells, the local stress, and the cell density and contact with other cells – should be an important factor in preserving the behavior that you want,” Lee said.
In the Pack
Cellasic joins a group of start-up companies that are attempting to commercialize products for more relevant cell-based toxicity testing.
Perhaps the farthest along of these is Beverly Hills, Calif.-based Hurel, which has already snagged pharmas Schering-Plough and Johnson & Johnson as early-access partners in its quest to commercialize a microfluidics-based “human-on-a-chip” technology that approximates in vivo conditions for several important cell types in toxicity testing (see CBA News, 7/28/2006).
Just behind Hurel in terms of progress is Solidus, a company founded by professors from UC Berkeley and Rensselaer Polytechnic Institute. Solidus last year won a $1.8 million Phase II SBIR grant from the National Institutes of Health to bring to market its sol-gel microarray that contains human P450 isoforms that, when coupled with a cell monolayer, is designed to mimic the human liver without using actual hepatocytes (see CBA News, 12/26/2006).
“These are all different approaches” to the same end, Lee said, and the penetration of each technology into the market can only help the other technologies in the short term. “The biggest hurdle for this kind of technology is the adoption part,” he said.
For the rest of this year, Lee said, Cellasic will be evaluating the device internally “to make sure when you put the cells in there, they are doing what you want them to.” Lee and Hung also hope to develop an interface “that will connect the microfluidics part of these chips to the macro world,” which will make the chips usable in a real-world setting.
Most of this will be done on a small scale, but Cellasic plans to have a prototype chip designed for use in academic research by the end of the year, Lee said.
“We’ve been slowly working through academic channels to get feedback about how these devices perform, and what kind of issues a typical researcher will find in this kind of thing,” he said. “Once we get past that, we’ll start to do broader product-exploration type work. When we go into the second phase, if we get it approved, that will allow us to build up the entire instrument, and do more of a high-throughput screening system.”
One other important note about the technology, Lee said, is that Cellasic is designing it with broader applications in mind.
“We’re not just limited to toxicity screening or a specific market,” he said. “We potentially can address anything that uses living cells, and that’s sort of the broader vision of what we hope to accomplish.
“If you can look at cells, you can look at tissue engineering, stem cells, and even clinical diagnostics,” he added. “We are not immediately addressing those markets, but we believe the technology can find applications in those areas if we’re successful in this first step.”
Cellasic has applied for patents on its technology through the UC Berkeley technology-transfer office, from which the company would need to license the appropriate IP once awarded for further commercialization.