Cell-culture automation shop Global Cell Solutions last month received a $71,630 Phase I Small Business Innovation Research grant from the National Science Foundation that it will use to develop a system to cryopreserve cells without needing to expand and culture the cells post-thaw.
If successful, GCS’ system could provide researchers with a greater number of uniform cell samples, thereby taking the cell-based assay industry one step closer to overcoming the challenges surrounding specimen variability.
“One challenge that the industry currently faces is the amount of cell culture that is required to do a high-throughput screening campaign,” Brad Justice, director of research for GCS, told CBA News this week. “It’s a limiting factor in terms of being able to run HTS equipment.”
Justice, who is the principal investigator for the SBIR grant, added that different facilities are rarely able to exactly replicate each other’s results, which means that additional work often needs to be done to control for the variability between two sites or between two experiments performed at the same site.
Data is meaningless if one cannot control for variability, Justice said.
GEM of a Substrate
Charlottesville, Va.-based GCS was spun out of the University of Virginia in 2004. The basis of its technology is the Global Eukaryotic Microcarrier microsphere, dubbed GEM, on which the cells are grown. The microsphere, which is less than 100 µm, has a curved face, compared with the flat format of a standard T-75 flask. The curved sphere forces cells into a 3D format, similar to that on which they would be grown in vivo.
In addition, the microsphere is made of porous alginates that allow the media to move through it, Justice said.
In doing so, alginates allow cells to receive nutrients from both the exterior surface, which would be facing the culture media, and the interior surface, which would be facing the substrate. Justice explained that this removes some of the polarity associated with 2D cell culture.
“We have done some validation work to show that cells grown on our microcarrier tend to display more of an in vivo phenotype,” Justice said.
Another feature of the GEM substrate is that it is embedded with magnetic particles, which makes the cell culture process more convenient to handle, said Uday Gupta, president and CEO of GCS.
The GEMs are magnetic, so GCS’ existing technology, the BioLevitator cell culture device, pulls them to the bottom, removes the media, and adds new media. Justice said that this automation removes both the inconsistency and the cost associated with having a technician do the cell culture.
According to Justice, the BioLevitator, which is completely self-contained, is about 18 inches wide and 8 inches deep. Cells can be grown on the GEM microspheres in the BioLevitator without the need for an incubator.
“One challenge that the industry currently faces is the amount of cell culture that is required to do a high-throughput screening campaign.”
The BioLevitator has the ability to create magnetic fields, which can be used to manipulate the microspheres to cool them down for media changes, said Justice. This field can also suspend the microspheres in the media and ensure that they are moving through the solution, he said.
GCS has been selling the GEM and BioLevitator technologies for more than 18 months, said Gupta, adding that a number of US and European drug makers have taken an interest in the technologies.
“The applications that our pharmaceutical and biotech clients are interested in … range from cell expansion for HTS, to human therapeutics, to basic academic research,” Gupta said. Their varied interests reflect the common challenges that cell culture scientists face in different subsegments of the industry, he added.
Ultimately, the goal of the SBIR grant, which begins on Jan. 1 and lasts six months, is to enable the cell expansion portion of the cell culture process to be performed on the substrate, said Justice. He said cells can be grown and frozen on the GEM, and customers can then purchase whole cell lots.
Researchers wanting to perform an HTS campaign could buy a validated cell lot from GCS for either a multiple timepoint study, multi-site study, or a single study at one site where the in-house cell culture facility cannot provide enough output to keep the cell culture equipment running, said Justice.
The grant, he said, will enable GCS to explore what kind of consistency it can get from these cell lots. Specifically, he said the company hopes to demonstrate that it can freeze large numbers of cells, thaw them out, and get the consistency required to use them in studies.
“We have noticed that the survivability of GCS’ cells post-thaw is higher than that of other cells out there,” Gupta told CBA News this week. In addition, the company is using its technology with cell lines that are more sensitive, difficult-to-grow, and difficult-to-preserve, yet can yield more relevant responses, he said.
“Many of the cell lines coming out of the labs these days require special media formulations and handling techniques,” Gupta said, adding that transferring techniques and knowledge between labs can be cumbersome. Consequently, if all of a cell line’s special requirements can be consolidated to a single site where the cells can be grown and then sold to other sites, those customers will not be required to train technicians on how to handle the cells.
Justice said that he will use the SBIR funding for salaries and buying consumables and cell lines. GCS hopes to apply sometime in 2008 for a Phase 2 grant that will focus on commercializing the system, he said.
In the meantime, Gupta said he “will be looking for additional partners to make these cryopreserved cells more accessible to the global pharmaceutical and biotech markets,” adding that he is already in discussions with several undisclosed potential partners.
In May GCS and fluid measurement systems company Hamilton, located in Bonaduz, Switzerland, announced plans to co-develop and market the BioLevitator and the GEM. The companies will incorporate the GEM technology and the BioLevitator on Hamilton’s STAR platform to completely automate the cell culture process.
GCS developed a 3D biology-based approach to cell culture and Hamilton plays in the automated cell culture-systems market. “We are combining these two strengths to develop solutions for our customers, such as 3D cell culture workstations,” Jörg Pochert, Hamilton’s director of pharma and biotech, told CBA News in an e-mail.
Pochert added, “GCS's technology has the potential to offer unparalleled convenience in manual and automated cell culture and first indications also show several biological advantages compared to standard 2D cell culture techniques.”
All the liquid handling required for cell culture will be done inside the fully automated cell-culture platform, called the CellSTAR 3D, Justice said. “You can turn out hundreds of millions of cells directly on a substrate from one benchtop platform that takes up maybe one to two square feet. You do not even have to remove them from the GEM to put them into, for example, a cyclic AMP assay,” he said.