The objective of this project is to demonstrate the feasibility of a novel approach to culturing cells in order to precisely determine their response to environmental changes. This approach will allow for rapid optimization of culture conditions so that expression of a desired biochemical can be maximized. In contrast to chemostat culture where our experience has demonstrated that 10-20 days are required in order to achieve a new steady state after culture conditions are perturbated, this new approach will allow new steady states to be achieved in a matter of hours. The advantage of greatly reduced time constants when examining multivariable situations such as cell culture systems are great. In fact, without this improvement, thorough exploration of cell-culture kinetics is impossible. The central component of this approach is the CentriCell, an integrated system for the culture of cells, which has been invented by Verax personnel. The theory behind the system is that centrifugal force is used in balance with a counter medium flux dry force in order to fluidize a slurry of cells. The apparatus design permits quick changes in the cells' environment. Consequent alterations of the cells' physiology can be observed with existing assay methods. Use of the CentriCell in Verax's continuing research program promises to reduce greatly the cost of manufacture of pharmaceutical proteins. In addition, the Company is patenting the CentriCell concept and intends to make it available to cell biologists through the auspices of a major laboratory-equipment supply house. Phase I will demonstrate concept feasibility with a bread-board model. Phase II, if granted, will utilize the CentriCell in an extensive research program involving the optimization of hybridoma and mammalian cell cultures for minimum cost of manufacture of pharmaceutical proteins.
