SBIR-STTR Award

This Small Business Innovation Research Phase I project describes the development of a disposable, highly efficient suspension bioreactor for primary hematopoietic (blood cell-forming) cell culture. The unique challenges (heterogeneous nature, donor variability, and shear-sensitivity) of these cultures leave traditional flask or suspension cultures unable to consistently produce sufficient quantities of cells. In Phase I, small scale experiments will guide a redesign of a suspension system to better accommodate hematopoietic cultures. The first objective is to balance the requirements of oxygen transfer with shear sensitivity by using novel mixing protocols. Second, the biocompatibility, mechanical integrity, and fouling characteristics of several perfusion membranes will be examined. Third, a low-cost monitoring system using disposable pH and DO probes will be developed. In Phase II, a large-scale prototype will be constructed and tested under a wide range of conditions. The final product will be a system that combines the simple, disposable nature of flask culture with the control and monitoring capabilities of a suspension bioreactor. The resulting system will enable the cost-effective production of large numbers of primary hematopoietic cells and will improve the effectiveness and decrease the cost of medical procedures in the fields of transplantation, immunotherapy, and gene therapy.

This Small Business Innovation Research Phase II project describes the development of a disposable, highly efficient suspension bioreactor for primary hematopoietic (blood cell-forming) cell culture. The unique challenges (heterogeneous nature, donor variability, and shear-sensitivity) of these cultures render traditional flask or suspension cultures unable to economically and consistently produce large quantities of cells. In Phase I, the feasibility and characteristics of a disposable suspension bioreactor was demonstrated. In Phase II, a scaled-up prototype of a large, agitated disposable bioreactor designed for clinical use (stem cell transplantation) will be constructed, characterized, and tested for reliability and durability. Gas and mass transfer correlations established in Phase I will be verified and extended. The use of medium optical density as a surrogate measure for cell density will be investigated. The final product will be a system that combines the simple, disposable nature of flask culture with the control and monitoring capabilities of a suspension bioreactor. The resulting system will enable the cost-effective production of large numbers of primary hematopoietic cells and will improve the effectiveness and decrease the cost of medical procedures in the fields of transplantation, immunotherapy, and gene therapy.