(470b) Incorporating Computational Fluid Dynamics into the Study of Cell Damage Due to Hydrodynamic Stress in Bioreactors and Pumps

With the ever growing health care market, the demand for cost-effective systems for the cultivation of various types of animal cells continues to grow. Recently, the sub-field of “cell therapy” has demonstrated significant growth which presents unique demands on the market: instead of the cells making products, the cells are the product. Since the product is the cell, which is hygienically and nutritionally more sensitive than the other products in the health care market, greater regulatory restrictions as well as specific cellular functions are needed which create greater demands on bioprocessing. For this study, the hydrodynamic stress imposed upon the growing cells in bioreactors and pumps will be investigated, focusing on the interaction between rotating impeller and the Chinese Hamster Ovary (CHO) cells. A commercial blood pump, which supports hemodynamic stabilization, was connected to a standard 3L bioreactor to run CHO cells at 1100, 1600, 2200 and 3000 RPM for 10 days, while the LDH level, viable cell density and cell size were measured to quantify the cell damage. Computational fluid dynamics (CFD), which employs finite element method to solve numerical flow dynamics problems, was used to simulate the experimental condition for comparison with the experimental data. Energy dissipation rate (EDR) was calculated using post-CFD translation software inside the pump to quantify and visualize the cell damage. Furthermore, a 3-D printer will be incorporated to test the feasibility of 3-d printing the blood pump and the rotor. While the change in blood pump’s RPM appeared to have no effect on the LDH level and cell size, an increase in RPM from 2200 to 3000 resulted in a significant drop in viable cell density. Therefore, the simulation data of 2200 and 3000 RPM was further investigated to compare the EDR values between the two rates. Based on the histogram analysis, the two rate showed similar energy dissipation rate distribution except for the region between 10⁴ – 10⁵ W/m³, which is in agreement with the reported literature values. Use of post-CFD translation software allows users to visualize the user-defined variable (EDR), and the visual analysis pointed our attention to the escape neck area of the blood pump, where high EDR values were reported for both 2200 and 3000 RPM. After analyzing the results, we have come to a conclusion that different geometrical design of escape neck area might lead to less damaging blood pump. Therefore, the geometry of the pump was recreated in the 3 dimensional computer-aided design to be 3-D printed, and the product that displayed the same physical characteristic was made, showing the feasibility of incorporating 3d printing into the further study. There are several advantages for incorporating CFD and 3-D printing into the study of cell damage due to hydrodynamic stress. It is relatively straight forward to design/modify current pump designs, simulate them with CFD, potentially modify the design, and then actually produce a pump with a 3-D printer. This easy, iterative process will allow researchers in the field of health care to develop medical device involving flow with limiting resources. Furthermore, accurate description of the stress interaction between the impeller blades and the growing cell will benefit significant number of bioprocesses involving shear-sensitive cellular materials. The bio-industry will be able to design their product or process with less damage on cells, which will lead to more efficient process and benefit both the health care industry and the customers.