Analysis and Comparison of Parallel Plate Flow Chambers to Determine Consistency of Fluid forces on Cells

Biological cells are constantly exposed to fluid forces inside the body. These fluid forces aid in certain physical and chemical reactions that cells need to maintain physiological function. To observe these forces in vitro, parallel plate flow chambers (PPFC) are used, where cells are placed inside the chamber and a fluid medium runs through the device exposing the cells to fluid forces to initiate a response. This has aided in proving that fluid forces influence cell function and are factors in various disease and physiological processes, such as the development of atherosclerotic plaque in blood vessels or bone growth. Many designs for PPFCs have been used for various types of flow and simulation protocols, such as computational fluid dynamics (CFD), have sometimes been used to determine flow characteristics and to model chamber performance under a specific use; however, nearly all of these chambers are modeled without the presence of biological cells. In this thesis, a CFD protocol was used (i.e., STAR-CCM+) to compare the fluid performance of the most commonly published PPFC designs and to determine how reliably they may expose cells to specifically controlled flow conditions. In addition to simulating the published conditions of each chamber, they were each simulated at a respective flow rate that theoretically yielded a shear stress of 10 dyne/cm2 in their flow channel. For all CFD models, a uniform mesh size of 100 µm was used and all CFD calculations were obtained through 1,000 iterations or until convergence occurred. Machining tolerance was also applied to one of the designs in order to observe the effects of machining inconsistencies that would not normally be modeled in an ideal simulation. In addition, this thesis simulated biological cells (endothelial cells) within an arbitrary parallel plate PPFC system, in order to determine the effects of their presence on parallel plate flow patterns. Shear stress and velocity distributions were calculated at 1 µm above the bottom surface of the flow channel and yielded similar distribution patterns across the test areas of the flow channels (i.e., area where cells are placed). In addition, the percentage of a consistent shear stress was calculated and found to be 97%, 81%, 36%, 98%, and 89%, respectively, across the test section of five commonly used PPFCs. The pressure along the length of each flow channel was also calculated and showed that each chamber has different levels of fluid pressure that biological cells are exposed to. It was also found that altering the height of chamber by 25 µm resulted in changes in shear stress that varied ±0.3 dyne/cm2 from the original height. The simulations of arbitrary PPFCs with the inclusion of biological cells proved that there is a significant variation of shear stress on the biological cells. Shear stress levels on the biological cells ranged from 50 to 250% of the target value (i.e., 10 dyne/cm2) and showed that what has been published by PPFC researchers has to be reassessed, since most publications presented results of simulations without biological cells. A better understanding of the fluid flow would help determine if this wide range of shear stress levels is acceptable to the particular biological cells being exposed. It would also aid in making improvements to PPFCs in order to more accurately simulate in vitro conditions. In designing these chambers and accurately analyzing them, biological cells must be included into the simulation as the exposure forces are different from the forces seen in a “clean” chamber that contains no cells. Utilization of CFD aided in providing numerical data for comparison of PPFC designs and allowed for a better understanding of the flow regions and how biological cells would be exposed to fluid forces. The results of this thesis reaffirmed the need to better understand the level, or range of levels, of shear stress and pressure that is needed in order to invoke a cellular response. In addition, there is a need to better understand the amount of surface area on a cell exposed to fluid shear that also invokes a cellular response, including the amount of the response. Finally, CFD can be used to optimize the design of a chamber so that the performance is reliable and meets the need of an individual, or general, application especially at the cellular level