(230ay) Modeling of Ultra-High Density Bio-Reactor

Ultra High Density well plates are one of the leading concepts using small foot print formats towards culture of large number of cells. In this presentation, we present a CFD model for modeling the fluid flow characteristics for a single pit and orifice of an ultra- high density well plate bioreactor. An analytical tool was developed based on the principle of conservation of energy to estimate the minimum velocity needed to dislodge the biological cell spheroids from the pits. The design changes from the CFD model were suggested based on the criteria of increasing the fluid velocities in the pit to increase convective mass transfer along with retaining the spheroids inside them. Some of the designs concepts tested appear to be feasible, thereby presenting the scope of improvement for this particular cell culture device. Another challenge in the design of Ultra High Density bioreactors is air-entrapment in the pit of the bioreactor. This phenomenon which is known as â??air lockâ?? can be detrimental to the functionality of the bioreactor as the entrapped air prevents complete filling of the pits with culture media. We have developed a transient two-dimensional computational fluid dynamics model to analyze the effect of UHD pit geometry, pit wall surface energy, and filling rate on air-entrapment. Through modeling, we identified conditions that allow us to completely fill the pits with culture media and calculated the amount of time that is required to fill the pit. Our analysis showed that making the pit surface hydrophilic and therefore decreasing surface energy, is an efficient means to ensure complete filling of the pits and reduce the time of filling. This modification can also make steeper pit wall designs work which usually show severe air entrapment issues.