PREDICTIVE NUMERICAL MODEL FOR OPTIMAL DELIVERY OF OXYGEN IN A NOVEL CELL EXPANSION BIOREACTOR

BACKGROUND

SwRI staff members recently developed a scalable cell expansion bioreactor prototype to facilitate a simple process of expanding 10,000-fold more cells than that of the traditional flask-based process. The success of the new prototype bioreactor system relies on optimal deliveries of oxygen to sustain cell growth on bioreactor walls. Preliminary experiments with the SwRI bioreactor suggested that a linear inflow rate inside the bioreactor is critical for oxygen deliveries to cells. The optimal inflow rate needs to be determined to assess the maximum performance of the SwRI bioreactor and sustainable cell growth. A 3D pore-scale numerical model that operates exclusively with measurable parameters can circumvent experimental costs and time in determining the optimal inflow rate required for more efficient oxygen deliveries across the bioreactor to maximize the cell growth on bioreactor walls. Development of such a 3D model was crucial to increase the winning chance of the targeted Advanced Regenerative Manufacturing Institute (ARMI) solicitation, in which ARMI RFP requires that the prototype (bioreactor) be suitable for use in verification and validation of critical design features of the final project deliverable. This would be possible with the help of a versatile 3D modeling capability.

APPROACH

As part of IR&D project 18-R8602, SwRI staff members developed 2D advective-diffusive transport based on the lattice-Boltzmann method (2D ADT-LB) model and validated it with benchmark problems. As part of IR&D project 18-R8833, 2D ADT-LB was upgraded to 3D ADT-LB for 3D oxygen transport simulations. Then, 3D ADT-LB was upgraded to the 3D ADRT-LB model to account for oxygen adsorption on bioreactor walls. In the 3D ADRT-LB model, oxygen adsorption on the walls was represented as a sink process. In this process, when dissolved oxygen adsorbs onto bioreactor walls, it is permanently removed from the total dissolved oxygen mass in the system. The adsorption processes was implemented in the bounce-back scheme of the LB method, in which only certain fraction, λ, of the concentration populations (in LB terms) bounce back from solid walls into the fluid, but the rest would adsorb onto walls. Here, λ=k/N, in which k is the experimentally determined adsorption rate and N is the number of links, extends from a fluid node in the computational cell to the adjacent solid nodes occupied by bioreactor wall surfaces.

ACCOMPLISHMENTS

A new 3D numerical model (3D-ADRT-LB) was successfully developed to simulate advective and diffusive transport of oxygen in the actual geometry of the bioreactor scaffold and oxygen adsorption on bioreactor walls. Simulations are numerically stable regardless of the range of realistic flow rates, flow domain geometry, and experimentally determined transport parameters. The 3D-ADRT-LB model is suitable for validation and verification of the performance of the customized bioreactor designs with diverse geometric peculiarities and optimization of bioreactor design for maximum cell growth. The new model and simulation results successfully supported SwRI’s ARMI proposal, which was submitted on May 14, 2018. The proposal was awarded on June 8, 2018, with a budget of $1.88 million for two years. As of October 16, 2018, the ARMI project has not been set up or kicked off. SwRI staff members are planning to leverage the 3D-ADRT-LB model with further upgrades for forthcoming National Institutes of Health and Department of Defense solicitations.