Proliferation Characteristics of CHO-K1 cells Upon Microfluidic Media Flows

Abstract

In the microfluidic perfusion culture, flow rate is one of the most important modulator to control cell behaviors and functions based on mass transports and on hydrodynamic shear stress exerted on cells [1-3]. In this study, we investigated the proliferation characteristics of CHO-K1 cells under a variety of flow rate conditions. Microwell-type three-dimensional cell culture compartments were adopted in order to minimize and/or to isolate the flow effects on cells in the compartments. Pillar-array type microfilter was introduced both at entrance and at exit to keep uniform seeding densities in each compartment by preventing cell loss out of compartments during cell seeding process. In order to predict hydrodynamic properties of fluid flow based on culture well dimensions, three-dimensional (3D) finite element simulation was used. Based on diffusion velocity of growth factor, seven conditions of flow rate were determined, and physical properties of extracellular environment around the culture well corresponding to the flow rate were established. Under the perfusion culture, the proliferation rate and morphological changes of CHO-K1 cells were observed and compared. As a result, when NDV (non-dimensional velocity) is 500 (media residence time is 4.4 s), their proliferation rate was significantly promoted. The proposed chip and experimental results described here offer a useful platform and information for culturing CHO-K1 cells in perfusion culture.