(471h) Particle Dynamics in a Rotating Wall Vessel Bioreactor

Rotating bioreactors such as the High Aspect Ratio Vessel (HARV) provide a low shear and gentle mixing environment, ideal for mammalian cell culture in 3D. The HARV is a cylindrical ?disc-shaped? batch culture vessel with no internal moving parts, that rotates about a single axis. Oxygenation is provided by a permeable silicon rubber membrane, allowing the passive exchange of gases to and from the medium [1]. Cell culture in this bioreactor may be carried out by encapsulating cells within hydrogel particles. In our lab, tissue engineering from Embryonic Stem cells is of interest, and this has been implemented by inoculating the vessel with cells that have been previously encapsulated within Calcium alginate particles [4] (Figure 1).

For a single spherical particle moving in the HARV, it has been shown that particle motion may be affected by: density difference between particle and fluid, vessel rotation rate and particle radius. Particles denser than the fluid medium (heavy) migrate outwards towards the vessel wall, whereas particles that are less dense (light) migrate towards its centre [2]. In this study, a mathematical model describing the motion of a single particle has been developed. The model is 2-dimensional, and takes into account weight, buoyancy, drag, and Centrifugal forces, and is formulated in the rotating frame of reference [see also 3].

It has been found that a light particle spirals towards and orbits the vessel's centre and the heavy particle migrates towards the vessel's wall. Each individual loop traced out by the particle corresponds to a revolution of the vessel. The light particle's speed oscillates for a very short period and then settles to a constant value, whereas for the heavy particle, the speed constantly increases.

References:

1. Pollack SR. Meany DF. Levine EM. Litt M. Johnston ED. (2000). Numerical model and experimental validation of microcarrier motion in a rotating bioreactor. Tissue Engineering 6(5): 519-30.

2. Gao H. Ayyaswamy PS. Ducheyne P. (1997). Dynamics of a microcarrier particle in the simulated microgravity environment of a rotating-wall vessel. Microgravity Science and Technology, X/3, 154-165.

3. Kessler JO. (1992). The Internal Dynamics of Slowly Rotating Biological Systems. ASGSB Bulletin 5(2): 11-21.

4. Randle WL. (2006). Bone Tissue Engineering from Embryonic Stem Cells. PhD Thesis, Imperial College London.

Figure 1. Murine Embryonic stem cells encapsulated within a Calcium alginate bead [4]