Photographs of the rotating disc bioreactor. (a) The bioreactor array prior to installation into a cell culture incubator. (b) Installed bioreactor with fixed vessels containing culture solutions with seeded EL-4 cells.

Relationship between fluid shear stress and location at the RDB vessel base. Compuational simulation of shear stresses calculated at the vessel base with respect to distance away from centre axis, expressed as the ratio of base radius () to the impeller disc radius ()(Pa = pascal). The term “dimple” represents the small dome-shaped manufacturing artefact observed in the centre all RDB disposable vessels, representing a nonideal boundary.

Effect of stirring rate on cell growth in bioreactors. Graph of the biomass increase of EL-4 cell colonies after culture in stirred rotating bioreactors at a range of rotational speeds, compared to no rotation.

Lactate production in bioreactor cultures. Graph of lactate production by EL-4 colonies after culture in rotating disc bioreactors with stirring (Re = 600) or without stirring, compared to values of static flask cultures. Bars represent the means of 3 experimental groups; error bars represent standard error of the mean; the asterisk pertains to .

Schematic of the rotating disc bioreactor. Diagrammatic representation of the prototype rotating disc bioreactor rig designed for mammalian cell culture.

Computational modeling of fluid flow patterns in the RDB. (a) Cross sectional streamlines emanating from fluid surface in the vicinity of the fluid surface, demonstrating a laminar flow vortex pattern. (b) Simulated trajectory of a single semibuoyant particle (an idealized cell aggregate) moving passively in response to flow in the meridional direction. (c) Three-dimensional simulation of the same particle from (b) after having been seeded near the fluid surface, and coming to rest passively near the RDB vessel centre.

Micrographs of bioreactor cultures. (a) Base of a sector of an RDB bioreactor vessel following culture of EL-4 cells (without impeller agitation). EL-4 cells are dispersed across the surface as irregularly shaped plaques, with plaques merging into more confluent, continuous layers centrally (C) and along the circumferential edge (E), near the vessel side-wall. Intervening plaques located closer to the sidewall appear more focal punctate (FP) compared to more centrally located flattened discoid plaques (FD). (b) Base of a bioreactor vessel following culture of EL-4 cells with impeller agitation. Adherent plaques are larger discoid plaques, predominantly located centrally (C) and circumferentially (E), with a larger confluent tumor-like plaque with similarly smooth and flattened discoid appearance. (c) Magnified image of the central aggregate or “tumor” appearing in (b) showing a discoid, opaque colony with smooth edges. The centre of the plaque appears transparent due to a central dimple (manufacturing artefact) located on the plastic surface, a manufacturing artefact of the vessel over which a type of attenuated monolayer is visible (M). (d) Image of EL-4 aggregates of variable size, as viewed within a static tissue culture flasks. (e) Magnified image of EL-4 spheroid aggregates and disaggregated single cells contained on a hemocytometer slide, showing that spheroids are comprised of a homogeneous colony of densely packed, adherent cells. Scale bar = 10 mm (a)–(d) and 0.25 mm (e).

Cell growth in bioreactors versus standard vessels. Graph of biomass increase in EL-4 colonies after culture in rotating disc bioreactors with stirring (Re = 600) or without stirring, compared to values of static flask cultures. Bars represent a mean of 6 experimental groups; error bars represent standard error of that mean.

Cytokine production in bioreactor cultures. Graph of interleukin-4 production by EL-4 colonies after culture in rotating disc bioreactors with stirring (Re = 600) or without, compared to values of static flask cultures. Bars represent the means of 3 experimental groups; error bars represent standard error of the mean; the asterisk pertains to .