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The commercial success of mammalian cell-derived recombinant proteins has fostered an increase in demand for novel single-use bioreactor (SUB) systems that facilitate greater productivity, increased flexibility and reduced costs (Zhang et al., 2010). These systems exhibit fluid flow regimes unlike those encountered in traditional glass/stainless steel bioreactors because of the way in which they are designed. With such disparate hydrodynamic environments between SUBs currently on the market, traditional scale-up approaches applied to stirred tanks should be revised. One such SUB is the Mobius® 3L CellReady, which consists of an upward-pumping marine scoping impeller. This work represents the first experimental study of the flow within the CellReady using a Particle Image Velocimetry (PIV) approach, combined with a biological study into the impact of these fluid dynamic characteristics on cell culture performance. The PIV study was conducted within the actual vessel, rather than using a purpose-built mimic. PIV measurements conveyed a degree of fluid compartmentalisation resulting from the up-pumping impeller. Both impeller tip speed and fluid working volume had an impact upon the fluid velocities and spatial distribution of turbulence within the vessel. Cell cultures were conducted using the GS-CHO cell-line (Lonza) producing an IgG4 antibody. Disparity in cellular growth and viability throughout the range of operating conditions used (80–350rpm and 1–2.4L working volume) was not substantial, although a significant reduction in recombinant protein productivity was found at 350rpm and 1L working volume (corresponding to the highest Reynolds number tested in this work). The study shows promise in the use of PIV to improve understanding of the hydrodynamic environment within individual SUBs and allows identification of the critical hydrodynamic parameters under the different flow regimes for compatibility and scalability across the range of bioreactor platforms.

In the present work an effort is made to determine the suspension speed of microcarriers in an orbitally shaken bioreactor of cylindrical geometry, and to assess the associated two-phase flow by means of Particle Image Velocimetry (PIV). Microcarrier technologies are commonly used in the bioprocess industry to culture adherent-dependent cells in three dimensional flow. Commercial GE Cytodex microcarriers were employed throughout this study to best mimic the flow conditions occurring in a bioreactor under standard operating conditions. Suspension speed measurements were obtained at different solid concentrations, that are typical for cell cultures, and for different combinations of orbital to cylinder diameters’ ratio, d o / d i ( c = 2.5–12.5 g/L; d o / d i = 0.2–0.7; N = 0–200 RPM). The current two-phase PIV results show that mean flow dynamics occurring in the cylindrical bioreactor are not significantly affected by the presence of the microcarriers, and that their suspension is directly associated to the flow transition reported by Weheliye et al. (2013) . The flow scaling law included in their study can be successfully employed to predict the full suspension speed across bioreactors of different scales and working under different operating conditions (i.e. inner diameter of the cylinder, d i , orbital diameter, d o , and filling volume, V f ).