Study of hydrodynamics in microcarrier culture spinner vessels: A particle tracking velocimetry approach

The potential of hydrodynamic damage to animal cells of industrial relevance: current understanding

“…Early reports of microcarrier culture also suggest that if the culture is not excessively mixed, it is possible that cells can migrate from microcarrier to another while the microcarriers remain suspended (Crespi and Thilly 1981) Therefore, the hydrodynamic sensitivity in this case is really a question of what hydrodynamic forces are needed to remove a cell attached to a surface. It is interesting to note that the experimentally estimated EDR that started to remove CHO cells from microcarriers in a spinner vessel (Venkat et al 1996), is the same order of magnitude level of EDR that removes cells from microcarriers when the suspended microcarriers are passed through a flow contraction device (Ma et al 2002). In addition, they reported that the levels of laminar shear stress (N/m 2 ) that begins to metabolically effect animal cells corresponds to similar levels of EDR as reported to remove CHO cells from microcarriers.…”

“…In contrast, endothelial cells (EC), which in their native state line the walls of arteries and veins, have been extensively studied, and a large number of non-lethal effects from hydrodynamic forces have been well documented. While a summary of all of the EC response to these forces is beyond the scope of this review, the responses of EC to shear stress include rearrangement of cytoskeleton, activation of molecules at the luminal cell surface such as kinases, integrins, and G proteins, and up and Agitation Volume average energy dissipation rate in typical animal cell culture bioreactors Varley and Birch (1999) 2 Agitation Volume average energy dissipation rate in a 10L mixing vessel (Rushton Turbine impeller, 700 RPM) Zhou and Kresta (1996a) 3 Agitation Maximum local energy dissipation rate in a 10L mixing vessel (Rushton Turbine impeller, 700 RPM) Zhou and Kresta (1996a) 4 Agitation Volume average energy dissipation rate in a 22,000L fermentor (Rushton Turbine impeller, 140 RPM) Wernersson and Tragardh (1999) 5 Agitation Maximum local energy dissipation rate in a 22,000L fermentor (Rushton Turbine impeller, 140 RPM) Wernersson and Tragardh (1999) 6 Agitation Maximum local energy dissipation rate in a spinner vessel Venkat et al (1996) 7 Bubble rupture Pure water (bubble diameter: 6.32 mm) Garcia-Briones et al (1994) 8 Bubble rupture Pure water (bubble diameter: 1.7 mm) Boulton-Stone and Blake ( down regulation of a number of genes and signaling cascades (Li et al 2005). It is hypothesized that a number of these mechanisms might also be applicable to cells cultured in suspension.…”

“…It is important to note, however, that this inhibitory effect of rpm was typically observed on VERO or CHO cell attached to microcarriers (Hirtenstein and Clark, 1980;Croughan et al 1987Croughan et al , 1989Papoutsakis 1988, 1989;Venkat et al 1996). These results led to a perception by some people that suspension animal cell culture in a large scale, typically agitated and sparged bioreactor was considered to be unpractical.…”

Influence of hydrodynamic shear stress on microcarrier-attached cell growth: Cell line dependency and surfactant protection

“…The hydrodynamic shear stress could inhibit culturing of anchorange-dependent cells on microcarriers [1], since the cells adhering to microcarrier surface are less robust to disperse¯uid-mechanical forces than the freely-suspended single cells. Fluid-mechanical damages incurred on microcarriergrown cells have been investigated based on the Kolmogorov isotropic turbulence model [1], turbulent/impeller collision severity [2], and three-dimensional particle tracking velocimetry [3]. However, determining and applying the detailed¯uid mechanic patterns (particular for the local shear stress distribution around microcarrierattached cells) for industrial bioreactor cultivation are extremely dif®cult [4].…”

Comparisons of microcarrier cell culture processes in one hundred mini-liter spinner flask and fifteen-liter bioreactor cultures

“…The fact that the suspension-type bioreactor vessels are scalable accounts for why the microcarrier process has been successfully applied to mass-produce viral vaccines [2±4]. However, the performance of the microcarrier cell culture process in large bioreactor vessels is generally less prominent than with spinner vessels and bench scale reactors due to limited understandings of the complex behaviors in large reactors [5,6]. In this study we investigated the microcarrier process in 100 ml spinner¯ask and 15-liter bioreactor cultures.…”