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

Venkat, Raghavan; Stock, Louis R.; Chalmers, Jeffrey J.

doi:10.1002/(sici)1097-0290(19960220)49:4<456::aid-bit13>3.0.co;2-8

Cited by 48 publications

(8 citation statements)

References 22 publications

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“…The observed MC transport form the outer part of the vessel to the vessel center was mainly driven by the induced secondary flow, previously discussed in Section 3.1. Similar findings were also reported by Berry et al [31], Liovic et al [28], and Venkat et al [43] in other types of small scale spinner flasks.…”

Section: Resultssupporting

confidence: 90%

Growth Behavior of Human Adipose Tissue-Derived Stromal/Stem Cells at Small Scale: Numerical and Experimental Investigations

et al. 2018

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Human adipose tissue-derived stromal/stem cells (hASCs) are a valuable source of cells for clinical applications, especially in the field of regenerative medicine. Therefore, it comes as no surprise that the interest in hASCs has greatly increased over the last decade. However, in order to use hASCs in clinically relevant numbers, in vitro expansion is required. Single-use stirred bioreactors in combination with microcarriers (MCs) have shown themselves to be suitable systems for this task. However, hASCs tend to be less robust, and thus, more shear sensitive than conventional production cell lines for therapeutic antibodies and vaccines (e.g., Chinese Hamster Ovary cells CHO, Baby Hamster Kidney cells BHK), for which these bioreactors were originally designed. Hence, the goal of this study was to investigate the influence of different shear stress levels on the growth of humane telomerase reversed transcriptase immortalized hASCs (hTERT-ASC) and aggregate formation in stirred single-use systems at the mL scale: the 125 mL (=SP100) and the 500 mL (=SP300) disposable Corning® spinner flask. Computational fluid dynamics (CFD) simulations based on an Euler–Euler and Euler–Lagrange approach were performed to predict the hydrodynamic stresses (0.06–0.87 Pa), the residence times (0.4–7.3 s), and the circulation times (1.6–16.6 s) of the MCs in different shear zones for different impeller speeds and the suspension criteria (Ns1u, Ns1). The numerical findings were linked to experimental data from cultivations studies to develop, for the first time, an unstructured, segregated mathematical growth model for hTERT-ASCs. While the 125 mL spinner flask with 100 mL working volume (SP100) provided up to 1.68 × 105 hTERT-ASC/cm2 (=0.63 × 106 living hTERT-ASCs/mL, EF 56) within eight days, the peak living cell density of the 500 mL spinner flask with 300 mL working volume (SP300) was 2.46 × 105 hTERT-ASC/cm2 (=0.88 × 106 hTERT-ASCs/mL, EF 81) and was achieved on day eight. Optimal cultivation conditions were found for Ns1u < N < Ns1, which corresponded to specific power inputs of 0.3–1.1 W/m3. The established growth model delivered reliable predictions for cell growth on the MCs with an accuracy of 76–96% for both investigated spinner flask types.

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Section: Resultssupporting

confidence: 90%

Growth Behavior of Human Adipose Tissue-Derived Stromal/Stem Cells at Small Scale: Numerical and Experimental Investigations

et al. 2018

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“…Specifically, at an EDR greater than 10 3 W/m 3 , CHO cells bound to 175 μm Cytodex® 3 microcarriers (Pharmacia Fine Chemicals, Piscataway, NJ) were sheared away from the microcarriers (Gregoriades et al, 2000). This is consistent with estimates of EDR made by Venkat et al (1996) who removed CHO cells, attached to microcarriers, as a result of the physical agitation in a spinner vessel. Given that a typical islet is about 150 μm across, it is plausible to assume that this same level of EDR, roughly 10 3 W/m 3 , will disaggregate the constituent cells of an islet.…”

Section: Introductionsupporting

confidence: 89%

Effects of energy dissipation rate on islets of Langerhans: Implications for isolation and transplantation

Shenkman

Godoy-Silva

Papas

et al. 2009

Biotech & Bioengineering

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Acute physical stresses can occur in the procurement and isolation process and potentially can contribute to islet death or malfunction upon transplantation. A contractional flow device, previously used to subject suspended cells to well-defined hydrodynamic forces, has been modified and used to assess the vulnerability of porcine islets of Langerhans to hydrodynamic forces. The flow profiles and velocity gradients in this modified device were modeled using commercial CFD software and characterized, as in previous studies, with the scalar parameter, energy dissipation rate (EDR). Porcine islets were stressed in a single pass at various stress levels (i.e., values of EDR). Membrane integrity, oxygen uptake rate, caspase 3/7 activity, and insulin release were not affected by the levels of fluid stress tested up to an EDR of 2 × 10 3 W/m 3 . Visual observation of the stressed islets suggested that cells at the islet exterior were peeled away at EDR greater than 10,000 W/m 3 , however, this observation could not be confirmed using image analysis software, which determined the ratio of surface perimeter to total area. The result of this study suggests an upper limit in fluid stress to which islets can be subjected. Such upper limits assist in the design and operation of future islet processing equipment and processes.

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“…It is certainly not fully turbulent or "completely turbulent" as suggested by Sucosky et al (2004). A more reasonable expression might be "moderately turbulent" (Venkat et al 1996). Thus, there are a number of difficulties in addressing the problem via turbulence theory.…”

Section: Resultsmentioning

confidence: 99%

Expansion of human mesenchymal stem cells on microcarriers

et al. 2011

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

Cited by 48 publications

References 22 publications

Growth Behavior of Human Adipose Tissue-Derived Stromal/Stem Cells at Small Scale: Numerical and Experimental Investigations

Growth Behavior of Human Adipose Tissue-Derived Stromal/Stem Cells at Small Scale: Numerical and Experimental Investigations

Effects of energy dissipation rate on islets of Langerhans: Implications for isolation and transplantation

Expansion of human mesenchymal stem cells on microcarriers

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