Study of hydrodynamics in wave bioreactors by computational fluid dynamics reveals a resonance phenomenon

Zhan, Caijuan; Hagrot, Erika; Brandt, Luca; Chotteau, Véronique

doi:10.1016/j.ces.2018.08.017

Cited by 41 publications

(23 citation statements)

References 30 publications

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“…After the rocking frequency was further elevated to 40 rpm, the laminar flow was no longer observed even in the middle region of the bag and the liquid showed a vigorous turbulent behavior. As recently reported, the Reynolds number can oscillate with time over a broad range in a single rocking cycle (Zhan et al, ). This indicates that there can exist several patterns of flow during a single rocking cycle, which distinguishes the wave bioreactor significantly from other types of bioreactors when it comes to engineering characterizations.…”

Section: Resultsmentioning

confidence: 62%

“…Therefore, the cross‐sectional area perpendicular to the liquid flow direction can be further reduced to a rectangular shape in the definition of Reynolds number. This is similar to the definition based on hydraulic diameter proposed by Eibl et al () with simplifications to make

italicRe

easier to determine, but different from the

italicRe

proposed by Marsh et al () or Zhan et al () who selected a different characteristic length, namely the length of the bag (

L

). The characteristic velocity (

c

) in the Reynolds number is the linear phase velocity of the wave (described below), and therefore the final form of Reynolds number in this study is given in following equation:

Re = \frac{c ∙ r_{normalh}}{v} .

…”

Section: Mass Transfer Model Developmentmentioning

confidence: 63%

“…These values were relatively lower than the calculated linear phase velocity in this study (Equation ), which could be possibly due to differences in liquid loadings and bag geometry. Zhan et al () reported in their CFD simulation that the center line liquid velocity fluctuated between 0.05 and 0.4 m/s with an averaged value of approximately 0.25 m/s using 30 rpm and 7° rocking conditions with 5 L loading in a 10 L bag. In this study, the predicted value at 30 rpm and 8° with 5 L loading in a 10 L bag yielded a value of 0.49 m/s, which was similar to their maximum but approximately double their averaged velocity.…”

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

A mechanistic model for gas–liquid mass transfer prediction in a rocking disposable bioreactor

Bai

Moo‐Young

Anderson

2019

Biotech & Bioengineering

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Rocking disposable bioreactors are a newer approach to smaller-scale cell growth that use a cyclic rocking motion to induce mixing and oxygen transfer from the headspace gas into the liquid. Compared with traditional stirred-tank and pneumatic bioreactors, rocking bioreactors operate in a very different physical mode and in this study the oxygen transfer pathways are reassessed to develop a fundamental mass transfer (k L a) model that is compared with experimental data. The model combines two mechanisms, namely surface aeration and oxygenation via a breaking wave with air entrainment, borrowing concepts from ocean wave models. Experimental data for k a L across the range of possible operating conditions (rocking speed, angle, and liquid volume) confirms the validity of the modeling approach, with most predictions falling within ±20% of the experimental values. At low speeds (up to 20 rpm) the surface aeration mechanism is shown to be dominant with a k a L of around 3.5 hr −1 , while at high speeds (40 rpm) and angles the breaking wave mechanism contributes up to 91% of the overall k a L (65 hr −1 ). This model provides an improved fundamental basis for understanding gas-liquid mass transfer for the operation, scale-up, and potential design improvements for rocking bioreactors.

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Section: Resultsmentioning

confidence: 62%

italicRe

easier to determine, but different from the

italicRe

proposed by Marsh et al () or Zhan et al () who selected a different characteristic length, namely the length of the bag (

L

). The characteristic velocity (

c

) in the Reynolds number is the linear phase velocity of the wave (described below), and therefore the final form of Reynolds number in this study is given in following equation:

Re = \frac{c ∙ r_{normalh}}{v} .

…”

Section: Mass Transfer Model Developmentmentioning

confidence: 63%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

A mechanistic model for gas–liquid mass transfer prediction in a rocking disposable bioreactor

Bai

Moo‐Young

Anderson

2019

Biotech & Bioengineering

View full text Add to dashboard Cite

show abstract

“…The shear stress in the fermentation broth is not just a function of the shear rate of mixing; an increasing viscosity drastically changes the shear stress conditions to which the cells are exposed [36,37]. Therefore, the shear forces in S. clavuligerus fermentation broths were expected to exceed the values reported for Newtonian fluids at similar agitation conditions in STR and single-use reactors [22,29,35].…”

Section: Discussionmentioning

confidence: 98%

“…Previous studies have shown that S. clavuligerus can be cultivated in STR reactors at mixing velocities up to 800 rpm without compromising cell viability [33,34]. In contrast with STR, it has been widely reported that shear forces in rocking and wave reactors are considerably lower than those arising in reactors with axial or orbital agitation [29,35], which is also in agreement with our results considering the calculated maximum shear stress ranging between 0.06 and 0.63 Pa. For the sake of comparison, the typical shear stress for water as a fluid model in wave reactors is in the range of 0.01 to 0.1 Pa at agitation rates from 15 to 30 rpm [29,35]. The shear stress in the fermentation broth is not just a function of the shear rate of mixing; an increasing viscosity drastically changes the shear stress conditions to which the cells are exposed [36,37].…”

Section: Discussionmentioning

confidence: 99%

Characterization of the Metabolic Response of Streptomyces clavuligerus to Shear Stress in Stirred Tanks and Single-Use 2D Rocking Motion Bioreactors for Clavulanic Acid Production

et al. 2019

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Streptomyces clavuligerus is a gram-positive filamentous bacterium notable for producing clavulanic acid (CA), an inhibitor of β-lactamase enzymes, which confers resistance to bacteria against several antibiotics. Here we present a comparative analysis of the morphological and metabolic response of S. clavuligerus linked to the CA production under low and high shear stress conditions in a 2D rocking-motion single-use bioreactor (CELL-tainer ®) and stirred tank bioreactor (STR), respectively. The CELL-tainer® guarantees high turbulence and enhanced volumetric mass transfer at low shear stress, which (in contrast to bubble columns) allows the investigation of the impact of shear stress without oxygen limitation. The results indicate that high shear forces do not compromise the viability of S. clavuligerus cells; even higher specific growth rate, biomass, and specific CA production rate were observed in the STR. Under low shear forces in the CELL-tainer® the mycelial diameter increased considerably (average diameter 2.27 in CELL-tainer® vs. 1.44 µm in STR). This suggests that CA production may be affected by a lower surface-to-volume ratio which would lead to lower diffusion and transport of nutrients, oxygen, and product. The present study shows that there is a strong correlation between macromorphology and CA production, which should be an important aspect to consider in industrial production of CA.

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Computational fluid dynamics analysis of mixing and gas–liquid mass transfer in wave bag bioreactor

Svay

Urrea

Shamlou

et al. 2020

Biotechnology Progress

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Single use bioreactors provide an attractive alternative to traditional deep-tank stainless steel bioreactors in process development and more recently manufacturing process. Wave bag bioreactors, in particular, have shown potential applications for cultivation of shear sensitive human and animal cells. However, the lack of knowledge about the complex fluid flow environment prevailing in wave bag bioreactors has so far hampered the development of a scientific rationale for their scale up. In this study, we use computational fluid dynamics (CFD) to investigate the details of the flow field in a 20-L wave bag bioreactor as a function of rocking angle and rocking speed. The results are presented in terms of local and mean velocities, mixing, and energy dissipation rates, which are used to create a process engineering framework for the scaleup of wave bag bioreactors. Proof-of-concept analysis of mixing and fluid flow in the 20-L wave bag bioreactor demonstrates the applicability of the CFD methodology and the temporal and spatial energy dissipation rates integrated and averaged over the liquid volume in the bag provide the means to correlate experimental volumetric oxygen transfer rates (k L a) data with power per unit volume. This correlation could be used as a rule of thumb for scaling up and down the wave bag bioreactors.

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Study of hydrodynamics in wave bioreactors by computational fluid dynamics reveals a resonance phenomenon

Cited by 41 publications

References 30 publications

A mechanistic model for gas–liquid mass transfer prediction in a rocking disposable bioreactor

A mechanistic model for gas–liquid mass transfer prediction in a rocking disposable bioreactor

Characterization of the Metabolic Response of Streptomyces clavuligerus to Shear Stress in Stirred Tanks and Single-Use 2D Rocking Motion Bioreactors for Clavulanic Acid Production

Computational fluid dynamics analysis of mixing and gas–liquid mass transfer in wave bag bioreactor

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