Effect of baffle structure on flow field characteristics of orbitally shaken bioreactor

Lu, Zhiming; Li, Chengtuo; Fei, Liangqi; Zhang, Hongliang; Pan, Yong

doi:10.1007/s00449-020-02469-4

Cited by 7 publications

(5 citation statements)

References 20 publications

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“…Among the unbaffled variants, TS yielded comparable results to bottom-baffled flasks. It would be interesting to investigate whether a combination of the cylindroconical design and the integration of baffles as investigated by Lu et al would lead to a further improvement (Lu et al 2021 ). While several flask designs showed suitability, the application of WAF as substrate in the microwell scale is much more challenging.…”

Section: Discussionmentioning

confidence: 99%

Workflow for shake flask and plate cultivations with fats for polyhydroxyalkanoate bioproduction

Riedel,

Donicz,

Ferré-Aparicio

et al. 2023

Appl Microbiol Biotechnol

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Since natural resources for the bioproduction of commodity chemicals are scarce, waste animal fats (WAF) are an interesting alternative biogenic residual feedstock. They appear as by-product from meat production, but several challenges are related to their application: first, the high melting points (up to 60 °C); and second, the insolubility in the polar water phase of cultivations. This leads to film and clump formation in shake flasks and microwell plates, which inhibits microbial consumption. In this study, different flask and well designs were investigated to identify the most suitable experimental set-up and further to create an appropriate workflow to achieve the required reproducibility of growth and product synthesis. The dissolved oxygen concentration was measured in-line throughout experiments. It became obvious that the gas mass transfer differed strongly among the shake flask design variants in cultivations with the polyhydroxyalkanoate (PHA) accumulating organism Ralstonia eutropha. A high reproducibility was achieved for certain flask or well plate design variants together with tailored cultivation conditions. Best results were achieved with bottom baffled glass and bottom baffled single-use shake flasks with flat membranes, namely, >6 g L-1 of cell dry weight (CDW) with >80 wt% polyhydroxybutyrate (PHB) from 1 wt% WAF. Improved pre-emulsification conditions for round microwell plates resulted in a production of 14 g L-1 CDW with a PHA content of 70 wt% PHB from 3 wt% WAF. The proposed workflow allows the rapid examination of fat material as feedstock, in the microwell plate and shake flask scale, also beyond PHA production. Key points • Evaluation of shake flask designs for cultivating with hydrophobic raw materials • Development of a workflow for microwell plate cultivations with hydrophobic raw materials • Production of polyhydroxyalkanoate in small scale experiments from waste animal fat Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

Workflow for shake flask and plate cultivations with fats for polyhydroxyalkanoate bioproduction

Riedel,

Donicz,

Ferré-Aparicio

et al. 2023

Appl Microbiol Biotechnol

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“…CFD is already routinely used for STRs with great success to calculate mixing times and inhomogeneities, the k L a, gas hold-up, volumetric power input and shear stress 3 – 13 . In contrast, CFD applications for small scale, shaken bioreactors, such as microtiter plates 14 – 18 and shake flasks 19 – 22 , are scarce in the scientific literature. Zhang et al used a CFD model for shake flasks to calculate the volumetric power input and k L a for a variety of shaking parameters 19 .…”

Section: Introductionmentioning

confidence: 99%

Validation of computational fluid dynamics of shake flask experiments at moderate viscosity by liquid distributions and volumetric power inputs

Dinter,

Gumprecht,

Menze

et al. 2024

Sci Rep

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Computational fluid dynamics (CFD) has recently become a pivotal tool in the design and scale-up of bioprocesses. While CFD has been extensively utilized for stirred tank reactors (STRs), there exists a relatively limited body of literature focusing on CFD applications for shake flasks, almost exclusively concentrated on fluids at waterlike viscosity. The importance of CFD model validation cannot be overstated. While techniques to elucidate the internal flow field are necessary for model validation in STRs, the liquid distribution, caused by the orbital shaking motion of shake flasks, can be exploited for model validation. An OpenFOAM CFD model for shake flasks has been established. Calculated liquid distributions were compared to suitable, previously published experimental data. Across a broad range of shaking conditions, at waterlike and moderate viscosity (16.7 mPa∙s), the CFD model's liquid distributions align excellently with the experimental data, in terms of overall shape and position of the liquid relative to the direction of the centrifugal force. Additionally, the CFD model was used to calculate the volumetric power input, based on the energy dissipation. Depending on the shaking conditions, the computed volumetric power inputs range from 0.1 to 7 kW/m3 and differed on average by 0.01 kW/m3 from measured literature data.

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“…For scalable production of cell products, it is better to establish a dynamic 3D culture system with enhanced dissolved oxygen content in the medium to improve cellular energy metabolism and expansion potential 19,20 . Several studies have indicated that disposable orbital rotary bioreactors with baffled‐flow enable large‐scale production of mammalian suspension cell cultures 21,22 . Therefore, it is valuable to evaluate whether such a dynamic culture system with baffled flasks and an orbital rotator can improve the manufacture of MKs derived from hESCs.…”

Section: Introductionmentioning

confidence: 99%

“… 19 , 20 Several studies have indicated that disposable orbital rotary bioreactors with baffled‐flow enable large‐scale production of mammalian suspension cell cultures. 21 , 22 Therefore, it is valuable to evaluate whether such a dynamic culture system with baffled flasks and an orbital rotator can improve the manufacture of MKs derived from hESCs.…”

Section: Introductionmentioning

confidence: 99%

Baffled‐flow culture system enables the mass production of megakaryocytes from human embryonic stem cells by enhancing mitochondrial function

Zhang

Chen

et al. 2023

Cell Proliferation

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Human embryonic stem cells (hESCs) have become an ideal cell source for the ex vivo generation of megakaryocyte (MK) and platelet products for clinical applications. However, an ongoing challenge is to establish scalable culture systems to maximize the yield of stem cell‐derived MKs that release platelets. We defined a specific dynamic 3D manufacturing system in a baffled‐flow manner that could remarkably facilitate megakaryopoiesis and increase the yield of platelet‐producing MKs from hESCs within a 12‐day induction period. Additionally, an increased number of >16N ploidy MKs, proplatelets, and platelets were generated from induced cells harvested on Day 12 using the specific dynamic culture method. The specific dynamic culture method significantly enhanced endothelium‐to‐haematopoietic transition and early haematopoiesis. More importantly, MK fate was significantly facilitated in a specific dynamic manner during early haematopoiesis. Mechanistically, this dynamic culture significantly enhanced mitochondrial function via the oxidative phosphorylation pathway and caused differentiation skewing of hESCs toward megakaryopoiesis. This study can aid in the automatic and scalable production of MKs from stem cells using baffled‐flow bioreactors and assist in the manufacturing of hESC‐derived MK and platelet products.

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Effect of baffle structure on flow field characteristics of orbitally shaken bioreactor

Cited by 7 publications

References 20 publications

Workflow for shake flask and plate cultivations with fats for polyhydroxyalkanoate bioproduction

Workflow for shake flask and plate cultivations with fats for polyhydroxyalkanoate bioproduction

Validation of computational fluid dynamics of shake flask experiments at moderate viscosity by liquid distributions and volumetric power inputs

Baffled‐flow culture system enables the mass production of megakaryocytes from human embryonic stem cells by enhancing mitochondrial function

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