On the measurement and scaling of mixing time in orbitally shaken bioreactors

Rodriguez, G.; Anderlei, Tibor; Micheletti, Martina; Yianneskis, M.; Ducci, Andrea

doi:10.1016/j.bej.2013.10.021

Cited by 53 publications

(66 citation statements)

References 34 publications

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“…From this figure, the advantages of using the ratio Fr=Fr c are evident, as all the datasets tend to collapse on each other irrespective of the Re, and a single curve can be identified, aiding a more effective scaling of the turbulent kinetic energy between cylindrical bioreactors of different sizes and using different working fluids. These results help to explain the findings of Rodriguez et al, 18 who compared mixing time data obtained in different laboratories for cylindrical bioreactors of different sizes and operating in different conditions, and concluded that bioreactors mixing performances can be scaled if the mixing number NT m , is plotted against Fr=Fr c . Their data show that mixing number is nearly constant for Fr=Fr c !…”

Section: The Variation Ofsupporting

confidence: 74%

“…To better compare the datasets obtained at different Re and overcome their differences in terms of transitional Fr c , a turbulent kinetic energy scaling methodology based on the ratio

F r / F r_{normalc}

is proposed in Figure b. This normalization proved to be effective as the curves associated to the different Re collapsed on each other, and can help to explain the nearly constant mixing number obtained by Rodriguez et al for

F r / F r_{normalc} \geq 1.4

.…”

Section: Discussionmentioning

confidence: 99%

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Orbitally shaken bioreactors—viscosity effects on flow characteristics

Ducci

Weheliye

2014

AIChE Journal

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Phase-resolved particle image velocimetry measurements were carried out to assess the flow dynamics occurring in orbitally shaken bioreactors of cylindrical geometry when working fluids of increasing viscosity are considered. Study of the phase-resolved flow characteristics allowed to built a Re-Fr map, where four quadrants associated to different flow regimes are identified: in-phase toroidal vortex (low Fr and high Re), out-of-phase precessional vortex (high Fr and high Re), in-phase single vortex (low Fr and low Re), out-of-phase counter-rotating toroidal vortex (high Fr and low Re). Turbulence levels are found to be significant only in the top right quadrant (high Fr and low Re) and scaling of the turbulent kinetic energy obtained with fluid of varying viscosity is obtained using the ratio of the operating Froude number to the critical Froude number associated to the mean flow transition, Fr=Fr c . Estimates of the mean flow strain deformation as well as of the flow dissipative scale are provided, while a comparison is made between the flow circulation times obtained for different regimes.

show abstract

Section: The Variation Ofsupporting

confidence: 74%

“…To better compare the datasets obtained at different Re and overcome their differences in terms of transitional Fr c , a turbulent kinetic energy scaling methodology based on the ratio

F r / F r_{normalc}

F r / F r_{normalc} \geq 1.4

.…”

Section: Discussionmentioning

confidence: 99%

Orbitally shaken bioreactors—viscosity effects on flow characteristics

Ducci

Weheliye

2014

AIChE Journal

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“…The conventional experiments performed in shaken flasks contribute to the knowledge of the operational conditions necessary to achieve the correct degree of mixing or the oxygen quantity needed in biochemical reactions. The main parameter considered in most studies is the rotational speed, which itself does not quantify other important engineering parameters as the oxygen mass transfer [9,10], the specific power consumption [11,12] or the hydromechanical stress [13][14][15] As mentioned before, the specific power consumption has been used as key parameter for scaling up of growing culture processes [16]. Besides the power drawn, the influence of the flask geometry on the hydrodynamic performance should be also considered for scaling up purposes.…”

Section: Introductionmentioning

confidence: 99%

A hydrodynamic description of the flow behavior in shaken flasks

Mancilla

Palacios-Morales

Córdova-Aguilar

et al. 2015

Biochemical Engineering Journal

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“…Mitigating the greater noise that resulted from the optical effects led to the simple moving average (SMA) of the normalized standard deviation

((), σ ((), G_{i, j}^{*}))

of the red channel being used for analysis of the mixing time. Noise levels in plots of the SMA of the

((), σ ((), G_{i, j}^{*}))

were still too high to determine the specific point at which 95% mixing was obtained as per Rodriguez et al Therefore, an automated method of determining the frame at which mixing had started and a semi‐automated method of calculating the point at which the SMA of the

((), σ ((), G_{i, j}^{*}))

plateaued were utilized.…”

Section: Resultsmentioning

confidence: 99%

Electromagnetic stirring in a microbioreactor with non‐conventional chamber morphology and implementation of multiplexed mixing

Tan

Davies

McCluskey

et al. 2015

J of Chemical Tech & Biotech

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BACKGROUNDMicrobioreactors have emerged as novel tools for early bioprocess development. Mixing lies at the heart of bioreactor operation (at all scales). The successful implementation of micro‐stirring methods is thus central to the further advancement of microbioreactor technology. The aim of this study was to develop a micro‐stirring method that aids robust microbioreactor operation and facilitates cost‐effective parallelization.RESULTSA microbioreactor was developed with a novel micro‐stirring method involving the movement of a magnetic bead by sequenced activation of a ring of electromagnets. The micro‐stirring method offers flexibility in chamber designs, and mixing is demonstrated in cylindrical, diamond and triangular shaped reactor chambers. Mixing was analyzed for different electromagnet on/off sequences; mixing times of 4.5 s, 2.9 s, and 2.5 s were achieved for cylindrical, diamond and triangular shaped chambers, respectively. Ease of micro‐bubble free priming, a typical challenge of cylindrical shaped microbioreactor chambers, was obtained with a diamond‐shaped chamber. Consistent mixing behavior was observed between the constituent reactors in a duplex system.CONCLUSIONA novel stirring method using electromagnetic actuation offering rapid mixing and easy integration with microbioreactors was characterized. The design flexibility gained enables fabrication of chambers suitable for microfluidic operation, and a duplex demonstrator highlights potential for cost‐effective parallelization. Combined with a previously published cassette‐like fabrication of microbioreactors, these advances will facilitate the development of robust and parallelized microbioreactors. © 2015 The Authors. Journal of Chemical Technology & Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

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On the measurement and scaling of mixing time in orbitally shaken bioreactors

Cited by 53 publications

References 34 publications

Orbitally shaken bioreactors—viscosity effects on flow characteristics

Orbitally shaken bioreactors—viscosity effects on flow characteristics

A hydrodynamic description of the flow behavior in shaken flasks

Electromagnetic stirring in a microbioreactor with non‐conventional chamber morphology and implementation of multiplexed mixing

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