Extensive validation of computed laminar flow in a stirred tank with three Rushton turbines

Zalc, Jeffrey M.; Álvarez, Mario Moisés; Muzzio, Fernando J.; Arik, B. E.

doi:10.1002/aic.690471003

Cited by 76 publications

(40 citation statements)

References 27 publications

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“…This increase was linearly dependent on the rate of energy dissipation in the capillary, independently of the flow regime (laminar or turbulent with 500 < Re < 6,000) and residence time. Due to the fact that industrial culture systems (small and large scale) are characterized by a heterogeneous environment (Soos et al, 2007) and often exhibit laminar regions (Lara et al, 2006;Zalc et al, 2001), the investigation of laminar shear flow on cell death is of practical importance to improve biopharmaceutical processes.…”

Section: Introductionmentioning

confidence: 99%

Induction of mammalian cell death by simple shear and extensional flows

Tanzeglock

Šoóš

Stephanopoulos

et al. 2009

Biotech & Bioengineering

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In this work we investigated whether the type of shear flow, to which cells are exposed, influences the initiation of cell death. It is shown that mammalian cells, indeed, distinguish between discrete types of flow and respond differently. Two flow devices were employed to impose accurate hydrodynamic flow fields: uniform steady simple shear flow and oscillating extensional flow. To distinguish between necrotic and apoptotic cell death, fluorescence activated cell sorting and the release of DNA in the culture supernatant was used. Results show that Chinese Hamster Ovaries and Human Embryonic Kidney cells will enter the apoptotic pathway when subjected to low levels of hydrodynamic stress (around 2.0 Pa) in oscillating, extensional flow. In contrast, necrotic death prevails when the cells are exposed to hydrodynamic stresses around 1.0 Pa in simple shear flow or around 500 Pa in extensional flow. These threshold values at which cells enter the respective death pathway should be avoided when culturing cells for recombinant protein production to enhance culture longevity and productivity.

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Section: Introductionmentioning

confidence: 99%

Induction of mammalian cell death by simple shear and extensional flows

Tanzeglock

Šoóš

Stephanopoulos

et al. 2009

Biotech & Bioengineering

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“…Laser-Doppler anemometry measurements coupled with computational fluid dynamics (CFD) simulations were used to determine the effect of the impeller to tank diameter ratio (D/T) on mixing using a mixed flow impeller by Ozcan-Taskin and Wei (2003). Laminar flow and mixing in a stirred-tank reactor equipped with three Rushton turbine impellers were investigated both computationally (CFD) and experimentally (PIV) by Zalc et al (2001). Their CFD studies agreed with PIV data for bulk-flow patterns at several different agitation rates and locations of poorly mixed regions were identified by Zalc et al (2002).…”

Section: Introductionmentioning

confidence: 99%

Flow characterization of a wavy-walled bioreactor for cartilage tissue engineering

Bilgen

Sucosky

Neitzel

et al. 2006

Biotechnol. Bioeng.

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Cartilage tissue engineering requires the use of bioreactors in order to enhance nutrient transport and to provide sufficient mechanical stimuli to promote extracellular matrix (ECM) synthesis by chondrocytes. The amount and quality of ECM components is a large determinant of the biochemical and mechanical properties of engineered cartilage constructs. Mechanical forces created by the hydrodynamic environment within the bioreactors are known to influence ECM synthesis. The present study characterizes the hydrodynamic environment within a novel wavy-walled bioreactor (WWB) used for the development of tissue-engineered cartilage. The geometry of this bioreactor provides a unique hydrodynamic environment for mammalian cell and tissue culture, and investigation of hydrodynamic effects on tissue growth and function. The flow field within the WWB was characterized using two-dimensional particle-image velocimetry (PIV). The flow in the WWB differed significantly from that in the traditional spinner flask both qualitatively and quantitatively, and was influenced by the positioning of constructs within the bioreactor. Measurements of velocity fields were used to estimate the mean-shear stress, Reynolds stress, and turbulent kinetic energy components in the vicinity of the constructs within the WWB. The mean-shear stress experienced by the tissue-engineered constructs in the WWB calculated using PIV measurements was in the range of 0-0.6 dynes/cm2. Quantification of the shear stress experienced by cartilage constructs, in this case through PIV, is essential for the development of tissue-growth models relating hydrodynamic parameters to tissue properties.

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“…Particles seeded within regular regions do not leave them even after several hours. Those seeded in the chaotic regions apparently exhibit a higher frequency of visitation to the high shear areas, as revealed by the higher intensity of laser light reflection in areas previously associated with high shear stresses (see for example Zalc et al, 2001). Cells will certainly not be exempt of such dynamics.…”

Section: Flow Short-cutsmentioning

confidence: 95%

“…At the macroscale, mixing issues arising from geometrical and operational factors have been documented conclusively. The surprisingly wide distribution of shear stresses within a vessel has also been demonstrated in laboratory and industrial-scale equipment (see for example Alvarez, 2000;Zalc et al, 2001, and the very complete critical review on multiple impeller geometries by Gogate et al, 2000). Also, various problems related to mixing have been reported on the operation of large-scale bioreactors.…”

Section: Introductionmentioning

confidence: 92%