Cell Separations Using Differential Sedimentation in Inclined Settlers

Davis, Robert H.; Lee, Ching-Yuan; Batt, Brian C.; Kompala, Dhinakar S.

doi:10.1021/bk-1991-0464.ch008

Cited by 6 publications

(10 citation statements)

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“…Numerous approaches have been adopted in of cells by sedimentation using inclined settlers (Davis et al, 1991) has been shown to be effective in separating viable from nonviable hybridoma cells. Density centrifu gation has been used for fractionation of cell populations, but this method is difficult to scale for handling large flow rates.…”

Section: Introductionmentioning

confidence: 99%

Fractionation of cell mixtures using acoustic and laminar flow fields

Kumar

Feke

Belovich

2004

Biotechnol. Bioeng.

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A fractionation method applicable to different populations of cells in a suspension is reported. The sepa ration was accomplished by subjecting the suspension to a resonant ultrasonic field and a laminar flow field propa gating in orthogonal directions within a thin, rectangular chamber. Steady, laminar flow transports the cell suspen sion along the chamber, while the ultrasonic field causes the suspended cells to migrate to the mid-plane of the chamber at rates related to their size and physical proper ties. A thin flow splitter positioned near the outlet divides the effluent cell suspension into two product streams, thereby allowing cells that respond faster to the acoustic field to be separated from those cells that respond more slowly. Modeling of the trajectories of individual cells through the chamber shows that by altering the strength of the flow relative to that of the acoustic field, the desired fractionation can be controlled. Proof-of-concept experi ments were performed using hybridoma cells and Lactoba cillus rhamnosus cells. The two populations of cells could be effectively separated using this technique, resulting in hybridoma/Lactobacillus ratios in the left and right prod uct streams, normalized to the feed ratio, of 6.9 F 1.8 and 0.39 F 0.01 (vol/vol), respectively. The acoustic method is fast, efficient, and could be operated continuously with a high degree of selectivity and yield and with low power consumption.

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Section: Introductionmentioning

confidence: 99%

Fractionation of cell mixtures using acoustic and laminar flow fields

Kumar

Feke

Belovich

2004

Biotechnol. Bioeng.

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“…From the previous work, it is recommended to keep the 30 angle of inclination from the vertical for the best performance. 5,6,18,24 Minimizing the ratio of bioreactor working volume to settler holdup volume was considered in the geometric design to reduce the residence time of the cells outside of the bioreactor. Fractional factorial DOE in CFX-Post was implemented in the statistical analysis of simulation results.…”

Section: Resultsmentioning

confidence: 99%

“…19,20,24 The sedimentation Reynolds number, Re s , and the ratio of sedimentation Grashof number to Re s , K (representing the significance of gravitational forces to inertial forces), can be calculated for the system to verify the applicability of the PNK model: 30,31 Re…”

Section: Settler Characterization Methodsmentioning

confidence: 99%

“…21 This theory was later applied to cell separations processes. 6,24 For more concentrated suspensions, hindered settling is more predominant such that the settling velocity increasingly becomes more of a function of the particle concentration. 25 While the theoretical correlations capture the impact of the inclined plate dimensions, number of plates, and the angle of inclination, the impact of the complex flow behavior in the gravity settler during continuous flow operation on the settling performance is not considered.…”

Section: Introductionmentioning

confidence: 99%

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CFD‐aided cell settler design optimization and scale‐up: Effect of geometric design and operational variables on separation performance

Shen

Yanagimachi

2011

Biotechnology Progress

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The inclined multiplate (lamella) gravity settler has proven to be an effective cell retention device in industrial perfusion cell culture applications. Investigations on the effects of geometric design and operational variables of the cell settler are crucial to understanding how to best improve the settler performance. Maximizing the harvest/perfusion flow rate while minimizing viable cell loss out of the harvest is the primary challenge for optimization of the settler design. This study demonstrated that computational fluid dynamics (CFD) can be utilized to accurately model and evaluate the settler separation performance for near-monodisperse suspensions and therefore aid in the design optimization of the settler under these baseline conditions. With the preferred geometric features that were identified from CFD modeling results, we proposed design guidelines for the scale-up of these multiplate settler systems. With these guidelines and performance verification using the CFD model, a new large-scale settler was designed and fabricated for a perfusion cell culture process using a minimally aggregating production cell line. Perfusion cell culture runs with this particular cell line were performed with this settler, and the CFD model was able to predict the initial ramp-up performance, proving it to be a valuable scale-up design tool for this production process.

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“…Separation of cells from the product stream can be achieved using gravity- [4] or centrifugeassisted [5] sedimentation or membrane separation [6] and recycle, or immobilization within the fermenter. Separation and recycle requires additional equipment and energy consumption and is therefore less suitable for the manufacture of marginal-cost products such as renewable fuels.…”

Section: Introductionmentioning

confidence: 99%

Natural immobilisation of microorganisms for continuous ethanol production

Baptista

Cóias

Oliveira

et al. 2006

Enzyme and Microbial Technology

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Using a growth medium based on cane blackstrap molasses, we compared ethanol production by two strains of Saccharomyces cerevisiae that were immobilized in polyurethane foam cubes in a fluidised-bed fermenter. One strain (NCYC 1119) was adhesive and extremely flocculent, whilst the other strain was not adhesive and only weakly flocculent. The strong flocs of NCYC 1119 caused blockage of the bed, so that stable operation could not be achieved beyond 15 days. Nevertheless, it was able to produce 40 g L −1 ethanol at a rate up to 16 g L −1 h −1 (D = 0.4 h −1 ), although this production period was limited to 192 h. In contrast, the non-adhesive strain was only capable of producing 28 g L −1 ethanol at a rate of 11 g Lat the same dilution rate, even though production continued for 576 h. Despite the conversion of sugars to ethanol not being complete during these trials (up to 47 g L −1 was expected), it was clearly demonstrated that the productivity of the adhesive strain was higher than that of the non-adhesive one. However, further work is required to develop this process into a robust, industrial system.

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Cell Separations Using Differential Sedimentation in Inclined Settlers

Cited by 6 publications

References 0 publications

Fractionation of cell mixtures using acoustic and laminar flow fields

Fractionation of cell mixtures using acoustic and laminar flow fields

CFD‐aided cell settler design optimization and scale‐up: Effect of geometric design and operational variables on separation performance

Natural immobilisation of microorganisms for continuous ethanol production

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