Centrifuges, Animal Cells

Hanle, Daniel D.

doi:10.1002/0471250589.ebt045

Cited by 3 publications

(4 citation statements)

References 24 publications

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“…In this article we focus on solid liquid separation, which is typically the next stage after fermentation, and specifically on centrifugation, which is often chosen for liquid solid separation because of its cost effectiveness, robust operation and applicability to continuous operation (Axelsson, 1999;Hanle, 1999). Scale-down to the laboratory based on the ratio of the flow rate (Q) and equivalent settling area (S) scale is well characterized (Leung, 1998;Maybury et al, 2000) and is an established method for centrifugation scaleup.…”

Section: Introductionmentioning

confidence: 99%

Ultra scale‐down prediction using microwell technology of the industrial scale clarification characteristics by centrifugation of mammalian cell broths

Tait

Aucamp

Bugeon

et al. 2009

Biotech & Bioengineering

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This article describes how a combination of an ultra scale-down (USD) shear device feeding a microwell centrifugation plate may be used to provide a prediction of how mammalian cell broth will clarify at scale. In particular a method is described that is inherently adaptable to a robotic platform and may be used to predict how the flow rate and capacity (equivalent settling area) of a centrifuge and the choice of feed zone configuration may affect the solids carry over in the supernatant. This is an important consideration as the extent of solids carry over will determine the required size and lifetime of a subsequent filtration stage or the passage of fine particulates and colloidal material affecting the performance and lifetime of chromatography stages. The extent of solids removal observed in individual wells of a microwell plate during centrifugation is shown to correlate with the vertical and horizontal location of the well on the plate. Geometric adjustments to the evaluation of the equivalent settling area of individual wells (Sigma(M)) results in an improved prediction of solids removal as a function of centrifuge capacity. The USD centrifuge settling characteristics need to be as for a range of equivalent flow rates as may be experienced at an industrial scale for a machine of different shear characteristics in the entry feed zone. This was shown to be achievable with two microwell-plate based measurements and the use of varying fill volumes in the microwells to allow the rapid study of a fivefold range of equivalent flow rates (i.e., at full scale for a particular industrial centrifuge) and the effect of a range of feed configurations. The microwell based USD method was used to examine the recovery of CHO-S cells, prepared in a 5 L reactor, at different points of growth and for different levels of exposure to shear post reactor. The combination of particle size distribution measurements of the cells before and after shear and the effect of shear on the solids remaining after centrifugation rate provide insight into the state of the cells throughout the fermentation and the ease with which they and accumulated debris may be removed by continuous centrifugation. Hence bioprocess data are more readily available to help better integrate cell culture and cell removal stages and resolve key bioprocess design issues such as choice of time of harvesting and the impact on product yield and contaminant carry over. Operation at microwell scale allows data acquisition and bioprocess understanding over a wide range of operating conditions that might not normally be achieved during bioprocess development.

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Section: Introductionmentioning

confidence: 99%

Ultra scale‐down prediction using microwell technology of the industrial scale clarification characteristics by centrifugation of mammalian cell broths

Tait

Aucamp

Bugeon

et al. 2009

Biotech & Bioengineering

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“…Centrifugation is a common technique used to harvest large-scale cell culture vessels as it combines low running costs with uncomplicated process development and operating robustness (Axelsson, 1999;Abraham et al, 2003;Hanle, 1999). Multichamber, tubular bowl, and disc stack designs are all available, however, the disc stack centrifuge is convenient as it can provide intermittent solids discharge ideally suited to the relatively low solids volume fraction in the feed stream.…”

Section: Introductionmentioning

confidence: 99%

Shear stress analysis of mammalian cell suspensions for prediction of industrial centrifugation and its verification

Hutchinson

Bingham

Murrell

et al. 2006

Biotechnol. Bioeng.

101

118

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This article describes the use of ultra scale-down studies requiring milliliter quantities of process material to study the clarification of mammalian cell culture broths using industrial-scale continuous centrifuges during the manufacture of a monoclonal antibody for therapeutic use. Samples were pretreated in a small high-speed rotating-disc device in order to mimic the effect on the cells of shear stresses in the feed zone of the industrial scale centrifuges. The use of this feed mimic was shown to predict a reduction of the clarification efficiency by significantly reducing the particle size distribution of the mammalian cells. The combined use of the rotating-disc device and a laboratory-scale test tube centrifuge successfully predicted the separation characteristics of industrial-scale, disc stack centrifuges operating with different feed zones. A 70% reduction in flow rate in the industrial-scale centrifuge was shown to arise from shear effects. A predicted 2.5-fold increase in throughput for the same clarification performance, achieved by the change to a centrifuge using a feed zone designed to give gentler acceleration of the bioprocess fluid, was also verified at large-scale.

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“…Bacterial and yeast cells are quite hardy, and they can be separated rather simply from the suspending fluid by flocculation (Boonaert et al, 1999;Sharma, 1999), mechanical filtration and centrifugation (Axelsson, 1999;Hanley, 1999). Introductory discussions are readily available (Harrison et al, 2003;Lydersen et al, 1994;Wheelwright, 1991), and more extended treatments are available in Flickinger and Drew (Flickinger and Drew, 1999).…”

Section: Primary Recoverymentioning

confidence: 99%

“…They may, in fact, be the desired product, as in aphoresis (Zydney, 2000), and we shall have much more to say about them in connection with microfiltration in the section on equipment performance below. Increasingly however, they are being removed by disk-stack centrifugation (Abraham et al, 2003;Axelsson, 1999;Hanley, 1999;Shpritzer, 2003;Tebbe et al, 1996). Where the cells are the desired product, the next and final stage is fractionation of cell types (Palsson and Bhatia, 2003), for example by flow cytometry (Shapiro, 2003).…”

Section: Primary Recoverymentioning

confidence: 99%

Bioseparations

Lightfoot

Moscariello

2004

Biotech & Bioengineering

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Here we review key applications of separation technology in applied biology. We first sketch out the field as a whole, but then narrow our scope to the processing of fermentation products, particularly to high-value biologicals such as proteins and nucleotides. We go on to provide a qualitative overview describing the importance and general nature of this large field, major trends, and the strategies that have proven most fruitful in evolving effective separation and purification processes. We then give a detailed description of individual separations equipment and the principles governing their operation. We concentrate throughout on making the available literature accessible to the reader; we provide what is hoped to be a representative set of basic references. However, these references, in turn, include some that suggest promising new developments as well as a number of more specialized reviews. We hope that our overall result provides the reader with access to the most relevant literature. B

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Centrifuges, Animal Cells

Cited by 3 publications

References 24 publications

Ultra scale‐down prediction using microwell technology of the industrial scale clarification characteristics by centrifugation of mammalian cell broths

Ultra scale‐down prediction using microwell technology of the industrial scale clarification characteristics by centrifugation of mammalian cell broths

Shear stress analysis of mammalian cell suspensions for prediction of industrial centrifugation and its verification

Bioseparations

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