High density culture of hybridoma cells using a perfusion culture vessel with an external centrifuge

Tokashiki, Michiyuki; Arai, Takami; Hamamoto, Kimihiko; Ishimaru, Kenji

doi:10.1007/bf00365487

Cited by 66 publications

(23 citation statements)

References 5 publications

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“…Several investigators designed custom centrifuges for perfusion culture, working either continuously (Tokashiki et al, 1990) or semicontinuously (Hamamoto et al, 1989;Takamatsu et al, 1996). During the perfusion cultures using a centrifuge for cell retention, no report was made concerning a detrimental effect of centrifugation on animal cells.…”

Section: Voisard Et Al: Large-scale Retention Of Mammalian Cellsmentioning

confidence: 98%

Potential of cell retention techniques for large‐scale high‐density perfusion culture of suspended mammalian cells

Voisard

Meuwly

Ruffieux

et al. 2003

Biotech & Bioengineering

244

150

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This review focuses on cultivation of mammalian cells in a suspended perfusion mode. The major technological limitation in the scaling-up of these systems is the need for robust retention devices to enable perfusion of medium as needed. For this, cell retention techniques available to date are presented, namely, cross-flow filters, hollow fibers, controlled-shear filters, vortex-flow filters, spin-filters, gravity settlers, centrifuges, acoustic settlers, and hydrocyclones. These retention techniques are compared and evaluated for their respective advantages and potential for large-scale utilization in the context of industrial manufacturing processes. This analysis shows certain techniques have a limited range of perfusion rate where they can be implemented (most microfiltration techniques). On the other hand, techniques were identified that have shown high perfusion capacity (centrifuges and spin-filters), or have a good potential for scale-up (acoustic settlers and inclined settlers). The literature clearly shows that reasonable solutions exist to develop large-scale perfusion processes.

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Section: Voisard Et Al: Large-scale Retention Of Mammalian Cellsmentioning

confidence: 98%

Potential of cell retention techniques for large‐scale high‐density perfusion culture of suspended mammalian cells

Voisard

Meuwly

Ruffieux

et al. 2003

Biotech & Bioengineering

244

150

View full text Add to dashboard Cite

show abstract

“…Filtration might have clogging problem (Tokashiki et al, 1990), and centrifugation might damage plant cells because of their shear sensitivity (De Dobbeleer et al, 2006). So gravitational sedimentation was considered as the most efficient way to retain the cells and separate the medium containing secreted metabolites (Wang et al 2010).…”

Section: Perfusion Bioreactormentioning

confidence: 99%

Bioreactor technology for clonal propagation of plants and metabolite production

2015

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Plant cell culture in bioreactors is an enabling tool for large scale production of clonal elite plants in agriculture, horticulture, forestry, pharmaceutical sectors, and for biofuel production. Advantages of bioreactors for plant cell culture have resulted in various types of bioreactors differing in design, operating technologies, instrumentations, and construction of culture vessels. In this review, different types of bioreactors for clonal propagation of plants and secondary metabolites production are discussed. Mechanical and biochemical parameters associated with bioreactor design, such as aeration, flow rate, mixing, dissolved oxygen, composition of built-up gas in the headspace, and pH of the medium, are pivotal for cell morphology, growth, and development of cells within tissues, embryos, and organs. The differences in such parameters for different bioreactor designs are described here, and correlated to the plant materials that have been successfully cultured in different types of bioreactors.

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“…Most mammalian cell retention devices used for perfusion processes (Woodside et al, 1998) are based on size, e.g., cross-flow filters (Van Reis et al, 1991;Mercille et al, 1994) and spin filters (Himmelfarb et al, 1969;Deo et al, 1996;Roth et al, 1997) or combined size and density differences between the cells and the medium, e.g., inclined settlers (Batt et al, 1990;Thompson et al, 1994) and centrifuges (Tokashiki et al, 1990;Johnson et al, 1996). Devices based on filtering have the advantage of clarifying particulates from the permeate.…”

Section: Introductionmentioning

confidence: 98%

“…Devices based on filtering have the advantage of clarifying particulates from the permeate. Settlers (Batt et al, 1990) and centrifuges (Tokashiki et al, 1990) are less prone to fouling (Deo et al, 1996) and can provide high separation efficiencies at high flow rates.…”

Section: Introductionmentioning

confidence: 99%

Scale‐up and optimization of an acoustic filter for 200 L/day perfusion of a CHO cell culture

Gorenflo

Smith

Dedinsky

et al. 2002

Biotech & Bioengineering

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Acoustic cell retention devices have provided a practical alternative for up to 50 L/day perfusion cultures but further scale-up has been limited. A novel temperature-controlled and larger-scale acoustic separator was evaluated at up to 400 L/day for a 10(7) CHO cell/mL perfusion culture using a 100-L bioreactor that produced up to 34 g/day recombinant protein. The increased active volume of this scaled-up separator was divided into four parallel compartments for improved fluid dynamics. Operational settings of the acoustic separator were optimized and the limits of robust operations explored. The performance was not influenced over wide ranges of duty cycle stop and run times. The maximum performance of 96% separation efficiency at 200 L/day was obtained by setting the separator temperature to 35.1 degrees C, the recirculation rate to three times the harvest rate, and the power to 90 W. While there was no detectable effect on culture viability, viable cells were selectively retained, especially at 50 L/day, where there was a 5-fold higher nonviable washout efficiency. Overall, the new temperature-controlled and scaled-up separator design performed reliably in a way similar to smaller-scale acoustic separators. These results provide strong support for the feasibility of much greater scale-up of acoustic separations.

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High density culture of hybridoma cells using a perfusion culture vessel with an external centrifuge

Cited by 66 publications

References 5 publications

Potential of cell retention techniques for large‐scale high‐density perfusion culture of suspended mammalian cells

Potential of cell retention techniques for large‐scale high‐density perfusion culture of suspended mammalian cells

Bioreactor technology for clonal propagation of plants and metabolite production

Scale‐up and optimization of an acoustic filter for 200 L/day perfusion of a CHO cell culture

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