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Animal cell culture in stirred bioreactors: Observations on scale-up

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Abstract

Scale-up of stirred tank bioreactors from 0.02 m3 to 0.3 m3 commercial plant is discussed for hybridoma suspension culture. Schemes for dissolved oxygen control with sparged air in serum containing media are described as well as mechanical breakage of foam in small and large bioreactors. Porous metal spargers (180−200×10−6 m) are found to produce foams which are hard to control. Aeration with larger (> 0.001 m) multihole spargers is recommended.

Combined cell damage due to foam formation and control, and possible damage at mechanical seals or submerged bearings, are found to have no measurable effect on cell growth relative to roller bottle production. Hybridomas are shown to withstand significant impeller tip speed (> 1 ms−1) and fluid turbulence as evidenced by impeller Reynolds numbers in excess of 105. The size of the energy dissipating terminal eddies is calculated to be > 10-fold that of the hybridoma cells. Specific fluid turnover rate is employed as the scale-up criterion.

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Abbreviations

C m:

Clearance of impeller from bottom of tank

D m:

Diameter of tank

DO kg/m3 :

Dissolved oxygen

d i m:

Diameter of impeller

k L a L 1/s:

Overall gas-liquid volumetric mass transfer coefficient

L m:

Static liquid height

l m:

Length of terminal eddies

N 1/s:

Rotational speed of impeller

P W:

Power

Po :

Power number

Q m3/s:

Volume flow of impeller

Re i :

Impeller Reynolds number given by Eq. (1)

RO:

Reverse osmosis

T m/s:

Tip speed of impeller

V m3 :

Volume of bioreactor

ɛ W/kg:

Specific energy dissipation rate

μ Pa · s:

Viscosity of liquid

ρ kg/m3 :

Density of liquid

1:

0.02 m2 bioreactor

2:

0.3 m3 bioreactor

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Authors and Affiliations

  1. Department of Chemical Engineering, University of Waterloo, Waterloo, Ontario, Canada

    Y. Chisti

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  1. Y. Chisti
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Chisti, Y. Animal cell culture in stirred bioreactors: Observations on scale-up. Bioprocess Engineering 9, 191–196 (1993). https://doi.org/10.1007/BF00369402

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