Abstract
The specific characteristics of mammalian cells discussed in Chap. 2 require adapted solutions for bioreactor design and operation. Especially, cell damage by shear stress and aeration has to be considered. Therefore this chapter starts with a detailed discussion of shear stress effects on mammalian cells (anchorage-dependent and suspendable cells) in model systems and bioreactors, respectively, and consequences for reactor design. Appropriate oxygen supply is another critical issue, as adapted oxygen supply systems are required. Techniques for immobilization of cells, either grown on microcarriers in suspension culture or within macroporous carriers in fixed bed or fluidized bed reactors, are discussed as well. With respect to the operation of bioreactors, the characteristics of different culture modes (batch, fed-batch, chemostat, perfusion) are introduced and practical examples are given. Finally, concepts for monitoring of bioreactors, including offline and online methods as well as control loops (e.g. O2, pH), are considered.
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Abbreviations
- A :
-
membrane area
- b :
-
width
- c :
-
concentration
- C :
-
constant
- c * :
-
equilibrium solubility of oxygen — oxygen saturation
- c *0 :
-
oxygen solubility at zero solute concentration
- c 1, c 2 :
-
concentrations of both sides of a dialysis membrane
- c AL :
-
concentration of oxygen at steady state
- c crit :
-
critical oxygen concentration
- c iL :
-
concentration of ionic component i in the liquid
- c jL :
-
concentration of non-ionic component j in the liquid
- c L :
-
concentration of oxygen in solution
- c O2 :
-
concentration of oxygen
- c P :
-
product concentration
- c S :
-
substrate concentration
- c S0 :
-
substrate concentration in feed
- D :
-
dilution rate in chemostat and perfusion mode
- D a :
-
dilution rate in outer chamber of membrane dialysis reactor
- d B :
-
bubble diameter
- D crit :
-
critical (maximal) dilution rate
- D e :
-
diffusive coefficient
- D i :
-
dilution rate in inner chamber of membrane dialysis reactor
- d 1 :
-
inner diameter of the membrane tube
- d i,cou :
-
diameter of inner cylinder in couette viscometer
- d 2 :
-
orifice diameter
- DO:
-
dissolved oxygen
- d o :
-
outer diameter of the membrane tube
- D R :
-
vessel diameter
- d R :
-
impeller diameter
- D s :
-
diffusion coefficient of oxygen in the membrane
- d s :
-
Sauter mean diameter
- d T :
-
bubble column vessel diameter
- F :
-
liquid flow rate
- g :
-
acceleration due to gravity
- h :
-
height
- He:
-
Henry constant
- Hes :
-
Henry constant of oxgen in membrane material
- Hew :
-
Henry constant of oxgen in water
- H i :
-
constant for ionic component i
- h L :
-
height of fluid in bubble column
- H R :
-
filling height of the stirred reactor — impeller located at the interface
- ISF:
-
integrated shear factor
- k :
-
mass transfer coefficient at the gas liquid interface
- k d :
-
cell specific death rate
- K j :
-
constant for non-ionic component j in the liquid
- k L :
-
mass transfer coefficient at the liquid-side interface
- k La:
-
mass transfer coefficient, which is the product of k L, the overall mass transfer coefficient from the gas to the liquid phase (two film model), and a the gas-liquid interfacial area per unit of the reactor liquid volume
- k O2 :
-
monod-constant for oxygen
- k s :
-
Monod-constant for substrate limitation
- K SV :
-
Stern-Volmer quenching constant
- l Kol :
-
Kolmogorov length scale
- M d :
-
torque
- n R :
-
rotation speed
- OTR:
-
oxygen transfer rate
- OUR:
-
oxygen uptake rate
- P :
-
power input
- P/V :
-
power input per unit volume
- P mem :
-
permeability coefficient of a dialysis membrane
- P O2 :
-
partial pressure of oxygen in the gas phase
- Q :
-
volumetric aeration rate
- Q O2,max :
-
maximal cell specific oxygen uptake rate
- q P :
-
cell specific production rate
- q S :
-
cell specific substrate uptake rate
- r :
-
radius
- Re :
-
Reynolds number
- r i,cou :
-
inner radius of a couette viscometer
- r P :
-
particle radius
- r Z :
-
cell radius
- Ta:
-
Taylor number
- S:
-
molecular flow
- t :
-
time
- T :
-
temperature
- U :
-
flow velocity in flow chamber
- U T :
-
peripheral speed in couette viscometer
- V :
-
volume
- v :
-
superficial gas velocity
- v 0 :
-
gas velocity at the sparger
- V k :
-
hypothetical killing volume
- w :
-
gap width
- X t :
-
total cell concentration
- X :
-
cell density
- X d :
-
concentration of dead cells
- X v :
-
concentration of viable cells
- Y :
-
length scale in flow chamber
- Yz :
-
valency of ionic component i
- α :
-
exponent (further function of superficial velocity)
- β :
-
exponent independent of scale and impeller type
- α perf :
-
recirculation rate in perfusion culture, ratio between feed and recirculated flow
- β perf :
-
concentration factor in perfusion culture, ration between biomass, concentration in the reactor and in recirculated flow
- γ :
-
shear rate
- η fl :
-
fluid viscosity
- η i :
-
effectiveness factor for internal mass transfer resistance
- Φ 0 :
-
Thiele-Modulus for zero-order kinetic
- μ :
-
cell specific growth rate
- μ max :
-
maximal cell specific growth rate
- Δρ :
-
density difference
- ε :
-
energy dissipation rate per unit mass
- ν :
-
kinematic fluid viscosity
- ρ fl :
-
fluid density
- σ :
-
surface tension
- σ Z :
-
surface tension of cell membrane at cell burst
- τ :
-
shear stress
- τ crit :
-
critical shear stress
- τ w :
-
wall shear stress
- τ 10 :
-
fluorescent lifetimes in the absence of oxygen
- τ 1 :
-
fluorescent lifetimes in the presence of oxygen
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Czermak, P., Pörtner, R., Brix, A. (2009). Special Engineering Aspects. In: Cell and Tissue Reaction Engineering. Principles and Practice. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-68182-3_4
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