Cell and Tissue Reaction Engineering pp 83-172

Part of the Principles and Practice book series (PRINCIPLES) | Cite as

Special Engineering Aspects

  • P. Czermak
  • R. Pörtner
  • A. Brix

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.

List of Symbols

A

membrane area

b

width

c

concentration

C

constant

c*

equilibrium solubility of oxygen — oxygen saturation

c0*

oxygen solubility at zero solute concentration

c1, c2

concentrations of both sides of a dialysis membrane

cAL

concentration of oxygen at steady state

ccrit

critical oxygen concentration

ciL

concentration of ionic component i in the liquid

cjL

concentration of non-ionic component j in the liquid

cL

concentration of oxygen in solution

cO2

concentration of oxygen

cP

product concentration

cS

substrate concentration

cS0

substrate concentration in feed

D

dilution rate in chemostat and perfusion mode

Da

dilution rate in outer chamber of membrane dialysis reactor

dB

bubble diameter

Dcrit

critical (maximal) dilution rate

De

diffusive coefficient

Di

dilution rate in inner chamber of membrane dialysis reactor

d1

inner diameter of the membrane tube

di,cou

diameter of inner cylinder in couette viscometer

d2

orifice diameter

DO

dissolved oxygen

do

outer diameter of the membrane tube

DR

vessel diameter

dR

impeller diameter

Ds

diffusion coefficient of oxygen in the membrane

ds

Sauter mean diameter

dT

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

Hi

constant for ionic component i

hL

height of fluid in bubble column

HR

filling height of the stirred reactor — impeller located at the interface

ISF

integrated shear factor

k

mass transfer coefficient at the gas liquid interface

kd

cell specific death rate

Kj

constant for non-ionic component j in the liquid

kL

mass transfer coefficient at the liquid-side interface

kLa

mass transfer coefficient, which is the product of kL, 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

kO2

monod-constant for oxygen

ks

Monod-constant for substrate limitation

KSV

Stern-Volmer quenching constant

lKol

Kolmogorov length scale

Md

torque

nR

rotation speed

OTR

oxygen transfer rate

OUR

oxygen uptake rate

P

power input

P/V

power input per unit volume

Pmem

permeability coefficient of a dialysis membrane

PO2

partial pressure of oxygen in the gas phase

Q

volumetric aeration rate

QO2,max

maximal cell specific oxygen uptake rate

qP

cell specific production rate

qS

cell specific substrate uptake rate

r

radius

Re

Reynolds number

ri,cou

inner radius of a couette viscometer

rP

particle radius

rZ

cell radius

Ta

Taylor number

S

molecular flow

t

time

T

temperature

U

flow velocity in flow chamber

UT

peripheral speed in couette viscometer

V

volume

v

superficial gas velocity

v0

gas velocity at the sparger

Vk

hypothetical killing volume

w

gap width

Xt

total cell concentration

X

cell density

Xd

concentration of dead cells

Xv

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

αperf

recirculation rate in perfusion culture, ratio between feed and recirculated flow

βperf

concentration factor in perfusion culture, ration between biomass, concentration in the reactor and in recirculated flow

γ

shear rate

ηfl

fluid viscosity

ηi

effectiveness factor for internal mass transfer resistance

Φ0

Thiele-Modulus for zero-order kinetic

μ

cell specific growth rate

μmax

maximal cell specific growth rate

Δρ

density difference

ε

energy dissipation rate per unit mass

ν

kinematic fluid viscosity

ρfl

fluid density

σ

surface tension

σZ

surface tension of cell membrane at cell burst

τ

shear stress

τcrit

critical shear stress

τw

wall shear stress

τ10

fluorescent lifetimes in the absence of oxygen

τ1

fluorescent lifetimes in the presence of oxygen

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Copyright information

© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  • P. Czermak
    • 1
    • 2
  • R. Pörtner
    • 3
  • A. Brix
    • 2
  1. 1.Institute of Biopharmaceutical TechnologyUniversity of Applied Sciences Giessen-FriedbergGiessenGermany
  2. 2.Department of Chemical EngineeringKansas State UniversityManhattanUSA
  3. 3.Institute of Bioprocess and Biosystems EngineeringHamburg University of Technology (TUHH)HamburgGermany

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