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Chemostat

This lecture discusses biological reactors called chemostats. A chemostat maintains cells at steady state by balancing the influx of fresh media against cell growth and efflux. At steady state, the dilution rate D equals the specific growth rate μ. The Monod model relates μ to substrate concentration S. Operating at the maximum dilution rate Dmax risks washout. Fed-batch reactors feed substrate slowly to achieve very high cell densities while controlling μ. They require calculating exponential substrate feed rates to maintain μ.

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263 views6 pages

Chemostat

This lecture discusses biological reactors called chemostats. A chemostat maintains cells at steady state by balancing the influx of fresh media against cell growth and efflux. At steady state, the dilution rate D equals the specific growth rate μ. The Monod model relates μ to substrate concentration S. Operating at the maximum dilution rate Dmax risks washout. Fed-batch reactors feed substrate slowly to achieve very high cell densities while controlling μ. They require calculating exponential substrate feed rates to maintain μ.

Uploaded by

Yiğit Ilgaz
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We take content rights seriously. If you suspect this is your content, claim it here.
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10.37 Chemical and Biological Reaction Engineering, Spring 2007 Prof. K.

Dane Wittrup Lecture 13: Biological Reactors- Chemostats This lecture covers: theory of the chemostat, fed batch or semi-continuous fermentor operations

Biological Reactors (Chemostat)


Concentration/Combustion constant Biological CSTR [S]0 F

[S], x

V
F Figure 1. Diagram of a chemostat. F = Volumetric flow rate

x=

biomass volume

[S]0 = Concentration of growth limiting substrate. (for growing cells) At steady-state, biomass balance In Out + Prod = Acc Sterile feed: In=0 Steady state: Acc=0

Fx + rx V = 0 at steady-state Cell growth kinetics rx = x Fx + x V = 0 F Solve = V F 1 = D=Dilution rate V

=D
Biological Mechanical

Cite as: K. Dane Wittrup, course materials for 10.37 Chemical and Biological Reaction Engineering, Spring 2007. MIT OpenCourseWare (http://ocw.mit.edu), Massachusetts Institute of Technology. Downloaded on [DD Month YYYY].

When at steady-state, can control cell mass. Allows precisely reproducible cell states. Not easy to run at steady-state. Material balance on [S] (sugar concentration) In Out + Prod = Acc 0 at steady-state

F [ S ]0 F [ S ]

1 x V = 0 Yx
s

Yield coefficient

mass biomass created mass substrate consumed

Divide by V

x D ([ S ]0 [ S ]) = Yx
change in sugar concentration s

At steady-state

=D

x = Yx ([ S ]0 [ S ])
s

What is the value of

[ S ] ? What more information do we need?

= f ([ S ])

must choose a growth model to connect

and

[S ]

Monod growth model:

max [ S ]
K s + [S ]

at steady-state

D=

max [ S ]
K s + [S ]

[S ] =

Ks D max D

substitute in x equation

10.37 Chemical and Biological Reaction Engineering, Spring 2007 Prof. K. Dane Wittrup

Lecture 13 Page 2 of 6

Cite as: K. Dane Wittrup, course materials for 10.37 Chemical and Biological Reaction Engineering, Spring 2007. MIT OpenCourseWare (http://ocw.mit.edu), Massachusetts Institute of Technology. Downloaded on [DD Month YYYY].

Ks D x = Yx [ S ]0 max D s
Specifying

max , K s , Yx , D , [ S ]0 , can predict x , [ S ] .


s

x < 0 is non-physical but formally in solution

max D

can go to 0. If you turn knobs incorrectly: if D is too high, the cells cannot

grow fast enough to reach steady-state. Washout will occur. so use x = 0 to find Dmax

Dmax =

max [ S ]0
K s + [ S ]0

For D > Dmax washout, no steady-state.

x, S
mass volume

S
x
washout

Dmax

Figure 2. Biomass/volume versus dilution rate. Beyond the maximum dilution rate, washout occurs. For real systems K s << [ S ]0 . Most cell growth systems reach maximum at fairly low

concentrations; hence x is flat, then drops off sharply. If biomass is the product, is there a best operating condition? What should we consider?

dx optimize x with respect to D? D=0 (no, because this would be batch reactor) dD
Define productivity as biomass

(reactor

volume )( time )

= xD

10.37 Chemical and Biological Reaction Engineering, Spring 2007 Prof. K. Dane Wittrup

Lecture 13 Page 3 of 6

Cite as: K. Dane Wittrup, course materials for 10.37 Chemical and Biological Reaction Engineering, Spring 2007. MIT OpenCourseWare (http://ocw.mit.edu), Massachusetts Institute of Technology. Downloaded on [DD Month YYYY].

d ( xD) = 0 for optimum. (is a maximum) dD


x

xD

D
Doptimum

Figure 3. Left: Biomass/volume versus dilution rate. Right: Productivity versus dilution rate.

Ks Doptimum = max 1 K s + [ S ]0
K s << [ S ]0
Doptimum max

Dmax
Close to washout conditions. Operability would be difficult. We would not want to run too close to washout conditions. Fed-batch fermentor (microbes or mammalian cells) -used to achieve very high cell densities (e.g. hundreds of grams cell dry weight (c.d.w)/liter) If you want x final =

100 g L wt 200 g 20% Toxic, sugar content cells will die L volume

If Yx 0.5 , [ S ]0 =
s

Why do we not feed all at once? Cells will die.

Calculate medium feed rate in order to hold

constant.
Lecture 13 Page 4 of 6

10.37 Chemical and Biological Reaction Engineering, Spring 2007 Prof. K. Dane Wittrup

Cite as: K. Dane Wittrup, course materials for 10.37 Chemical and Biological Reaction Engineering, Spring 2007. MIT OpenCourseWare (http://ocw.mit.edu), Massachusetts Institute of Technology. Downloaded on [DD Month YYYY].

[S]0

x(t) S(t), very small


Figure 4. Diagram of a fed-batch fermentor.

If

is constant, biomass = biomass t =0 e

There is a dilution term, because as we feed in fresh medium, volume will change. Volume often doubles.

x V = x0 V0 e t
Feed

F [ S ]0 =
sugar feed

x0 V0 e t
sugar consumed

Yx s

Assume all converted into biomass.

F=

x0 V0 e t [ S ]0 Yx
s

Exponential flow rate. Typically Dilution:

specified as small.

dV =F dt
x0 V(t ) = V0 1 + e t 1) ( [ S ]0 Yx s
x=
biomass

V
t

= 1+

x0 e t x0 e t 1) ( Yx [ S ]0
s

x0 V0 e V

10.37 Chemical and Biological Reaction Engineering, Spring 2007 Prof. K. Dane Wittrup

Lecture 13 Page 5 of 6

Cite as: K. Dane Wittrup, course materials for 10.37 Chemical and Biological Reaction Engineering, Spring 2007. MIT OpenCourseWare (http://ocw.mit.edu), Massachusetts Institute of Technology. Downloaded on [DD Month YYYY].

Logistic equation

Figure 5. Graph of logistic growth.

t
If product is something cells are making: Product synthesis kinetics 1)

1 dP = x dt

growth associated (e.g. ethanol)

P
2)

product volume not growth associated (e.g. antibiotics, proteins, antibodies) integrate for amount of product.

1 dP = x dt
P = xdt
0 t

10.37 Chemical and Biological Reaction Engineering, Spring 2007 Prof. K. Dane Wittrup

Lecture 13 Page 6 of 6

Cite as: K. Dane Wittrup, course materials for 10.37 Chemical and Biological Reaction Engineering, Spring 2007. MIT OpenCourseWare (http://ocw.mit.edu), Massachusetts Institute of Technology. Downloaded on [DD Month YYYY].

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