2.6 Bioreactor Design 2

Lecture 2.
Bioreactor Design 2
CH148 Biochemical Engineering
Contents
• Design of Continuous Bioreactors
• stirred tank bioreactors
• plug-flow bioreactors
2
Design of Continuous Bioreactors
3
Stirred Tank Bioreactors
Bioreactors are operated continuously in a few bioprocess industries such as brewing, production
of bakers’ yeast, and waste treatment. Enzyme conversion can also be carried out using continuous
systems.
When continuous bioreactors are used with freely
suspended cells or enzymes, the catalyst is continuously
withdrawn from the vessel in the product stream. For
enzymes, this is a major shortcoming; for cell culture,
growth replenishes these withdrawn cells.
Continuous reactors are used only with free enzymes if
the enzyme is inexpensive and can be added continuously
to maintain the catalyst concentration.
Otherwise, enzymes must be immobilized.
4
Continuous stirred tank bioreactors are also called continuous stirred tank fermenters, or CSTFs.
There are different steady-state strategies for CSTFs.
• chemostats
liquid volume kept constant by setting 𝑣 = 𝑣0
constant “dilution rate”
concentrations in the chemostat adjust themselves to
the feed rate
• turbidostats
liquid volume kept constant also by setting 𝑣 = 𝑣0
inlet flow rate 𝑣0 adjusted to keep the biomass
concentration constant
dilution rate adjusts to achieve desired biomass
concentration
more complex monitoring and control systems
5
Recall that for continuous reactors, the residence time 𝜏 is defined as:
Another characteristic parameter for continuous reactors, called the dilution rate, is defined as:
6
Stirred Tank Bioreactors - Homogeneous
Enzyme Reactions in CSTFs
The mole balance on the substrate for a flow reactor is:
The rate law for substrate consumption, assuming it follows MM kinetics, is:
Again, the stoichiometry will be relevant if conversion is to be used.

Combining the previous expressions and evaluating, with 𝑣 = 𝑣0 ,
For immobilized enzymes,
7
Cell Culture in CSTFs
The mass balance on the biomass for a flow reactor is:
The rate law for cell growth is:
Combining the previous expressions,
Usually, the feed stream is sterile: 𝑐𝑥0 = 0. If, in addition, the death rate is negligible, 𝑘𝑑 ≈ 0. With
𝑣0 = 𝑣, the design equation simplifies to:
From the Monod equation,
8
The mass balance on the substrate for the same reactor is:
The rate law for substrate consumption, with product formation not coupled to energy generation,
is:
Combining the previous expressions,
9
The expression for the steady-state concentration of biomass can be simplified.
Without product synthesis, or if production is directly coupled to energy metabolism,
If maintenance effects can also be ignored,
From before,
10
The mass balance on the product for the same reactor is:
The rate law for product formation is:
Combining and evaluating,
For 𝑣 = 𝑣0 ,
Again, evaluation of 𝑞𝑃 depends on the type of product formed, and 𝑐𝑋 can be evaluated as before.
11
At low feed rates, nearly all

substrate is consumed at steady
state, so that 𝑐𝑋 ≈ 𝑌𝑋𝑆 𝑐𝑆0 .
As D increases, 𝑐𝑆 increases slowly
at first and then more rapidly as 𝐷
approaches 𝜇𝑚𝑎𝑥 ; 𝑐𝑋 → 0 as 𝐷 →
𝜇𝑚𝑎𝑥 . This is called washout.
12
Washout occurs when the rate of

cell removal in the stream is greater
than the rate of generation by
growth. That is, at 𝐷𝑐𝑟𝑖𝑡 , 𝑐𝑋 = 0:
13
Maximum Rate of Biomass Production
The volumetric rate of biomass production, when feed is sterile, is
The stead-state concentration 𝑐𝑋 , neglecting cell death and maintenance, and for product formation
not coupled to energy metabolism, is:
Thus, the rate of biomass production is:
14
Maximum Rate of Biomass Production
Operation of a
chemostat at
𝐷𝑜𝑝𝑡 gives the
maximum rate
of biomass
production from
the reactor.
However, since
it is usually very
close to 𝐷𝑐𝑟𝑖𝑡 , it
may not be
practical to
operate at 𝐷𝑜𝑝𝑡 .
15
Exercise 2.6.1
Zymomonas mobilis is used to convert glucose to ethanol in a 60-m3 CSTF under anaerobic
conditions. The yield of biomass from substrate is 0.06 g g-1, and 𝑌𝑃𝑋 is 7.7 g g-1. The maintenance
coefficient, 𝑚𝑆 , is 2.2 g g-1 h-1, and 𝑚𝑃 is 1.1 h-1. The maximum specific growth rate of Z. mobilis is
approximately 0.3 h-1, with 𝐾𝑆 = 0.2 g/L. The feed contains 12 g/L glucose.
(a) What flow rate is required for a steady-state substrate concentration of 1.5 g/L?
(b) At the flow rate of (a), what is the cell density?
(c) At the flow rate of (a), what concentration of ethanol is produced?
16
Exercise 2.6.1
17
Exercise 2.6.1
18
Exercise 2.6.1
19
Exercise 2.6.2
A 5-m3 fermenter is operated continuously using a feed substrate concentration of 20 kg m-3. The
microorganism cultivated in the reactor has the following characteristics: 𝜇𝑚𝑎𝑥 = 0.45 h-1; 𝐾𝑆 = 0.8
kg m-3; 𝑌𝑋𝑆 = 0.55 kg kg-1. Neglect cell death, non-energy-coupled product formation, and
maintenance.
(a) What feed flow rate is required to achieve 90% substrate conversion?
(b) How does the biomass productivity at 90% substrate conversion compare with the maximum
possible?
20
Exercise 2.6.2
21
Exercise 2.6.2
22
Exercise 2.6.2
23
Stirred Tank Bioreactors - Heterogeneous
Chemostat with Immobilized Cells
Consider the CSTF shown using immobilized
cells kept suspended and well mixed by
agitation.
The concentration of immobilized cells per
unit volume of liquid in the reactor is 𝒄𝑿𝒊𝒎 ;
assume it is constant. Assume also that all
particles are retained in the bioreactor.
Cells produced by immobilized cell growth
are released into the medium, comprising
suspended cells at a concentration of 𝑪𝑿𝒔 .
24
During operation, only suspended cells are
removed in the product stream.
We make the following assumptions in our
analysis:
• cell death is negligible
• maintenance requirements are negligible
• reactor feed is sterile
• intrinsic growth rates are the same for
suspended and immobilized cells
• product synthesis is directly coupled with
energy metabolism
25
At steady state, the mass balance on cells is:
The rate law is:
However, in the presence of mass transfer

limitations, the growth rate for immobilized
cells must be appended: 𝜇𝑜𝑏𝑠 = 𝜂 𝑇 𝜇
Combining,
26
Using the same assumptions and in addition,
the value of 𝑌𝑋𝑆 being the same for all cells, a
similar derivation following the design
algorithm gives:
27
Immobilized-cell chemostats can

be operated at D considerably
greater than 𝐷𝑐𝑟𝑖𝑡 without
washout.
Immobilization also improves
substrate conversion, but
reaction rates may be reduced
significantly by mass transfer
effects.
28
Plug Flow Bioreactors
In plug flow operation, no mixing occurs in the direction of the length of the
reactor. The liquid flows through it as a discrete “plug.”
As reaction in the vessel proceeds, concentration gradients of substrate and
product develop in the direction of flow.
At the feed end, the substrate concentration is at its highest.
At the outlet, the substrate concentration is at its lowest.
We consider the operation of a plug flow reactor with volumetric flow rate
𝑣0 = 𝑣, inlet substrate concentration 𝑐𝑆0 , and outlet substrate concentration 𝑐𝑆 .
29
Enzyme Reaction
In PFRs, the concentration varies with reactor volume (or length, for constant-
area PFRs). The general mass/mole balance on the substrate in differential
form is:
For an enzyme reaction following MM kinetics, the rate law is:
Combining,
30
Enzyme Reaction
Evaluating,
Plug flow is generally impractical for enzyme conversions unless the enzyme is
immobilized. For immobilized enzyme reactions,
However, 𝜂 𝑇 is a function of 𝑐𝑆 ; the preceding equation cannot be integrated

directly.
31
Lecture 2.6
Bioreactor Design 2
CH148 Biochemical Engineering
-end-

2.6 Bioreactor Design 2

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Lecture 2.

Again, the stoichiometry will be relevant if conversion is to be used.

For immobilized enzymes,

The rate law for cell growth is:

Combining the previous expressions,

From the Monod equation,

Combining the previous expressions,

If maintenance effects can also be ignored,

The rate law for product formation is:

Combining and evaluating,

At low feed rates, nearly all

Washout occurs when the rate of

Thus, the rate of biomass production is:

The rate law is:

However, in the presence of mass transfer

Immobilized-cell chemostats can

For an enzyme reaction following MM kinetics, the rate law is:

However, 𝜂 𝑇 is a function of 𝑐𝑆 ; the preceding equation cannot be integrated

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