0 tayangan

Diunggah oleh Nicoly Didoné

book skript kapitel 5

- Chemical Engineering paper
- Final HP
- cre2
- solution pengpro.pdf
- Scale-Up Problems Mold
- Modeling Ald Sim of ATR in Amonnia Plant
- Citric Acid Production Stirred Tank
- set1ans-10
- Comparison of Different Reactor Types Used in the Manufacture of Ethoxylated, Propoxylated Products
- kinetics of the homogeneous reverse water-gas shift reaction.pdf
- Multiphase Flow
- Catalytic Rates & Pressure Drop in PFR Reactors
- CDB2043 Course Outline and Planning May 2016 Student Copy
- 4 vs 3
- www.ijerd.com
- 1-s2.0-S1359431113006674-main.pdf
- August 2015 - International
- 8 Unit
- 247119610-Lab-5-Production-of-Ethyl-Chloride.docx
- The Effect of Hydrodynamics on Riser Reactor Performance of the FCCU

Anda di halaman 1dari 55

Rainer Buchholz

5. Fermentation Processes

pH-Adjustment H 2O

Preparation of the Mixing

Addition of salts, Culture medium

P-, N - sources etc. Cultivation of the

production strain

Sterilisation

Inoculum

Energy

CO2 and other Gases

Aeration Fermentation

Measurement and Energy

control

Separation of Remaining culture broth

Filtration and / or

biomass and

culture broth

Separation Biomass

confection

reactor)

2. Reactor type (stirred-tank, bubble-column, etc.)

3. Reactor volume

4. Reactor material

5. Reaction conditions (temperature, pressure, concentrations, residence

time, mixing time, degree of dispersion of gas-phase or cells, purity of

educts)

87

- -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

the quantity of the product, its quality and the raw materials. Its also

important to consider the national laws and environmental boundary

conditions. During process development it is necessary to keep the

production costs under the given conditions described above as low as

possible. But in any case the production costs are strongly influenced by all

these parameters.

capacity are briefly discussed:

A common relation between the relative increase of investment for bigger

equipment and its capacity is given by the following equation.

x

investment capacity

(5 1)

investment 0 capacity 0

Whereby x = 0.6

plant never leads to a reduction of the invest amount. A reduction is only

possible in the state of planning while using one bigger plant with a higher

capacity. The estimation of a correct reactor-scale leads to less production

costs and in this way to an increase of profit.

88

- -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

1 Chlorine-alkali-electrolysis

5 (x = 0.38)

a

2 Ethanol (x = 0.6)

3 3 Ethylene (x = 0.71)

4

3 4 Ethyleneoxide (x = 0.78)

2 5 Low pressure polyethylene

b

2 (x = 0.9)

1 Fermentation plants

a > 200 m3

b < 200 m3

1

Fig 5-2: Relation between the relative investment and the relative plant

capacity

x. In the case of x ~ 1 it makes more sense to increase plant-capacity by

installation of a secondary (parallel) plant. In this case the equipment is

more suitable to react on the request of the market situation.

always run at high level. Only in this case the production costs are as low as

possible and the higher investment for the bigger plant is taken into

account.

products consist of two types of costs:

1. Fixed costs

2. Variable costs

89

- -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

productive capacity used) productive capacity used)

1.) depreciation of plant or rent for 1.) raw material costs

production plant

2.) interests for invested capital 2.) energy costs

3.) taxes depending on company 3.) other costs (water,

property cleaning....)

4.) wages for permanent 4.) wages for additional

production staff production staff

5.) cost for strain culture 5.) distribution costs, transport

costs

6.) costs for environmental

protection ("social costs") not

included in investment costs

90

- -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

1

2

6000

Profit

3

3000

Loss

B

S 4

20 40 60 80 100 120

Capacity [%]

Fig 5-3: Production cost as a figure of use of the capacity

1 realised proceed

2 constant + variable costs

3 variable costs

4 constant costs

B break even point; S shut down point

In fig. 2-6 the constant and variable costs are plotted. The constant costs are

independent from the amount of production rate while the variable ones

show a proportional increase with the amount of production rate. The total

production cost is calculated by adding both parts.

The proceeding is also increasing proportional with the sold amount of the

product. The difference between realised proceeding and production cost is

the profit. In this example the plant is running under profitable conditions in

the case of running capacity over 50%. Less running capacity leads to

91

- -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

losses. From a running capacity over 35% up to 50% the loss is less than

the constant costs of the production plant, in this case it's more economic

not to shut down the plant. In the case that the loss exceeds the constant

cost it is necessary to shut down the plant.

biotechnology the "break even point" can vary over a broad range. It

depends on the type of product: while commodities as single cell protein

also need a similar range of the "break even point" like a petrochemical

plant, other products like diagnostics, therapeutics or high value enzymes

are economical by even reaching only a few percent of the running capacity

of the plant.

minimizing the production costs. Therefore it is necessary to consider the

whole production process (that means all steps like up-stream, fermentation,

down-stream process) and optimise the whole process over all. Optimising

single steps often leads to suboptimal results!

process conditions (e.g. aerobic, anaerobic). Furthermore, the running

conditions (T, p, pH, C), the type and scale of the bioreactor and its running

mode (batch, continuous) have to be according to the biological

requirements.

92

- -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

1. Batch mode

2. Steady state mode

3. Semi-continuous mode

5.1.1 Batch mode

characteristics:

(monoseptic mode) and cultivated for a defined reaction time. During this

time a change in biomass and substrate concentration occurs. Due to

effective mixing within the reactor there is no local gradient in concentration

and temperature. The reactor is characterized by its non-stationary

behaviour. As a reactor model the discontinuous ideal mixed vessel can be

used.

in time in space

C C

Ca Ca t=a

Ce Ce t=e

DIK

t z

BSTR

Advantages:

- low investment costs due to relatively low control equipment

93

- -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

- high conversion rate by given reaction time

- due to relatively short cultivation time there is a minor risk of infection

and mutation

Disadvantages:

- non-productive dead times for filling and idling, heating and cooling

- high personnel costs for running the non-stationary process

- higher risk for the operating staff coming in contact with the pathogen

organisms or poisonous products

- higher wear on the equipment by numerous sterilizations

- only small amounts of products are formed

- the reactor should be used for different products

- there is a high risk of infection

- the organisms show the tendency towards mutation

- the product recovery from the biomass is difficult (e.g. break up of the

cells)

characteristics:

The culture broth is introduced into the reactor by constant feed. The feed

stream can be sterile or contaminated by the production strain. The same

amount of culture broth is taken out of the fermentor. All reactants,

concentrations of the compound, and of the cells, temperature etc. will be

kept constant. In the case of a continuous tube reactor (ideal plug flow

94

- -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

homogeneous.

In the case of a stirred tank reactor (ideal mixed flow reactor), there is no

local and no time gradient in concentration and temperature due to

effective mixing within the reactor. The reactor is described as being

capable of stationary behaviour and homogeneity. As a reactor model the

continuous ideal mixed vessel can be used.

in time in space

C C

Ca Ce

Ca z=a Ca

KIR Ce z=e Ce

CPFR t z

in time in space

C C

Ca Ce

Ca Ca

Ce Ce

KIK t z

CSTR

Advantages:

- high standard of automation

95

- -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

- smaller reaction volumes due to no non-productive times for filling and

idling, heating and cooling

- constant product quality due to constant operation conditions

- lower risk for the operation staff caused by non-manual operations

- lower wear on the equipment by reducing the sterilization cycles

Disadvantages:

- low flexibility due to fixed operation conditions

- demand for a constant quality of the raw materials

- high investment costs for automation and measurement devices

- higher risk of infection and mutation due to the long cultivation times

the advantages and disadvantages there is an applicability only for bulk

production and, if microorganisms are used that are stable and show no

mutation.

the steady state. In this case some components are running under batch

conditions, others (e.g. oxygen) under continuous conditions.

Due to the low solubility of oxygen it is necessary for all aerobe cultivations

to add oxygen continuously. Therefore, all batch reactors for aerobe

cultivations are running in a semi-continuous mode.

Furthermore, during the fermentation process the production of undesired

by-products occurs. These disturbing materials have to be constantly

removed (e.g. CO2 or organic acids).

96

- -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

Most of the reactors used in practice are describable with more or less

complicated mathematical models. One successful application uses a few

basic Ideal Reactor Types, which are combined or expanded to describe the

non ideal reactors.

In a BSTR one finds ideal mixing conditions realised by intensive stirring.

This reactor type runs under uniform composition everywhere in the

reactor, but of course the composition changes with time. For a batch

reactor the input and output rates are zero!

Therefore the balance equation is given:

dn i

VR ri (5 2)

dt

This reactor works homogeneous but not under steady-state conditions.

This reactor type runs under continuous conditions, but like the BSTR this

reactor type is uniformly mixed. That means same composition everywhere,

within the reactor and at the exit. While this reactor runs under steady-state

conditions the accumulation term becomes zero in Equ. 5 - 2.

dn i

0 (5 3)

dt

While there is no change in composition during time and volume this

reactor type is running under homogeneous and steady-state conditions.

97

- -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

dni

0 (5 4)

dt x const

This reactor type is an idealised long tube without any back-mixing inside,

which means fluid flows with a flat velocity profile. It also runs under steady-

state conditions but the composition changes progressively through the

reactor.

The discussed two ideal flow patterns, plug flow, and mixed flow can give

very different behaviour depending on order of reaction rate. But these two

cases are extrema and often not realisable in technical equipments. In the

following part the real mixing in technical equipments will be discussed.

The residence time t of a defined element of the volume leaving the

reactor is the period of this element staying in the reactor. These periods of

each volume element (and even single molecules) differ from each other.

This fact leads to the residence time distribution.

The average residence time t of all volume elements is not easy to

define in general for all cases of mixing conditions. This is the reason to

introduce the space time.

The space time is defined as that time one needs to run the same

volume as reactor volume at starting conditions through the vessel.

VR

a

time (5 5)

V

VR - reactor volume

a

V - feed stream at reactor entrance

98

- -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

Space time is the relation between reactor volume and volumetric feed flow

(at reactor entrance and under defined conditions). If there is no change in

density of culture medium inside the reactor then space time is equivalent to

the average residence time.

1 V 1

s a time (5 6)

VR

This is the relation between volumetric feed flow and the reactor volume.

Batch Stirred Tank Reactor (BSTR)

Equations for calculating the reaction time and the reaction volume:

Residence time t:

A

d A n Ka n K

t n Aa conversion (5 7)

a V rA n Ka

V = const.:

cA

dc A

t rA

(5 8)

c Aa

1 c Aa

t ln (5 9)

k cA

1 1

fr Aa 0 : t ln (5 10)

k 1 A

A

d A

beiV Va 1 A : t n Aa rA Va 1 A (5 11)

Aa

99

- -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

Ideal Stirred

Ideal Tube Reactor (KIR)

Tank (KIK)

(plug flow)

(for Aa 0 )

A

d A n Aa

Reactor Volume n Aa

rA A

Aa rA

Space time =

A

d A c Aa

a) generally c Aa rA rA

A

Aa

b) First order

reaction, 1 1 1 A

ln

constant density, k 1 A k 1 A

Aa 0

c) 1 order reaction,

1 1 1 A

a 1 A

V

V 1 ln A 1 A

k 1 A k 1 A

Aa 0

(5-12) to (5-14)

- 38 -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

Ideal Stirred Tank (KIK)

(KIR)

(for Aa 0 )

(plug flow)

Mean

Generally

residence time

A

d A c Aa A

t c Aa a

V t

Aa

rA V rA 1 A 1 A

For 1. order

1 A

reaction,

k 1 A

constant density

(5-15)

- 85 -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

chemical processes. These continuous methods have replaced the non

stationary processes in many cases. Particularly in the production of

commodities there are numerous advantages of using continuous methods:

S higher productivity

S simplier process automation

S homogeneous product composition

In contrast to chemical technology continuous methods are rarely used in

biotechnology. One important application is the biological waste water

treatment.

The most essential reasons that have prevented the use of continuous

methods in biotechnology until now are:

S Problems of sterility

It is difficult to run long time fermentations in a sterile mode.

S Specification of product charges

For the validation of pharmaceutical products, a charge number has

to be assigned to the product necessary.

S Danger of mutation and degeneration of cells

High productivity mutants are often unstable and due to their

degeneration a decrease in productivity occurs.

- 86 -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

optimal automation

Biological processes are subject to a broader spread, contrary to

chemical reactions, which run under a far reaching reproductiveness

obtaining the same productive quality. The knowledge of the course

of biological reactions is often missing.

Fermentations with external control are indicated by a constant growth rate.

This growth rate lies below the maximum value due to a controlled influx.

The growth of the cells is kept constant by the concentration of the

nutrients. Each substrate can be used as a limiting factor. In practice such a

system is controlled by keeping the liquid level constant in the fermentor.

The cell concentration is measured (optical density, biomass probes) and its

growth is kept constant by the adjustment of the substrate influx. This type

of control is particularly desirable.

This classification is similar to that of chemical reactors and is based on

physical and operational criteria. The nature of the fermentation and

biological criteria is not taken into account.

- 87 -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

a) open systems

b) closed systems

1) homogeneous systems

2) heterogeneous systems

3) mixed systems

diluted out of the fermentor. In the closed systems, the biomass is held

back in the fermentor by either immobilization or back flow. The back flow

as part of the biomass is also possible in open systems.

Homogeneous systems are using well mixed reactor types (ideal stirred

tank characteristic). There are no local gradients in the concentration of the

cells and of the substrate. Those gradients are found in heterogeneous

systems (as a rule, they are desired in this case).

only one homogeneous liquid phase. Contrarily, multi phase systems

contain a second phase (gas or solid phase). If two or more non mixable

fluids are used, the system is called multi component system.

- 88 -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

homogeneous

100 % recycled cells

S

100%

100%

with 100 % recycled cells 100 % recycled cells

- 89 -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

homogeneous

(single stage)

particular recycled cells

- 90 -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

homogeneous

(multi stage)

S S Z Z

heterogeneous

single phase multi phase

cells in substrate out

S

cells out substrate in

mixed system

- 91 -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

5.3.2.1 Mass balance

balance of all the involved compounds (microorganisms, substrates and

products).

The construction of mass balance equations are clarified in the following

chapter.

cA cA2

1

1. Definition of the balance area

2. Estimation of the in- and out-flow

3. Determination of the involved compounds

4. Formulation of the balance equation

- 92 -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

V0 Ve

ci

o V R ci

For the general case of the continuous stirred tank fermentor, the mass

balance for the cell density can be formulated as follows:

F [l/h] F

X0 [g/l] X

S0 [g/l] S11

F flow rate

X0 cell density (in-flow)

X1 cell density (out-flow)

S0 substrate concentration (in-flow)

S1 substrate concentration (out-flow)

(for the CSTR also the concentration inside the fermentor)

V reaction volume

- 93 -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

Balance

dX1 dX

V F X 0 F X1 V 1 (5 17)

dt dt growth

2

dX1 F F dX

X 0 X1 1 (5 18)

dt V V dt growth

Definition:

F flow rate

D dilution rate

V reaction volume

The increase of cell density due to growth is given by:

dX1

X1

dt

Combining these expressions one obtains:

dX1

D X 0 X1 X1 (5 19)

dt

For a stationary case the change of biomass in time is equivalent to zero. If

the in-flow contains no microorganisms (X0 = 0), the following result is

obtained:

D X1 X1 or

(5 20)

D

For a steady state the specific growth rate is equivalent to the dilution rate.

- 94 -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

a stirred tank cascade containing n vessels

arbitrary stirred tank depicting a cascade.

F [l/h ]

X [g/l]

0

S [g/l] X1 X Xn

0 n-1

p [g /l] S1

0 V V .. S n-1 V Sn

P1

P Pn

n-1

1 2 n

The mass balance for the cell density X inside the nth vessel is given by:

dX n

V F X n 1 F X n V n X n (5 21a)

dt

or, after divided by the volume:

dX n

DX n 1 X n n X n (5 21b)

dt

The mass balance for the substrate S inside the nth vessel is given by:

dSn dS

V F Sn 1 F Sn V n (5 22a)

dt dt growth

- 95 -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

dSn 1

DSn 1 Sn nXn

dt YX / S

(5 22b)

Y

DSn 1 Sn P / X n X n

YP / S

whereby:

X

YX / S cell substrate yield

S

P

YP / S product substrate yield

S

P X

YP / X YX / S

X S

The mass balance for the product P inside the nth vessel is given by:

dPn dP

V F Pn 1 V n F Pn (5 23a)

dt dt production

or:

dPn

DPn 1 Pn YP / X n X n (5 23b)

dt

In the case of the steady state, the left sides of the equations (5 21) to (5

23) are zero. Therefore, the biomass of the nth vessel is given as:

D X n 1

Xn for n 1

D n

D X n 2

X n 1

D n 1

D X n 1 D2 Xn 2

Xn ..........

D n D n D n 1

- 96 -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

D n 1 X1

Xn n

(5 24)

D i

i2

Equation (5 24) allows the estimation of biomass Xn within the nth vessel.

Moreover, the specific growth rate n can be calculated from the biomass

Xn, Xn-1, etc.

As for the boundary condition n=1, meaning the cascade has only one

vessel, the biomass X0 on the right side of equation (5 21) to approach

zero. Because the functional correlation between the specific growth rate

and the substrate concentration, defined by Monod, is valid, the following

equation applies:

S1

1 D max (5 25)

K S S1

Since

S1

1

K S S1

the maximum specific growth rate can never be reached under those

conditions, the conclusion is

D max

so that no wash-out of the cells occur.

The stationary product concentration for the nth vessel can be determined in

an analogue way:

D Pn 1 YP / X n X n

Pn (5 26)

D

- 97 -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

YP / X 1 X1

Pn YP / X X1 (5 27)

D

The stationary substrate concentration can be calculated by:

1 YP / X

Sn Sn 1 n Xn

D YP / S

or:

1 1

Sn Sn 1 nXn (5 28)

D YX / S

YP / X / YP / S

S1 S0 1X1

D

or, for = D

The result for S1 is:

YP / X

S1 S0 X1

YP / S

1

S1 S0 X1 (5 29)

YX / S

For the stationary mode, in the case of which one single vessel is used, Eq.

(5 25) can be transformed into:

KS

S1 (5 30)

max

- 98 -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

Accepting that D = :

D KS

S1

max D

or transformed:

KS

S1 (5 31)

max

1

D

As long as the dilution rate is much smaller than max, the substrate

concentration can be obtained from Eq. (5 31) as:

D KS

S1 (5 32)

max

transformation as:

D KS

X1 YX / S S0 (5 33)

max

It is evident according to Eq. (5 31) and (5 32), that for D<<max the

concentration of the limiting substrate proportional increase starts at zero. If

D approaches the value of max, the concentration of S1 increases rapidly

and becomes infinite by D = max.

However, this case can not occur in reality, due to the fact that:

S1 S0

That means S1 can never overcome the initial substrate concentration!

The cell concentration is given at small values of D approximately by YX/S

S 0.

- 99 -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

For

D max and S S0 follows X1 0 !

This condition is called wash-out, and it appears when the provided dilution

rate is greater than the specific growth rate.

Conclusion: the residence time of the microorganisms inside the bioreactor

gets shorter than the average generation time.

The relations during continuous fermentations are shown in a clear

representation by the graph X over D, or S over D.

5 X 5

4 8 4

3 6 DX 3

2 4 S0 2

1 2 S 1

flow rate (h-1)

- 100 -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

max = 1,0 h-1

YX/S = 0,5

S0 = 10 g/l

KS = 0,2 g/l

Pr X D

using Eq. (5 33) and (5 31) it follows:

D KS

X D D YX / S S0 (5 34)

max D

To identify the value of D which leads to a maximum of XD, it is necessary

to formulate the expression:

dX D

0

dD

and solve it for the dilution rate (D)Pr,max. This calculation is the result for the

maximum productivity:

KS

D Pr,max max 1

(5 35)

K S S0

Due to the fact that KS << S0, it consequently shows that generally the

maximum of productivity is the yield near the wash-out point.

- 101 -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

The biomass at the dilution rate for maximum productivity can be obtained

from Eq. (5 33) and (5 31):

KS

X1 YX / S S0 (5 36)

max

1

D

Substitution of D by Eq. (5 35) leads to:

KS

X1 YX / S S0

max

1

KS

max 1

K S S0

KS

KS KS

K S S0

X1 YX / S S0

KS

K S S0

K K S S0

X1 YX / S S0 S KS

KS

X1 YX / S S0 K S K S S0 K S (5 37)

- 102 -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

Graphic methods

determined graphically in the case of equilibrium. From the balance

equation (5 - 19) under the boundary condition X0 = 0 and steady state

one obtains:

dX1 dX

0 1 D X1

dt dt growth

or transformed:

dX1

dt growth

X1 (5 38)

D

The growth rate (dX1/dt)growth is obtained directly from the grade of the

growth curve given by the cultivation under batch conditions.

X

d X1

X1

d t

t

Fig. 5 - 14: Growth curve

- 103 -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

Plotting dX/dt versus X, one obtains a straight line with the gradient:

1 dX

gradient

X dt

which is similar to the dilution rate D under steady state conditions of the

continuous culture.

The point of intersection between the straight line with the grade D and the

growth curve from the batch culture is a stationary operating point of the

continuous culture.

dX

d t Operating point

D

X1

X

The point of intersection between the straight line with the grade D and the

growth curve from the batch culture is a stationary operating point of the

continuous culture.

- 104 -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

dX 2 dX

0 2 D X 2 X1 (5 39)

dt dt growth

dX 2

dt growth

X 2 X1 (5 40)

D

The positions on the operating points are shown in Fig. 5-16. This graphic

method can only be applied, if the growth curve of the batch culture is

equivalent to those of the continuous culture. This assumption is often not

fulfilled due to the continuous change of the environmental conditions of a

batch culture!

Nevertheless, this method can be consulted to estimate the stable operating

point of a continuous culture approximately from batch data.

Operating point 1

dX

d v

Operating point 2

D

X1 X2

X

- 105 -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

5.4.1 Vessel with cell recycling

FR=(1+" )F

F

S0 X1 F,X2,S1

X0= 0 S1

FX,XX,S1

V, X 1

"F, XX, S1

F = flow rate (inflow)

FR = flow rate (outflow of the reactor)

F* = flow rate (clearified outflow of the separator)

F*X = flow rate (concentrated outflow of the separator)

= relation of back flow

F = flow rate of the recycled cell suspension

FR 1 F (5 41)

and:

F F* FX* (5 42)

- 106 -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

Calculating the cell density by applying the mass balance, the result is:

dX1 dX

V X X F 1 FX1 1

dt dt growth

dX1

X X D 1 DX1 1X1 (5 43)

dt

Introducing the Monod equation:

dX1 S1

X X D 1 DX1 max X1 (5 44)

dt K S S1

Subsequently, the mass balance can be applied for the determination of

substrate as follows:

dS1 S

V FS0 FS1 1 FS1 V 1

dt dt growth

dS1 1

DS0 DS1 1 DS1 1X1 (5 45)

dt Y / S

dS1 1 S1

DS0 DS1 1 DS1 max X1 (5 46)

dt Y / S K S S1

1 dX1 X

1 D X D

X1 dt X1

or:

X

D1 1 X (5 47)

X1

- 107 -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

1 FX1 F*X 2 FX* X X FX X

F* X 2 X X FX* F

1 F F*

X2 XX *

X 1 X1

FX F

From this follows:

XX X

1 F F 2

X1 X1

FX* F

or:

F* X 2

1

XX F X1

X1 FX*

F* X 2

1

XX F X1

(5 48)

X1 F*

1

F

By inserting equation (6-48) into equation (6-47), one gets:

F* X 2

1

F X1

D1 1 (5 49)

F*

1

F

- 108 -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

1

D1 1 (5 50)

F*

1

F

1,0

F*

: F

=0

D 0,8

0,6

0,6

0,4 0,8

0,9

0,2

F* 0,95

= 1

F 0,98

0

0 1 2 3

"

Fig. 5-18: Influence of the relation of back flow on /D

bioreactor where the dilution rate D is greater than the specific growth rate

. Those conditions were used specifically in the field of waste water

treatment.

For the condition F*/F = 0 the same situation is found in a single vessel

system without recycled cells. In this case the specific growth rate must be

equal to the dilution rate for stationary behavior.

- 109 -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

S1 X

max 1 X D AD (5 51)

K S S1 X

with

X

1 X A

X

The substrate concentration S1 is given by:

AD

S1 K S S1

max

K S AD

S1 (5 52)

max AD

YX / S

X1 S0 S1 (5 53)

A

From the equations (5-51) to (5-53) the coherence between biomass X,

substrate concentration S, the productivity XD and the dilution rate can be

calculated. The courses are presented in fig. 5-19. To compare the

conditions without back flow of the cell are also pointed out in this graph.

- 110 -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

10

A

X 5 C

0

0 1 2

D

Fig. 5-19: Courses of concentration during a continuous fermentation

max = 1,0 [h-1] = 0,5

YX/S = 0,5 Xx/X = 2

S0 = 10 [g/l] KS = 0,2 [g/l]

A: Biomass concentration in the fermentor

B: Productivity

C: Cell concentration in the outlet

D: Cell concentration without back flow

E: Productivity without back flow

- 111 -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

known in the waste water treatment and in the case of different substrates

during induced conversions. Under normal conditions the substrate S will

be utilised nearly completely in the first level. That means that the

concentration of the substrate is decreasing to low values and in the case

without substrate addition, only a subordinating growth can be obtained!

Another point of view is to run the first reactor close to the wash out point,

then the utilisation of substrate is low in this vessel.

Third, it is possible to run both vessels under the same growth rate. But it

can easily be shown that under these conditions the productivity is the same

as the yield in one vessel with the equivalent volume.

Advantages of the use of multi stage systems are only found if

- a complex growth media is used

- a certain physiological growth condition is desired.

The case of complex media is given, if two or more substrates are present,

which leads to different growth rates. In such a broth the better usable

substrate can be utilised in the first vessel at relatively high dilution rate, and

the other substrate is converted much slower but nearly complete in the

second vessel as the only substrate (multi-stage waste water treatment).

The fermentor broth contains the substrate A and B and the following

assumptions are valid:

YXA/ S YXB/ S K SA K SB Amax Bmax

- 112 -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

F F

F

A A A

S0 S1 S2

B B

B S1 S2

S0

V1 X1 V2 X2

A

S0

X S B0

XB

S

XA

D

Fig. 5-20 and 5-21: Two stage facility without back flow of the cells

The mass balance of the first stage is equivalent to that of a single vessel, for

the second stage it is found for the biomass:

dX 2 B SB2

D 2 X1 D 2 X 2 max X 2 B (5 54)

dt K S SB2

- 113 -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

dSB2 1 SB

D 2 S1B D 2 SB2 Bmax B X 2 B 2 B (5 55)

dt YX / S K S S2

steady state:

X 2 X1 YXB/ S S1B SB2 (5 56)

D 2 X1

X2 (5 57)

D 2 K SB SB2 Bmax SB2

D

X1 YXA/ S S0A K SA A 1 B (5 58)

max S2

- 114 -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

vessel

the substrate S0 is utilised in the first vessel.

In the second stage a wash out can never happen, as long as the biomass

from the first stage is fed. That means D2 can even be greater than max.

F2 S0,2

F1

(F1 + F2 )

S0 S1 S2

X1 X2

V1 X1 F1 V2 X2

Fig. 5-22: Two stage facility with additional substrate in the second vessel

dS2 V1 F 1 S2

D1S1 2 S0, 2 D 2S2 max X 2 (5 59)

dt V2 V2 YX / S K

S S 2

with

F1 F F2

D1 andD 2 1

V1 V2

- 115 -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

second vessel

(Biotransformation)

F2 Z0

F1

(F1 + F2 )

S0 S1 S2

X1 X2

V1 X1 F1 V2 X2 P2

Z2

Fig. 5 - 23: Two stage facility with an additional second substrate in the

second vessel

Legend of fig. 5 - 23:

P = product

Z = convertible substrate

YP/Z = -dP/dZ

YP/Z = -dP/dZ

In these cases the following attempt is valid:

dZ dP Z

YP / Z k X (5 60)

dt dt KZ Z

For the case that KZ << Z the product formation rate is given:

dP

kX

dt

- 116 -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

For the dilution rates D1 and D2 the following equations are valid:

F1 F1 F2

D1 and D 2

V1 V2

vessel, the next equation directly follows:

X 2 F1 F2 F1 X1

or:

F1 F1

X 2 X1 YX / S S0 (5 61)

F

1 F2 F

1 F2

Due to the fact that the substrate for conversion is added in the second

vessel, the balance of Z is given by:

dZ 2 1 F F2 F

kX 2 1 Z 2 2 Z 0 (5 62)

dt YP / Z V2 V2

For steady state:

F2 V2 1

Z 2 Z 0 kX 2 (5 63)

F1 F2 F1 F2 YP / Z

exit of the second vessel (Z2) equal to zero. In this case the equation (5-45)

becomes:

1 1 F1

F2 Z 0 V2 kX 2 V2 k YX / SS0 (5 64)

YP / Z YP / Z F1 F2

- 117 -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

Ideal and non-ideal residence time behaviour

b) channel flow (bypass)

c) back flow

Fig. 5-24: Examples for reactor types with non-ideal residence time

distribution

2 extrema: a) plug flow reactor (ideal), CPFR,

b) stirred tank reactor (ideal), CSTR.

Step input at time t = 0 at the entrance of the reactor (t < 0: no tracer; t >

0 with tracer)

- 118 -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

All flow elements leaving the reactor at a given time (t = n) have an

identical residence time.

ci

c ia

1,0

0

J t

Fig. 5-27

c i part of volume elements at reactor exit

c ia with a residence time shorter than t

The concentration of ci within the reactor is constant at any place (ideal

mixed flow). The concentration at reactor exit must be identical with the

concentration ci within the reactor. Changing the input flow at time t = 0

from concentration ci to concentration cia leads to a change in concentration

at reactor exit as a function in time.

t

ci

1 e 1 e (5 65)

c ia

t

dimensionless time

Fr t :

ci

1 e 1 0,63212

c ia

- 119 -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

ci

c ia

1,0

0

J t

Fig. 5-28

The concentration course ci/cia as a function in t f(t) with cia = 1 gives the

step response curve, the so called Residence time sum function F.

The function F (t) gives that part of exit flow with a residence time shorter

than t within the reactor.

t0 F0

t F 1

The part of exit flow with a given residence time within the reactor could be

determined by differentiating the F-curve at t:

d Ft

E t (5 66)

dt

l t 1 F t (5 67)

That part of exit flow staying a time period between t and (t + dt) within the

reactor is given by:

d Ft Et d t (5 68)

- 120 -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

t

Ft Et d t

0

F Et d t 1 (5 69)

0

F0 0

The average residence time is given as the average value of residence time

of all flow elements.

t N t N t E t

t 0

0

t E t d t (5 70)

N N 0

(t + dt).

= N E(t)

VR

t (5 71)

V

change in density and chemical reaction (isothermal conditions), therefore:

V

a; VR

V t space time (5 72)

a

V

It may be suitable for comparing different reactor types with regard to their

characteristic residence time behaviour to use the dimensionless time :

t V t

(5 73)

VR

- 121 -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

dt

d

t

F Ft (5 74)

dF dF

E t t E t dimensionless

d dt

Function Distribution

Symbol F E

Ft Et d t E t

function dt

0

(IR) F 1 fr t E fr t

t

t

F 1 e E e

continuous tank (KIK)

- 122 -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

functions

(Heaviside-function).

b) The pulse experiment; input: pulse function, (Dirac-

function, Delta-function).

c) The periodic input experiment; input: periodic function (Sinus-

function)

d) The random input experiment; input: random function (white

noise)

Fig. 5-29:

- 123 -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

stirred vessels.

change in reactant concentration

by reaction

Damkhler number Da l

convective mass transport

(5 75)

VR rA

Da l

V c

A

a ; VR ;

V rA

V Da l

a

V cA

(5 76)

space time

For the continuous stirred tank reactor (CSTR):

A V

Da l with V a (5 77)

1 A

For a cascade of n ideal vessels (each of them with the same volume and

with constant density) the following equation is valid:

N

c Ne c e 1 V

a

with V

c1a c a N Da l 1

N

(5 78)

c 1

cascade N 1 e 1

ca N Da l 1

The conversion N N-vessel cascade with the same volume for each vessel is

given for a 1st order reaction at constant densty by:

V rA

N

1

Da l R k N 1 (5 79)

cA

V k i 1

- 124 -

Bioprocess Engineering Prof. Dr. Rainer Buchholz

1

N c a N

N i 1 (5 80)

k c e

1 1

N 1 N N 2 ... N N 1

2! N 1!

F 1 e

(5 81)

N

E N N 1 e N (5 82)

N 1!

- 125 -

- Chemical Engineering paperDiunggah olehsupermaqp
- Final HPDiunggah olehAniket Gawde
- cre2Diunggah olehfayaz5uin1234
- solution pengpro.pdfDiunggah olehHeda Heldiana
- Scale-Up Problems MoldDiunggah olehKeehong Kim
- Modeling Ald Sim of ATR in Amonnia PlantDiunggah olehCarlos Benavidez Aranibar
- Citric Acid Production Stirred TankDiunggah olehKarliiux Medina
- set1ans-10Diunggah olehhazzim
- Comparison of Different Reactor Types Used in the Manufacture of Ethoxylated, Propoxylated ProductsDiunggah olehfarah_affandy
- kinetics of the homogeneous reverse water-gas shift reaction.pdfDiunggah olehSutrisna Adi Wiguna
- Multiphase FlowDiunggah olehCarlos Manuel Romero Luna
- Catalytic Rates & Pressure Drop in PFR ReactorsDiunggah olehIntroCPA
- CDB2043 Course Outline and Planning May 2016 Student CopyDiunggah olehKinosraj Kumaran
- 4 vs 3Diunggah olehEvans Irabor
- www.ijerd.comDiunggah olehIJERD
- 1-s2.0-S1359431113006674-main.pdfDiunggah olehGary Kiel Palacios Espinoza
- August 2015 - InternationalDiunggah olehHarold Fernando Guavita Reyes
- 8 UnitDiunggah olehHrvn Gouthamrao
- 247119610-Lab-5-Production-of-Ethyl-Chloride.docxDiunggah olehlyn
- The Effect of Hydrodynamics on Riser Reactor Performance of the FCCUDiunggah olehAnonymous 7VPPkWS8O
- 1-s2.0-S138589471101151X-mainDiunggah olehmarcelcerri
- FCCUDiunggah olehsmrndrdas
- Dynamic Modeling and Process Optimization of Sulfuric Acid PlantDiunggah olehchikukotwal
- [2011]Enhanced degradation of caffeine and caffeine demethylase production by Pseudomonas sp. in bioreactors under fed-batch mode.pdfDiunggah olehChaitanya Naidu
- 1 Self Tuning Fuzzy PID Controller for a Chemical Process.pdfDiunggah olehGlan Devadhas
- A Hierarchical Optimization Approach to Optimal Production Scheduling in an Industrial Continuous Olefin Polymerization ReactorDiunggah olehMarco Ravelo
- JHuska_Performance of Immobilized Cells for Dihexyl...Diunggah olehDavid Muñoz Huachuhuillca
- CUMENE_1Diunggah olehParth
- minimiseDiunggah oleh力捷
- Heterogeneous Reactor DesignDiunggah olehS S S REDDY

- Relatório de eletricidadeDiunggah olehNicoly Didoné
- Rel Saponificação.Diunggah olehNicoly Didoné
- MATERIAL BALANCE NOTES.pdfDiunggah olehNicoly Didoné
- VOGEL ORGANICA PRATICA - Vogel Practical Organic Chemistry.pdfDiunggah olehNicoly Didoné
- Skript LSE Kapitel 3 Und 4Diunggah olehNicoly Didoné
- Manual para utilização do SI.pdfDiunggah olehNicoly Didoné
- 9 - Extração e Purificação Da Cafeína – BAC 2013Diunggah olehsambermeo
- 2.8 a Derivada Como Uma FunçãoDiunggah olehNicoly Didoné
- Análise Nodal e de MalhasDiunggah olehNicoly Didoné
- 2.7 Derivadas e Taxas de VariaçãoDiunggah olehNicoly Didoné
- Guia de Laboratório FQ Exp UFAM V3 2014Diunggah olehNicoly Didoné
- Aquecimento Global - QuimicaDiunggah olehNicoly Didoné
- Alga 1 VetoresDiunggah olehCarlos Mendonça
- conceitos básicos de MatFinDiunggah olehAna Paola Carvalho
- Trabalho De AnalíticaDiunggah olehNicoly Didoné
- critérios para diagnosticar mutismo.docxDiunggah olehNicoly Didoné
- Apostila Fenômenos de Transporte A.pdfDiunggah olehLauro Freitas Rodrigues
- Apostila Gestão AmbientalDiunggah olehNicoly Didoné
- cap01-14Diunggah olehJoyce Andrade

- 24 TPO Speaking SolutionsDiunggah olehAli Roony
- JBoss_Admin_Console_GuideDiunggah olehamarnathwissen
- Strength Design AppendixDiunggah olehdelurved2811
- 11 Chapter 2Diunggah olehharsitha
- phy-pdf-1Diunggah olehab
- 2. WTA-Lesson4Diunggah olehIman Jaff
- Ejercicio INFOTECHDiunggah olehUser22
- ForestryDiunggah olehRajanRanjan
- ES Development Tools1Diunggah olehlavanyakodidasu
- 2way2sat iDirect InstallationDiunggah olehDaniel Piette
- Advanced 2 MillanDiunggah olehAna Enclonar
- Ee6301 Dlc Question Bank RejinpaulDiunggah oleharuljothi
- Chapter 2 Cmos Fabrication Technology and Design RulesDiunggah olehvanarajesh62
- Non Asbestos Fibre Jointing SheetsDiunggah olehRohit Gadekar
- MCB-MCCBDiunggah olehNam Nguyen
- Generic Unpacking Using Entropy AnalysisDiunggah olehhmirzaei
- BARC Information_Brochure 2017.pdfDiunggah olehPreetham Saigal
- Sistema de Intercom Sem Servidor SP2Diunggah olehJuan Manosalva
- 2142Diunggah olehBikila Desalegn
- Estaca Brochure-2017 EnglishDiunggah olehAshish Malik
- An VI - Shell-Low SulphurDiunggah olehVictor Eugen
- Academic Sacred Cows and Exponential Growth (166181956)Diunggah olehEDUCAUSE
- LED EDGE Plus Street Lighting_BajajDiunggah olehsoumya mondal
- Boolean Algebra and Logic Simplification - Digital Electronics Questions and AnswersDiunggah olehchiranjibavi
- Special-Lite FRP Flush Door Testing Summary BrochureDiunggah olehSpecial-Lite Doors
- Industrial Management - Control and Profit - A Technical Approach - Gideon Halevi (Springer, 2014)Diunggah olehMeer Shakeel
- Surface Roughness TestDiunggah olehSusheel Petle
- ES-ACV-S100-S1100Diunggah olehWatts
- -_41a-KMK Panduan Praktik Klinis Bagi Dokter_1-785-1Diunggah olehAnnisa Rahmadhania
- MANUAL International.pdfDiunggah olehTallerGarza