第三章 生物反应器的操作模型

生物反应器的操作模式
§3.3 Modifying Batch and Continuous Reactors
Two Kinds of Modified Chemostat Bioreactors Involved
Chemostat with Recycle
Multistage Chemostat System

生物反应器的操作模式
Operability and reliability

Batch:
great variability. from one run to another, product quality and concentration create problems in downstream processing and are undesirable.
A simple batch and chemostat represent extremes. Now, let‘s consider productivity as a criterion.
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生物反应器的操作模式
Batch reactor
In exponential phase,
Xm 1 te ln Xm X 0 e μm X0 The total time to complete a batch cycle is:

Chemostat:
long-term continuous culture can be problematic. Pumps may break, controllers may fail, so on. Maintenance of sterility can be very difficult to achieve for periods of months. The consequence of a loss of sterility is more severe than with batch culture.
KS
KS Dopt Xexample, μ max 1 S i K S K S (S i K S ) opt YX S For E. coli fermentation, K S Si Xm X 0 20, t 1 5h, μ m 1.0h 1
YX S S i rb Xm 1 ln t1 μm X0
生物反应器的操作模式
Chemostat
d(DX) 0 dD
Dmax,ouput
Xopt
Solved
μ max 1
KS K S Si

Substitution
KSD YX S S i μm D YX S S i K S K S (S i K S )
What cells are; How they work; How to describe their growth in simple reactors; How to use these cells in real processes.
生物反应器的操作模式
We will explore some more complicated reactor strategies and why they might be considered for use in real processes, because the choice of reactor and operating strategy determines: Product concentration; Number and types of impurities; Degree of substrate conversion; Yields; Whether sustainable, reliable performance can be achieved. Unlike many traditional chemical processes, the reactor section represents a very major component (usually>50%) of the total capital expenditures.
K S (S i K S S) KComparison of batch reactor and chemostat K K (S K ) S
S S i S
K SSi
Si
i
:0 1
1
The productivity,
rc,opt rb
Xm ln μm t1 X0
生物反应器的操作模式
§3.2 Choosing the Cultivation Methods
How to choose a cultivation mode ?
batch culture – batch reactor Three Modes fed-batch culture
continuous culture – chemostat
dX1 FX0 αF CX1 (1 α )FX1 V μX1 V dt
conical tank
Where : recycle ratio based on volumetric flow rates;
C: concentration factor or ratio of cell concentration in the cell recycle stream to the cell concentration in the reactor effluent; F: nutrient flow rate; V: culture volume;
μm t
Rearranged
Xm 1 tc ln t1 μm X0
where t1 is the sum of time required for the lag phase, harvesting and preparation (cleaning, sterilizing and filling), usually 3~10 h. The rate of cell mass production in one batch cycle:
生物反应器的操作模式
§3.1 Introduction
Batch Reactor
Extremes
Ideal
Chemostat
Suspension
Reactor design Immobilized
Modification: with intermediate characteristics Nonideal
生物反应器的操作模式
Genetic instability The biocatalyst in most bioprocesses has undergone extensive selection. These high ―bred‖ organisms often grow less well than the parental strain. A chemostat places strong selection pressure for the most rapidly growing cells.
生物反应器的操作模式 Balance equations of the substrate:
μX1 dS FS 0 αFS (1 α)FS V V YX S dt dS At steady-state, 0 dt
Solved
D X1 YX S (S 0 S) μ
X0 X1: cell concentration in feed and recycle streams;
X2: cell concentration in effluent from the cell separator.
生物反应器的操作模式
At steady-state,
dX1 0 dt
For sterile feed, Then
From the Monod model for growth, K Sμ K S D(1 α αC) S μ m μ μ m D(1 α αC) Combining yields,
K S D(1 α αC) X1 S0 1 α αC μm D(1 α αC) YX S


The best productivity,
Dopt Xopt
YX S μ max 1
KS K S Si
S K S K S (S i K S ) i


生物反应器的操作模式
Under normal circumstances, Si >> KS Then the rate of chemostat biomass production is, K S :0 K S Si
Market economics

Chemostat: a dedicated processing system. -dedicated to a single product. provide much greater flexibility. Batch: The same reactor can be used for two months to make product A and then for the next three for product B and the rest of the year to make product C.
X0 0
dX1 FX0 αF CX1 (1 α )FX1 V μX1 V dt
Solved
μ (1 α αC)D 1 α(1 C) D
Since C>1, then <D. That is to say, a chemostat can be operated at dilute rates higher than the specific growth rate when cell recycle is used.
生物反应器的操作模式
§3.3.1 Chemostat with Recycle
Cells in the effluent stream are either centrifuged, filtered or settled in a conical tank for recycling. Balance equations of the cell:
rc,opt rb Xm ln μm t1 X0
applies only to growth-associated products. Many secondary products are not made by growing cells. Growth represses the product formation. Product is only made at very low dilutions, far below these values optimal for biomass formation. For secondary products, the productivity in a batch reactor may significantly exceed that in a simple chemostat.


Simplified
yields
rc,opt D Xopt YX S μ max S i opt r r 8 c,opt b
生物反应器的操作模式
But why most commercial bioprocesses are batch systems ?
Product species The equation,