PART 3 Flashcards
Types of Reactor
Batch and Chemostat (CSTR)
_________: changing conditions - transient (S, X, growth rate), high initial substrate, different phases of growth.
Batch
________: steady-state, constant low concentration of substrate, constant growth rate that can be set by setting the dilution rate (ie. the feed flow rate).
Chemostat
__________ is more efficient.·
Chemostat
____________ is more common.
Batch
CHOICE OF CONTINUOUS VS
BATCH PRODUCTION
Productivity
Flexibility
Control
Genetic stability
Operability
Economics
Regulatory
_________: rate of product per time per volume. Chemostat is better for growth-associated products. Wasted time in batch process.
Productivity
____________: the ability to make more than one product with the same reactor. Batch better.
Flexibility
___________: maintaining the same conditions for all of the products produced. In theory, the chemostat is better, steady state. In reality???
Control
____________: maintaining the organism with the desired characteristics. Chemostat selects for fast-growing mutants that may not have the desired characteristics.
Genetic stability
___________: maintaining a sterile system. Batch better.
Operability
____________: validating the process. Initially, many process batch, too expensive to re-validate after clinical trials.
Regulatory
Consider the production of a growth-associated product (like cell mass) in _________.
suspension culture
__________ of a chemostat is detrimental to engineered organisms.
Selective pressure
_______ is more mechanically reliable.
Batch
_______ system is more more flexible.
Batch
SPECIALIZED REACTORS
Chemostat with recycle
Multistage chemostat
Fed-batch
Perfusion
Can we operate a chemostat with a dilutio rate greater than
maximum growth rate?
Why or why not?
No
Because the cell growth cannot keep up with how fast the cells are removed from the reactor, and after some time the cells would washout of the reactor.
What conditions would we want to opera a chemostat with a dilution rate higher than the maximum growth rate?
We want a high dilution rate when we have a high volume of feed with a low concentration of substrate. Waste water treatment has these characteristics.
Chemostats ___________ if µmax <D. Higher dilution rates can be achieved with recycling.
cannot be operated
Recombinant product under the control of an inducible promoter.
Special Cases - Chemostat
_______________ grow at the same rate if the recombinant product is not expressed.
If the recombinant product is expressed, the ___________________.
Recombinant strain and wild type
recombinant strain grows much slower
First chemostat is fed with a non-inducing growth substrate, allowing the recombinant strain to be produced.
The effluent from the first chemostat feeds a second chemostat that is fed inducer, and the product is produced.
Note: new recombinant cells are continually added to the second chemostat not allowing take-over by a fast growing mutant.
MULTISTAGE CHEMOSTAT
_________ gain some advantages of a CSTR, retain some disadvantages of batch.
Fed-batch reactors
variable volume batch reactor
Reduces substrate inhibition or catabolic repression, allows for high conversion, and the extension of stationary phase.
Semi-batch nature usually leads to higher operation cost and batch variability.
Fed-batch Operation
____________ are started as batch cultures and grown to an initial cell concentration X, after which fed-batch operation begins.
Fed-batch cultures
Usually, fed-batch cultures are taken through many feeding cycles, with each feeding cycle followed by a harvest cycle during which the volume is drawn back down to Vo and the cycle begun again.
Repeated Fed-batch
Substrate is consumed at the same rate it is added.
QUASI-STEADY STATE
PERFUSION CULTURE
Animal Cell culture
Constat medium flow
Cell retention
Selective removal of dead cells
Removal of cell debris, inhibitory by products
High medium use, costs raw materials and sterilization.
