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The batch bioreactor is
the most extensively used in the biotechnology industry, yet this class
of bioreactor as compared to the continuous operating reactors has
several limitations. These include
heterogeneity of reaction fluid in the batch reactor when large
scale batch reactor designs are simply performed by the traditional
scale-up methods, the
death of cells during the emptying and recharging of reactors
for next run cycles, the
need to support of two consecutive reactions in same batch
reactor and inability to use high conversion but pathogenic microbes
in batch reactors among other considerations. However, heterogeneous
batch bioreactor, carefully and creatively designed and in which the microbes immobilization beads are
in suspended flow dynamics impressed on the reaction fluid by stirring
essentially, overcomes all the limitations.
In the sense that reactor as
per the fundamental design
is heterogeneous and as such on inheriting some of the features and characteristics of the
packed bed bioreactor such as the use of
immobilized
microbes in bioreactors, then to a great extent solves the issues of
microbes use limitations. Further, progressing to inherit other
features of the batch reactors that may have been solved through
such reactors, in essence the equipment design being adopted is the
same as for a packed bed bioreactor. The design of the
heterogeneous bioreactor effectively reflects the rationale that
overcomes the issue of rapid emptying and reconstitution as as well
as readiness for next run cycle.
Reactor Equipment Design Specialization
However, creative
design changes in the reactor are implemented to enable some
critical dynamics. First, inside the cylindrical vessel, at some
height above the level of the lower flange of the body cylinder, a
porous media, preferably an inert mesh, of pore size smaller than
the smallest diameter of the immobilization beads, is mounted. Below
this mesh is mounted a variable speed impeller of narrow span driven
by a motor below the reactor cylinder, such that when turned on, the
fluid is impelled up towards the top of the reactor.
Most importantly as a
specification of the
general design rationale, the design of the bioreactor must have
an integrated
Fermentation Mash Feeder equipment. The specific configuration
of the equipment is application-specific being dependent on the
reactants and
catalysts that must be added to the substrate to be termed the
Feed-Mash
necessary to also support the anabolic reactions for cell
maintenance. Further, the Mash Feeder outlet, which is the reactor
feed inlet, is designed or adapted to enable to introduction
of the
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immobilized microbe beads into the Mash and to allow the
pumping of resulting heterogeneous mixture into the reactor vessel
as well as to removal of same from the vessel.
The outlet of the reactor is
connected to a solid-fluid separator that rapidly separates the
immobilization beads from the effluent reaction mixture and the
fluid pumped into a product storage tank. The beads are automatically discharged into
a reconstitution vessel to prevent
the microbes cell death but of limited substrate and other growth
inhibiting substances to effect the reconstitution.
The Reactor Dynamics Analysis
At charging of the reactor
with feed, the impeller is set at low but fast enough speed to impel the
beads into a region of the fluid above the porous media. Upon the charging of the
feed, the impeller speed is then increased to cause enough reaction
mixture to flow through the porous media and to levitate the beads.
The impeller speed for production is calibrated to keep the beads bunched together
within the column of flow but without being convected out of that
column within the region of fluid.
When being operated under the
efficacious
operating conditions, the beads get to be suspended and remains
virtually stationary in the psuedo-column of flow than is created from the
impeller rotation. The fluid however flows past the beads and
re-circulates in the reactor vessel. The operation is sustained for
the length of the reaction time as pre-evaluated from an the
immobilized
microbes metabolic reaction kinetics analysis based on the use
of the Monod
equation or the more
rigorously
derived alternative. At the end of the reaction time the
impeller speed is increased to cause the beads to get convected with
the fluid in the circulation and then pumped out of the reactor.
Computational Design
Given, the precision settings
of the impeller speeds at various points of the operation, the
implicit characteristics of the impeller, and the degree of porosity
of the mesh media of the design of the stirred heterogeneous batch
bioreactor, the determination of such operating conditions and
design specifications are best determined through the computational
design of the equipment design, to support the dynamics under which
the design objectives are met.
The reactor by the mode
of operation is a Random Newtonian Many Body Media. In effect then,
the analysis can be undertaken using the Method of Reflection.
Effectively then, the mathematical description for the computational
design of the
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reactor can be developed
based on the Method of Reflections which is in essence a Cluster
Expansion Analysis of multi-body systems; and as such the solution
proffered is a convergent series of cluster solution of the
Newtonian Many Body Problem. However, these series is very fast
convergent and so the Single Body Problem often gives a very good
initial solution of the overall problem.
In effect then the
computational design of the reactor may sufficiently determine the
precise operating conditions by the computational analysis of the
representative single body problem, which is the
Heterogeneous Bioreactors Single Body Problem.
Of course, it is entirely
possible that there may have have to performed a level of design on
the impeller to determine its precise characteristics, however, that
would be quite effective in respect of the prospective return on
investments such design effort should bring as a result of efficacy
of the bioreactor in providing relative high productivity
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