|
Microbial metabolic fermentation
operations often are performed with the
Homogeneous Batch Bioreactors. By this mode of
operation, the microbes that are fed into the bioreactors together
with the substrates are generally not recovered at the end of the
reaction. The continuous disposals of the microbes however very
quickly adds up to a significant expense for the operation. Preferably,
therefore, the
microbes are immobilized then used in
heterogeneous bioreactors so as to be recovered at the end of the
reaction-time. The immobilization of the microbes is often carried
out in a vessel that is called microbes
Immobilization Reactor; however, the reactor may also be
designed for use to recondition or restore initial immobilization
state of the microbes prior to reintroduction into the bioreactor.
Such reactors deployed for the purposes of reconditioning the
immobilized states of microbes would be functioning as fermentors
for heterogeneous bioreactors.
In principle though, a
fermentor is a bioreactor dedicated to the growth of microbes for
various target-uses. and because the reconditioning immobilization
reactor will in essence provide microbes in their most active state
for use in heterogeneous bioreactors, this class of reactor is
effectively a fermentor for heterogeneous reactors. The design of a Fermentor for the purposes of supporting continuous biotechnology
process is both straight forward and tasking. The design of
Fermentors is straightforward because the functionality of the vessel is
often very well-defined. However, the design is just as tasking
because the vessel is expected to effect a precise re-initialization
of the microbes in the immobilized state.
The re-initialization is the
resetting of the carriers of immobilization back to the original
state before being introduced into the bioreactors. This
re-initialization is of critical importance because for the
bioreactor to provide performance that is reproducible, the carrier
- with the immobilized microbes - entry state must be the same every
time for every inlet feed. Besides in developing the
reactor design, an initial entry condition was assumed, which serves as the default reference
inlet condition for the assessment of the
in-use performance of the bioreactor.
The tasking aspect of the
re-initialization stems from the non-uniformity with which the
microbes grow during the stay in the bioreactors. Obviously by the
Monod equation, the microbes grow as per certain empirical rule.
However, it is also known that the microbes usually suffer product
inhibition as the degree of bio-reaction completion gets high;
|
and in fact begins to die at
a certain stage of the progress
of the reaction. Conceivably then, the microbes in the different
carrier units therefore will be in different qualities of active state.
This is without doubt also likely to occur to different degrees of
diversity as a function of the continuous bioreactors: Moving Bed
Bioreactor, Entrained Bed Bioreactor, Tubular Fixed-Bed (also called
Packed Bed) Bioreactor, and Semi-Continuous Batch BioReactors such as
Stirred Heterogeneous Batch Bioreactor; in which
the carriers were used. This is even more so when the bioreactor
design has inadvertently introduced factors that could effect
conditions of heterogeneity in the reaction-mixture during the
operation of the bioreactor, which is a situation that should obtain
when a Mash
Feeder is not integrated into the reactor during design.
The biofilm of the bioreactor
at the end of the reaction-time or at exit from the bioreactor will
have carriers that need to be restored to the reference
design-specified inlet state,
but will be at different active states that as such require different extents of restoration or
re-initialization. The task in some respects is to evaluate the
possible dominant - meaning statistically meaningful - exit state of
the microbes and then begin the restoration from that level of
assumed immobilization
activity. This evaluation process is by means a
trivial task, as it has to be constructed mathematically and implemented
as a
computational system in order to
accomplish the evaluation quickly. Two approaches for accomplishing
this task: An Empirical
Approach, analytically Rigorous Approach; are possible though both are based on the
use of Neural Network Analysis as the core method.
The Empirical
Re-initialization Approach
has the outlet state of the immobilized microbes measured for each
of the carrier under real-time operating conditions and during the
heterogeneous bioreactor operation. The
information is then feed into a Neural Network System for
construction of Fuzzy Math relationship. This relationship is then
employed to determine the statistically meaningful data for each
batch of effluent immobilized microbes.
The Analytically Rigorous
Re-initialization Approach takes an
entirely theoretical approach to modeling the movement of the
immobilization carriers, possibly with Stochastic
methods, within the bioreactor and from this calculation assess the
median values. These values are then incorporated into again a Neural
Network system for association with the measured data, in training
the systems to evaluate the results based on the theoretically
calculated and proffered data.
|
In either case after
the median data determination by the Neural Network System, the
result is then used to set the Fermentor operating time for the
re-initialization of the immobilized microbes.
Moreover, the prevailing state of microbe immobilization as
determined also defines the Mash feed-quality required for restoring
the reference active state of the microbes.
The use of this techniques for
Tubular Flow Fixed Bed Bioreactors as opposed to the other types of continuous bioreactors
involving random movement of the immobilizer carriers is somewhat
modified. First and foremost, the operating policy or protocol must
be such as to permit intermittent interruption to reset the microbes
state. In general, the design of the fixed bed bioreactor can be
such as to induce fluid circulation and therefore force a narrow
band of variation of the state of the immobilized microbes at the
end of the batch-wise run.
The Immobilization Re-initialization Fermentor
Reactor by design must necessarily have a means of keeping the
microbes carriers suspended in the mash during the restoration
operation; the reactor must have the substrate quality and anabolic
reaction reactants such as suitable for restoring the microbes, as
well. Rationally a suitable reactor is of the class of Transport Bed
Reactor, because this class of reactor offers the condition where
the microbes are exposed precisely to the required mash feed quality
that slowly degrades as the microbes re-gains the preferred active
state. A properly calibrated reactor therefore will be such that the
microbes will have been fully restored as the microbes-carrier beads
are exiting the reactor. Such a reactor, of course, can
necessarily be deployed with a Mash Feeder of the design as used in
the fermentors for growing microbes used for the initial
immobilization, although, the mash nutrients quality must be
adjusted to comply with the assessed microbes-active-state
re-initialization conditions. Further, given the need to maintain
the microbes concentration in the encapsulation beads as of initial
use, this class of reactor should provide the most efficacious
control enabling microbes growth during the entry periods until the
Mash quantities reduces to the point of cellular functions
maintenance support when such is required.
|
