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Report Catalogue Data

  Report Class   General Public Report
  Analysis Type   Situation Analysis
  Issue Category   Technology Analysis
  Release Date   07_02_2008
  Last Update   06_10_2009
  Reference Code   GPR-SA.TA.FT-20080702-FHR

Biological Technologies
Fermentors for Heterogeneous Continuous Bioreactors

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.


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