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- Axelsson, Jan Peter, et al.
(författare)
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Substrate Control of Biotechnical Fedbatch Processes. Robustness and the Role of Adaptivity
- 1990
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Konferensbidrag (refereegranskat)abstract
- Results from experiments on laboratory scale fedbatch processes are presented as well as analysis and design of the control system. The main reason for control is to track the drastic growth in feed demand during a cultivation. Variations in the amount and quality of the inocculum makes precalculated dosage schemes of limited value to obtain reproducible cultivation conditions. Two processes have been studied on a laboratory scale, production of bakers' yeast, and production of the enzyme salicylate hydroxylase using a strain of bacteria. Direct measurement was used to monitor the feed demand. A regulator structure is proposed based on an observer for the exponentially growing feed demand. It can be viewed as a modified PID regulator around a dosage scheme, but it is less sensitive to errors in the dosage scheme than conventional PID control. The a priori knowledge of the feed profile is further relaxed by introduction of adaptation of the growth rate parameter. The obtained non-linear control system has a simple structure and stability is garanteed for a wide range of initial values using the technique of Liapunov function. The linearized system is analysed in the frequency domain and the adaptation is shown to have negligible influence on the loop phase margin. The adaptive regulator is tested in simulation against real feed profiles and shows good results.
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- de Maré, Lena, et al.
(författare)
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A cultivation technique for E. coli fed-batch cultivations operating close to the maximum oxygen transfer capacity of the reactor
- 2005
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Ingår i: Biotechnology Letters. - : Springer Science and Business Media LLC. - 0141-5492 .- 1573-6776. ; 27:14, s. 983-990
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Tidskriftsartikel (refereegranskat)abstract
- A cultivation strategy combining the advantages of temperature-limited fed-batch and probing feeding control is presented. The technique was evaluated in fed-batch cultivations with E. coli BL21(DE3) producing xylanase in a 3 liter bioreactor. A 20% increase in cell mass was achieved and the usual decrease in specific enzyme activity normally observed during the late production phase was diminished with the new technique. The method was further tested by growing E. coli W3110 in a larger bioreactor (50 l). It is a suitable cultivation technique when the O2 transfer capacity of the reactor is reached and it is desired to continue to produce the recombinant protein.
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- de Maré, Lena, et al.
(författare)
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Temperature limited fed-batch cultivation with a probing feeding strategy for Escherichia coli
- 2004
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Ingår i: Computer Applications in Biotechnology 2004. - 008044251X ; , s. 73-79
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Konferensbidrag (refereegranskat)abstract
- A cultivation strategy combining the advantages of temperature limitedfed-batch and probing control is presented.This is a suitable way to produce recombinant proteins while minimizing therelease of endotoxins which complicates the downstream processing.The downside with the temperature limited fed-batch technique has been the difficulty to achieve a controlled excess of glucose inthe reactor without the accumulation of acetic acid when usingstandard sensors.A method using a probing feeding strategy withdown-pulses is here suggested. The technique is investigated insimulations and experiments.
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- Holst, Olle, et al.
(författare)
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Substrate Control in Fed-Batch Cultivations Using a Model-Based Modification of a PI-Controller
- 1992
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Ingår i: Proceedings of the 2nd IFAC Symposium on Modelling and Control of Biotechnical Processes.
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Konferensbidrag (refereegranskat)abstract
- A fedbatch process shows exponential growth under ideal conditions. To obtain good substrate concentration control it is necessary that the regulator can track an exponentially growing feed demand, and standard PI-control has to be supplemented with an estimated basic dosage to get reasonable control. However, an exponentially growing concentration error is impossible to avoid. An I-term could be interpreted as an observer of a constant demand, and we have proposed to replace it with a model-based observer for an exponentially growing demand. In the resulting controller the integrator is replaced by an unstable pole at s = μ, the specific growth rate, and the initial condition of this term is equivalent to the basic dosage part. The regulator can now track the exponentially growing feed demand without error. Pseudomonas cepacia was grown on salicylate as sole carbon and energy source. Salicylate is a toxic substrate, so it is important to have good substrate control. On-line measurement of salicylate concentration was carried out using a filtration system from which cell-free permeate was passed to a flow-through spectrophotometer. Introducing more instability into the controller requires attention to the anti-windup features. No such problems were found during the cultivations or in simulations of the effect of conceivable disturbances like pump-failure, air-bubbles in the spectrofotometer, and low oxygen concentration induced growth-rate reduction.
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