Model based control of fed-batch fermentations. Dr.sc.ing. Juris Vanags

Transcription

1 Model based control of fed-batch fermentations Dr.sc.ing. Juris Vanags

2 Substrate feeding in fed-batch fermentations general state (1) 1. Fed-batch is used, if it is necessary to ensure a high biomass concentration; 2. During fed-batch it is necessary to maintain sugar concentration in certain range; 3. Even a relatively short deviation from this range makes it impossible to return to the optimal performance of a process; 4. A particularity of the fermentation processes - impossibility of performing fully repeatable fermentations, even under absolutely identical cultivation conditions.

3 Substrate feeding in fed-batch fermentations general state (2) 5. As a result, to ensure optimal feeding during the fermentation, the feeding profile must be constantly corrected in respect to the performance of a particular fermentation process; 6. It means that the definition and input of corrections of the feeding profile in common cases directly depends on the skill of the operator; 7. This is contrary to the modern GMP requirements.

4 1. By po 2 control; Feeding control in fed-batch fermentations untill now Firstly, in this case it is impossible to control the ро 2 level by adjusting the stirrers rotation speed and/or oxygen enrichment of gas supplied during aeration; Secondly, reaching relatively high biomass densities, it becomes impossible to implement this control method inan optimal way. 2. The use of glucose sensors; The readings of these sensors, in the current state, are not reliable enough for fermentation control. 3. The use of ethanol and methanol measuring devices; The readings of these sensors can be successfully used for fed-batch control in yeast fermentations, however for other microorganism cultures the method is not applicable. 4. Specialy designed experimental systems. These systems are developed for specific microorganism cultures and are not available for other potential uses.

5 Availability and possibilities to control fed-batch 1. There are no available devices on the market that enable the control of feeding during fed-batch fermentations; 2. For the control of feeding during fed-batch it is necessary to apply on-line mathematic models; 3. Traditionally used process control systems (PLC and SCADA) can not perform such complicated mathematical operations; 4. In result, to control feeding during fed-batch fermentations, it is necessary to apply model based control.

6 Principle of model based control

7 Mathematical models

8 Example of the MATLAB program

9 Introduction to the model based control system To solve feeding control problems in fed-batch fermentations, we have developed a model based control system. Presented fed-batch control principle is oriented towards typical users, who are interested in fed-batch process control. Using off-line biomass and sugar analytical measurements, the current state of the process is compared to the reference data (desirable process). In case if any deviations are observed, the feeding profile is automatically corrected in order to run the process along the desired process path.

10 Block diagram of the offered approach

11 SCADA interface

12 Principles of the proposed approach The developed easy configurable system performs automatic corrections of the feeding profile using a MATLAB code based program, which is connected to the process controller PLC. PLC controls the feeding process by using scales and peristaltic pumps. The developed system can be applied using any bioreactor. Thanks to simplicity and robustness, this system can be used widely both in laboratory and industrial fed-batch fermentations.

13 Application of the system 1. Before running the fermentation process enter the reference profile (of the desired biomass growth dynamics) in to the program; 2. Run the application when the fermentation starts; 3. Periodically take biomass and sugar samples and enter the measurement results into the dialogue window of the program; 4. The system will compare the last entered results with the model, and when it is necessary, automatically correct the feeding profile; 5. Thereby the application will control the fermentation process so that it will be performed according to the reference biomass profile.

14 Selection of the reference biomass growth profile 1. The initial reference profile can be determined via mathematical modeling, based on batch fermentations and literature data; 2. Each subsequent fermentation process is analyzed, for potential improvement of the biomass yield by increasing the feeding rate at time points, where no significant sugar accumulation is observed. If such points are determined, the respective reference feeding profiles points are increased for higher biomass yield; 3. The improvements of the feeding profile can be carried out until the desired maximal biomass yield is achieved.

15 Example of reference profile improvement

16 Escherichia coli BL21 biomass production process improvement using model based control

17 Thank you for attention!