Tuning of dissolved oxygen and pH PID control parameters in large scale bioreactor by lag control

• Achieving satisfying DO and pH controllers are often challenges for pilot and large scale mammalian cultivation. Unsatisfactory DO or pH controls can imply fatal effects for the culture. Large scale bioreactors have long response times due to long mixing times compared to small scale systems where control tuning of DO and pH is not so challenging. A method was developed to tune the DO controller PID parameters of a 50 L bioreactor (wv) controlled by a continuous oxygen flow of microbubbles. DO control by continuous flow of pure oxygen microbubbles can oscillate quite widely showing instable behaviour. The method, called lag control here, was based on a lead lag control design by Bode analysis where the prediction part, i.e. ‘lead’ part was omitted. A comparison of this method with a pole placement approach showed the advantage of the lag control. It was decided to omit the derivate part which could lead to instability caused by the long delay observed between the applied oxygen flow and the response detected by the DO probe. Applying the lag control method resulted in a highly satisfactory DO control. In this system, the oxygen microbubbles were almost completely consumed before reaching the liquid surface as demonstrated by the absence of foam. So the oxygen flow used to maintain the DO gave an excellent indication of the cellular oxygen consumption. The control system was robust against all the perturbations of this system, i.e. cell growth, cell bleed, addition of air-saturated fresh medium, DO set point change and a second gas sparger used to strip out the carbon dioxide. The method was first tested with the sulphite oxidation method simulating the oxygen consumption with copper as catalyst to establish the PID parameters. Then the selected parameters were successfully used during cell cultivation. Following this, an adaptation of the method was done in order to avoid the sulphite oxidation method, which leaves copper traces in the bioreactor. This was successfully used in a 400 L bioreactor (wv) for the DO controller by continuous oxygen flow of microbbubles. The lag controller method was finally modified to tune the pH controller of the same 400 L bioreactor with control upward by alkali addition or downwards by pulsed carbon dioxide addition.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinsk bioteknologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Medical Biotechnology (hsv//eng)

Nyckelord

PID control

dissolved oxygen

pH

lead-lag control

SRA - Molecular Bioscience

SRA - Molekylär biovetenskap

Publikations- och innehållstyp

ref (ämneskategori)

kon (ämneskategori)