Figure 7: Size exclusion chromatography of two components with dynamic Kalman filter prediction of column profile using Orbit. Concentration profiles in the column together with outlet UV signal indicated at 100s, 140s, 170s and 210s.
As discussed above the integrated continuous downstream process can assume slow varying disturbances from the upstream process, like titer and other quality attributes. Other disturbances are buffer quality, which can change more drastically. For integrated downstream process with slow varying upstream disturbance it can be beneficial to control the separation using a batch-to-batch controller. The idea is to use previous batch behavior to compensate in the next batch. A batch-to-batch controller for retention time control using a salt gradient are presented in Espinoza et al (2022A) and (2022B), and an adaptive batch-to-batch controller for capture loading is presented in Löfgren et al (2021).
Note that the controller needs good information about the real system and this information can be retrieved in two different ways. The first way is by an automatic modelling with calibration as discussed above to generate a simplified model for controller tuning. The other way, presented in Espinoza et al (2022B) is by performing a set of on-line experiments for on-line controller tuning.