Figure captions

Figure 1. Block diagram of the integrated continuous process studied. The clarified supernatant is mixed with detergent and loaded onto the virus inactivation (VI) reactor. The output stream from the reactor is loaded onto two of the capture columns (C1 and C2) run with a PCC operation. The periodic eluate from one of the capture columns (C3) is conditioned inline and directly loaded onto the polishing column (P)
Figure 2. The two-system setup. The system on the left was used for the continuous virus inactivation and the capture step run with a PCC operation. The system on the right illustrates the polishing step. The red line indicates the flow path during the interconnected load phase of capture column 1 (C1) with the breakthrough going to capture column 2 (C2). The blue dotted line shows the flow path during elution of the fully loaded column 3 (C3) and the simultaneous loading of the polishing column (P). The gray lines show inactive flow paths. The versatile valves (VV) were used to select different flow paths, the loop valve (LV) directs the flow to one of the three capture columns, the column valve (CV) allows the diluted feed to pass through the virus inactivation reactor (VI), and two outlet valves (OutV) allowed product collection in different parts of the process. In the system on the left, Pumps AP and BP were used to load the supernatant onto the capture columns, and the sample pump (SampP) was used in the recovery phases of the capture columns. In the system on the right, the gradient pump (GradP) was used in the recovery phases of the polishing column, and the sample pump was used for the inline conditioning between the two steps.
Figure 3. Areas under the breakthrough curve in relation to the loaded volume.
Figure 4. Effect of the load volume on the resin utilization and yield for different scenarios with respect to the binding capacity in the capture column. Data in the graph correspond to an empirical model (Eq. (1)) calibrated with the experimental breakthrough curve. Load volume refers to the total volume loaded onto a column in the 100% capacity scenario. Yields for 80% and 90% capacity scenarios were calculated for loadings with the same amount of adsorbed product as that in the 100% capacity scenario.
Figure 5. Illustration of the iterative learning control strategy with a previous cycle learning scheme. The variables uk and yk are the control and output signals, respectively, at iteration k; and yref is the reference value of the output signal.
Figure 6. Upper panel: Chromatographic profile of the capture step including the UV absorbance signal from the breakthrough stream from the interconnected capture columns (UV Breakthrough) and the outlet stream from a capture column during the recovery phases (UV Recovery). Alternate PCC cycles are indicated by light and dark gray backgrounds. Lower panel: Chromatographic profile of the polishing step where the shaded peaks represent the product pool.
Figure 7 . Product pools in cycles 3 and 6 showing the absorbance cutoffs, obtained with the pooling control strategy based on the peak height.
Figure 8 . Effect of the controller on the evolution of the downstream process. The process in which the controller was implemented following a concentration disturbance (c1A) is compared to a process without disturbance but with the controller (c0), and a process with disturbance but without the controller (c1B).