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).