Figure 8: Batch-to-batch control of the peak retention time by the
gradient elution of a two component separation by cation exchange
chromatography, feed forward of desired set point, multivariable
feedback controller with decoupling. A pH disturbance in the elution
buffer is introduced in cycle 3, causing the controller to adjust the
gradient to restore the retention times.
Conclusions
This paper presents a methodology, based on a lab-scale platform, for
fast development of digital solutions in integrated continuous
downstream processes. The fundamental building block is the Orbit
supervisory controller that can control and communicate physical setups
and their associated local control software. Orbit is an open, flexible
and extendable software, which opens up the operation of the setup to
any computational tool. Many different kind of processing steps and
configurations has been implemented and operated using the methodology.
These setups can be connected and configured into complex processing
systems and a network of Orbit controllers makes it possible to operate
almost autonomous. Both the configuration and automation of multiple
processing steps and support systems are vital for sustainable and
autonomous operation for long-term studies of digital solutions.
During processing of the integrated continuous downstream process
platform data are streamed to the Orbit database. The on-line generated
data is heterogeneous, asynchronous and distributed. The data are design
and configuration information, real-time detector signals, asynchronous
chemical analysis data, real-time data analysis information and on-line
computational results. The Orbit software contains methods for automatic
generation of mechanistic models and model calibration. This makes it
possible to perform advanced data analysis, data-driven or mechanistic
modelling, optimization and machine learning. The results can directly
be implemented into the Orbit automation and control system for on-line
processing. The conclusion is that the physical and digital platform are
well suited for development, study and validation of real-time digital
twin application in downstream processing.
CRediT authorship contribution
statement
Niklas Andersson : Conceptualization, Methodology, Software,
Writing (review & editing), Supervision, Visualization, Project
administration.
Joaquín Gomis-Fons : Conceptualization, Methodology, Software,
Validation, Visualization.
Madèlene Isaksson: Conceptualization, Methodology, Software,
Validation, Visualization.
Simon Tallvod : Conceptualization, Methodology, Software,
Validation, Visualization.
Daniel Espinoza : Conceptualization, Methodology, Software,
Validation, Visualization
Linnea Sjökvist : Methodology, Software, Validation,
Visualization
Gusten Zandler Andersson : Methodology, Software, Validation,
Visualization
Bernt Nilsson : Conceptualization, Methodology, Resources,
Writing (review & editing), Supervision, Visualization, Project
administration, Funding acquisition.
Acknowledgement
This project has received funding Vinnova, (through the Competence
Centre for Advanced BioProduction by Continuous Processing, AdBIOPRO)
under Grant 2016‐05181, Grant 2019‐05314 (AutoPilot project), Grant
2022-01477 (AutoADD project) and finally from the European Union’s
Horizon 2020 research and innovation program under the Marie
Skłodowska-Curie grant agreement No 812909.
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