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Binary separation control in preparative gradient chromatography using iterative learning control

Espinoza, Daniel LU ; Andersson, Niklas LU orcid and Nilsson, Bernt LU (2022) In Journal of chromatography. A 1673.
Abstract
Purification of biopharmaceuticals has shifted toward continuous and integrated processes, in turn bringing along a need for monitoring and control to maintain a desired separation between the target pharmaceutical and any impurities it may carry. In this study, a cycle-to-cycle control of the retention volumes of two compounds in a chromatographic, ion exchange purification step was developed, allowing the process to maintain the desired retention volumes in the separation. The controller made use of a model-based, multivariate iterative learning control (ILC) algorithm that used a quadratic-criterion objective function for optimal set point control, along with feed-forward control based on direct model inversion for preemptive control of... (More)
Purification of biopharmaceuticals has shifted toward continuous and integrated processes, in turn bringing along a need for monitoring and control to maintain a desired separation between the target pharmaceutical and any impurities it may carry. In this study, a cycle-to-cycle control of the retention volumes of two compounds in a chromatographic, ion exchange purification step was developed, allowing the process to maintain the desired retention volumes in the separation. The controller made use of a model-based, multivariate iterative learning control (ILC) algorithm that used a quadratic-criterion objective function for optimal set point control, along with feed-forward control based on direct model inversion for preemptive control of set point changes. The model was calibrated using 3 experiments, allowing for fast setup. The controller was tested by introducing three different disturbances to a sequence of otherwise identical ion exchange separation processes: a change in the salt concentration of the elution buffer, a change in set point, and a change in the pH of the elution buffer. It was capable of correcting for all disturbances within at most 3 cycles, proving its efficacy. The successful application of ILC for separation control in biopharmaceutical purification paves the way for the development of further ILC-based control strategies within the field, as well as combination with other control strategies. (Less)
Please use this url to cite or link to this publication:
author
; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Preparative chromatography, Ion-exchange, Separation control, Iterative learning control, Feed-forward control, Model-based control
in
Journal of chromatography. A
volume
1673
article number
463078
pages
12 pages
publisher
Elsevier
external identifiers
  • scopus:85129237374
  • pmid:35512504
ISSN
1873-3778
DOI
10.1016/j.chroma.2022.463078
language
English
LU publication?
yes
id
1da556cb-209f-4e19-a3a9-81427d0d4b3b
date added to LUP
2022-05-02 17:09:17
date last changed
2023-12-19 18:48:09
@article{1da556cb-209f-4e19-a3a9-81427d0d4b3b,
  abstract     = {{Purification of biopharmaceuticals has shifted toward continuous and integrated processes, in turn bringing along a need for monitoring and control to maintain a desired separation between the target pharmaceutical and any impurities it may carry. In this study, a cycle-to-cycle control of the retention volumes of two compounds in a chromatographic, ion exchange purification step was developed, allowing the process to maintain the desired retention volumes in the separation. The controller made use of a model-based, multivariate iterative learning control (ILC) algorithm that used a quadratic-criterion objective function for optimal set point control, along with feed-forward control based on direct model inversion for preemptive control of set point changes. The model was calibrated using 3 experiments, allowing for fast setup. The controller was tested by introducing three different disturbances to a sequence of otherwise identical ion exchange separation processes: a change in the salt concentration of the elution buffer, a change in set point, and a change in the pH of the elution buffer. It was capable of correcting for all disturbances within at most 3 cycles, proving its efficacy. The successful application of ILC for separation control in biopharmaceutical purification paves the way for the development of further ILC-based control strategies within the field, as well as combination with other control strategies.}},
  author       = {{Espinoza, Daniel and Andersson, Niklas and Nilsson, Bernt}},
  issn         = {{1873-3778}},
  keywords     = {{Preparative chromatography; Ion-exchange; Separation control; Iterative learning control; Feed-forward control; Model-based control}},
  language     = {{eng}},
  month        = {{06}},
  publisher    = {{Elsevier}},
  series       = {{Journal of chromatography. A}},
  title        = {{Binary separation control in preparative gradient chromatography using iterative learning control}},
  url          = {{http://dx.doi.org/10.1016/j.chroma.2022.463078}},
  doi          = {{10.1016/j.chroma.2022.463078}},
  volume       = {{1673}},
  year         = {{2022}},
}