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Discretized multi-level elution trajectory: A proof-of-concept demonstration

Sellberg, Anton LU ; Holmqvist, Anders LU ; Magnusson, Fredrik LU ; Andersson, Christian LU and Nilsson, Bernt LU (2017) In Journal of Chromatography A 1481. p.73-81
Abstract
Biomolecular and pharmaceutical downstream processing is dominated by chromatographic separation, which is associated with high product quality, low capacity and high costs. The separation can be optimized to minimize the costs while achieving a high purity. This paper presents an experimental validation of a discretized multi-level elution (DiME) trajectory, implemented on commercially available chromatography equipment. The tertiary protein separation of ribonuclease A, cytochrome C and lysozyme was used as a case study. A mechanistic model was calibrated using step and linear gradient experiments. The model was simulated together with the state sensitivities with respect to model parameters, which was used in the Levenberg–Marquardt... (More)
Biomolecular and pharmaceutical downstream processing is dominated by chromatographic separation, which is associated with high product quality, low capacity and high costs. The separation can be optimized to minimize the costs while achieving a high purity. This paper presents an experimental validation of a discretized multi-level elution (DiME) trajectory, implemented on commercially available chromatography equipment. The tertiary protein separation of ribonuclease A, cytochrome C and lysozyme was used as a case study. A mechanistic model was calibrated using step and linear gradient experiments. The model was simulated together with the state sensitivities with respect to model parameters, which was used in the Levenberg–Marquardt algorithm to fit the model response to the experimental data. The model was used to solve the dynamic optimization problem of maximizing the yield of cytochrome C given a 95% purity requirement, 1000 s processing time and 50 salt concentration levels in the elution trajectory. The model was spatially discretized using finite volumes and temporally discretized using direct collocation. The corresponding non-linear programming problem was solved with IPOPT. Once the optimal salt trajectory was found it was experimentally implemented on an ÄKTA Pure using an OPC interface. The optimal trajectory was analyzed in-line by UV absorbance measurements and off-line by analysis of collected fractions. The results presented in this study show the successful experimental realization of DiME trajectories and how to use model calibration, optimization and control to realize DiME trajectories for any chromatography separation problem. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Chromatography A
volume
1481
pages
9 pages
publisher
Elsevier
external identifiers
  • scopus:85009888094
  • wos:000392681400009
ISSN
0021-9673
DOI
10.1016/j.chroma.2016.12.038
language
English
LU publication?
yes
id
2ee32c3d-c82c-4cad-a325-ee0ed883c12c
date added to LUP
2017-01-16 09:34:03
date last changed
2018-01-07 11:45:12
@article{2ee32c3d-c82c-4cad-a325-ee0ed883c12c,
  abstract     = {Biomolecular and pharmaceutical downstream processing is dominated by chromatographic separation, which is associated with high product quality, low capacity and high costs. The separation can be optimized to minimize the costs while achieving a high purity. This paper presents an experimental validation of a discretized multi-level elution (DiME) trajectory, implemented on commercially available chromatography equipment. The tertiary protein separation of ribonuclease A, cytochrome C and lysozyme was used as a case study. A mechanistic model was calibrated using step and linear gradient experiments. The model was simulated together with the state sensitivities with respect to model parameters, which was used in the Levenberg–Marquardt algorithm to fit the model response to the experimental data. The model was used to solve the dynamic optimization problem of maximizing the yield of cytochrome C given a 95% purity requirement, 1000 s processing time and 50 salt concentration levels in the elution trajectory. The model was spatially discretized using finite volumes and temporally discretized using direct collocation. The corresponding non-linear programming problem was solved with IPOPT. Once the optimal salt trajectory was found it was experimentally implemented on an ÄKTA Pure using an OPC interface. The optimal trajectory was analyzed in-line by UV absorbance measurements and off-line by analysis of collected fractions. The results presented in this study show the successful experimental realization of DiME trajectories and how to use model calibration, optimization and control to realize DiME trajectories for any chromatography separation problem.},
  author       = {Sellberg, Anton and Holmqvist, Anders and Magnusson, Fredrik and Andersson, Christian and Nilsson, Bernt},
  issn         = {0021-9673},
  language     = {eng},
  month        = {01},
  pages        = {73--81},
  publisher    = {Elsevier},
  series       = {Journal of Chromatography A},
  title        = {Discretized multi-level elution trajectory: A proof-of-concept demonstration},
  url          = {http://dx.doi.org/10.1016/j.chroma.2016.12.038},
  volume       = {1481},
  year         = {2017},
}