Parameter-by-parameter method for steric mass action model of ion exchange chromatography: Theoretical considerations and experimental verification

Chen, Yu‐Cheng; Yao, Shan‐Jing; Lin, Dong‐Qiang

doi:10.1016/j.chroma.2022.463418

Cited by 18 publications

(13 citation statements)

References 48 publications

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“…Our preliminary research has already elucidated how to design elution experiments to better utilize the PbP method. [33,34] The injection volumes of sample and elution conditions for bind-and-elute experiments are listed in to be modeled within the linear gradient phase.…”

Section: Bind-and-elute Experimentsmentioning

confidence: 99%

“…[6,9] However, the accurate calculation of σ was a complex and challenging task, and various approaches have been explored in recent studies. [33,34,57,58]…”

Section: F I G U R Ementioning

confidence: 99%

“…The SMA model was calibrated by the PbP method as published in our previous papers. [33,34] Experiments No. 1, 2, and 3 in Table 2 are used for LR1 calculation with Equation (12), where GH is a known parameter.…”

Section: Determination Of Sma Parametersmentioning

confidence: 99%

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Standardized approach for accurate and reliable model development of ion‐exchange chromatography based on parameter‐by‐parameter method and consideration of extra‐column effects

Chen,

Lu,

Wang

et al. 2024

Biotechnology Journal

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Developing an accurate and reliable model for chromatographic separation that meets regulatory requirements and ensures consistency in model development remains challenging. In order to address this challenge, a standardized approach was proposed in this study with ion‐exchange chromatography (IEC). The approach includes the following steps: liquid flow identification, system and column‐specific parameters determination and validation, multi‐component system identification, protein amount validation, steric mass action parameters determination and evaluation, and validation of the calibrated model's generalization ability. The parameter‐by‐parameter (PbP) calibration method and the consideration of extra‐column effects were integrated to enhance the accuracy of the developed models. The experiments designed for implementing the PbP method (five gradient experiments for model calibration and one stepwise experiment for model validation) not only streamline the experimental workload but also ensure the extrapolation abilities of the model. The effectiveness of the standardized approach is successfully validated through an application about the IEC separation of industrial antibody variants, and satisfactory results were observed with R2 ≈ 0.9 for the majority of calibration and validation experiments. The standardized approach proposed in this work contributes significantly to improve the accuracy and reliability of the developed IEC models. Models developed using this standardized approach are ready to be applied to a broader range of industrial separation systems, and are likely find further applications in model‐assisted decision‐making of process development.

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Section: Bind-and-elute Experimentsmentioning

confidence: 99%

“…[6,9] However, the accurate calculation of σ was a complex and challenging task, and various approaches have been explored in recent studies. [33,34,57,58]…”

Section: F I G U R Ementioning

confidence: 99%

See 1 more Smart Citation

Standardized approach for accurate and reliable model development of ion‐exchange chromatography based on parameter‐by‐parameter method and consideration of extra‐column effects

Chen,

Lu,

Wang

et al. 2024

Biotechnology Journal

Self Cite

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show abstract

“…To address these issues, we have recently developed a novel parameter-by-parameter (PbP) method for steric mass action (SMA) model calibration. , The PbP method features a one-by-one calibration strategy that yields physically meaningful parameters. Furthermore, it can be easily implemented using Microsoft Excel spreadsheets, known for their pedagogical potential in chromatography. − Therefore, in this activity, we would employ spreadsheets to implement the PbP method and utilize group learning to compare different calibration methods, assisting novice modelers in selecting the most suitable approach.…”

mentioning

confidence: 99%

“…To address these issues, we have recently developed a novel parameter-by-parameter (PbP) method for steric mass action (SMA) model calibration. 12,13 The PbP method features a oneby-one calibration strategy that yields physically meaningful parameters. Furthermore, it can be easily implemented using Microsoft Excel spreadsheets, known for their pedagogical potential in chromatography.…”

mentioning

confidence: 99%

Practical Teaching of Modeling Tools for Ion-Exchange Chromatography: A Case Study

Chen,

Lin

et al. 2023

J. Chem. Educ.

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The utilization of modeling tools has gained significant attention recently. These models typically involve a series of partial differential equations, which can be challenging for novice modelers. This paper presented an approach in practical teaching of modeling tools for ion-exchange chromatography with three parts: model introduction, model calibration through group learning using different calibration strategies, and model applications. This approach was integrated into the traditional bioseparation engineering curriculum as an activity, using the separation of monomer–dimer mixtures of monoclonal antibodies as an example. Results of competitive group learning and the Wilcoxon test revealed that the parameter-by-parameter method was more user-friendly than the Yamamoto method for novice modelers to obtain reasonable model parameters quickly. Then, students used the well-fitted model for process optimization and explored the effects of process parameters and material input variation on the chromatography process, which helped students appreciate the critical role of time and material savings achieved through modeling tools. Finally, the student questionnaire results revealed that over two-thirds of the students gave positive feedback on the activity. Through this practical teaching, students became familiar with chromatography modeling tools, moving away from the tedious formulaic descriptions found in traditional modeling courses. This well-designed activity can be expanded from academia to industry, transforming the novice modelers into experienced modelers who can meet the high demands of the modern biopharmaceutical industry.

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Realization of digital twin for dynamic control toward sample variation of ion exchange chromatography in antibody separation

Shi,

Chen,

Zhong

et al. 2024

Biotech & Bioengineering

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Digital twin (DT) is a virtual and digital representation of physical objects or processes. In this paper, this concept is applied to dynamic control of the collection window in the ion exchange chromatography (IEC) toward sample variations. A possible structure of a feedforward model‐based control DT system was proposed. Initially, a precise IEC mechanistic model was established through experiments, model fitting, and validation. The average root mean square error (RMSE) of fitting and validation was 8.1% and 7.4%, respectively. Then a model‐based gradient optimization was performed, resulting in a 70.0% yield with a remarkable 11.2% increase. Subsequently, the DT was established by systematically integrating the model, chromatography system, online high‐performance liquid chromatography, and a server computer. The DT was validated under varying load conditions. The results demonstrated that the DT could offer an accurate control with acidic variants proportion and yield difference of less than 2% compared to the offline analysis. The embedding mechanistic model also showed a positive predictive performance with an average RMSE of 11.7% during the DT test under >10% sample variation. Practical scenario tests indicated that tightening the control target could further enhance the DT robustness, achieving over 98% success rate with an average yield of 72.7%. The results demonstrated that the constructed DT could accurately mimic real‐world situations and perform an automated and flexible pooling in IEC. Additionally, a detailed methodology for applying DT was summarized.

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Parameter-by-parameter method for steric mass action model of ion exchange chromatography: Theoretical considerations and experimental verification

Cited by 18 publications

References 48 publications

Standardized approach for accurate and reliable model development of ion‐exchange chromatography based on parameter‐by‐parameter method and consideration of extra‐column effects

Standardized approach for accurate and reliable model development of ion‐exchange chromatography based on parameter‐by‐parameter method and consideration of extra‐column effects

Practical Teaching of Modeling Tools for Ion-Exchange Chromatography: A Case Study

Realization of digital twin for dynamic control toward sample variation of ion exchange chromatography in antibody separation

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