Parameter estimation and rate model simulation of partial breakthrough of bovine serum albumin on a column packed with large Q Sepharose anion-exchange particles

Gu, Tingyue; Iyer, Ganesh; Cheng, Kwok-Shun

doi:10.1016/j.seppur.2013.06.004

Cited by 12 publications

(8 citation statements)

References 25 publications

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“…This model considers axial dispersion, interfacial film mass-transfer resistance, and intraparticle diffusion in the multicomponent LC system. The dimensionless equations for eluite species i are as listed below for the bulk-fluid phase and the particle phase, respectively [12].…”

Section: Mass-transfer Modelmentioning

confidence: 99%

“…The other dimensionless mass transfer parameter, ξ i , is calculated from 3Bi i •η i (1−ε b )/ε b in which ε b is the bed voidage. The estimation of these mass-transfer parameters from existing masstransfer correlations were recently described in detail by Gu et al [12] who supplied a spreadsheet for their calculations as a supplement to their publication.…”

Section: Mass-transfer Modelmentioning

confidence: 99%

“…Unlike the Langmuir isotherm used in most LC models [12], the ion-exchange isotherm in the generalized form here is implicit, inherently multicomponent. In general there is no explicit analytical expression for Q i .…”

Section: Adsorption Equilibrium Modelmentioning

confidence: 99%

“…(9) is a subset of Eq. (12). When the rate constants are sufficiently large, local equilibrium is achieved such that ∂Q i /∂t=0, Eq.…”

Section: Adsorption Equilibrium Modelmentioning

confidence: 99%

“…For a typical IEC system, one or two interior OC points together with a built-in exterior OC point are sufficient to describe the concentration profiles in the particle phase. For large beads in some preparative-and large-scale applications, more OC points are needed as recently demonstrated by Gu et al in adsorption LC [12]. After the discretization of Equations (1) and (2), the resultant ordinary differential equation (ODE) system will consist of N s (2N e +1)(2N c +1) ODEs if Ne number of finite elements and N c number of interior OC points are used for a system with N s species.…”

Section: Numerical Solutionmentioning

confidence: 99%

See 4 more Smart Citations

A General Rate Model of Ion-Exchange Chromatography for Investigating Ion-Exchange Behavior and Scale-up

Mehay¹,

Gu²

2014

J Microb Biochem Technol

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This work presents a general rate model for ion-exchange in column chromatography with the steric massaction isotherm that is suitable for ion-exchange systems involving macromolecules such as large proteins. This comprehensive model considers axial dispersion, interfacial film mass transfer between the bulk-fluid phase and the particle phase, and intraparticle diffusion. The model system has been solved numerically using the finite element method and the orthogonal collocation method with a graphical user interface for Windows based personal computers. The effect of pH is modeled by including buffers, acids, and bases as species in the model system, allowing the induced pH gradients resulted from H + or OH -sorption by the ion exchanger to be described in the model. Feed profiles of all the species can be specified individually allowing complicated gradient patterns. The software, known as Chromulator-IEX, may be a useful tool for the investigation of ion-exchange chromatography behavior and its scale-up.

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Section: Mass-transfer Modelmentioning

confidence: 99%

Section: Mass-transfer Modelmentioning

confidence: 99%

Section: Adsorption Equilibrium Modelmentioning

confidence: 99%

“…(9) is a subset of Eq. (12). When the rate constants are sufficiently large, local equilibrium is achieved such that ∂Q i /∂t=0, Eq.…”

Section: Adsorption Equilibrium Modelmentioning

confidence: 99%

Section: Numerical Solutionmentioning

confidence: 99%

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A General Rate Model of Ion-Exchange Chromatography for Investigating Ion-Exchange Behavior and Scale-up

Mehay¹,

Gu²

2014

J Microb Biochem Technol

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High‐Throughput Process Development

Pirrung

Ottens

2017

Preparative Chromatography for Separation of Proteins

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Digital twin of a continuous chromatography process for mAb purification: Design and model‐based control

Tiwari

Masampally

Agarwal

et al. 2022

Biotech & Bioengineering

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Model‐based design of integrated continuous train coupled with online process analytical technology (PAT) tool can be a potent facilitator for monitoring and control of Critical Quality Attributes (CQAs) in real time. Charge variants are product related variants and are often regarded as CQAs as they may impact potency and efficacy of drug. Robust pooling decision is required for achieving uniform charge variant composition for mAbs as baseline separation between closely related variants is rarely achieved in process scale chromatography. In this study, we propose a digital twin of a continuous chromatography process, integrated with an online HPLC‐PAT tool for delivering real time pooling decisions to achieve uniform charge variant composition. The integrated downstream process comprised continuous multicolumn capture protein A chromatography, viral inactivation in coiled flow inverter reactor (CFIR), and multicolumn CEX polishing step. An online HPLC was connected to the harvest tank before protein A chromatography. Both empirical and mechanistic modeling have been considered. The model states were updated in real time using online HPLC charge variant data for prediction of the initial and final cut point for CEX eluate, according to which the process chromatography was directed to switch from collection to waste to achieve the desired charge variant composition in the CEX pool. Two case studies were carried out to demonstrate this control strategy. In the first case study, the continuous train was run for initially 14 h for harvest of fixed charge variant composition as feed. In the second case study, charge variant composition was dynamically changed by introducing forced perturbation to mimic the deviations that may be encountered during perfusion cell culture. The control strategy was successfully implemented for more than ±5% variability in the acidic variants of the feed with its composition in the range of acidic (13%–17%), main (18%–23%), and basic (59%–68%) variants. Both the case studies yielded CEX pool of uniform distribution of acidic, main and basic profiles in the range of 15 ± 0.8, 31 ± 0.3, and 53 ± 0.5%, respectively, in the case of empirical modeling and 15 ± 0.5, 31 ± 0.3, and 53 ± 0.3%, respectively, in the case of mechanistic modeling. In both cases, process yield for main species was >85% and the use of online HPLC early in the purification train helped in making quicker decision for pooling of CEX eluate. The results thus successfully demonstrate the technical feasibility of creating digital twins of bioprocess operations and their utility for process control.

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Parameter estimation and rate model simulation of partial breakthrough of bovine serum albumin on a column packed with large Q Sepharose anion-exchange particles

Cited by 12 publications

References 25 publications

A General Rate Model of Ion-Exchange Chromatography for Investigating Ion-Exchange Behavior and Scale-up

A General Rate Model of Ion-Exchange Chromatography for Investigating Ion-Exchange Behavior and Scale-up

High‐Throughput Process Development

Digital twin of a continuous chromatography process for mAb purification: Design and model‐based control

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