Evaluation of Three Kinetic Equations in Models of Protein Purification Using Ion-Exchange Membranes

Yang, Heewon; Etzel, Mark R.

doi:10.1021/ie020561u

Cited by 63 publications

(47 citation statements)

References 23 publications

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“…Recently, an analogous BTC asymmetric behavior was reported for pDNA membrane chromatography [27]. The steric hindrance and spreading models have been used to explain these results [28]. In these studies very dilute feed solutions were used, furthermore in three of the cases (including the pDNA study) an extremely low residence time in the membrane system was also used.…”

Section: Introductionmentioning

confidence: 80%

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Breakthrough performance of linear-DNA on ion-exchange membrane columns

Montesinos-Cisneros

Ortega

Guzmán

et al. 2006

Bioprocess Biosyst Eng

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Breakthrough performance of linear-DNA adsorption on ion-exchange membrane columns was theoretically and experimentally investigated using batch and fixed-bed systems. System dispersion curves showed the absence of flow non-idealities in the experimental arrangement. Breakthrough curves were not significantly affected by flow-rate or inlet solution concentration. In the theoretical analysis a model was integrated by the serial coupling of the membrane transport model and the system dispersion model. A transport model that considers finite kinetic rate and column dispersed flow was used in the study. A simplex optimization routine coupled to the solution of the partial differential model equations was employed to estimate the maximum adsorption capacity constant, the equilibrium desorption constant and the forward interaction rate-constant, which are the parameters of the membrane transport model. Through this approach a good prediction of the adsorption phenomena is obtained for inlet concentrations and flow rates greater than 0.2 mg/ml and 0.16 ml/min.

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Section: Introductionmentioning

confidence: 80%

“…To describe the adsorption behavior in membrane columns a simple method which involves serial coupling of BTC and SDC models is often used [28,31,32].…”

Section: Membrane Column Modelmentioning

confidence: 99%

Breakthrough performance of linear-DNA on ion-exchange membrane columns

Montesinos-Cisneros

Ortega

Guzmán

et al. 2006

Bioprocess Biosyst Eng

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show abstract

“…In many studies, attempts have been made to quantitatively model different adsorption mechanisms [12], different binding isotherms [14,24] and the entire membrane chromatographic process, i.e., the mass transfer coupled with binding kinetics [11,13]. In these approaches, dead volumes in membrane chromatography systems are traditionally modeled by one plug flow reactor (PFR) and one continuous stirred tank reactor (CSTR) in series [10,11], or by lumping the overall peak broadening and tailing effects into a fixed volume of a mixing cell [15].…”

Section: Introductionmentioning

confidence: 99%

Model Based Quantification of Internal Flow Distributions from Breakthrough Curves of Flat Sheet Membrane Chromatography Modules

2010

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A novel model for quantifying radial flow distributions in flat sheet membrane chromatography modules under non-binding conditions is presented and applied for the practical analysis of two modules. The proposed model partitions the total void volume of the chromatography module into zones that are considered homogeneous with respect to flow velocity. The corresponding solute concentrations are time variant, but also spatially homogeneous within each zone. The model is mathematically represented and analytically solved as a network of continuously stirred tank reactors (CSTR). An additional plug flow reactor (PFR) is connected in series with the CSTR network in order to account for a time-lag that is not associated with the system dispersion. The capability of the model to describe experimental breakthrough data is compared to the frequently applied standard model for extra-membrane system dispersion, which consists of a single CSTR in series with a PFR. Non-binding conditions are deliberately chosen for studying the impact of module geometries on breakthrough curves separately from chromatographic membrane performance. The commercial CIM module and a custom designed cell (Scell) are studied with acetone and lysozyme as test tracers at varied flow rates and for various membrane pore sizes under non-binding conditions. In all studied cases, the proposed model fits the measured breakthrough curves better than the standard model. Moreover, the minimal number of radial flow zones that are required to accurately describe observed breakthrough curves and the estimated flow fractions through these zones provide valuable information for the analysis and optimization of internal module designs.

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“…Several authors have applied the spreading model to predict the adsorption properties of membrane adsorbers [38] and HIC adsorbents [37]. Haimer et al coupled the spreading model with the continuity equation to describe the mass transport process within a HIC column.…”

Section: Introductionmentioning

confidence: 99%

Modeling of protein monomer/aggregate purification and separation using hydrophobic interaction chromatography

McCue

Engel

et al. 2008

Bioprocess Biosyst Eng

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Hydrophobic interaction chromatography (HIC) is commonly used to separate protein monomer and aggregate species in the purification of protein therapeutics. Despite being used frequently, the HIC separation mechanism is quite complex and not well understood. In this paper, we examined the separation of a monomer and aggregate protein mixture using Phenyl Sepharose FF. The mechanisms of protein adsorption, desorption, and diffusion of the two species were evaluated using several experimental approaches to determine which processes controlled the separation. A chromatography model, which used homogeneous diffusion (to describe mass transfer) and a competitive Langmuir binary isotherm (to describe protein adsorption and desorption), was formulated and used to predict the separation of the monomer and aggregate species. The experimental studies showed a fraction of the aggregate species bound irreversibly to the adsorbent, which was a major factor governing the separation of the species. The model predictions showed inclusion of irreversible binding in the adsorption mechanism greatly improved the model predictions over a range of operating conditions. The model successfully predicted the separation performance of the adsorbent with the examined feed.

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Evaluation of Three Kinetic Equations in Models of Protein Purification Using Ion-Exchange Membranes

Cited by 63 publications

References 23 publications

Breakthrough performance of linear-DNA on ion-exchange membrane columns

Breakthrough performance of linear-DNA on ion-exchange membrane columns

Model Based Quantification of Internal Flow Distributions from Breakthrough Curves of Flat Sheet Membrane Chromatography Modules

Modeling of protein monomer/aggregate purification and separation using hydrophobic interaction chromatography

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