Estimating plate heights in stacked-membrane chromatography by flow reversal

Roper, D. Keith; Lightfoot, E. N.

doi:10.1016/0021-9673(94)01068-p

Cited by 46 publications

(16 citation statements)

References 29 publications

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“…membranes. In spite of the excellent hydrodynamic characteristics of the membrane itself [11] use is limited because of pronounced peak broadening caused by high extra column effects and low binding capacity related to the low specific surface area [12]. The third type of the convective based supports are the so-called monoliths.…”

Section: Introductionmentioning

confidence: 98%

Dynamic Capacity Studies of CIM (Convective Interaction Media)® Monolithic Columns

Mihelič¹,

Koloini²,

Podgornik³

et al. 2000

J. High Resol. Chromatogr.

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Section: Introductionmentioning

confidence: 98%

Dynamic Capacity Studies of CIM (Convective Interaction Media)® Monolithic Columns

Mihelič¹,

Koloini²,

Podgornik³

et al. 2000

J. High Resol. Chromatogr.

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“…A necessary component of establishing this model‐building formalism is the accurate accounting of contributions to band spreading occurring in the pre‐ and post‐column hold‐up volumes so as to properly isolate and characterize solute dispersion and mass transport within the membrane stack itself. Due to the low length to diameter ratio of stacked membrane chromatography columns, dispersion resulting from mixing, channeling, and other processes leading to unequal solute residence times in the extra‐column volumes is known to contribute to elution band broadening (Francis et al, 2011; Ghosh and Wong, 2006; Lightfoot et al, 1995; Roper and Lightfoot, 1995b). Several models have therefore been proposed to account for these extra‐column nonidealities, with most employing a plug flow reactor (PFR) in series with a stirred tank reactor (CSTR) (e.g., Boi et al, 2007; Sarfert and Etzel, 1997; Yang et al, 1999; Yang and Etzel, 2003).…”

Section: Introductionmentioning

confidence: 99%

“…Several models have therefore been proposed to account for these extra‐column nonidealities, with most employing a plug flow reactor (PFR) in series with a stirred tank reactor (CSTR) (e.g., Boi et al, 2007; Sarfert and Etzel, 1997; Yang et al, 1999; Yang and Etzel, 2003). Roper and Lightfoot (1995b) extended this concept with a second PFR/CSTR sequence following the membrane stack to address solute dispersion in the eluent collection manifold. However, it is now known that models that incorporate a linear PFR/CSTR sequence on either one or both sides of the membrane stack do not in general provide a quantitative description of breakthrough from axial‐flow IEXM modules (Montesinos‐Cisneros et al, 2007; Sarfert and Etzel, 1997; Yang et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

“…Column loading therefore does not occur in the desired plug‐flow manner, resulting in solute breakthrough from the centerline of the membrane stack prior to saturation of binding sites in the outer radial positions, even when the axial velocity through the stack is invariant of radial and angular position. The ZRM quantitatively captures this nonideality by extending sequential PFR/CSTR models (e.g., Boi et al, 2007; Roper and Lightfoot, 1995b; Sarfert and Etzel, 1997; Yang et al, 1999; Yang and Etzel, 2003) through the partitioning of the membrane stack and its associated pre‐ and post‐column hold‐up volumes into virtual zones that account for differences in radial path lengths traveled by solute molecules within the feed and eluent distributors of the column. A defined set of pulse or frontal loading experiments under nonretention conditions are used to determine the extra‐column parameters and zone configuration of the ZRM, as well as the axial dispersion coefficient D ax for solute transport within the membrane stack.…”

Section: Introductionmentioning

confidence: 99%

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Zonal rate model for stacked membrane chromatography part II: Characterizing ion‐exchange membrane chromatography under protein retention conditions

Francis

Lieres

Haynes

2011

Biotech & Bioengineering

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The Zonal Rate Model (ZRM) has previously been shown to accurately account for contributions to elution band broadening, including external flow nonidealities and radial concentration gradients, in ion-exchange membrane (IEXM) chromatography systems operated under nonbinding conditions. Here, we extend the ZRM to analyze and model the behavior of retained proteins by introducing terms for intra-column mass transfer resistances and intrinsic binding kinetics. Breakthrough curve (BTC) data from a scaled-down anion-exchange membrane chromatography module using ovalbumin as a model protein were collected at flow rates ranging from 1.5 to 20 mL min(-1). Through its careful accounting of transport nonidealities within and external to the membrane stack, the ZRM is shown to provide a useful framework for characterizing putative protein binding mechanisms and models, for predicting BTCs and complex elution behavior, including the common observation that the dynamic binding capacity can increase with linear velocity in IEXM systems, and for simulating and scaling separations using IEXM chromatography. Global fitting of model parameters is used to evaluate the performance of the Langmuir, bi-Langmuir, steric mass action (SMA), and spreading-type protein binding models in either correlating or fundamentally describing BTC data. When combined with the ZRM, the bi-Langmuir, and SMA models match the chromatography data, but require physically unrealistic regressed model parameters to do so. In contrast, for this system a spreading-type model is shown to accurately predict column performance while also providing a realistic fundamental explanation for observed trends, including an observed increase in dynamic binding capacity with flow rate.

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“…These considerations have resulted in one of the breakthrough technologies of the past 15 years -membrane chromatography [9][10][11]. Membranes are in fact a special type of filter, equipped with ligands allowing for selective adsorption and are characterized by a very short bed height (100 lm) and very wide diameter.…”

Section: Introductionmentioning

confidence: 99%

Convective Interaction Media short monolithic columns: Enabling chromatographic supports for the separation and purification of large biomolecules

Barut¹,

Podgornik

Brne

et al. 2005

J of Separation Science

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New therapeutics that are being developed rely more and more on large and complex biomacromolecules like proteins, DNA, and viral particles. Manufacturing processes are being redesigned and optimized both upstream and downstream to cope with the ever-increasing demand for the above target molecules. In downstream processing, LC still represents the most powerful technique for achieving high yield and high purities of these molecules. In most cases, however, the separation technology relies on conventional particle-based technology, which has been optimized for the purification of smaller molecules. New technologies are, therefore, needed in order to push the downstream processing ahead and into the direction that will provide robust, productive, and easy to implement methods for the production of novel therapeutics. New technologies include the renaissance of membranes, various improvements of existing technologies, but also the introduction of a novel concept--the continuous bed or monolithic stationary phases. Among different introduced products, Convective Interaction Media short monolithic columns (SMC) that are based on methacrylate monoliths exhibit some interesting features that make them attractive for these tasks. SMC can be initially used for fast method development on the laboratory scale and subsequently efficiently transferred to preparative and even more importantly to industrial scale. A brief historical overview of methacrylate monoliths is presented, followed by a short presentation of theoretical considerations that had led to the development of SMC. The design of these columns, as well as their scale-up to large units, together with the methods for transferring gradient separations from one scale to another are addressed. Noninvasive methods that have been developed for the physical characterization of various batches of SMC, which fulfill the regulatory requirements for cGMP production, are discussed. The applications of SMC for the separation and purification of large biomolecules, which demonstrate the full potential of this novel technology for an efficient downstream processing of biomolecules, are also presented.

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Estimating plate heights in stacked-membrane chromatography by flow reversal

Cited by 46 publications

References 29 publications

Dynamic Capacity Studies of CIM (Convective Interaction Media)® Monolithic Columns

Dynamic Capacity Studies of CIM (Convective Interaction Media)® Monolithic Columns

Zonal rate model for stacked membrane chromatography part II: Characterizing ion‐exchange membrane chromatography under protein retention conditions

Convective Interaction Media short monolithic columns: Enabling chromatographic supports for the separation and purification of large biomolecules

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