Mechanical Deformation of Compressible Chromatographic Columns

Keener, Ronald N.; Maneval, James E.; Östergren, Karin; Fernandez, Erik J.

doi:10.1021/bp020051v

Cited by 18 publications

(14 citation statements)

References 30 publications

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“…However, there are few reports detailing the effect of different procedures of bed compression, i.e. mechanical compression, on packed polymeric particles . At high flow rates bed compression occurs with a concomitant decrease in column permeability .…”

Section: Introductionmentioning

confidence: 99%

Effects of bed compression on protein separation on gel filtration chromatography at bench and pilot scale

Kong

Gerontas

McCluckie

et al. 2017

J of Chemical Tech & Biotech

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BACKGROUNDPoorly packed chromatography columns are known to reduce drastically the column efficiency and produce broader peaks. Controlled bed compression has been suggested to be a useful approach for solving this problem. Here the relationship between column efficiency and resolution of protein separation are examined when preparative chromatography media were compressed using mechanical and hydrodynamic methods. Sepharose CL‐6B, an agarose based size exclusion media was examined at bench and pilot scale. The asymmetry and height equivalent of a theoretical plate (HETP) was determined by using 2% v/v acetone, whereas the void volume and intraparticle porosity (ϵ p) were estimated by using blue dextran. A protein mixture of ovalbumin (chicken), bovine serum albumin (BSA) and γ'‐ globulin (bovine) with molecular weights of 44, 67 and 158 kDa, respectively, were used as a ‘model’ separation challenge.RESULTSMechanical compression achieved a reduction in plate height for the column with a concomitant improvement in asymmetry. Furthermore, the theoretical plate height decreased significantly with mechanical compression resulting in a 40% improvement in purity compared with uncompressed columns at the most extreme conditions of compression used.CONCLUSIONThe results suggest that the mechanical bed compression of Sepharose CL‐6B can be used to improve the resolution of protein separation. © 2017 The Authors. Journal of Chemical Technology & Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

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Section: Introductionmentioning

confidence: 99%

Effects of bed compression on protein separation on gel filtration chromatography at bench and pilot scale

Kong

Gerontas

McCluckie

et al. 2017

J of Chemical Tech & Biotech

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“…Östergren et al developed a two‐dimensional model for steady‐state flow through a chromatography column assuming pure elastic deformation of the media . A one‐dimensional model based on pure elasticity of the media to describe mechanical deformation of compressible chromatography beds was published by Keener et al Further publications deal with modeling of packing and scale‐up of chromatography columns again assuming pure elastic deformation of the media . A comparison of mechanical compression and flow packing was given.…”

Section: Introductionmentioning

confidence: 99%

Modeling of transient flow through a viscoelastic preparative chromatography packing

Hekmat

Kühn

Meinhardt

et al. 2013

Biotechnology Progress

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The common method for purification of macromolecular bioproducts is preparative packed-bed chromatography using polymer-based, compressible, viscoelastic resins. Because of a downstream processing bottleneck, the chromatography equipment is often operated at its hydrodynamic limit. In this case, the resins may exhibit a complex behavior which results in compression-relaxation hystereses. Up to now, no modeling approach of transient flow through a chromatography packing has been made considering the viscoelasticity of the resins. The aim of the present work was to develop a novel model and compare model calculations with experimental data of two agarose-based resins. Fluid flow and bed permeability were modeled by Darcy's law and the Kozeny-Carman equation, respectively. Fluid flow was coupled to solid matrix stress via an axial force balance and a continuity equation of a deformable packing. Viscoelasticity was considered according to a Kelvin-Voigt material. The coupled equations were solved with a finite difference scheme using a deformable mesh. The model boundary conditions were preset transient pressure drop functions which resemble simulated load/elution/equilibration cycles. Calculations using a homogeneous model (assuming constant variables along the column height) gave a fair agreement with experimental data with regard to predicted flow rate, bed height, and compression-relaxation hysteresis for symmetric as well as asymmetric pressure drop functions. Calculations using an inhomogeneous model gave profiles of the bed porosity as a function of the bed height. In addition, the influence of medium wall support and intraparticle porosity was illustrated. The inhomogeneous model provides insights that so far are not easily experimentally accessible.

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“…While frictional forces at the walls of the column provide a degree of bed support and can allow higher flow rates, the impact of shear wall stresses decreases with increasing column diameter (2). A direct consequence of this “wall support” effect is that the superficial mobile phase velocities developed and used during bench‐scale optimization may not necessarily be suitable for large‐scale operation.…”

Section: Introductionmentioning

confidence: 99%

“…Scale-up techniques therefore need to account for not only the effect of increasing column diameter but also other variables that will affect the critical velocity, such as bed height, the hydrodynamic properties of the mobile phase, and the type of chromatographic resins used. Several studies have attempted to model pressure drop in compressible packed beds by accounting for the varying contribution of friction in conjunction with force balances for both mechanical and flow-induced compression (2)(3)(4)(5)(6)(7)(8). However the complexity of these models limits their use in practical applications.…”

Section: Introductionmentioning

confidence: 99%

“…As is the case with mobile phase viscosity, a limited amount of work has been carried out to determine the effect of matrix rigidity upon the critical velocity of a chromatographic system (1)(2)(3)(4)(5). Higher resin rigidity will lead to higher critical velocities; however, quantitative relationships between u crit and resin rigidity have yet to be determined.…”

Section: Introductionmentioning

confidence: 99%

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A Framework for the Prediction of Scale‐Up When Using Compressible Chromatographic Packings

Tran

Joseph

Sinclair³

et al. 2007

Biotechnology Progress

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Experimental data are given for the solid pressure distributions in chromatography columns of various column aspect ratios packed with four types of agarose-based resin. The loss of column wall support at large scales can result in unexpectedly high pressures caused by the compression of the matrix via drag forces exerted by fluid flow through the bed. The need for an accurate model to predict flow conditions at increasing scale is essential for the scaling-up of chromatographic processes and for avoiding bed compression during operation. Several studies have generated correlations that allow for the prediction of column pressure drops, but they either are mathematically complex, which impairs their practical use, or require a large number of experiments to be performed before they can be used. In this study an empirical correlation was developed based on a previously proposed model, which links the critical velocity of operation of a chromatographic system (microcrit), to the gravity-settled bed height (L0), the column diameter (D), the feed viscosity (micro), and the compressibility of the chromatographic media used (micro 10%). The methodology developed in this study is straightforward to use and significantly reduces the burden of preceding laboratory-scale experimentation. The approach can be used to predict the critical velocity of any chromatographic system and will be useful in the development of chromatographic operations and for column sizing.

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Mechanical Deformation of Compressible Chromatographic Columns

Cited by 18 publications

References 30 publications

Effects of bed compression on protein separation on gel filtration chromatography at bench and pilot scale

Effects of bed compression on protein separation on gel filtration chromatography at bench and pilot scale

Modeling of transient flow through a viscoelastic preparative chromatography packing

A Framework for the Prediction of Scale‐Up When Using Compressible Chromatographic Packings

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