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Athanasios I. Liapis - One of the best experts on this subject based on the ideXlab platform.
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The dynamic behavior of a stratified column bed packed with porous adsorbent particles having partially fractal structures and a nonuniform Ligand Density distribution.
Journal of Separation Science, 2012Co-Authors: Min Li, Athanasios I. LiapisAbstract:The dynamic behavior of adsorption in a single column and in stratified column beds packed with porous adsorbent particles having partially fractal structures is studied when all columns have the same total length and the spatial Ligand Density distribution in the porous microspheres from which the porous adsorbent particles are made, is either uniform or nonuniform and such that the concentration of the immobilized Ligands (active sites) increases monotonically from the center of the microspheres to their outer surface. The total number of immobilized Ligands in the porous adsorbent particles has the same value whether the spatial Ligand Density distribution is uniform or nonuniform. The results in this study clearly show that for a given value of the superficial velocity of the flowing fluid stream in the column (for a given value of throughput) the breakthrough time is significantly increased when the radius of the microspheres is decreased, the total number of sections of the stratified column bed is increased, and the spatial Ligand Density distribution employed in the microspheres is nonuniform. Furthermore, when the superficial velocity of the flowing fluid stream in the column is increased (throughput is increased) the effect that (i) the reduction in the radius of the microspheres and (ii) the increase in the number of sections of the stratified column bed have on providing robust and effective dynamic adsorptive capacity and smaller reductions on the breakthrough time is substantially larger than that realized through the use of the nonuniform Ligand Density distribution. Similar trends are also observed in the dynamic behavior of adsorption in the systems studied here when the value of the concentration of the adsorbate in the flowing fluid stream entering the column (inlet concentration) has such a high magnitude that the value of the equilibrium concentration of the adsorbate in the adsorbed phase determined from the equilibrium Langmuir isotherm that would correspond to the inlet concentration of the adsorbate in the flowing fluid stream is, for all practical purposes, at its saturation limit.
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Effects on the dynamic utilization of the adsorptive capacity of chromatographic columns induced by non-uniform Ligand Density distributions.
Journal of separation science, 2010Co-Authors: Athanasios I. Liapis, Enrico Riccardi, Jee-ching WangAbstract:The dynamic behavior of the breakthrough curves of a single adsorbate obtained from columns employing adsorbent media which differ from one another only on the spatial distribution of the immobilized Ligands in the porous particles is examined. The spatial distributions of the immobilized Ligands considered in this study are uniform and non-uniform, but the total number of immobilized Ligands in the particles has the same value whether the spatial distribution is uniform or non-uniform. The results clearly show that the columns employing adsorbent particles in which the spatial distribution of the immobilized Ligands is non-uniform and such that the concentration of the immobilized Ligands increases monotonically from the center of the particle to the outer particle surface, exhibit (i) larger breakthrough times, (ii) steeper breakthrough curves, and (iii) higher dynamic utilization of the adsorptive capacity of the column as the superficial velocity of the flowing fluid stream in the column increases (throughput increase) than the columns using adsorbent particles in which the spatial distribution of the immobilized Ligands is uniform. The importance of employing in the columns adsorbent media whose spatial Ligand Density distributions satisfy the mathematical property of monotonically increasing Ligand concentration with increasing from the particle center radial position, will be significantly enhanced when (i) the size of the particle radius is increased, and (ii) continuous counter-current and periodic counter-current (simulated moving beds) operations are employed.
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Adsorption of a single protein interacting with multiple Ligands: inner radial humps in the concentration profiles induced by non-uniform Ligand Density distributions.
Journal of separation science, 2009Co-Authors: Enrico Riccardi, Athanasios I. LiapisAbstract:The dynamic behavior of the concentration profiles of a single protein in the pore solution and the adsorbed phase is studied in different adsorbent media when the spatial Density distribution of the immobilized Ligands is either uniform or non-uniform and at the same time the single protein is forming one-site and two-site adsorbate-Ligand complexes with the immobilized monovalent Ligands. The competition for the formation of one-site and two-site interaction complexes leads to the formation of inner radial humps in the concentration profiles of the two-site adsorbate-Ligand complex in adsorbent particles having either uniform or non-uniform spatial Ligand Density distributions. The results show that inner radial humps in the concentration profiles of the adsorbed protein (total concentration of adsorbed protein by one-site and two-site interactions) occur only in adsorbent media whose spatial Ligand Density distributions are non-uniform and have maxima or minima occurring in radial positions located between the center and the outer surface of the particles. The non-uniform spatial Ligand Density distributions satisfying this property provide the cause for the occurrence of inner radial humps in the concentration profiles of a single adsorbed protein, while the multi-site adsorption interactions affect the magnitude and the rate of propagation of the inner radial humps in the concentration profiles of the single adsorbed protein. It is also demonstrated that adsorbent media having certain non-uniform functional forms of spatial distribution in the Density of immobilized Ligands could provide more efficient adsorption of a protein than an adsorbent medium whose spatial distribution of the Density of immobilized Ligands is uniform. Furthermore, the results in this study suggest the type of information that could be obtained from finite bath experiments and could be used to (i) determine whether multi-site adsorbate-Ligand complexes are formed during the adsorption of a single adsorbate and (ii) select between alternative adsorbent media the adsorbent particles that could provide the highest overall adsorption rate for a given adsorbate of interest. The results clearly indicate that it is very important to study the dynamic behavior of an adsorption system having a non-uniform spatial Ligand Density distribution and where the values of the pH and ionic strength are such that the electrophoretic effects are active.
Abraham M Lenhoff - One of the best experts on this subject based on the ideXlab platform.
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Ionic strength-dependent changes in tentacular ion exchangers with variable Ligand Density. II. Functional properties.
Journal of chromatography. A, 2017Co-Authors: Rahul Bhambure, Heiner Graalfs, James M Angelo, Christopher M Gillespie, Michael Phillips, Abraham M LenhoffAbstract:The effect of Ligand Density was studied on protein adsorption and transport behavior in tentacular cation-exchange sorbents at different ionic strengths. Results were obtained for lysozyme, lactoferrin and a monoclonal antibody (mAb) in order to examine the effects of protein size and charge. The combination of Ligand Density and ionic strength results in extensive variability of the static and dynamic binding capacities, transport rate and binding affinity of the proteins. Uptake and elution experiments were performed to quantify the transport behavior of selected proteins, specifically to estimate intraparticle protein diffusivities. The observed trend of decreasing uptake diffusivities with an increase in Ligand Density was correlated to structural properties of the Ligand-Density variants, particularly the accessible porosity. Increasing the ionic strength of the equilibration buffer led to enhanced mass transfer during uptake, independent of the transport model used, and specifically for larger proteins like lactoferrin and mAb, the most significant effects were evident in the sorbent of the highest Ligand Density. For lysozyme, higher Ligand Density leads to higher static and dynamic binding capacities whereas for lactoferrin and the mAb, the binding capacity is a complex function of accessible porosity due to ionic strength-dependent changes. Ligand Density has a less pronounced effect on the elution rate, presumably due to ionic strength-dependent changes in the pore architecture of the sorbents.
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Ionic strength-dependent changes in tentacular ion exchangers with variable Ligand Density. I. Structural properties.
Journal of chromatography. A, 2016Co-Authors: Rahul Bhambure, Heiner Graalfs, Michael Phillips, Christopher Gillespie, Abraham M LenhoffAbstract:The effect of Ligand Density was studied on protein adsorption and transport behavior in tentacular cation-exchange sorbents at different ionic strengths. Results were obtained for lysozyme, lactoferrin and a monoclonal antibody (mAb) in order to examine the effects of protein size and charge. The combination of Ligand Density and ionic strength results in extensive variability of the static and dynamic binding capacities, transport rate and binding affinity of the proteins. Uptake and elution experiments were performed to quantify the transport behavior of selected proteins, specifically to estimate intraparticle protein diffusivities. The observed trend of decreasing uptake diffusivities with an increase in Ligand Density was correlated to structural properties of the Ligand-Density variants, particularly the accessible porosity. Increasing the ionic strength of the equilibration buffer led to enhanced mass transfer during uptake, independent of the transport model used, and specifically for larger proteins like lactoferrin and mAb, the most significant effects were evident in the sorbent of the highest Ligand Density. For lysozyme, higher Ligand Density leads to higher static and dynamic binding capacities whereas for lactoferrin and the mAb, the binding capacity is a complex function of accessible porosity due to ionic strength-dependent changes. Ligand Density has a less pronounced effect on the elution rate, presumably due to ionic strength-dependent changes in the pore architecture of the sorbents.
Heiner Graalfs - One of the best experts on this subject based on the ideXlab platform.
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Mechanistic modeling of Ligand Density variations on anion exchange chromatography.
Journal of separation science, 2020Co-Authors: Gabriela Sanchez‐reyes, Heiner Graalfs, Mathias Hafner, Christian FrechAbstract:Ion exchange chromatography is a powerful and ubiquitous unit operation in the purification of therapeutic proteins. However, the performance of an ion-exchange process depends on a complex interrelationship between several parameters, such as protein properties, mobile phase conditions, and chromatographic resin characteristics. Consequently, batch variations of ion exchange resins play a significant role in the robustness of these downstream processing steps. Ligand Density is known to be one of the main lot-to-lot variations, affecting protein adsorption and separation performance. The use of a model-based approach can be an effective tool for comprehending the impact of parameter variations (e.g., Ligand Density) and their influence on the process. The objective of this work was to apply mechanistic modeling to gain a deeper understanding of the influence of Ligand Density variations in anion exchange chromatography. To achieve this, 13 prototype resins having the same support as the strong anion exchange resin Fractogel® EMD TMAE (M), but differing in Ligand Density, were analyzed. Linear salt gradient elution experiments were performed to observe the elution behavior of a monoclonal antibody and bovine serum albumin. A proposed isotherm model for ion exchange chromatography, describing the dependence of Ligand Density variations on protein retention, was successfully applied.
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Ionic strength-dependent changes in tentacular ion exchangers with variable Ligand Density. II. Functional properties.
Journal of chromatography. A, 2017Co-Authors: Rahul Bhambure, Heiner Graalfs, James M Angelo, Christopher M Gillespie, Michael Phillips, Abraham M LenhoffAbstract:The effect of Ligand Density was studied on protein adsorption and transport behavior in tentacular cation-exchange sorbents at different ionic strengths. Results were obtained for lysozyme, lactoferrin and a monoclonal antibody (mAb) in order to examine the effects of protein size and charge. The combination of Ligand Density and ionic strength results in extensive variability of the static and dynamic binding capacities, transport rate and binding affinity of the proteins. Uptake and elution experiments were performed to quantify the transport behavior of selected proteins, specifically to estimate intraparticle protein diffusivities. The observed trend of decreasing uptake diffusivities with an increase in Ligand Density was correlated to structural properties of the Ligand-Density variants, particularly the accessible porosity. Increasing the ionic strength of the equilibration buffer led to enhanced mass transfer during uptake, independent of the transport model used, and specifically for larger proteins like lactoferrin and mAb, the most significant effects were evident in the sorbent of the highest Ligand Density. For lysozyme, higher Ligand Density leads to higher static and dynamic binding capacities whereas for lactoferrin and the mAb, the binding capacity is a complex function of accessible porosity due to ionic strength-dependent changes. Ligand Density has a less pronounced effect on the elution rate, presumably due to ionic strength-dependent changes in the pore architecture of the sorbents.
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Ionic strength-dependent changes in tentacular ion exchangers with variable Ligand Density. I. Structural properties.
Journal of chromatography. A, 2016Co-Authors: Rahul Bhambure, Heiner Graalfs, Michael Phillips, Christopher Gillespie, Abraham M LenhoffAbstract:The effect of Ligand Density was studied on protein adsorption and transport behavior in tentacular cation-exchange sorbents at different ionic strengths. Results were obtained for lysozyme, lactoferrin and a monoclonal antibody (mAb) in order to examine the effects of protein size and charge. The combination of Ligand Density and ionic strength results in extensive variability of the static and dynamic binding capacities, transport rate and binding affinity of the proteins. Uptake and elution experiments were performed to quantify the transport behavior of selected proteins, specifically to estimate intraparticle protein diffusivities. The observed trend of decreasing uptake diffusivities with an increase in Ligand Density was correlated to structural properties of the Ligand-Density variants, particularly the accessible porosity. Increasing the ionic strength of the equilibration buffer led to enhanced mass transfer during uptake, independent of the transport model used, and specifically for larger proteins like lactoferrin and mAb, the most significant effects were evident in the sorbent of the highest Ligand Density. For lysozyme, higher Ligand Density leads to higher static and dynamic binding capacities whereas for lactoferrin and the mAb, the binding capacity is a complex function of accessible porosity due to ionic strength-dependent changes. Ligand Density has a less pronounced effect on the elution rate, presumably due to ionic strength-dependent changes in the pore architecture of the sorbents.
Esmaiel Jabbari - One of the best experts on this subject based on the ideXlab platform.
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Modeling Cell Adhesion to a Substrate With Gradient in Ligand Density
AIChE Journal, 2009Co-Authors: Alireza Sarvestani, Esmaiel JabbariAbstract:Surface Density profile of bioadhesive Ligands greatly influences spreading and migration of cells on substrates. A 1D peeling model is developed to predict the equilibrium adhesion strength and peeling tension of a cell membrane, adhered on a substrate with linearly increasing Density of Ligands. Cell membrane is modeled as a linear elastic shell subjected to a tensile force applied at the free extremity and adhesive traction due to specific receptor-Ligand interactions with the substrate. Membrane peeling tension increased with gradient slope and reached an asymptotic limit independent of gradient slope but proportional to receptor-Ligand interaction energy. Peeling tension from substrates with negative gradient slope, at the rear edge of adhesion zone, was considerably lower than the tension from substrates with positive gradient slope at the leading edge, indicating that detachment is more likely to be initiated at the rear edge. This prediction leads to a possible mechanism for experimentally observed haptotactic locomotion of motile cells toward the direction of higher Ligand Density. © 2009 American Institute of Chemical Engineers AIChE J, 2009
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Effect of Ligand Density Gradient on the Adhesion Kinetics of Biological Membranes
MRS Online Proceedings Library, 2008Co-Authors: Alireza Sarvestani, Esmaiel JabbariAbstract:An analytical model is developed for the effect of surface gradient in Ligand Density on the adhesion kinetics of a curved elastic membrane with mobile receptors. The displacement and speed of spreading at the edge of the adhesion zone as well as the Density profile of receptors along the membrane are predicted as a function of time. According to results, in the diffusion-controlled regime, the front edge displacement of adhesion zone and the rate of membrane spreading decreased with increasing Ligand Density in a certain direction. Furthermore, the displacement of the edge of the adhesion zone did not scale with the square root of time, as observed on substrates with uniform Ligand Density.
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Modeling the Kinetics of Cell Membrane Spreading on Substrates with Ligand Density Gradient
Journal of biomechanics, 2007Co-Authors: Alireza Sarvestani, Esmaiel JabbariAbstract:An analytical model is developed for the effect of surface gradient in Ligand Density on the adhesion kinetics of a curved elastic membrane with mobile receptors. The displacement and speed of spreading at the edge of adhesion zone as well as the Density profile of receptors along the membrane are predicted as a function of time. According to results, in the diffusion-controlled regime, the front edge displacement of adhesion zone and the rate of membrane spreading decreased with increasing the Ligand Density in a certain direction. Furthermore, the displacement of the edge of the adhesion zone did not scale with the square root of time, as observed on substrates with uniform Ligand Density.
Rahul Bhambure - One of the best experts on this subject based on the ideXlab platform.
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Ionic strength-dependent changes in tentacular ion exchangers with variable Ligand Density. II. Functional properties.
Journal of chromatography. A, 2017Co-Authors: Rahul Bhambure, Heiner Graalfs, James M Angelo, Christopher M Gillespie, Michael Phillips, Abraham M LenhoffAbstract:The effect of Ligand Density was studied on protein adsorption and transport behavior in tentacular cation-exchange sorbents at different ionic strengths. Results were obtained for lysozyme, lactoferrin and a monoclonal antibody (mAb) in order to examine the effects of protein size and charge. The combination of Ligand Density and ionic strength results in extensive variability of the static and dynamic binding capacities, transport rate and binding affinity of the proteins. Uptake and elution experiments were performed to quantify the transport behavior of selected proteins, specifically to estimate intraparticle protein diffusivities. The observed trend of decreasing uptake diffusivities with an increase in Ligand Density was correlated to structural properties of the Ligand-Density variants, particularly the accessible porosity. Increasing the ionic strength of the equilibration buffer led to enhanced mass transfer during uptake, independent of the transport model used, and specifically for larger proteins like lactoferrin and mAb, the most significant effects were evident in the sorbent of the highest Ligand Density. For lysozyme, higher Ligand Density leads to higher static and dynamic binding capacities whereas for lactoferrin and the mAb, the binding capacity is a complex function of accessible porosity due to ionic strength-dependent changes. Ligand Density has a less pronounced effect on the elution rate, presumably due to ionic strength-dependent changes in the pore architecture of the sorbents.
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Ionic strength-dependent changes in tentacular ion exchangers with variable Ligand Density. I. Structural properties.
Journal of chromatography. A, 2016Co-Authors: Rahul Bhambure, Heiner Graalfs, Michael Phillips, Christopher Gillespie, Abraham M LenhoffAbstract:The effect of Ligand Density was studied on protein adsorption and transport behavior in tentacular cation-exchange sorbents at different ionic strengths. Results were obtained for lysozyme, lactoferrin and a monoclonal antibody (mAb) in order to examine the effects of protein size and charge. The combination of Ligand Density and ionic strength results in extensive variability of the static and dynamic binding capacities, transport rate and binding affinity of the proteins. Uptake and elution experiments were performed to quantify the transport behavior of selected proteins, specifically to estimate intraparticle protein diffusivities. The observed trend of decreasing uptake diffusivities with an increase in Ligand Density was correlated to structural properties of the Ligand-Density variants, particularly the accessible porosity. Increasing the ionic strength of the equilibration buffer led to enhanced mass transfer during uptake, independent of the transport model used, and specifically for larger proteins like lactoferrin and mAb, the most significant effects were evident in the sorbent of the highest Ligand Density. For lysozyme, higher Ligand Density leads to higher static and dynamic binding capacities whereas for lactoferrin and the mAb, the binding capacity is a complex function of accessible porosity due to ionic strength-dependent changes. Ligand Density has a less pronounced effect on the elution rate, presumably due to ionic strength-dependent changes in the pore architecture of the sorbents.