Macroscopic continuum and molecular dynamics modeling and simulation studies of the transport and adsorption of charged macromolecules in ion -exchange chromatography systems

An analysis based on a macroscopic continuum rigorous model of the conditions necessary for the development of an overshoot in the concentration of a charged bioactive macromolecule in the adsorbed phase of charged adsorbent particles is presented, and the parametric sensitivity of the concentration overshoot phenomenon with respect to its enhancement or suppression is studied. Practical implications of this phenomenon on operational policies and configurations of ion-exchange chromatography (IEC) systems for the separation of bioactive macromolecules are indicated.;Molecular dynamics (MD) modeling and simulation studies are performed and their results indicate the physical mechanisms that are relevant and actively involved in the transport and adsorption of charged macromolecules in IEC systems, as well as their relative importance. The results obtained from the MD simulations show that when a charged macromolecule is adsorbed, it is restrained by a strong dominant Coulombic interaction and is trapped by a hydration layer adjacent to the surface and these lead to zero lateral displacement of the adsorbed macromolecule. It is shown through the development of a novel method of analysis that from MD modeling and simulation studies the values of the pore radius and length that could provide efficient separation of macromolecules could be estimated, and could then be used to guide the design and construction of porous adsorbent particles whose pore surfaces are charged.;Also, dextran polymer porous layers attached on a base matrix are constructed by MD modeling and simulation studies and these polymer porous layers significantly increase the surface area in porous matrices for the attachment of affinity groups/ligands, as well as the adsorption capacity of the adsorbent particles employed in IEC systems.*.;*This dissertation is a compound document (contains both a paper copy and a CD as part of the dissertation).