Studies Of Electrostatic Adsorption Equilibria And Mass Transfer Kinetics Of Proteins

Whereas the studies of nonlinear adsorption equilibrium and adsorption kineticsis imperfect and important in the optimization and scale-up of preparativeion-exchange chromatography process, the related studies are carried out in the thesis.The details in this work are summarized as follows.1. Based on statistical thermodynamic theory, a statistical thermodynamic model(ST model) describing ion-exchange adsorption equilibrium was obtained withprotein-adsorbent and protein-protein interactions considered. Another ion-exchangeadsorption equilibrium model, non-ideal adsorption phase model (NIAP model), wasalso proposed through the approach of solution thermodynamics. The NIAP modeltakes into account the discrepancy of adsorption phase with ideal dilute solution ofprotein arising from interaction between adsorbed protein molecules and localcomposition non-ideality due to the difference between protein-protein andprotein-counterion interaction. Both ST model and the NIAP model fit well with theadsorption equilibrium data of a single-component protein (bovine serum albumin,BSA). The effects of pH, ionic strength and buffer type on model parameters arediscussed. In order to test the validity of multi-component ST model, binary-component adsorption equilibrium data of bovine serum albumin and lysozyme at thecation adsorbent was used. Compared with the available area model (AA model), theST model that takes into consideration of interactions between adsorbed proteinmolecules fit better with the experimental data of binary protein ion-exchangeadsorption equilibrium.2. With the presupposition that only electrical interaction act between proteinmolecules and adsorption interface, molecular mean field theory was utilized toexplain the influences of protein net charge, ionic strength, buffer type, proteinmolecular size, adsorption orientation on single-component protein adsorptionequilibrium. Influences of protein net charge, ionic strength and protein molecularsize on binary protein adsorption equilibrium were also investigated. The actingmechanisms of these factors are clarified.3. Giving up the Fick law, we adopted the Maxwell-Stefan equation (MS equation)that uses chemical potential gradient instead of concentration gradient as diffusiondriving force to reveal the effect of protein concentration. Simulation of the dynamicuptake process of BSA on anion adsorbent Q-Sepharose FF was performed byemploying parallel diffusion model and MS equation. The influences of pH, ionicstrength and initial bulk protein concentration on protein diffusion coefficient werestudied.