| Summary: |
The purification and concentration of biologic products involves, in most cases, the use of an extraction step. However, the selection of a separation agent to extract biologic materials is limited by the potential denaturation that may occur in non-aqueous as well as in aqueous solvents, if the temperature, ionic strength or pH conditions are not the "best" ones. For that purpose, the use of the liquid-liquid extraction technique in aqueous two-phase systems (ATPS) appears to be a promising alternative. Among the majors advantages that have contributed to their success are the ability to provide innocuous environments for the treatment of biologic materials, the easy way to scale up, as well the possibility to apply them directly to fermentation broths.
Despite that, the scientific knowledge of the mechanisms behind the phase properties of these systems as well as behind the partition of solutes in ATPS is now beginning to come to light. The permanent emergence of new systems, their enormous complexity, besides the interdependence between the several factors that control their properties, are behind the slow technologic progress that has been noticed.
Among the several factors that control the solute partition behaviour in ATPS, the chemical structure of the phase-forming polymers is one of the most important ones. Despite that, it is the less studied.
Thus, the first objective of the present project is related to the study of the influence of the chemical structure of the ATPS phase-forming polymers, in both the phase diagram and solute partition in the same systems. For that purpose, new phase diagrams will be experimentally obtained formed by chemically modified polymers (e.g. PED, Dex, Ucon, PES), by the addition of chemical groups. At another step, model protein (e.g. BSA) partition in these systems will be studied.
For the design, operation and optimization of extraction processes it is advantageous to have mathematical tools describing acc  |
Summary
The purification and concentration of biologic products involves, in most cases, the use of an extraction step. However, the selection of a separation agent to extract biologic materials is limited by the potential denaturation that may occur in non-aqueous as well as in aqueous solvents, if the temperature, ionic strength or pH conditions are not the "best" ones. For that purpose, the use of the liquid-liquid extraction technique in aqueous two-phase systems (ATPS) appears to be a promising alternative. Among the majors advantages that have contributed to their success are the ability to provide innocuous environments for the treatment of biologic materials, the easy way to scale up, as well the possibility to apply them directly to fermentation broths.
Despite that, the scientific knowledge of the mechanisms behind the phase properties of these systems as well as behind the partition of solutes in ATPS is now beginning to come to light. The permanent emergence of new systems, their enormous complexity, besides the interdependence between the several factors that control their properties, are behind the slow technologic progress that has been noticed.
Among the several factors that control the solute partition behaviour in ATPS, the chemical structure of the phase-forming polymers is one of the most important ones. Despite that, it is the less studied.
Thus, the first objective of the present project is related to the study of the influence of the chemical structure of the ATPS phase-forming polymers, in both the phase diagram and solute partition in the same systems. For that purpose, new phase diagrams will be experimentally obtained formed by chemically modified polymers (e.g. PED, Dex, Ucon, PES), by the addition of chemical groups. At another step, model protein (e.g. BSA) partition in these systems will be studied.
For the design, operation and optimization of extraction processes it is advantageous to have mathematical tools describing accurately the thermodynamic properties of the process-associated systems. There are in the literature mainly two kinds of models describing ATPS: the osmotic virial-expansion models and those that lie on the lattice theory. Despite the relative practical success obtained with some of the foregoing models, they sometimes exhibit low accuracy in predicting simultaneously the phase diagrams of homologous ATPS (that differ only in the polymer molecular weight) and, in some cases, they use different sets of model parameters to predict homologous ATPS.
Thus, the second objective of the present project consists on the development of thermodynamic models that allow us to adequately describe the equilibrium properties of these rather complex systems. The models will be based on the local composition concept and in statistical mechanics, eventually including terms that take into account the electrostatic interactions, present in the systems. The perturbation theory will be also submitted to evaluation. |