Rational construction by molecular dynamics modeling and simulations of porous adsorbent media for bioseparation

Ion-exchange chromatography employing porous adsorbent particles or monoliths in which charged ligands are immobilized onto polymeric extender molecules grafted on the pore surfaces of a base matrix has become a very important method for bioseparations. In this dissertation, a novel fundamental and systematic methodology has been developed that uses the molecular dynamics (MD) modeling and simulation approach to rationally design, construct, and characterize polymeric porous adsorbent media and study the transport and adsorption of a charged biomolecule (desmopressin) in a representative adsorbent medium. The MD results have also been utilized in a macroscopic model to study the large-scale dynamic behavior of protein adsorption in the polymeric adsorbent media. The results in this dissertation show that the use of non-flat surfaces permits indirect control of the pore structure in the polymeric adsorbent media and provides computational efficiency for simulating such adsorption systems. By varying the polymeric extender surface density, different porous adsorbent media can be generated for different types of bioseparations. In these porous media, local nonelectroneutrality is found to exist and the spatial density distribution of immobilized ligands is most likely non-uniform. When such non-uniform ligand distributions have local maxima or minima along the direction of net transport, inner radial humps in the concentration profiles of adsorbed biomolecules can occur according to the macroscopic model, which also suggests use of confocal scanning laser microscopy for quality control of the adsorbent media. The charged adsorbate biomolecule exhibits decreased mass transport coefficients in the porous medium and its adsorption evolves from one-site to multi-site interactions --Abstract, page iv