In this study, solid-phase adsorption by macroporous and hyper-diffusive resins was investigated in a batch uptake adsorption system to quantify solid-phase diffusion rates as a function of bulk phase viscosity. The performance of chromatographic resins used for adsorption of proteins is dependent on several factors including solid and liquid-phase diffusivity, boundary layer mass transfer, and intraparticle mass transfer effects. Understanding these effects is critical to process development and optimization of both packed and fluidized bed adsorption systems. The macroporous resin used here was Streamline SP, and the hyper-diffusive resin was S-HyperD LS. Both have been frequently used in fluidized bed adsorption of proteins; however, factors that affect uptake rates of these media are not well quantified. Adsorption isotherms were well represented by an empirical fit of a Langmuir isotherm. Solid-phase diffusion coefficients obtained from simulations were in agreement with other models for macroporous and hyper-diffusive particles. S-HyperD LS in the buffer system had the highest uptake rate, but increased bulk phase viscosity decreased the rate by approximately 50%. Increases in bulk phase viscosity increased film mass transfer effects, and uptake was observed to be a strong function of the film mass transfer coefficient. Uptake by Streamline SP particles was slower than S-HyperD in buffer, due to a greater degree of intraparticle mass transfer resistance. The effect of increased film mass transfer resistance coupled with intraparticle mass transfer resistances at an increased bulk phase viscosity resulted in a decrease of 80% in the uptake rate by Streamline SP relative to S-HyperD.

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Despite numerous advantages, fluidized bed adsorption is limited in commercial applications due to a poor understanding of the relationships between mass transfer, hydrodynamics, and adsorption. To obtain a better understanding of these parameters, we used two commercially available resins to compare the adsorption of lysozyme as a function of bed expansion and bulk-phase viscosity using frontal analysis. Under static conditions adsorption was well represented by a Langmuir isotherm. Dynamic capacities at breakthrough were measured and normalized relative to the equilibrium capacity of each resin to facilitate direct comparison of resin performance under each condition. To quantify the impact of resin characteristics in expanded bed adsorption, we carried out a comparison of mass-transfer effects using a macroporous resin, Streamline SP, and a hyper-diffusive resin, S-HyperD LS. Both resins are designed for fluidized bed adsorption of proteins. In this study the results of frontal analysis showed that breakthrough was due to mass-transfer limitations of the adsorbing particles at expansions of 2 times the settled bed height. At expansions of 3 and 4 times the settled bed height, axial dispersion increased significantly; however mass-transfer limitations were still the dominant mechanistic feature contributing to early breakthrough at reduced dynamic capacity. Adsorption capacity under all conditions in this study was poorer for the macroporous resin than for the hyper-diffusive resin due to intraparticle mass-transfer limitations.

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