Viscosity measurements of antibody solutions by photon correlation spectroscopy: an indirect approach - limitations and applicability for high-concentration liquid protein solutions

Photon correlation spectroscopy (PCS) is compared with classic rheological measurements using the cone-and-plate technique for the determination of the viscosity of protein solutions. The potential advantages using PCS are small sample volume and fast determination of zero-shear viscosity. The present study assesses potentials and limitations of the applicability of this method for the determination of viscosity of antibody solutions in protein science development. The principle of the assay is based on the determination of the apparent hydrodynamic radius of commercial available latex beads of known size added to protein solutions. Using the Stokes-Einstein equation, the hydrodynamic radius can be converted to viscosity. Several latex particle sizes and concentrations were evaluated and the assay optimized. The PCS assay for viscosity determination was tested using water/glycerol-mixtures, where the viscosity was measured with rheometer using the cone-and-plate method and also compared with published data. Different protein solutions of bovine serum albumin, lysozyme and monoclonal antibodies were then used and the PCS results were compared with viscosity data obtained by the cone-and-plate method. It could be shown that the PCS assay has limitations for the determination of the viscosity of protein solutions, especially monoclonal antibodies. The main reason is due to protein-latex bead interactions leading to the formation of larger aggregates. The use of surface modification of the latex beads can in principle prevent this interaction.