THE EFFECTS OF pH AND SALT CONCENTRATION ON PROTEIN FOULING OF VIRESOLVE PRO VIRUS FILTRATION MEMBRANES

Open Access
Author:
Hoying, David
Area of Honors:
Chemical Engineering
Degree:
Bachelor of Science
Document Type:
Thesis
Thesis Supervisors:
  • Andrew Zydney, Thesis Supervisor
  • Wayne Roger Curtis, Honors Advisor
Keywords:
  • Virus Filtration
  • Protein Fouling
  • Viresolve Pro
Abstract:
Virus filtration plays an essential role as part of the overall viral clearance strategy during the purification of therapeutic proteins. However, one critical problem during virus filtration is protein fouling which results in decreased filtering capacity and economically inefficient purification processes. The objective of this study was to examine the effects of pH and salt concentration on protein fouling during virus filtration through the Viresolve Pro virus filtration membrane. Data were obtained using immunoglobulin G (IgG) as a model protein dissolved in solutions containing 0 mM, 10 mM, 100 mM, and 250 mM KCl at pH 5.5, 7, and 8.5. Filtration was performed at constant transmembrane pressure with the Viresolve Pro membrane oriented in the skin-side down position. At pH 5.5, there was only a weak dependence of the flux on salt concentration, with relatively similar flow rate decays. In contrast, at pH 8.5, the salt free solution showed significantly less protein fouling compared to the solutions containing 10 mM, 100 mM, and 250 mM KCl. Overall, the protein fouling was least during filtration of a salt free solution at pH 8.5, conditions where the IgG is largely negatively-charged. This behavior is consistent with a reduction in protein-membrane interactions due to the presence of electrostatic repulsion between the negatively-charged protein and the negatively-charged membrane. These results provide valuable insights on how solution conditions such as pH and salt concentration can affect the performance of the Viresolve Pro membrane during virus filtration of important bio-therapeutic products.