Optimizing particle morphology during antibody precipitation for enhanced tangential flow filtration performance

Mirko Minervini, Ali Behboudi, Jovana R. Marzella, Andrew L. Zydney

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Recent advances in cell culture have led to substantial increases in monoclonal antibody titer, leading to renewed interest in using precipitation for the initial capture and purification of high-value therapeutic proteins. One of the major challenges in developing continuous precipitation processes is ensuring stable operation of the tangential flow microfiltration membranes used for dewatering and washing. The objective of this study was to increase the filterability of the protein precipitate by addition of salts to control the particle morphology. Experiments were performed with human serum Immunoglobulin G (IgG) in different buffers and in the presence of different salts using zinc chloride and polyethylene glycol as precipitating agents. The addition of 300 mM CaCl2 caused more than a 2-fold increase in the critical flux. This behavior was not due simply to a shift in the particle size distribution, but it was instead related to an increase in the density of the precipitate. The precipitate density was readily measured by centrifugation, providing a rapid method for identifying precipitation conditions that lead to good filterability. Data obtained during a 24-hour filtration process showed minimal fouling with high degrees of purification, demonstrating the viability of this approach for optimizing precipitation conditions.

Original languageEnglish (US)
Article number126574
JournalSeparation and Purification Technology
StatePublished - Jun 19 2024

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry
  • Filtration and Separation

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