Volume 30, Issue 6 p. 1291-1300
Bioseparations and Downstream Processing

Understanding and modeling alternating tangential flow filtration for perfusion cell culture

William Kelly

Corresponding Author

William Kelly

Dept. of Chemical Engineering, Villanova University, 318 White Hall, 800 Lancaster Ave, Villanova, PA, 19085

Correspondence concerning this article should be addressed to W. Kelly at [email protected].Search for more papers by this author
Jennifer Scully

Jennifer Scully

Dept. of Chemical Engineering, Villanova University, 318 White Hall, 800 Lancaster Ave, Villanova, PA, 19085

Search for more papers by this author
Di Zhang

Di Zhang

Dept. of Mechanical Engineering, Villanova University, Tolentine Hall, 800 Lancaster Ave, Villanova, PA, 19085

Search for more papers by this author
Gang Feng

Gang Feng

Dept. of Mechanical Engineering, Villanova University, Tolentine Hall, 800 Lancaster Ave, Villanova, PA, 19085

Search for more papers by this author
Mathew Lavengood

Mathew Lavengood

API-LM Pharmaceutical Development and Manufacturing Sciences, Janssen R&D, 1400 McKean Rd, Spring House, PA

Search for more papers by this author
Jason Condon

Jason Condon

API-LM Pharmaceutical Development and Manufacturing Sciences, Janssen R&D, 1400 McKean Rd, Spring House, PA

Search for more papers by this author
John Knighton

John Knighton

API-LM Pharmaceutical Development and Manufacturing Sciences, Janssen R&D, 1400 McKean Rd, Spring House, PA

Search for more papers by this author
Ravinder Bhatia

Ravinder Bhatia

API-LM Pharmaceutical Development and Manufacturing Sciences, Janssen R&D, 1400 McKean Rd, Spring House, PA

Search for more papers by this author
First published: 30 July 2014
Citations: 60

Abstract

Alternating tangential flow (ATF) filtration has been used with success in the Biopharmaceutical industry as a lower shear technology for cell retention with perfusion cultures. The ATF system is different than tangential flow filtration; however, in that reverse flow is used once per cycle as a means to minimize fouling. Few studies have been reported in the literature that evaluates ATF and how key system variables affect the rate at which ATF filters foul. In this study, an experimental setup was devised that allowed for determination of the time it took for fouling to occur for given mammalian (PER.C6) cell culture cell densities and viabilities as permeate flow rate and antifoam concentration was varied. The experimental results indicate, in accordance with D'Arcy's law, that the average resistance to permeate flow (across a cycle of operation) increases as biological material deposits on the membrane. Scanning electron microscope images of the post-run filtration surface indicated that both cells and antifoam micelles deposit on the membrane. A unique mathematical model, based on the assumption that fouling was due to pore blockage from the cells and micelles in combination, was devised that allowed for estimation of sticking factors for the cells and the micelles on the membrane. This model was then used to accurately predict the increase in transmembane pressure during constant flux operation for an ATF cartridge used for perfusion cell culture. © 2014 American Institute of Chemical Engineers Biotechnol. Prog., 30:1291–1300, 2014