Quantitative interpretation of protein breakthrough curves in small-scale depth filter modules for bioprocessing

Seon Yeop Jung^a,2, Negin Nejatishahidein^a, Minyoung Kim^a, Ehsan Espah Borujeni^b,1, Lara Fernandez-Cerezo^c, David J. Roush^b, Ali Borhan^a, Andrew L. Zydney^a

Department of Chemical Engineering, The Pennsylvania State University, University Park, PA, 16802, USA.

Abstract

Depth filters are used throughout downstream bioprocessing, with specialized filter chemistries developed for removal of host cell proteins, DNA, and protein aggregates. These filters often show very broad breakthrough curves, but there have not been any previous analyses of this phenomenon. Protein breakthrough curves were evaluated for Ribonuclease A and α-chymotrypsin in two small-scale depth filter modules using PDH4 media containing diatomaceous earth. Computational fluid dynamics (CFD) simulations were developed, with flow in the porous media described using the modified Navier-Stokes equations incorporating a Brinkman flow term and a Langmuir binding model. The breakthrough curve in the stainless-steel module was much sharper than that in the commercial Supracap™ 50 capsule due to the more uniform axisymmetric flow field. The behavior in the Supracap™ 50 capsule was more complex, with multiple inflection points observed due to the different flow paths and the time-dependent saturation of the two layers of the depth filter media. These results provide important insights into the factors controlling protein binding/breakthrough in commercial depth filter modules.

Keywords: Depth filtration, Protein binding, CFD, Flow structure, Clarification.