TY - JOUR
T1 - Quantitative interpretation of protein breakthrough curves in small-scale depth filter modules for bioprocessing
AU - Jung, Seon Yeop
AU - Nejatishahidein, Negin
AU - Kim, Minyoung
AU - Espah Borujeni, Ehsan
AU - Fernandez-Cerezo, Lara
AU - Roush, David J.
AU - Borhan, Ali
AU - Zydney, Andrew L.
N1 - Funding Information:
The authors would like to acknowledge Merck & Co., Inc. , Kenilworth, NJ, USA for their financial support of this project. We also thank Dr. Kyung Hyun Ahn and Dr. Tae Gon Kang for their support in providing the computational resources used for the binding analysis.
Publisher Copyright:
© 2021 Elsevier B.V.
PY - 2021/6/1
Y1 - 2021/6/1
N2 - 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.
AB - 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.
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U2 - 10.1016/j.memsci.2021.119217
DO - 10.1016/j.memsci.2021.119217
M3 - Article
AN - SCOPUS:85102818957
SN - 0376-7388
VL - 627
JO - Journal of Membrane Science
JF - Journal of Membrane Science
M1 - 119217
ER -