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A scale-down cross-flow filtration technology for biopharmaceuticals and the associated theory

Paper ID Volume ID Publish Year Pages File Format Full-Text
22710 43373 2016 7 PDF Available
Title
A scale-down cross-flow filtration technology for biopharmaceuticals and the associated theory
Abstract

•Novel scale-down cross-flow filter is constructed to mimic larger scale systems.•Theory developed for scaling down cross-flow ultrafiltration and microfiltration.•Module performance is compared with verified laboratory scale using the theory.•Partially transmissible phage T7 is employed for validating the scale down filter.•It is a means for low-volume, low-cost, and high-throughput biopharma processing.

Use of microfiltration (MF) and ultrafiltration (UF) in cross-flow mode has been intensifying in downstream processing for expensive biopharmaceuticals. A scale-down cross-flow module with ring channel was constructed for reducing costs and increasing throughput. Commensurate with its validation, a new scale down (or scale up) theoretical framework has been further developed to 3 operational parities: (1) ratio of initial sample volume to membrane area, (2) shear force adjacent to membrane surface, and (3) initial permeate flux. By keeping identical initial physicochemical properties, we show that these 3 operational parities are equivalent to 2 further time-dependent theoretical parities for flux and transmission respectively. Importantly, transmission sensitively reflects membrane conditions for partially transmissible molecules or particles. Computational fluid dynamics simulation was conducted to confirm nearly identical shear forces for the mini and its reference filters. Permeate fluxes in suspension containing Escherichia coli phage T7, a monoclonal antibody (MAb) or other proteins, and transmission (with phage T7) were measured. For application demonstration, diafiltration and concentration modes were applied to the MAb, and separation mode to a mixture of bovine serum albumin and lysozyme. In conclusion, the developed scale-down filter has been shown to behave identically or similarly to its reference filter.

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Keywords
Polymethyl methacrylate (PubChem CID:6658); IgG (PubChem CID:190955); Lysozyme (PubChem CID:24839946); Trifluoroacetic acid (PubChem CID:6422); Acetonitrile (PubChem CID:6342)Bioprocessing scale-down; Cross-flow filtration; Microfiltration; Monoclonal ant
First Page Preview
A scale-down cross-flow filtration technology for biopharmaceuticals and the associated theory
Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Biotechnology - Volume 221, 10 March 2016, Pages 25–31
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering