Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/54808
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Type: Journal article
Title: Prediction of shear damage of plasmid DNA in pump and centrifuge operations using an ultra scale-down device
Author: Zhang, H.
Kong, S.
Booth, A.
Boushaba, R.
Levy, M.
Hoare, M.
Citation: Biotechnology Progress, 2007; 23(4):858-865
Publisher: Amer Chemical Soc
Issue Date: 2007
ISSN: 8756-7938
1520-6033
Statement of
Responsibility: 
Hu Zhang, Simyee Kong, Andrew Booth, Rihab Boushaba, M. Susana Levy, Michael Hoare
Abstract: Supercoiled circular (SC) plasmid DNA is often subjected to fluid stress in large-scale manufacturing processes. It is thus important to characterize the engineering environment within a particular unit operation as well as within the associated ancillary equipment during process design for plasmid DNA manufacture so as to avoid shear-induced degradation of the SC isoform, which would compromise product efficacy in therapeutic applications. In the past few years, ultra scale-down (USD) tools were developed within our laboratory to mimic the engineering environments experienced by biomolecules within a range of manufacturing-scale ancillary, primary recovery, and purification operations, using milliliter quantities of material. Through the use of a USD shear device, the effect of elongational strain rate on SC plasmid DNA degradation was studied in this paper, and from that, the impact of a centrifugal pump, a Mono pump, and a disk-stack centrifuge feed zone on SC plasmid DNA degradation was predicted and experimentally verified at scale. Model predictions, over the range of conditions studied, were in good agreement with experimental values, demonstrating the potential of the USD approach as a decisional tool during bioprocess design.
Keywords: Alcohols
DNA
DNA, Superhelical
Electrophoresis, Agar Gel
Models, Statistical
Equipment Design
Industrial Microbiology
Biotechnology
Fermentation
Plasmids
Stress, Mechanical
Models, Theoretical
Time Factors
DOI: 10.1021/bp070066z
Appears in Collections:Aurora harvest 5
Chemical Engineering publications

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