Optimal operation of high-pressure homogenization for intracellular product recovery

• Published in: Bioprocess and biosystems engineering 2004-12, Vol.27 (1), p.25-37
• Main Authors: KELLY, William J, MUSKE, Kenneth R
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Biotechnology; Cell Fractionation - instrumentation; Cell Fractionation - methods; Computer Simulation; Deoxyribonucleic acid; DNA; DNA, Bacterial - chemistry; DNA, Bacterial - isolation & purification; E coli; Escherichia coli; Escherichia coli - genetics; Escherichia coli - isolation & purification; Fluid dynamics; Fundamental and applied biological sciences. Psychology; Homogenization; Hydrodynamics; Intracellular Fluid - chemistry; Microfluidics - instrumentation; Microfluidics - methods; Models, Chemical; Plasmids - chemistry; Plasmids - isolation & purification; Pressure; Studies
• ISSN: 1615-7591; 1615-7605
• DOI: 10.1007/s00449-004-0378-9

An optimal control methodology for the homogenization of bacterial cells to recover intracellular products is presented. A Fluent computational fluid dynamics (CFD) model is used to quantify the hydrodynamic forces present in the homogenizer, and empirical models are used to relate these forces to experimentally obtained cell disruption and product recovery data. The optimal homogenizer operation, in terms of either constant cell breakage or maximum intracellular product recovery, is determined using these empirical models. We illustrate this methodology with an Escherichia coli bacterial system used to produce DNA plasmids. Homogenization is performed using an industrial APV-Gaulin high-pressure homogenizer. The modeling and optimization results for this E. coli-DNA plasmid system show good agreement with the experimental data.