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Bioprocess and Biosystems Engineering

, Volume 27, Issue 1, pp 25–37 | Cite as

Optimal operation of high-pressure homogenization for intracellular product recovery

  • William J. Kelly
  • Kenneth R. Muske
Original papers

Abstract

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.

Keywords

Operating Pressure Hydrodynamic Force Computational Fluid Dynamic Model Intracellular Product Impact Distance 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

List of symbols

d

Impact distance (mm)

fc

Total fraction of broken cells

ff

Fraction of cell breakage due to channel forces

fτ

Fraction of cell breakage due to shear stress

fr

Fraction of cell breakage due to impact ring impingement

gf

Plasmid in the homogenizer feed pellet (g)

gh

Plasmid in the homogenate pellet (g)

h

Gap space (μm)

L

Channel length (m)

P

Operating pressure (psig)

Pr

Impact ring pressure (psig)

Q

Volumetric flow rate (ml/s)

rp

Fraction of free plasmid recovered from homogenization

β

Proportionality constant

ΔE

Post-channel turbulence energy dissipation rate (m/s)

ΔPc

Pressure drop across the channel (psi)

ΔPi

Channel inlet pressure gradient (Pa/m)

μ

Viscosity (cp)

ρ

Fluid density (g/ml)

τm

Maximum channel shear stress (psi)

τw

Fully developed channel wall shear stress (psi)

Notes

Acknowledgements

We would like to thank APV–Gaulin for providing technical and financial support for this work. We would also like to acknowledge the contributions of Justin Miller, Mark Rogowski, and Mike Clemson in obtaining the Fluent simulation and experimental homogenizer results in this paper.

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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  1. 1.Department of Chemical EngineeringVillanova UniversityVillanovaUSA

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