The biopharmaceutical industry, which relates to human health, witnessed very fast development in the last few years to match the biodrug market demand. Manufacture of high value therapeutics usually requires the use of at least 2 or 3 chromatographic steps, which contributes to the significant cost of downstream processes. Therefore, chromatographic process optimization is an essential part of bioproduct manufacture development. In chromatographic separation, the compressible agarose-base matrices, which are most widely, used as column packing material. Over the past years there has been a steady move toward the adoption of more rigid, porous particles in order to combine ease of manufacture with increased levels of productivity. The latter is still constrained by the onset of compression where the level of wall support becomes incapable of withstanding flow-induced particle drag. In this study it investigates how, by the installation of cylindrical column inserts, it is possible to enhance the level of wall support to improve the column hydrodynamic performance. Experiments were conducted to examine the effect of the position of the insert in the column, and also of the insert dimensions on the critical velocity at which the onset of compression occurs. It was found that when installed at the bottom of the column, single inserts in different dimensions can provide 5% to 15% critical velocity increment, and inserts combination can provide up to a 20% increase in critical velocity without significantly affecting column hydrodynamics (less than 10%), as measured by the level of axial dispersion. A solid mechanics model was established to simulate the pressure drop, flowrate, and packing material compression properties in a chromatography column. Based on the Biot’s theory, which describes consolidation of porous materials, the model can relate the pressure drop to compression in chromatographic process. Darcy’s law is also applied, and combines with the Konezy-Carman equation for permeability. Comsol Multiphysics software, which can solve physical phenomenon by the finite element method, was employed for the model established. The inverse method in Matlab is used for parameter determination. With this simulation, the Young’s modulus, and bed voidage fraction were specified in one experiment condition. The determined parameters were then input to the model to simulate the flowrate, pressure drop, and bed displacement. The simulation results fit the experimental result quite well. The average error between experimental and simulation data was 3% for linear velocity and 4% for pressure drop. The simulation could also predict the superficial critical velocity for the same column packed but with inserts in different dimensions. Besides the experimental and simulation study on hydrodynamics in chromatography column having inserts, the effects of inserts applied on protein separation were also considered. The column inserts allowed higher operational flowrates, and process duration, which is positive to process productivity. However, it had a negative effect on the resolution, and caused larger elution volumes, especially when more than one insert present. In a case study of column inserts affecting on productivity, the productivity could increase 18% by two inserts setup in a 1 L column. These inserts lead 20% critical velocity increment, and 10% plate number decrement.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:626308 |
| Date | January 2013 |
| Creators | Lan, T. |
| Publisher | University College London (University of London) |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://discovery.ucl.ac.uk/1400714/ |
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