Scale-down characterization of post-centrifuge flocculation processes for high-throughput process development.
Bottom Line: The authors present a novel ultra scale-down (USD) methodology for the characterization of flocculation processes.This USD method, consisting of a multiwell, magnetically agitated system that can be fitted on the deck of a liquid handling robot, mimicked the flocculation performance of a nongeometrically similar pilot-scale vessel representing greater than three orders of magnitude scale-up.Mixing scales (i.e. macromixing, mesomixing or micromixing) modulated the flocs' size and determined the success of some of the scale-up correlations reviewed in the literature.
Affiliation: The Advanced Centre for Biochemical Engineering, Department of Biochemical Engineering, University College London, Torrington Place, London, WC1E 7JE, UK; Lonza Biologics plc, Slough, Berkshire, SL1 4DX, UK.Show MeSH
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Mentions: Pilot scale STR - see Figure 2A for diagram. This was a 2L vessel of 125 mm diameter (DT) and 1.5 L working volume (VL), equipped with a 41.5 mm diameter (Di) six-bladed disk turbine. Reagent additions were via a 3.0 mm internal diameter pipe positioned 13 mm away from the center of the impeller blade and controlled with a syringe pump (Ultra programmable PHD Ultra, Harvard Apparatus Ltd., Kent, UK). USD 96-well plate – see Figure 2B for a diagram of a single well of the plate. The impeller was a parylene encapsulated magnetic disc (V&P Scientific, San Diego) mounted on a perforated Perspex lid through a fixed Teflon seal. The microplate was a standard storage plate (1.2 mL square round-bottom plate, ABGene Ltd, Epsom, UK) with 800 µL working volume per well located on a magnetic stirrer (710CI, V&P Scientific) and mounted on the deck of a liquid handling robot (Evo 150, Tecan UK Ltd, Reading, UK). A calibrated stroboscope was used to confirm the coupling between magnetic discs and the magnetic drive. Reagent additions were via stainless steel tips of 1 mm internal diameter located in the center of the microwell with the outlet 1.0 mm above the disc tip.
Affiliation: The Advanced Centre for Biochemical Engineering, Department of Biochemical Engineering, University College London, Torrington Place, London, WC1E 7JE, UK; Lonza Biologics plc, Slough, Berkshire, SL1 4DX, UK.