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: Figure 8A shows the USD flocculation system predicted the pilot scale PSD within a ±5% error margin when micromixing was the controlling mixing time scale. For this mixing regime, the PSD curves generated by the two non-geometrically similar systems (Fig. 8B) overlapped each other with their peak volume frequencies between 9 and 10 µm. The influence of mesomixing led to broader PSDs at both flocculation scales. Under the micromixing and mesomixing-controlled regime the values of d10, d50, and d90 for the STR were predicted within a ±11% error margin by the USD system. However, the PSD curves revealed a shift towards larger particles in the USD and STR flocculation systems. In the mesomixing-controlled regime the STR d10 data set was predicted within a ±5% error margin. However, the d50 and d90 STR data sets were almost 50% larger in size than those of the USD system. When compared to smaller mixing times scales, the mesomixing regime led to an increase in the value of d90 between 30–170% in the STR and between 5–60% in the USD system. The greater sensitivity of the pilot scale flocculation system to the influence of mesomixing was possible due to a longer lasting effect of the flooding of the STR impeller region by the polymer caused by the fast flocculant addition rates used (see section 4.1).
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.