Abstract
Flocculation is a key purification step in cell-based processes for the food and pharmaceutical industry where the removal of cells and cellular debris is aided by adding flocculating agents. However, finding the best suited flocculating agent and optimal conditions to achieve rapid and effective flocculation is a non-trivial task. In conventional analytical systems, turbulent mixing creates a dynamic equilibrium between floc growth and breakage, constraining the determination of floc formation rates. Furthermore, these systems typically rely on end-point measurements only. We have successfully developed for the first time a microfluidic system for the study of flocculation under well controlled conditions. In our microfluidic device (μFLOC), floc sizes and growth rates were monitored in real time using high-speed imaging and computational image analysis. The on-line and in situ detection allowed quantification of floc sizes and their growth kinetics. This eliminated the issues of sample handling, sample dispersion, and end-point measurements. We demonstrated the power of this approach by quantifying the growth rates of floc formation under forty different growth conditions by varying industrially relevant flocculating agents (pDADMAC, PEI, PEG), their concentration and dosage. Growth rates between 12.2 μm s-1 for a strongly cationic flocculant (pDADMAC) and 0.6 μm s-1 for a non-ionic flocculant (PEG) were observed, demonstrating the potential to rank flocculating conditions in a quantitative way. We have therefore created a screening tool to efficiently compare flocculating agents and rapidly find the best flocculating condition, which will significantly accelerate early bioprocess development.
Highlights
The pressure to decrease operation costs and to increase the efficiency of existing industrial bioprocesses has led to a renewed interest in flocculation.[1,2] During flocculation, colloidal particles are selectively aggregated with the aid of a flocculating agent and subsequently settle under the influence of gravity.[3,4] In industrial bioprocesses, this selective removal of key impurities is applied to remove cells and cellular debris from the fermentation medium during primary recovery, i.e. before further purification steps yield the desired product
Microfluidic device design The microfluidic device was comprised of a ψ-shaped hydrodynamic focussing inlet evolving into a 607 mm long inwards spiralling channel with the width (w) and depth (d) of the channels being 0.5 mm (Fig. 1)
We successfully developed for the first time a microfluidic device for flocculation analysis, the μFLOC, and we have shown for the first time on-line and in situ detection and quantification of floc sizes and of growth kinetics of floc formation
Summary
The pressure to decrease operation costs and to increase the efficiency of existing industrial bioprocesses has led to a renewed interest in flocculation.[1,2] During flocculation, colloidal particles are selectively aggregated with the aid of a flocculating agent and subsequently settle under the influence of gravity.[3,4] In industrial bioprocesses, this selective removal of key impurities is applied to remove cells and cellular debris from the fermentation medium during primary recovery, i.e. before further purification steps yield the desired product. It is critical to understand floc growth and the physical characteristics of flocs to enhance removal efficiency These depend on a number of process parameters. The growth rate of the flocs is known to depend strongly on the dosage of the flocculants,[2,11,12] on their physical properties, such as charge densities and molecular weight, and on the properties of
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