Optimization of a Droplet-Based Millifluidic Device to Investigate the Phase Behavior of Biopolymers, Including Viscous
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ORIGINAL ARTICLE
Optimization of a Droplet-Based Millifluidic Device to Investigate the Phase Behavior of Biopolymers, Including Viscous Conditions Chloé Amine 1 & Adeline Boire 1
&
Joëlle Davy 1 & Anne-Laure Reguerre 1 & Patrice Papineau 1 & Denis Renard 1
Received: 14 January 2020 / Accepted: 25 June 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Phase diagrams are widely used to map and control the assembly states of biopolymers. However, these studies are highly time and material consuming. Here, we present the optimization of a simple tool based on millifluidics to screen phase diagram of biopolymers, pure or in mixtures with other biopolymers. It is used (i) to generate a homogeneous mixture of biopolymers/buffer and/or biopolymers 1/ biopolymers 2 in a short time (~s), (ii) to vary the composition of the mixtures by adjusting the flow rates, and (iii) to determine the turbidity of the drop by grey level analysis. The mixing efficiency and the calibration turbidity vs. grey level were performed using colloidal titanium dioxide dispersions. The use of millifluidics reduced the amount of material of tenfold and the experimentation time by a factor five compared to a conventional bulk approach. This set-up was used to explore functional synergies between proteins and polysaccharides as an example of application. Keywords Millifluidics . Phase diagram . Biopolymers phase separation
Introduction Phase separation phenomena between biomacromolecules, and more particularly coacervation, are complex processes that depend on the physical-chemical conditions and the intrinsic parameters of each compound. Phase-separated systems are of particular interest from a technological point of view to design new functional microstructures, with potential applications in pharmaceutical, biomedical, cosmetics or food industry [1, 2]. For example, aqueous mixtures of protein and polysaccharide are widely used to enhance textural, structural and stabilizing properties of food products. Understanding and characterizing specific conditions and factors leading to phase-separated systems is an essential preliminary step in the further development of high values products. Such screening studies, usually performed in bulk, are highly time-consuming and require large quantities of raw materials. Miniaturized systems based on microfluidics are suitable for investigating phase diagrams with reduced raw material quantities and faster time [3, 4]. One of the first microfluidic
* Adeline Boire [email protected] 1
INRAE, UR BIA, F-44316 Nantes, France
devices, based on glass capillaries of a few microliters, was proposed to investigate the phase diagram of a polymer as a function of temperature [5]. However, each capillary had to be filled manually limiting the screening ability of the system. The development of microfluidic chips based on photolithography led to new high-throughput screening tools for protein crystallization [3, 6, 7]. The development of such microfluidic chips requires a high le
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