Fluid dynamics alters liquid–liquid phase separation in confined aqueous two-phase systems

Author:

Hester Eric W.12ORCID,Carney Sean12,Shah Vishwesh3,Arnheim Alyssa3,Patel Bena3,Di Carlo Dino234ORCID,Bertozzi Andrea L.124ORCID

Affiliation:

1. Department of Mathematics, University of California, Los Angeles 90095, CA

2. California NanoSystems Institute, University of California, Los Angeles 90095, CA

3. Department of Bioengineering, University of California, Los Angeles 90095, CA

4. Department of Mechanical and Aerospace Engineering, University of California, Los Angeles 90095, CA

Abstract

Liquid–liquid phase separation is key to understanding aqueous two-phase systems (ATPS) arising throughout cell biology, medical science, and the pharmaceutical industry. Controlling the detailed morphology of phase-separating compound droplets leads to new technologies for efficient single-cell analysis, targeted drug delivery, and effective cell scaffolds for wound healing. We present a computational model of liquid–liquid phase separation relevant to recent laboratory experiments with gelatin–polyethylene glycol mixtures. We include buoyancy and surface-tension-driven finite viscosity fluid dynamics with thermally induced phase separation. We show that the fluid dynamics greatly alters the evolution and equilibria of the phase separation problem. Notably, buoyancy plays a critical role in driving the ATPS to energy-minimizing crescent-shaped morphologies, and shear flows can generate a tenfold speedup in particle formation. Neglecting fluid dynamics produces incorrect minimum-energy droplet shapes. The model allows for optimization of current manufacturing procedures for structured microparticles and improves understanding of ATPS evolution in confined and flowing settings important in biology and biotechnology.

Funder

Simons Foundation

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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