Exploring New Horizons in Liquid Compartmentalization via Microfluidics

Spatial organization of cellular processes is crucial to efficiently regulate life's essential reactions. Nature does this by compartmentalization, either using membranes, such as the cell and nuclear membrane, or by liquid-like droplets formed by aqueous liquid-liquid phase separation. Aqueous liquid-liquid phase separation can be divided in two different phenomena, associative and segregative phase separation, of which both are studied for their membraneless compartmentalization abilities. For centuries, segregative phase separation has been used for the extraction and purification of biomolecules. With the emergence of microfluidic techniques, further exciting possibilities were explored because of their ability to fine-tune phase separation within emulsions of various compositions and morphologies and achieve one of the simplest forms of compartmentalization. Lately, interest in aqueous liquid-liquid phase separation has been revived due to the discovery of membraneless phases within the cell. In this Perspective we focus on segregative aqueous phase separation, discuss the theory of this interesting phenomenon, and give an overview of the evolution of aqueous phase separation in microfluidics.