Microfluidic Production and Characterization of Lipid Vesicles, Polymer Vesicles, and Hybrid Polymer/Lipid Vesicles

Abstract

Lipid vesicles are aqueous volumes surrounded by a bilayer of lipid molecules, which are amphiphilic molecules with their head groups facing water and tail groups facing oil. These vesicles are simple models for cell membranes and can be used for drug delivery. Similarly, block copolymers are amphiphilic molecules that form vesicles by themselves or with lipids. Like lipid vesicles, polymer vesicles can also be used for drug delivery and cell membrane mimicry. Here, we create new microfluidic platforms to fabricate lipid, polymer, and hybrid lipid/polymer vesicles. Microfluidics offers precise control of vesicle size and composition, which unlike the conventional methods that often end up with highly poly disperse samples. To achieve this, vesicles are produced using water/oil /water emulsions in a glass capillary device, with different lipids/polymers immersed in the oil phase. To characterize the stiffness of the vesicles, we use an instrument called micropipette aspiration, which we learned to build. We find that pure lipid vesicles are very soft with low lysis tension, while pure polymer vesicles (PEG-B-PLA) with high molecular weight are brittle. Hybrid lipid/polymer vesicles have intermediate stiffness between pure lipid vesilces and pure polymer vesicles. We also study the effect of bilayer asymmetry on hybrid vesicle properties. The vesicles are called symmetric when its bilayer is composed of two identical mixed polymer/lipid leaflets. Meanwhile, the vesicles are called asymmetric, in which its bilayer is composed of one polymer leaflet and one lipid leaflet. A triple emulsion device for water/oil1/oil2/water emulsions is created to fabricate asymmetric vesicles. The two oil phases contain different lipid or polymer materials that form two dissimilar leaflets in the vesicle membranes. We use micropipette aspiration to characterize the asymmetric vesicles versus symmetric vesicles. Importantly, we find asymmetry enhances mechanical toughness of the membrane. In the future, we envision microfluidic approach could be a reliable platform for producing vesicles with desired properties.