Cross-Interface Emulsification for Generating Size-Tunable Droplets

Abstract

We report the cross-interface emulsification (XiE), a simple method for generation of monodisperse droplets of controllable volumes from picoliter to nanoliter. A simple system is set up, in which a fused-silica capillary is vibrating across the surface of the continuous phase (mineral oil) in a reservoir, and the flow of the dispersed phase (aqueous solution) in the capillary is segmented into monodisperse droplets at the air-oil interface. We find that the volume of droplets is mainly dominated by the flow rate and vibrating frequency, and not significantly influenced by other factors, such as the viscosity of continuous phase and dispersed phase, inner diameter of the capillary (20 ~ 100 μm), and the shape of the tip (tapered or flat). These features reflect high robustness, flexibility and precision of the XiE method in on demand volume control of droplets. The droplets automatically assembled into planar monolayer droplet arrays (PMDA) in flat-bottomed microwells of 96-well plates, offering excellent convenience for imaging of droplets. As a representative application, we successfully performed digital loop-mediated isothermal amplification using PMDAs with multivolume droplets for the absolute quantification of nucleic acids. Our results demonstrate XiE is simple and inexpensive for the production of monodisperse size-tuneable droplets, and offers opportunities for common laboratories, even without microfabrication facilities, to perform digital quantification, singe cell analysis and other biochemical assays with high throughput.