Cross-Interface Emulsification for Generating Size-Tunable Droplets.

We report cross-interface emulsification (XiE), a simple method for the generation of monodisperse droplets of controllable volumes from picoliter to nanoliter. A device 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 the continuous phase and dispersed phase, the inner diameter of the capillary (20-100 μm), or the shape of the tip (tapered or flat). These features reflect high robustness, flexibility, and precision of XiE for on-demand volume control of droplets. The droplets automatically assemble 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 carry out digital loop-mediated isothermal amplification using PMDAs with multivolume droplets for the absolute quantification of nucleic acids. Our results demonstrate that XiE is simple and controllable for the production of monodisperse size-tunable droplets, and it offers opportunities for common laboratories, even without microfabrication facilities, to perform digital quantification, single cell analysis, and other biochemical assays with high throughput.