A versatile and robust microfluidic device for capillary-sized simple or multiple emulsions production

TL;DR

This paper introduces a versatile microfluidic device capable of producing monodisperse, capillary-sized simple and multiple emulsions below 5 microns, suitable for targeted drug delivery and in vivo applications.

Contribution

A novel microchip design enabling efficient production of biocompatible, capillary-sized emulsions for drug delivery, surpassing previous limitations in droplet size and yield.

Findings

Droplet size is mainly controlled by interfacial tension forces.

Capillary and viscosity ratios influence droplet characteristics.

The device achieves polydispersity index down to 5%.

Abstract

Ultrasound-vaporizable microdroplets can be exploited for targeted drug delivery. However, it requires customized microfluidic techniques able to produce monodisperse, capillary-sized and biocompatible multiple emulsions. Recent development of microfluidic devices led to the optimization of microdroplet production with high yields, low polydispersity and well-defined diameters. So far, only few were shown to be efficient for simple droplets or multiple emulsions production below 5 microns in diameter, which is required to prevent microembolism after intravenous injection. Here, we present a versatile microchip for both simple and multiple emulsion production. This parallelized system based on microchannel emulsification was designed to produce perfluorocarbon in water or water within perfluorocarbon in water emulsions with capillary sizes (<5 $\mu$m) and polydispersity index down to 5 % for in vivo applications such as spatiotemporally-triggered drug delivery using Ultrasound. We show that droplet production at this scale is mainly controlled by interfacial tension forces, how capillary and viscosity ratios influence droplet characteristics and how different production regimes may take place. The better understanding of droplet formation and its relation to applied pressures is supported by observations with a high-speed camera. Compared to previous microchips, this device opens perspectives to produce injectable and biocompatible droplets with a reasonable yield in order to realize preclinical studies in mice.