Droplet microfluidics: fundamentals and its advanced applications

Abstract

Droplet-based microfluidic systems have been shown to be compatible with many chemical and biological reagents and capable of performing a variety of operations that can be rendered programmable and reconfigurable. This platform has dimensional scaling benefits that have enabled controlled and rapid mixing of fluids in the droplet reactors, resulting in decreased reaction times. This, coupled with the precise generation and repeatability of droplet operations, has made the droplet-based microfluidic system a potent high throughput platform for biomedical research and applications. In addition to being used as micro-reactors ranging from the nano- to femtoliter (10^-15 liters) range; droplet-based systems have also been used to directly synthesize particles and encapsulate many biological entities for biomedicine and biotechnology applications. For this, in the following article we will focus on the various droplet operations, as well as the numerous applications of the system and its future in many advanced scientific fields. Due to advantages of droplet-based systems, this technology has the potential to offer solutions to today's biomedical engineering challenges for advanced diagnostics and therapeutics.

Fig. 1. From wetting to superwetting with different fluids.

Fig. 2. Droplet formation with different mechanisms: (a) T junction (ref. 43), (b) capillary flow-focusing (ref. 43), and (c) di-electrophoresis-based generation (ref. 44).

Fig. 3. (a) Formation of water-in-silicone oil droplets using a flow focusing design with an embedded circular orifice. (b) Graph showing decreasing droplet size and increasing frequency of formation with increasing oil flow rate (ref. 48).

Fig. 4. (a) Bifurcating channel geometry used to halve droplets at each junction (ref. 70). (b) Pillar in channels demonstrates asymmetric fission of water-in-oil droplets (ref. 71). (c–e) Active fission of droplets using DEP through surface electrodes in EWOD system (ref. 72).

Fig. 5. (a) Schematic of dome-shaped chamber for micromixing using surface acoustic wave. (b) Cross sectional image of dome-shaped chamber on the line A–A′ depicted in (a). (c) Cross sectional image of fabricated dome-shaped chamber device for acoustic mixing.

Fig. 6. DEP-based cell sorting.

Fig. 7. The schematic comparison of conventional culture method and the microchip-based C. albicans detection.

Fig. 8. Schematic diagram showing the ESI-MS-based droplet analysis system.

Fig. 9. Schematic of the structure and sequential operation of a compartmented-on-demand droplet platform.

Fig. 10. The schematics of multi-drug delivery systems.