As ‘miniaturized reactors”, droplets in microfluidic systems have various unique features including high-throughput, minimal reagent consumption, contamination-free, fast response, automated handling, and isolation of individual space. In the past decade, droplet-based microfluidics has emerged as a versatile platform for molecule detection, material synthesis, compartmentalized reactions or high throughput screening in the field of chemistry and biology. Conventional microfluidic devices for droplet generation usually demand tight control over the flow condition of the continuous and dispersed phases. With precise fluid control, the resulting droplets size can range from tens to hundreds of micrometers. However, when the desired droplet size is further reduced, especially to submicron...[ Read more ]

As ‘miniaturized reactors”, droplets in microfluidic systems have various unique features including high-throughput, minimal reagent consumption, contamination-free, fast response, automated handling, and isolation of individual space. In the past decade, droplet-based microfluidics has emerged as a versatile platform for molecule detection, material synthesis, compartmentalized reactions or high throughput screening in the field of chemistry and biology. Conventional microfluidic devices for droplet generation usually demand tight control over the flow condition of the continuous and dispersed phases. With precise fluid control, the resulting droplets size can range from tens to hundreds of micrometers. However, when the desired droplet size is further reduced, especially to submicron or several hundred nanometers range, generation of monodisperse droplets in a controllable manner remains technical challenging but fundamentally significant. In addition, with conventional devices, droplet generation throughput is difficult to scale up for massive production to meet the practical applications. In this thesis, we developed two novel platforms for droplet production to address on the above concerns.

The first droplet generation platform addresses on the formation of submicron droplets. As liquid perfluorocarbon (PFC) nanodroplets may take advantage of the EPR effect for extravascular imaging, it holds promise as an innovative strategy for imaging-guided drug delivery. To produce monodisperse PFC nanodroplets, we developed a flame-shaped glass capillary and polydimethylsiloxane (PDMS) hybrid device that created a concentric flow of the dispersed phase enclosed by the focusing continuous phase at the cross-junction. A stable tip-streaming mode can be obtained for PFC nanodroplets generation. Various kinds of PFC nanodroplets as small as 200 nm in diameter with excellent uniformity are prepared and subjected to the ultrasound exposure to demonstrate the liquid PFC nanodroplets can be used for enhancing the ultrasound imaging upon activation.

The second platform is able to induce the fluid thread self-breakup in a high aspect ratio structure for droplet spontaneous generation. A high-throughput droplet generator was developed by paralleling a large number of the basic units. This device enables facile and rapid compartmentalization of aqueous samples into millions of uniform compartments.

Finally, an integrated workflow for droplet digital PCR has been implemented based on the droplet generation and manipulation technology we have developed. An integrated droplet detection system has also been set up for digital quantification of the low abundance molecule in a single molecular level.

This thesis presents the technology for the controllable and scalable droplet generation that is superior to the conventional emulsification methods. We believe that our work has impacts on the basis of droplet microfluidics and sheds new light on the way of the development of droplet microfluidics as the versatile platforms for biological and chemical applications.