Microfluidic-generated Double Emulsions for Cell Study, Drug Delivery and Particle Therapeutics Fabrication
Droplet microfluidics is a powerful platform for both fundamental and applied biomedical research. The droplets are small in size with a diameter of 1-300 um. Thus, they could function as a miniaturized environment for quantitative and qualitative analysis. Each droplet composes of water shielded by an immiscible organic shell which enables independent control over different droplets. The large surface to volume ratio of spherical structure allows rapid mass and heat transfer, which could enable more homogeneous chemical reactions. Moreover, since multiple identical droplets could be generated simultaneously, parallel analysis for large amount of samples are possible. The use of microfluidics brings more power to droplet technology. The precise control over the flow allows droplet with preferable size and structure to be generated, which is critical for quantitative analysis, homogeneous chemical reaction as well as some in vivo applications.
Nonetheless, generation of stable, monodispersed and well controlled emulsions to meet specific biological functions are still challenging. First of all, to form more biocompatible W/O/W DE, the microfluidics devices must be patterned with desired surface wettability. W/O emulsion could only form in hydrophobic environment and the O/W emulsions could only form in hydrophilic environment. Differential patterning of the surface wettability to meet the needs are challenging. Second, DE are stabilized by two amphiphilic surfactants, one for the oil phase and the other for the water phase. Selection of appropriate surfactants should hook with specific biological application to ensure stability and biocompatibility. Third, the choice of fluid and contents in the fluid will affect the viscosity and capillary number of interfacial interaction, and eventually influences the droplet formation. The choice of biocompatible medium and buffer must take this into consideration. Fourth, the adoption of emulsions for the specific application requires optimization of the processing techniques in order to meet the needs for final analysis. For instance, control of droplet rupture for content release, modulation of oil phase permeability, quantitative analysis of content with flow cytometry, etc.
In this thesis, we will first demonstrate the design and fabrication of PDMS-based devices for automatic and high-throughput DE formation in Chapter 2. In the following chapters, we will demonstrate the successful adoption of the microfluidics generated DE for different biological applications. In chapter 3, we will illustrate the application of DE as a micro-incubator for cellular studies such genetic circuit behavior and performance in bacterial cells cultured in DE droplets and formation of 3D mammalian cell spheroid. In chapter 4, we will show the successful application of DE as drug carriers for intranasal drug delivery. In chapter 5, we showed the application of microfluidics generated DE as template for microparticle synthesis and the use of these microparticles as therapeutic agents in nucleic acid induced inflammations in autoimmune diseases.
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