Gordon Christopher — 2005-06 Fellow
Conventional approaches to synthesizing polymeric particles for controlled release of drugs involve bulk emulsification in the presence of vigorous mixing. One problem with these methods is that the result is frequently a heterogeneous population of particles with widely varying size and microstructure. Size is particularly important since it is a key factor in the rate of release, and also it is known that cells process particles used for non-viral gene delivery differently depending on their size. In contrast, Microfluidic methods have previously been demonstrated as an effective platform for generating highly monodisperse emulsions. Using microfluidic channels, two immiscible liquids will flow into a t-junction and dropletw will be sheared off one liquid phase by the viscous stresses induced by the other liquid. By forming droplets from a polymeric material combined with appropriate initiators we have the ability to subsequently apply external stimuli like heat and light to trigger gelation or polymerization.
The initial stage of this research program probes two main issues. One part of the project involves optimizing the initial drop formation. Droplet size is influenced by such factors as liquid flow rates, device geometry, viscosities, and interfacial tension. Though the general dependence of drop size on each of these parameters is known, comprehensive experiments over the full range of parameter space and development of an accompanying predictive model is lacking. More importantly, polymers and surface active molecules that are typically used in drug delivery dramatically influence the bulk and interfacial properties, and their effects on drop formation are not well understood. Using a high speed CCD camera, we will characterize droplet size as a function of those parameters listed. The outcome of this part of the project will be a model that characterizes the relationship between the microfluidic parameters and the droplet sizes.
The second part of the project will proceed concurrently with the drop formation study. Controlling the local chemical and thermal environment of a droplet is key to directing its transformation into a gel or polymer particle. Our goal is first to mimic conventional processes in a microfluidic device (thermal gelation, emulsion or interfacial polymerization) using inline heating elements, focused UV light, and additional fluid lines to introduce chemical initiators. We expect that microfluidic devices will offer access to regions of parameter space that are not convenient in traditional methods. The outcome of this part will be a model characterizing physical and mechanical properties of particles as a function of processing conditions. This knowledge is vital to drug delivery since these properties influence the ability of a particle to adhere to a targeted surface and to release its contents in a desired manner. Further, geometric confinement during gelation and sequential application of microfluidic elements allows us to think beyond uniform spherical shapes and consider novel shapes (plugs, rods) and microstructures (core-shell, dual-sided, multiple emulsions).