Microfluidic fabrication of polymer-based microparticles for biomedical applications

Abstract

Delivery vehicles that can encapsulate and release active ingredients of pre-determined volumes at the target site on-demand present a challenge in biomedical field. Due to their tunable physiochemical properties and degradation rate, polymeric particles are one of the most extensively employed delivery vehicles. Generally they are fabricated from emulsion templates. Conventional bulk emulsification technique provides little control over the characteristics of droplets generated. Thus the properties of the subsequent particles cannot be controlled. The advance of droplet microfluidics enables the generation and manipulation of designer single, double or higher-order emulsion droplets with customizable structure. These droplets are powerful and versatile templates for fabricating polymeric delivery vehicles with pre-determined properties. Due to the monodispersity of droplet templates by microfluidics, the relationship between size, size distribution, shape, architecture, elastic responses and release kinetics can be systematically studied. These understandings are of key importance for the design and fabrication of the next generation polymeric delivery vehicles with custom-made functions for specific applications.

In the present work, we engineer the droplet templates generated from microfluidics to fabricate designer polymeric microparticles as delivery vehicles. We investigate and obtain the relationship between the particle size, size distribution, structure of microparticles and their release kinetics. Moreover, we also identify an innovative route to tune the particle shape that enables the investigation of the relationship between particle shape and release kinetics. We take advantage of the dewetting phenomena driving by interfacial tensions of different liquid phases to vary the droplet shape. We find that the phase-separation-induced shape variation of polymeric composite particles can be engineered by manipulating the kinetic barriers during droplet shape evolution.

To predict the performance of our advanced polymer particles in practical applications, for instance, in narrow blood vessels in vivo, we also develop a novel capillary micromechanics technique to characterize the linear and non-linear elastic response of our polymer particles on single particle level. The knowledge of the mechanical properties enables the prediction as well as the design of the mechanical aspects of polymer particles in different applications.

The ability to control and design the physical, chemical, mechanical properties of the delivery vehicles, and the understanding between these properties and the biological functionalities of delivery vehicles, such as the release kinetics, lead towards tailor-designed delivery vehicles with finely-designed functionalities for various biomedical applications. Our proposed electro-microfluidic platform potentially enables generation of submicron droplet templates with a narrow size distribution and nanoscaled delivery vehicles with well-controlled properties, leading to a next generation of intracellular delivery vehicles. Microfluidic-based technique has the potential to be scaled up by parallel operation. Therefore, we are well-equipped for the massive production of custom-made droplet templates of both micron-size and nanosized, and we can design the physiochemical properties and biological functionalities of the delivery vehicles. These abilities enable us to provide solutions for applications and fundamental topics where encapsulation, preservation and transportation of active ingredients are needed.