Fabrication of Polymersomes using Microfluidic Devices
The fabrication of diblock copolymer vesicles, so-called polymersomes, from poly(2-vinylpyridine)-block-poly(ethylene glycol) (P2VP-b-PEG) and poly(ethylene glycol)-block-poly(lactid acid) (PEG-b-PLA) by means of microfluidics is described. The experiments were performed in microfluidic devices made by soft lithography in poly(dimethylsiloxane) (PDMS). To gain insight into the fluid dynamics in the microfluidic devices, 2D and 3D simulations based on the finite element method (FEM) were performed. This allowed for optimization of the microchannel geometry, and thus precise control over the formation process and properties of the polymersomes, which were extensively characterized by dynamic light scattering (DLS), confocal laser scanning microscopy (CLSM) and cryo transmission electron microscopy (cryo-TEM). Two distinct approaches to control the vesicular self-assembly of copolymer molecules into polymersomes were studied: the undirected self-assembly using hydrodynamic flow focusing (HFF) and the directed self-assembly using copolymer-stabilized water/organic solvent/water (W/O/W) double emulsion templates. In the former case, the formation of polymersomes occurred at the interface of a flow-focused, copolymer-loaded solvent stream and a selective solvent in a simple microchannel cross junction. Investigations revealed that the polymersome size is in proportion with the flow rate ratio of polymer solution and the selective solvent; a nucleation and growth model explaining the observed relation between flow conditions and polymersome size was proposed. In the latter case, the formation of polymersomes was directed by W/O/W double emulsions during evaporation of the organic solvent in which the copolymer was dissolved. The formation of vesicles from diblock copolymers in microfluidic devices not only enables continuous fabrication of polymersomes with controlled size and narrow polydispersity (PDI), but also offers the ability to tune the polymersome size over several orders of magnitude from less than 50 nm using HFF to more than 100 micron using double-emulsion templates. To allow for the aforementioned studies, preliminary work focusing on increasing the resistance of PDMS towards swelling due to organic solvents was performed. By using a glass-like coating based on sol-gel chemistry, the swelling of PDMS was decisively decreased. Analyses of coated devices by scanning electron microscopy (SEM) illustrated that the coating could be homogeneously distributed even in complex microfluidic devices as employed for the preparation of double-emulsion templates. To simplify the fabrication of microfluidic devices with patterned wettability as required for the formation of double emulsions, a novel method to spatially pattern the surface properties of microchannels using flow confinement was developed. For a better understanding of the formation of double emulsions, a fundamental investigation of multiple emulsion formation in microfluidic devices in general was performed. Results show that, depending on the number of dripping instabilities present in the device, multiple emulsions can either be formed in a sequence of emulsification steps or in a one-step process. It was furthermore demonstrated that one-step formation of multiple emulsions provides a novel way to create emulsions from liquids, which otherwise cannot be emulsified controllably, such as viscoelastic polymer solutions or liquids exhibiting a low surface tension. Finally, the development of a novel microfluidic spray dryer based on a conventional microfluidic device for forming double emulsions was presented and its application for fabricating drug nanoparticles from hydrophobic active pharmaceutical ingredients (APIs) was demonstrated.
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