Polymer microparticles by membrane emulsification: Production and applications

Abstract

The objective of the work reported in this thesis is to evaluate the potential of microstructured systems for the production of µm-sized polymer particles. For this purpose, we investigated a method of emulsifying monomer followed by a controlled suspension polymerization process in which the droplet size distribution can be maintained. Additionally, the option of emulsifying dissolved polymer to exclude the complexity of a suspension polymerization process was also taken into consideration. For emulsification experiments, we selected straight-through microchannel (MC) arrays as they show a promising performance in terms of both monodispersity of the emulsions produced and potential for scale-up. The operating window for emulsification of monomer with straight-through MC arrays is reported in Chapter 2. Coefficients of variation (CVs) below 5% have been obtained with hydrophobic monomers such as styrene or n-butyl methacrylate or mixtures of hydrophobic solvents such as toluene and hydrophobic monomers. Mixtures of hydrophobic and more hydrophilic monomers such as methyl methacrylate result in broader droplet size distributions. The emulsification process is quite stable and variations in the cross-flow velocity and applied pressure up to a certain blow-up point do not significantly affect the final droplet size distribution. Chapter 3 describes the suspension polymerization for styrene-in-water emulsions prepared with straight-through MC arrays. The main focus is on maintaining the size distribution of the original monomer droplets during polymerization. It has been shown that significant broadening of the droplet size distribution occurs already on time scales of the emulsification process. In addition, secondary nucleation of submicron particles occurs. The molecular weight distribution of these secondary nucleated particles points to emulsion polymerization as the dominating mechanism. The initiator concentration as well as the monomer volume fraction in the reaction mixture have a strong influence on secondary particle nucleation. Even the addition of a water soluble inhibitor such as NaNO2 can only partly suppress secondary nucleation. The potential for scale-up of styrene emulsification with straight-through MC arrays with subsequent suspension polymerization is evaluated in Chapter 4. At this point, feasibility is only expected for a small scale process, such as an annual production of 103 kg of monodisperse polystyrene microparticles. A preliminary economic evaluation points to a required selling price between 847 and 540 €/kg polystyrene microparticles. The required selling price is mainly influenced by the pore activity and the applied pressure. The influence of fouling on emulsification performance has also been investigated. Fouling occurs in a time frame of a few days and causes a strong deterioration in the droplet size distribution of the final emulsion. The rate of deterioration is stronger for sodium dodecyl sulfate (SDS) than for sodium dodecyl benzene sulfonate (SDBS), indicating limitations in the choice of the surfactant system. Direct emulsification of a polymer solution or melt can avoid complex issues such as secondary particle formation during suspension polymerization. The viscosity reduction required for emulsification of polymer is usually achieved by dissolving the polymer in an organic solvent. In Chapter 5, the plasticizing effect of CO2 is investigated as an alternative for organic solvents. In a setup with a system pressure of up to 100 bar and a constant pressure difference over the MC module in the order of 0.1 bar, emulsification of CO2-plasticized polystyrene is only possible for oligomers. The combined knowledge on emulsification with straight-through MC arrays is applied in Chapter 6 to produce monodisperse perfluorohexane emulsions for a completely different area of science, i.e. quantitative targeted ultrasound contrast imaging. For this purpose, strictly monodisperse echogenic perfluorohexane emulsions with a preset droplet size are required, since too small droplets will not generate sufficient ultrasound reflection and droplets which are too large will not provide sufficient coverage of specific ligands foreffective adhesion under physiological shear stress conditions. Standard perfluorocarbon emulsions do not satisfy both requirements, i.e. adhesion and echogenicity. Ultrasound experiments demonstrate that the perfluorohexane emulsions produced with straightthrough MC arrays clearly enhance echogenicity. Surface functionalization of the perfluorohexane droplets with a biotinylated fluoro-surfactant enables them to bind avidine-coated SiO2 particles. So we demonstrated that these emulsions can provide novel insights into the development and early detection of important vascular diseases, such as atherosclerosis or, more general, in the field of selective targeting. In retrospect, the author of this thesis is convinced that emulsification of monomer with straight-through MC arrays is a promising technique for the production of small-scale specialty microparticles. This potential is not limited to monodispersity, it also comprises particles with advanced functionality and morphology. Understanding and controlling all of the mechanisms during polymerization will be a key concern for future developments.