Precision Polymer Particles by Flash Nanoprecipitation and Microfluidic Droplet Extraction

Abstract

We comparatively review two versatile approaches employed in the precise formation of polymer particles, with length scales from 10s of nm to to 100s μm, from ternary polymer(s), solvent and nonsolvent mixtures. Flash nanoprecipitation (FNP) utilizes an opposing jet arrangement to mix a dilute polymer solution and a nonsolvent in confinement, inducing a rapid (∼millisecond) chain collapse and eventual precipitation of nanoparticles (NPs) of 10–1000 nm diameters. FNP of polymer mixtures and block copolymers can yield a range of multiphase morphologies with various functionalities. While droplet solvent extraction (DSE) also involves the exposure of a polymer solution to a nonsolvent, in this case the polymer solution is templated into a droplet prior to solvent extraction, often using microfluidics, resulting in polymer particles of 1–1000 μm diameter. Droplet shrinkage and solvent exchange are generally accompanied by a series of processes including demixing, coarsening, phase inversion, skin formation, and kinetic arrest, which lead to a plethora of possible internal and external particle morphologies. In the absence of external flow fields, DSE corresponds effectively to nonsolvent induced phase separation (NIPS) in a spherical geometry. In this review, we discuss the requirements to implement both approaches, detailing consequences of ternary solution phase behavior and the interplay of the various processes underpinning particle formation and highlighting the similarities, differences, and complementarity of FNP and DSE. In addition to reviewing previous work in the field, we report comparative experimental results on the formation of polystyrene particles by both approaches, emphasizing the importance of solution phase behavior in process design.

SANS Study of PPPO in Mixed Solvents and Impact on Polymer Nanoprecipitation

“… 43 However, these employed water as nonsolvent, which is thought to impart charge stabilization to NPs due to its high dielectric constant, whereas precipitation by low dielectric nonsolvents (e.g., organic) is more likely to result in aggregates. 4 , 57 This appears to be the case for higher initial heptane concentrations especially, for which the NP size distribution becomes particularly broad ( Figure 8 i).…”

“…PPPO nanoparticles were generated by flash nanoprecipitation (FNP), ,, which rapidly impinges opposing jets of dilute polymer solution and nonsolvent within a confined geometry, typically a confined impinging jet (CIJ) mixer or a multi-inlet vortex mixer (MIVM). Typical volumetric flow rates of ∼1 mL/s per inlet fluid, in typical operation of a CIJ mixer, yield jet velocities of ∼1 m/s, which result in the rapid mixing (∼milliseconds), quenching the mixture in the two-phase region, and cause a chain-to-globule transition of dilute chains.…”

“…Liquid–liquid demixing of polymer solutions is a versatile and ubiquitous manufacturing process exploited in the fabrication of polymeric membranes, scaffolds, and porous materials and particles. − Applications of such materials range from drug delivery and food to catalysis and sensing . Demixing is generally induced by a temperature change, by the addition of a poor solvent (nonsolvent-induced phase separation, NIPS), or by a pressure change .…”

Engineered Polymer-Supported Biorthogonal Nanocatalysts Using Flash Nanoprecipitation

“…Flash nanoprecipitation (FNP) is an efficient nanoparticle fabrication process that uses engineered mixing geometries to stabilize insoluble compounds into nanosized polymer-based delivery vehicles. − The high flow rate of two impingent streams enables microsecond mixing and creates supersaturation conditions, generating nanoparticles with narrow size distribution and high loading capacity. , In this technique, stabilizing polymers are usually designed to have hydrophobic segments that encapsulate solute particles as well as hydrophilic segments that provide steric stabilization. In this study, we encapsulated a palladium-based TMC, Pd­(dppf)­Cl 2 , into polymeric nanoparticles via FNP for efficient bioorthogonal catalysis in biological environments (Figure a).…”

Multilayer Poly(ionic liquid) Microcapsules Prepared by Sequential Phase Separation and Subsequent Photopolymerization in Ternary Emulsion Droplets

“…In the fields of colloidal and interfacial chemistry, the development of polymer particles with complex structures using liquid–liquid phase separation (LLPS) in emulsion droplets has garnered increasing attention. − This is because LLPS enables the production of multiple emulsion droplets resulting in polymer particles with complex structures via one-step emulsification. These complex structures endow particles with unique properties, which is not possible with simple solid particles or hollow microcapsules.…”