synthesizing-lipid-nanoparticles-turbulent-flow-confined-impinging

Synthesizing Lipid Nanoparticles by Turbulent Flow in Confined Impinging Jet Mixers

Lipid nanoparticles (LNPs) have demonstrated their enormous potential as therapeutic delivery vehicles, as evidenced by the approval and global usage of ...

Princeton University

Polymer colloids arise in a variety of contexts ranging from synthetic to natural systems. The structure of polymeric colloids is crucial to their function and application. Hence, understanding the mechanism of structure formation in polymer colloids is important to enabling advances in their production and subsequent use as enabling materials in new technologies. Here, we demonstrate how the specific pathway from precipitation to vitrification dictates the resulting morphology of colloids fabricated from polymer blends. Through continuum simulations, free energy calculations, and experiments, we reveal how colloid structure changes with the trajectory taken through the phase diagram. We demonstrate that during solvent exchange, polymer-solvent phase separation of a homogeneous condensate can precede polymer-polymer phase separation for blends of polymers that possess some degree of miscibility. For less-miscible, higher-molecular-weight blends, phase separation and kinetic arrest compete to determine the final morphology. Such an understanding of the pathways from precipitation to vitrification is critical to designing functional structured polymer colloids.

Evolution of Polymer Colloid Structure During Precipitation and Phase Separation.

Functionalized cellulosics have shown promise as naturally derived thermoresponsive gelling agents. However, the dynamics of thermally induced phase transitions of these polymers at the lower critical solution temperature (LCST) are not fully understood. Here, with experiments and theoretical considerations, we address how molecular architecture dictates the mechanisms and dynamics of phase transitions for cellulose ethers. Above the LCST, we show that hydroxypropyl substituents favor the spontaneous formation of liquid droplets, whereas methyl substituents induce fibril formation through diffusive growth. In celluloses which contain both methyl and hydroxypropyl substituents, fibrillation initiates after liquid droplet formation, suppressing the fibril growth to a sub-diffusive rate. Unlike for liquid droplets, the dissolution of fibrils back into the solvated state occurs with significant thermal hysteresis. We tune this hysteresis by altering the content of substituted hydroxypropyl moieties. This work provides a systematic study to decouple competing mechanisms during the phase transition of multi-functionalized macromolecules.

Hysteresis in the thermally induced phase transition of cellulose ethers.

Hybrid nanoparticles (hNPs), or nanoparticles composed of both organic and inorganic components, hold promise for diverse energy and environmental applications due to their ability to stabilize reactive nanomaterials against aggregation, enhancing their ability to pervade tortuous spaces and travel long distances to degrade contaminants . Past studies have investigated the use of polymer or surfactant coatings to stabilize nanomaterials against aggregation. However, fabrication of these materials often requires multiple steps and lacks specificity in the control of their morphologies and reactivities. Here, we demonstrated a method of producing stable hNPs with tunable morphologies by incubating polystyrene nanoparticles formed via Flash NanoPrecipitation with citrate-stabilized gold nanocatalysts. Using this simple fabrication technique, we found that gold adsorption to polystyrene nanoparticles was enabled by the presence of a good solvent for polystyrene. Furthermore, changing process parameters, such as gold incubation time, and molecular parameters, such as polymer molecular weight and end-group functionality, provided control over the resultant nanocatalyst loading and dispersal atop hNPs. We classified these morphologies into three distinct regimes─aggregated, dispersed, or internalized─and we showed that the emergence of these regimes has key implications for controlling reaction rates in applications such as heterogeneous catalysis or groundwater remediation. Specifically, we found that hNPs with gold nanocatalysts embedded  the surfaces of polystyrene nanoparticles exhibited slower bulk catalytic reduction capacity than their disperse, surface-decorated counterparts. Taken together, our work demonstrates a simple way by which hNPs can be fabricated and presents a method to control catalytic reactions using reactive nanomaterials.

Tuning Morphologies and Reactivities of Hybrid Organic-Inorganic Nanoparticles.

Complex fibrillar networks mediate liquid-liquid phase separation of biomolecular condensates within the cell. Mechanical interactions between these condensates and the surrounding networks are increasingly implicated in the physiology of the condensates and yet, the physical principles underlying phase separation within intracellular media remain poorly understood. Here, we elucidate the dynamics and mechanics of liquid-liquid phase separation within fibrillar networks by condensing oil droplets within biopolymer gels. We find that condensates constrained within the network pore space grow in abrupt temporal bursts. The subsequent restructuring of condensates and concomitant network deformation is contingent on the fracture of network fibrils, which is determined by a competition between condensate capillarity and network strength. As a synthetic analog to intracellular phase separation, these results further our understanding of the mechanical interactions between biomolecular condensates and fibrillar networks in the cell.

Liquid-liquid phase separation within fibrillar networks.

The physical properties of a semicrystalline polymer thin film are intimately related to the morphology of its crystalline domains. While the mechanisms underlying crystallization of flat-on oriented polymer crystals are well known, similar mechanisms remain elusive for edge-on oriented thin films due to the propensity of substantially thin films to adopt flat-on orientations. Here, we employ an epitaxial polymer-substrate relationship to enforce edge-on crystallization in thin films. Using matrix-assisted pulsed laser evaporation (MAPLE), we deposit films in which crystal nucleation is spatially separated from subsequent epitaxial crystallization. These experiments, together with phase-field simulations, demonstrate a highly anisotropic and localized material depletion during edge-on crystallization. These results provide deeper insight into the physics of polymer crystallization under confinement and introduce a processing motif in the crystallization of ultrathin structured films.

Article	Year
Evolution of Polymer Colloid Structure During Precipitation and Phase Separation. JACS Au\| PubMed ID: 34467340	2021
Hysteresis in the thermally induced phase transition of cellulose ethers. Soft matter\| PubMed ID: 35946517	2022
Tuning Morphologies and Reactivities of Hybrid Organic-Inorganic Nanoparticles. ACS nano\| PubMed ID: 36223069	2022
Liquid-liquid phase separation within fibrillar networks. Nature communications\| PubMed ID: 37770446	2023
Anisotropic material depletion in epitaxial polymer crystallization. Soft matter\| PubMed ID: 37811707	2023

Jason Liu

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