Fabrication of Tailored Microgels in Continuous Processes

Fabrication of Tailored Microgels in Continuous Processes von Wolff,  Hanna J. M.
Soft microgels with temperature-responsive behavior are of growing interest in drug delivery, tissue engineering, and chemical engineering. Spherical and anisometric microgels are exciting materials in this variety of possible applications due to their compelling properties. Besides their responsiveness, they can provide softness, bio-compatibility, and an open pore structure. Complex-shaped microgels further present a promising building block for microgel assemblies, for example, in the field of tissue engineering. The numerous possible applications and compelling properties lead to increasing demand for microgels. Yet, the standard microgel fabrication methods do not offer high throughput rates for spherical or anisometric microgels. Therefore, this thesis aims to develop fabrication methods with high throughput for large amounts of spherical and anisometric microgels. First, a high throughput fabrication method for spherical temperature-responsive microgels is developed by transferring the typical batch precipitation polymerization into a continuous process. In this context, a continuous tubular flow reactor is established and investigated, along with a detailed comparison of the properties of the microgels from standard batch and novel continuous synthesis. Microgels with similar properties are indeed fabricated continuously. The inner structure stays unaltered by the applied fabrication methods. In a second approach, the fabrication of anisometric microgels is enhanced by adapting the common stop-flow lithography, developing a new temperature-responsive polymerization system, and investigating the process limitations. For the first time, the fabrication of soft temperature-responsive microgels of complex shapes is presented using NIPAmmonomer. It is found that a threshold amount of 10 wt% crosslinker in comparison to the monomer amount is required for the fabrication of stable particles with the stated properties. Above that threshold, the crosslinker amount allows tailoring the stiffness of the responsive microgels from very soft to comparably stiff. Of particular interest is the dynamic swelling behavior of the fabricated NIPAm microgels with complex shapes. A fast contortion during swelling before snapping back into the original shape is evident. In further investigations of the process limits, it is shown that the process has numerous influencing parameters with complex coherency. Significantly, the diffusion of components needs to be considered in a three-dimensional way to predict particle shapes and process stability precisely. Also, the fluidic parameters are essential for process stability, as automated fabrication shows a start-up behavior. Finally, the properties of anisometric microgels are broadened by tailoring the porosity of their polymeric network with methanol and adding inorganic nanoparticles for conductivity and magnetic remote control. Ultimately, this work lays the foundation towards industrial fabrication rates of spherical and anisometric microgels with various properties for multiple applications.
Aktualisiert: 2022-09-08
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Prediction of Reaction Rate Constants for the Synthesis of Microgels

Prediction of Reaction Rate Constants for the Synthesis of Microgels von Kröger,  Leif Christian
The accurate prediction of reaction kinetics data, e.g., reaction rate constants, for the microgel synthesis is highly desired because its usage in model-based design approaches promises the development of more specialized microgels and enables new applications. The complexity and the diversity of the microgel synthesis, however, often prevent experimental approaches but depict challenges for prediction approaches, as well. Therefore, this thesis analyzes a wide range of aspects relevant for the microgel synthesis individually and proposes prediction strategies for each. Here, the focus is on three main aspects: (i) The prediction of reaction kinetics in homogenous liquid reaction environments by combining high-level density functional theory and COSMO-RS, (ii) improving the property prediction of ionic species by applying the Cluster-Continuum approach and analyzing the uncertainty of the reference data, and (iii) enabling the kinetics prediction for inhomogeneous reaction environments with ReaxFF reactive molecular dynamics (MD) simulations. The results show that macroscopic properties of microgels, e.g., the crosslinker distribution, can be linked to the elementary reaction kinetics. In addition, the prediction of the solvation free energy of ionic solutes dissolved in neutral solvents is achieved with a deviation of just 2.0 kcal mol−1, which removes a main bottleneck for reaction kinetics prediction of such ionic systems. Furthermore, analyzing the statistical uncertainty of rare events in reactive MD simulations revealed that just a few reaction events are sufficient to obtain rate constants of sufficient quality. This is a key finding for the study of the microgel synthesis in reactive MD simulations because the required large system sizes and limited computational resources prevent the observation of more events practically. Also, force fields and their parametrizations should be evaluated regarding the eligibility for studying the microgel synthesis reactions based on the correct description of the vinyl group. In total, this thesis develops and presents a toolbox for reaction kinetics predictions for the microgel synthesis.
Aktualisiert: 2022-02-24
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