Assessing the Validity of Brain Glucose Concentration Measurement Using Microdialysis

Brain functions, such as learning, orchestrating locomotion, memory recall, and processing information, all require glucose as a source of energy. During these functions, the glucose concentration decreases as the glucose is being consumed by brain cells. By measuring this drop in concentration, it is possible to determine which parts of the brain are used during specific functions and consequently, how much energy the brain requires to complete the function. One way to measure in vivo brain glucose levels is with a microdialysis probe. The drawback of this analytical procedure, as with many steadystate fluid flow systems, is that the probe fluid will not reach equilibrium with the brain fluid. Therefore, brain concentration is inferred by taking samples at multiple inlet glucose concentrations and finding a point of convergence. The goal of this thesis is to create a three-dimensional, time-dependent, finite element representation of the brainprobe system in COMSOL 4.2 that describes the diffusion and convection of glucose. Once validated with experimental results, this model can then be used to test parameters that experiments cannot access. When simulations were run using published values for physical constants (i.e. diffusivities, density and viscosity), the resulting glucose model concentrations were within the error of the experimental data. This verifies that the model is an accurate representation of the physical system. In addition to accurately describing the experimental brain-probe system, the model I created is able to show the validity of zero-net-flux for a given experiment. A useful discovery is that the slope of the zero-net-flux line is dependent on perfusate flow rate and diffusion coefficients, but it is independent of brain glucose concentrations. The model was simplified with the realization that the perfusate is at thermal equilibrium with the brain throughout the active region of the probe. This allowed for the assumption that all model parameters are temperature independent. The time to steady-state for the probe is approximately one minute. However, the signal degrades in the exit tubing due to Taylor dispersion, on the order of two minutes for two meters of tubing. Given an analytical instrument requiring a five μL aliquot, the smallest brain process measurable for this system is 13 minutes.

Solid-State Compatibilization of Immiscible Polymer Blends: Cryogenic Milling and Solid-State Shear Pulverization

The blending of common polymers allows for the rapid and facile synthesis of new materials with highly tunable properties at a fraction of the costs of new monomer development and synthesis. Most blends of polymers, however, are completely immiscible and separate into distinct phases with minimal phase interaction, severelydegrading the performance of the material. Cross-phase interactions and property enhancement can be achieved with these blends through reactive processing or compatibilizer addition. A new class of blend compatibilization relies on the mechanochemical reactions between polymer chains via solid-state, high energy processing. Two contrasting mechanochemical processing techniques are explored in this thesis: cryogenic milling and solid-state shear pulverization (SSSP). Cryogenic milling is a batch process where a milling rod rapidly impacts the blend sample while submerged within a bath of liquid nitrogen. In contrast, SSSP is a continuous process where blend components are subjected to high shear and compressive forces while progressing down a chilled twin-screw barrel. In the cryogenic milling study, through the application of a synthesized labeledpolymer, in situ formation of copolymers was observed for the first time. The microstructures of polystyrene/high-density polyethylene (PS/HDPE) blends fabricated via cryomilling followed by intimate melt-state mixing and static annealing were found to be morphologically stable over time. PS/HDPE blends fabricated via SSSP also showed compatibilization by way of ideal blend morphology through growth mechanisms with slightly different behavior compared to the cryomilled blends. The new Bucknell University SSSP instrument was carefully analyzed and optimized to produce compatibilized polymer blends through a full-factorial experiment. Finally, blends of varying levels of compatibilization were subjected to common material tests to determine alternative means of measuring and quantifying compatibilization,