Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.

No description available.

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

The increasing prevalence of diabetes and the severity of long-term complications have emphasized the need for continuous glucose monitoring. Optically-based methods are advantageous as they have potential for noninvasive or minimally invasive detection. Fluorescence-based affinity assays, in particular, can be fast, reagentless, and highly specific. Poly(ethylene glycol) (PEG) microspheres have been used to encapsulate such fluorescently labeled molecules in a hydrogel matrix for implantation into the body. The matrix is designed to retain the sensing molecules while simultaneously allowing sufficient analyte diffusion. Sensing assays which depend upon a spatial displacement of molecules, however, experience limited motility and diminished sensor response in a dense matrix. In order to overcome this, a process of hydrogel microporation has been developed to create cavities within the PEG that contain the assay components in solution, providing improved motility for large sensing elements, while limiting leaching and increasing sensor lifetime. For an implanted sensor to be successful in vivo, it should exhibit long-term stability and functionality. Even biocompatible materials that have no toxic effect on surrounding tissues elicit a host response. Over time, a fibrous capsule forms around the implant, slowing diffusion of the target analyte to the sensor and limiting optical signal propagation. To prevent this biofouling, a thermoresponsive nanocomposite hydrogel based on poly(N-isopropylacrylamide) was developed to create a self-cleaning sensor membrane. These hydrogels exist in a swollen state at temperatures below the volume phase transition temperature (VPTT) and become increasingly hydrophobic as the temperature is raised. Upon thermal cycling around the VPTT, these hydrogels exhibit significant cell release in vitro. However, the VPTT of the original formula was around 33-34 degrees C, resulting in a gel that is in a collapsed state, ultimately limiting glucose diffusion at body temperature. The hydrogel was modified by introducing a hydrophilic comonomer, N-vinylpyrrolidone (NVP), to raise the VPTT above body temperature. The new formulation was optimized with regard to diffusion, mechanical strength, and cell releasing capabilities under physiological conditions. Overall, this system is a promising method to translate a glucose-sensitive assay from the cuvette to the clinic for minimally invasive continuous glucose sensing.

This thesis presents a novel method for the preparation of quantum dot-thermoresponsive polymer nanocomposite hydrogels. The quantum dots (QD’s) were synthesized in a microwave reactor using a high temperature organometallic synthesis procedure. The initial hydrophobic surface layer on the QD’s was coated with an amphiphilic polymer to enable phase transfer from non-polar solvent to water followed by physical immobilization of the QD’s in the thermoresponsive polymer hydrogel by photopolymerization. Their temperature dependent emission properties were investigated as a function of concentration of the incorporated QD’s. The resultant temperature dependent changes in the position of the peak emission wavelength of the QD-polymer nanocomposite hydrogels were found to be due to the change in the physical environment causing increased interaction between the embedded amphiphilic polymer coated QD’s and/or due to aggregation of QD’s. This change in peak emission position was found to be reversible in the temperature range from 29 to 37 °C.

Poly(N-isopropylacrylamide) (PNIPAM), a temperature responsive polymer, undergoes a phase change at a lower critical solution temperature (LCST) in aqueous solutions. For PNIPAM this temperature is 32 °C in water. Below the LCST, the polymer is readily solvated by water. As the temperature of the solution increases, the polymer undergoes a phase transition so that above the LCST it is no longer water soluble. The LCST of PNIPAM may be changed by the addition of salt solutions from the Hofmeister series which will follow the Hofmeister effect for salting-in and salting-out the polymer. Temperature responsive polymers may be grafted to a surface in a variety of methods to create responsive thin films that exhibit a change in wettability. The surface wettability is directly related to the polymers ability to be solvated in its coil conformation. When PNIPAM is grafted to a surface, the surface becomes alternatively hydrophobic and hydrophilic in response to both temperature and the anions in the Hofmeister series which take the surface either above or below the LCST of PNIPAM. The synthesis of responsive nanocomposite grafts was successfully applied to glass slides and three-dimensional surfaces, porous glass frits which were capable of controlling the passive flow rate. The nanocomposite graft was assembled in a covalent layer-by-layer approach to create more chemically robust surfaces, and also to incorporate nanoparticles into the graft for increased surface roughness and therefore improve wettability response. Because of a much greater inherent roughness to a glass frit, characterization of the polymers and nanoparticles was performed before they were covalently bound to the surface. The final product, a functionalized frit with a PNIPAM/SiO2 nanocomposite graft, was analyzed by observing changes in the passive permeation rate of the frit between water and salt solutions. These changes in flow were indicative of the surface bound PNIPAM changing between its hydrophilic and hydrophobic conformation in response to water and concentrations of kosmotropic salts such as sodium sulfate and sodium citrate. In addition to the solute response, the frit was also determined to be responsive to temperature and concentration. Water exhibited a passive flow rate 1000 times faster than a kosmotropic salt but had a similar flow rate to that a chaotropic salt. By measuring the flow rate of 0.5 M Na2SO4 at ~7 °C in a cold room and at room temperature it was observed that sodium sulfate in the cold room passed through the frit at a rate 100 times faster than at room temperature. Because of the hysteresis of PNIPAM documented in literature, washing procedures were kept consistent between experiments to achieve more reproducible results. It was concluded that the frits were temperature responsive and had relative standard deviations below 25 percent for flow rates on a single frit. However, standard deviations of flow rates between frits were higher. This was likely due to a combination of factors, such as the frits’ pore size range of 10 μm resulting in the possibility of varied degrees of functionalization of each frit.

Surface Laser Light Scattering (SLLS) is a heterodyne detection technique used to probe the surface properties of fluid interfaces. These interfaces are either liquid/liquid or vapor/liquid, and they may include insoluble monolayers or polymer films deposited on liquid surfaces as well as microemulsions in solution at low concentration. This technique provides one with a nonperturbative way to obtain surface tension and viscosity. A diffraction grating is employed to provide a stable local oscillatior, hence selecting an accurate ripplon wave vector . This thesis deals with the investigation of the interface between air and solution consisting of the methanol and water mixture and poly(N-isopropylacrylamide) or PNIPAM which is one of the fascinating polymeric materials. The polymer PNIPAM shows distinct responses to variations in the surrounding environment (such as thermal gradient, change in pH, etc.). The surface tension extracted from the SLLS data using the Kelvin equation is found to agree well with that obtained by using the Wilhelmy plate method. For the range of wave vectors cm-1, the power spectrum detected in frequency domain can be fit to a Lorentzian profile. Our experiments show that when the volume percentage of methanol increases, the interfacial property becomes insensitive to the presence of PNIPAM.

No description available.

Time-resolved fluorescence was applied to linear and branched pyrene-labelled macromolecules to study their internal dynamics. The linear macromolecules consisted of two series of pyrene-labelled poly(N-isopropylacrylamide)s where the polymer was either end-labelled (Py2-PNIPAM-Y where Y represents the molecular weight of the polymer and equals 6, 8, 14, 25, and 45 kDa) or randomly labelled (Py-PNIPAM-X% where X represents the pyrene content and is equal to 0.1, 2, 3, 4, 5, and 6 mol%) with pyrene. Four dendrimer generations based on a bis(hydroxymethyl)propionic acid backbone represented the branched macromolecules where the terminal sites were labelled with pyrene (PyX-GY-COOH where X represents the number of pyrene units incorporated into the Y`th generation dendrimer). A polystyrene-dendrimer hybrid was also synthesized (PyX-GY-PS). The fluorescence decays of the Py2-PNIPAM-Y and Py-PNIPAM-X% samples were acquired in solvents of varying viscosity and were analyzed with the Birks Scheme and the Fluorescence Blob Model (FBM) to yield the excimer formation rate constants and , respectively. The two parameters showed the same trends with varying viscosity, implying that the same information concerning chain dynamics is obtained from the randomly and end-labelled PNIPAM samples. The fluorescence decays of the Py2-PNIPAM-Y samples were acquired in ethanol and in water to determine how pyrene solubility affects the behavior of the polymers in solution, as probed by time-resolved fluorescence. It was found that the decreased pyrene solubility in water led to large amounts of intra- and intermolecular pyrene aggregation. Finally, the pyrene-labelled dendrimers were studied in tetrahydrofuran (THF) to probe the mobility of the chain ends as a function of generation number. The average rate of excimer formation, , obtained from the Model-Free analysis of the fluorescence decays in THF, increased linearly with generation number. This finding, combined with molecular mechanics optimizations, led to the conclusion that excimer formation was greatly enhanced due to the branched nature of the dendrimer molecule. Together, these studies illustrate three different applications of the use of time-resolved fluorescence to characterize the internal dynamics of pyrene-labelled macromolecules.