A partir de l'étude des effets de la chimie de surface des Nanodiamants (NDs) sur leurs propriétés électroniques, cette thèse a permis la mise en évidence d'un effet thérapeutique des NDs sur des cellules humaines. En particulier, il a été montré que les NDs de détonation peuvent générer des radicaux libres oxygénés sous radiation ionisante, ce qui pourrait améliorer l'efficacité de certains traitements de radiothérapie actuels. Les échanges électroniques entre le coeur des NDs et leur environnement sont en effet favorisés après des traitements de surface, notamment d'hydrogénation et de graphitisation de surface. Les conditions expérimentales permettant d'obtenir des NDs hydrogénées (NDs-H) sous plasma d'hydrogène ont été optimisées sous ultravide, puis ont été utilisées pour préparer de grandes quantités de NDs-H sous forme pulvérulente. La même procédure a été appliquée pour la graphitisation de surface des NDs, en utilisant des recuits sous vide à haute température. L'effet de ces traitements de surface sur les propriétés d'interactions électroniques des NDs a été étudié après exposition à l'air ambiant, puis en dispersion dans l'eau. Ces traitements de surface assurent notamment un potentiel Zeta positif aux NDs, dont l'origine a été discutée. Enfin, les interactions des NDs avec plusieurs lignées de cellules tumorales humaines ont été étudiées et l'efficacité des NDs pour radiosensibiliser des cellules radiorésistantes sous irradiation gamma a été montrée, ouvrant de nouvelles perspectives d'applications des NDs en nanomédecine. . / In this thesis, a therapeutic effect of nanodiamonds (NDs) has been evidenced by investigating the role of NDs surface chemistry on their electronic properties. More precisely, the generation of reactive oxygen species from detonation NDs under ionizing radiation, which could improve current radiotherapy treatments, has been demonstrated. To this end, surface treatments facilitating electron transfer from NDs to their environment, namely hydrogenation and surface graphitization, were developed. Experimental conditions ensuring an efficient hydrogenation by hydrogen plasma were determined under ultrahigh vacuum, before being used to prepare large quantities of NDs in powder phase. A similar procedure was applied to the surface graphitization of NDs, performed by annealing under vacuum at high temperature. The impact of such surface treatments on the electronic interaction properties of NDs has been investigated under ambient air and after dispersion in water. These surface treatments induce a positive Zeta potential to NDs in water, which origin has been discussed. Finally, their interactions with human tumor cells were observed. Radiosensitization of tumor cells using NDs under gamma irradiation was demonstrated, opening new perspectives for NDs in nanomedicine.

Drug based nanoparticle (NP) formulations have gained considerable attention over the past decade for their use in various drug delivery systems. NPs have been shown to increase bioavailability, decrease side effects of highly toxic drugs, and prolong drug release. Furthermore, polymer based, biodegradable nanodelivery has become increasing popular in the field of NP formulation because of their high degree of compatibility and low rate of toxicity. Due to their popularity, commercially available polymers such as poly lactic acid (PLA), poly glycolic acid (PGA) and polylactic-co-glycolic acid (PLGA) are commonly used in the development and design of new nano based delivery systems. Nonsteriodal anti-inflammatory drugs (NSAIDs) are commonly used for the treatment of pain and inflammation. NSAIDs such as diclofenac and celecoxib function by blocking cyclooxygenase expression and reducing prostaglandin synthesis. Unfortunately, the pharmacological actions of NSAIDs can lead to the development of several adverse side effects such as gastrointestinal ulceration and bleeding. The aim of this study was to formulate and optimize diclofenac or celecoxib entrapped polymer NPs using an emulsion-diffusion-evaporation technique. NP formulations were evaluated based on specific formula parameters such as particle size, zeta potential, morphology, and entrapment efficiency. Effects of stabilizer type, stabilizer concentration, centrifugal force, drug amount, and/or emulsifier (lecithin) on nanoparticle characterization were examined for formula optimization. Results of the formulation studies showed that NPs developed using polylactide-co-glycolide (PLGA) polymers and the stabilizer didodecyldimethylammonium bromide (DMAB) demonstrated enhanced stability, drug entrapment, and reduced particle size. These findings demonstrate an effective method for polymer NP formulation of diclofenac or celecoxib. Furthermore, the results reported herein support a novel method of drug delivery that may function to reduce known adverse effects of these pharmacotherapeutic agents.

This project focused on the study of self-assembling systems that can be inuenced by an external magnetic field, following the PhD research of Hauke Carstensen. My role was to study the behavior of beads and to optimize the tunable parameters so that the main force driving the dynamics of the system is the magnetic dipolar interaction between beads. To make sure that no other force plays an important role, we checked a number of things, the most problematic of which is flocculation in the colloid, which may happen if some beads get stuck to each other; to prevent them from aggregating we have to make sure that they have a large zeta potential, which will result in an electrically repulsive force between beads and will thus increase the stability of the colloid. We also have to make sure that other forces in the sample do not exceed the magnitude of magnetic forces between particles; examples of such forces can be the drag experienced while moving in the viscous ferrofluid, the gravity force or the random thermal movement of the molecules in the fluid. In order to study these efects, I measured the zeta potential of the magnetic and non-magnetic beads and later I added a surfactant compound (SDS) to our sample in order to increase said potential.

Understanding the mechanism of bubble-particle interactions plays a critical role in advancing flotation technology. In this study, submicron size bubbles with an average diameter less than 1 μm and a life time of at least several hours were generated using a novel hydrodynamic cavitation method. Effect of mechanical force and water chemistry on generation and stability of submicron size bubbles is investigated. With recent development in measuring zeta potential distributions of colloidal systems, interactions of bubbles and fine solid particles in various electrolyte, surfactant and frother solutions as well as in industrial process water were studied using the stable submicron size bubbles generated by hydrodynamic cavitation. The outcome of this study provides not only a better understanding of bubble-particle attachment mechanism and its role in flotation, but also a direct evidence of armour-coating of bubbles and enhanced bubble-particle interactions by in situ gas nucleation. / Chemical Engineering

Probiotics and prebiotic are becoming increasingly important to consumers to alleviate issues surrounding gut health, despite the lack of definitive efficacy studies to support health claims. The addition of both probiotics and prebiotics to foods is challenging due to the harsh environmental conditions within the food itself and during transit through the gastrointestinal (GI) tract. To circumvent these challenges encapsulation technology is being explored to protect sensitive ingredients and to control their release within the lower intestines thereby maximizing the health benefiting effects. The overall goal of this research was to design a protein delivery capsule using phase separated pea protein isolate (PPI)-alginate (AL) mixtures for the entrapment of the synbiot which includes the probiotics, Bifidobacterium adolescentis, and the prebiotic, fructooligosaccharides (FOS), such that the capsule design provides highly effective protection and release within the GI tract. Research was carried out in three studies.<p> In study 1, PPIn (native isolate) and AL interactions were studied in dilute aqueous solutions as a function of pH and biopolymer mixing ratio. Turbidimetric analysis and electrophoretic mobility during an acid titration was used to determine conditions where phase separation occurred. Critical structure forming events associated with the formation of soluble and insoluble complexes in a 1:1 PPIn-AL mixture were found to occur at pH 5.00 and 2.98, respectively, with optimal interactions occurring at pH 2.10. As the PPIn-AL ratio increased, critical pH values shifted towards higher pH until a mixing ratio between 4:1 and 8:1was reached, above which structure formation became independent of the ratios through to ratios of 20:1. Electrophoretic mobility measurements showed a similar trend, where the isoelectric point (pI) shifted from pH 4.00 (homogeneous PPIn) to pH 1.55 (1:1 PPIn-AL). As the ratio increased towards 8:1 PPIn-AL, net neutrality values shifted to higher pHs (~3.80) before becoming constant at higher ratios. Maximum coacervate formation occurred at a mixing ratio of 4:1. Based on these findings, capsule design by segregative phase separation was only used in future studies, due to the acidic nature associated with associative phase separation.<p> In study 2, capsule formation using a native and commercial PPI was studied, and showed no difference between the two formulations during challenge experiments in simulated gastric juice (SGJ). As a result study 3 focused on optimization and characterization of capsules prepared using the commercial PPI. Capsule designs were investigated as a function of protein concentration, prebiotic level, and extrusion conditions (20 vs. 27 G needle) in order to determine protective ability for B. adolescentis within SGJ. Capsule designs were also measured in terms of protein and prebiotic retention during the encapsulation process, geometric mean diameter and size distribution, swelling behaviour and release characteristics within simulated intestinal fluids (SIF). All capsules provided adequate protection over the 2 h duration within SGJ. Capsule breakdown and release was similar for all designs within SIF, with a release mechanism believed to be tied to enzymatic degradation of the PPI material within the wall matrix and/or the amount of excessive Na+ present in the SIF. Capsule size was found to be dependent only on the needle gauge used in the extrusion process. Swelling behaviour of the capsules with SGJ was also found to be dependent only on the protein concentration, where capsules shrank once immersed in SGJ.<p> A 2.0% PPI-0.5% AL capsule without FOS and extruded through a 20 G needle represents the best and most cost effective design for entrapping, protecting and delivering probiotic bacteria. Future work to establish the role FOS could play post-release as the entrapping probiotics colonize the GI tract, and the protective effect of the capsules wall on FOS structure during transit is recommended.

Electroosmotic flow is widely used as a solution pumping method in numerous microfluidic applications. This type of flow has several advantages over other pumping techniques, such as the fast response time, the ease of control and integration in different microchannel designs. The flow utilizes the scaling of channel dimensions, which enhances the effects of the electrostatic forces to create flow in microchannels under an electrical body force. However, the electrostatic properties of the solution/wall material pairings are unique and must be experimentally measured. As a consequence, accurate knowledge about the electrostatic properties of the solution and wall material pairings is important for the optimal design of microfluidic devices using electroosmotic flow. Moreover, the introduction of new solutions and new channel materials for different applications is common in the microfluidics area. Therefore, any improvement on the experimental techniques used to examine the electrostatic properties of microchannels is beneficial to the research community. In this work, an improvement to the current-monitoring technique for studying the electrokinetic properties of microchannels is achieved by replacing the conventional straight channel design with a new Y-channel design. The errors from both the undesired pressure driven flow and solution electrolysis were addressed and significantly reduced. The new design offers high accuracy in finding the electrokinetic properties of microchannels. The experimental outcome from the new channel design is better compared to the outcomes of the straight channel, which helps in distinguishing the important electroosmotic pumping regions from the current-time plot. Moreover the time effectiveness in performing the experiments with the new channel design is better compared to that for the straight channel design. A modified analysis approach is also presented and validated for finding the electrokinetic properties from the outcomes of the current-monitoring technique, which is called the current-slope method. This approach is validated by comparing its findings with the results of the conventional length method. It was found for most situations that the discrepancy between the two methods, the current-slope and total length method, are within the uncertainty of the experimental measurements, thus validating the new analysis approach. In situations where it is hard to distinguish the start and end of solution replacement from the current-time plot of the current-monitoring technique, the current-slope method is advised. With the new design, different parametric studies of electroosmotic flow in PDMS based microchannels are estimated. At first the zeta potential of biological buffers are studied. Moreover the effect of continuous electroosmotic pumping, the chip substrate structure, and temperature on the average zeta potential of microchannels are examined. It was found that for air plasma treated PDMS microchannels the chip substrate material does not have an effect on the average zeta potential of the microchannels. The following chemical treatments are attempted with the aim of improving the surface and electrostatic properties of PDMS based microchannels: prepolymer additive with acrylic acid, extraction of PDMS, and both heat and plasma induced HEMA (Hydroxyethyl methacrylate) grafting on the surface of PDMS. Extensive characterization is performed with different experimental methods. The stability of the artificial hydrophilic properties of the PDMS microchannels with time was improved with both the extraction and HEMA grafting techniques. On the other hand, there was no evidence of any improvement in the zeta potential of microchannels with the surface treatments.

Electroosmotic flow is widely used as a solution pumping method in numerous microfluidic applications. This type of flow has several advantages over other pumping techniques, such as the fast response time, the ease of control and integration in different microchannel designs. The flow utilizes the scaling of channel dimensions, which enhances the effects of the electrostatic forces to create flow in microchannels under an electrical body force. However, the electrostatic properties of the solution/wall material pairings are unique and must be experimentally measured. As a consequence, accurate knowledge about the electrostatic properties of the solution and wall material pairings is important for the optimal design of microfluidic devices using electroosmotic flow. Moreover, the introduction of new solutions and new channel materials for different applications is common in the microfluidics area. Therefore, any improvement on the experimental techniques used to examine the electrostatic properties of microchannels is beneficial to the research community. In this work, an improvement to the current-monitoring technique for studying the electrokinetic properties of microchannels is achieved by replacing the conventional straight channel design with a new Y-channel design. The errors from both the undesired pressure driven flow and solution electrolysis were addressed and significantly reduced. The new design offers high accuracy in finding the electrokinetic properties of microchannels. The experimental outcome from the new channel design is better compared to the outcomes of the straight channel, which helps in distinguishing the important electroosmotic pumping regions from the current-time plot. Moreover the time effectiveness in performing the experiments with the new channel design is better compared to that for the straight channel design. A modified analysis approach is also presented and validated for finding the electrokinetic properties from the outcomes of the current-monitoring technique, which is called the current-slope method. This approach is validated by comparing its findings with the results of the conventional length method. It was found for most situations that the discrepancy between the two methods, the current-slope and total length method, are within the uncertainty of the experimental measurements, thus validating the new analysis approach. In situations where it is hard to distinguish the start and end of solution replacement from the current-time plot of the current-monitoring technique, the current-slope method is advised. With the new design, different parametric studies of electroosmotic flow in PDMS based microchannels are estimated. At first the zeta potential of biological buffers are studied. Moreover the effect of continuous electroosmotic pumping, the chip substrate structure, and temperature on the average zeta potential of microchannels are examined. It was found that for air plasma treated PDMS microchannels the chip substrate material does not have an effect on the average zeta potential of the microchannels. The following chemical treatments are attempted with the aim of improving the surface and electrostatic properties of PDMS based microchannels: prepolymer additive with acrylic acid, extraction of PDMS, and both heat and plasma induced HEMA (Hydroxyethyl methacrylate) grafting on the surface of PDMS. Extensive characterization is performed with different experimental methods. The stability of the artificial hydrophilic properties of the PDMS microchannels with time was improved with both the extraction and HEMA grafting techniques. On the other hand, there was no evidence of any improvement in the zeta potential of microchannels with the surface treatments.

Probiotics and prebiotic are becoming increasingly important to consumers to alleviate issues surrounding gut health, despite the lack of definitive efficacy studies to support health claims. The addition of both probiotics and prebiotics to foods is challenging due to the harsh environmental conditions within the food itself and during transit through the gastrointestinal (GI) tract. To circumvent these challenges encapsulation technology is being explored to protect sensitive ingredients and to control their release within the lower intestines thereby maximizing the health benefiting effects. The overall goal of this research was to design a protein delivery capsule using phase separated pea protein isolate (PPI)-alginate (AL) mixtures for the entrapment of the synbiot which includes the probiotics, Bifidobacterium adolescentis, and the prebiotic, fructooligosaccharides (FOS), such that the capsule design provides highly effective protection and release within the GI tract. Research was carried out in three studies.<p> In study 1, PPIn (native isolate) and AL interactions were studied in dilute aqueous solutions as a function of pH and biopolymer mixing ratio. Turbidimetric analysis and electrophoretic mobility during an acid titration was used to determine conditions where phase separation occurred. Critical structure forming events associated with the formation of soluble and insoluble complexes in a 1:1 PPIn-AL mixture were found to occur at pH 5.00 and 2.98, respectively, with optimal interactions occurring at pH 2.10. As the PPIn-AL ratio increased, critical pH values shifted towards higher pH until a mixing ratio between 4:1 and 8:1was reached, above which structure formation became independent of the ratios through to ratios of 20:1. Electrophoretic mobility measurements showed a similar trend, where the isoelectric point (pI) shifted from pH 4.00 (homogeneous PPIn) to pH 1.55 (1:1 PPIn-AL). As the ratio increased towards 8:1 PPIn-AL, net neutrality values shifted to higher pHs (~3.80) before becoming constant at higher ratios. Maximum coacervate formation occurred at a mixing ratio of 4:1. Based on these findings, capsule design by segregative phase separation was only used in future studies, due to the acidic nature associated with associative phase separation.<p> In study 2, capsule formation using a native and commercial PPI was studied, and showed no difference between the two formulations during challenge experiments in simulated gastric juice (SGJ). As a result study 3 focused on optimization and characterization of capsules prepared using the commercial PPI. Capsule designs were investigated as a function of protein concentration, prebiotic level, and extrusion conditions (20 vs. 27 G needle) in order to determine protective ability for B. adolescentis within SGJ. Capsule designs were also measured in terms of protein and prebiotic retention during the encapsulation process, geometric mean diameter and size distribution, swelling behaviour and release characteristics within simulated intestinal fluids (SIF). All capsules provided adequate protection over the 2 h duration within SGJ. Capsule breakdown and release was similar for all designs within SIF, with a release mechanism believed to be tied to enzymatic degradation of the PPI material within the wall matrix and/or the amount of excessive Na+ present in the SIF. Capsule size was found to be dependent only on the needle gauge used in the extrusion process. Swelling behaviour of the capsules with SGJ was also found to be dependent only on the protein concentration, where capsules shrank once immersed in SGJ.<p> A 2.0% PPI-0.5% AL capsule without FOS and extruded through a 20 G needle represents the best and most cost effective design for entrapping, protecting and delivering probiotic bacteria. Future work to establish the role FOS could play post-release as the entrapping probiotics colonize the GI tract, and the protective effect of the capsules wall on FOS structure during transit is recommended.

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