Nanomaterials are either inorganic or organic nanosized particles which have many industrial and biological applications such as in cosmetics, environmental remediation, electronics, biosensing and imaging and in drug delivery. Some have toxic effect upon release to the environment causing death of microorganisms and others are biodegradable and nontoxic to the living beings. In this work, two types of nanoparticles were investigated: inorganic titania nanoparticles which have been shown to have toxic effects and organic Carbopol Aqua SF1 microgel particles which were shown to be nontoxic and biodegradable organic nanoparticles for drug delivery.Chapter one explores the current literature relating to nanoparticles. The types, chemical and physical properties, methods of synthesis, characterization and functionalization are discussed along with general applications and the toxicity of titania nanoparticles. The role of nanomaterials as drug delivery systems and their design in terms of stability, swelling studies, encapsulation, drug loading and release, response to stimuli and targeting is also discussed. Finally the use of microfluidics for screening nanoparticle activity is discussed including microfabrications of chips cell trapping methods and microfluidic cell based assay methods.Chapter two is the experimental chapter describing the chemicals and instrumentation used. It also includes the methods used for the synthesis of titania nanoparticles and effects of pH on the zeta potential measurement. In addition to that, methods for the testing of the cytotoxic effects of uncoated and coated titania nanoparticles are described. Finally the methods employed for studying the optimization of the encapsulation of berberine and chlorhexidine into Carbopol Aqua SF1 are also included.Chapter three describe the synthesis of titania nanoparticles (TiO2NPs) and their characterization, including crystallite size, particle size distribution, surface area measurement and zeta potential. It was found that as the temperature increased from 100oC to 800oC, the crystallite size and particle size increased while the surface area decreased. At 100oC, the crystallite size, particle size, surface area and zeta potential of the titania nanoparticles were 5 nm, 25±20 nm, 163 m2 g-1 and +40±9 mV, respectively with anatase as the dominant phase. However, the phase changed to rutile at the annealing temperature of 800oC with the crystallite size, particle size, surface area and zeta potential becoming 142 nm, 145±60 nm, 7.5 m2 g-1 and -26±8 mVrespectively. In addition to that, the zeta potential of the titania nanoparticles at 25 nm size was affected by changing the pH of the suspension, at low pH, the zeta potential was +40 mV giving high stability and fully dispersed particles while the nanoparticles flocculated in the basic medium with a zeta potential of -25 mV, with the isoelectric point of titania nanoparticles being pH 6.7. Changing the pH of the solution for titania nanoparticles caused an irreversible process as it was not possibility to convert the aggregated titania nanoparticles from microscale to nanoscale.Chapter four describes the investigation into the the nanotoxicity of the titania nanoparticles (TiO2NPs) at various hydrodynamic diameters and crystallite size on C. reinhardtii microalgae and S. cerevisiae (yeast) upon illumination with UV and visible light. The cell viability was assessed for a range of nanoparticle concentrations and incubation times. It was found that uncoated TiO2NPs affect the C. reinhardtii cell viability at a much lower particle concentrations than for yeast. It was also observed that the TiO2NPs toxicity increased upon illumination with UV light compared to dark conditions due to the oxidative stress of the reactive oxygen species produced. It was also found that TiO2NPs nanotoxicity increased upon illumination with visible light which indicated that the nanoparticles might also interfere with the microalgae photosynthetic system leading to decreased chlorophyll content upon exposure to TiO2NPs. The results showed that the larger the hydrodynamic diameter of the TiO2NPs the lower their nanotoxicity, with anatase TiO2NPs generally being more toxic than rutile TiO2NPs. A range of polyelectrolyte-coated TiO2NPs were also prepared using the layer by-layer method and their nanotoxicity on yeast and microalgae was studied. It was found that the toxicity of the coated TiO2NPs alternates with their surface charge. TiO2NPs coated with cationic polyeletrolyte as an outer layer exhibited much higher nanotoxicity than the ones with an outer layer of anionic polyelectrolyte. TEM images of sectioned microalgae and yeast cells exposed to different polyelectrolyte-coated TiO2NPs confirmed the formation of a significant build-up of nanoparticles on the cell surface for bare and cationic polyelectrolyte-coated TiO2NPs. The effect came from the increased adhesion of cationic nanoparticles to the cell walls. Significantly, coating the TiO2NPs with anionic polyelectrolyte as an outer layer led to a reduced adhesion and much lower nanotoxicity due to electrostatic repulsion with the cell walls.Chapter five describes the development and characterisation of berberine-loaded and chlorhexidine-loaded polyacrylic acid based microgels. The procedure for loading the Carbopol microgels with both berberine and chlorhexidine was developed using a swelling-deswelling cycle dependent on pH. The result of this protocol was a colloidal suspension of collapsed microgel particles loaded with fixed percentage of the antimicrobial agents, berberine and chlorhexidine, respectively. The initial microgel particle concentration, as well as the initial concentrations of berberine and chlorhexidine, were optimized to allow for maximum encapsulation efficiency of the loaded reagent in the microgel while maintaining the colloidal stability of the Carbopol microgel suspension. It was determined that 0.15 wt% berberine and 0.1% chlorhexidine could be successfully incubated with 0.1 wt% Carbopol microgel while the pH was varied from 8 to 5.5 with a measurable increase of the collapsed microgel due to electrostatic conjugation of these cationic antimicrobial agents with the carboxylic groups of the microgel.While for berberine, only 10% encapsulation efficiency was achieved, for chlorhexidine over 90% encapsulation efficiency was obtained without significant impact on the colloidal stability of the microgel. The zeta potential of the loaded microgels remained negative in the range of -35 mV - -40 mV with very moderate increase of the collapsed (and loaded) microgel particle size. The release of berberine and chlorhexidine from these microgel materials was studied and sustained release from the formulations was demonstrated upon dilution over the period of up to 6 hours. The berberine- and chlorhexidine-loaded microgel particles were then further coated with cationic polyelectrolytes, PAH and PDAC. This carried out to increase the adhesion of these antimicrobial particles to the cell membranes. These studies showed a reversal of the zeta-potential of the PDAC coated microgels after their loading with berberine and chlorhexidine, respectively.In chapter six, the antimicrobial activity of both berberine and chlorhexidine loaded Carbopol microgel was studied upon incubation with algae, yeast and E.coli. It was noticed that an increase in the antimicrobial activity of berberine and chlorhexidine Carbopol microgel occurred after 6 hours incubation time for algae and after 24 hours for E.coli while there was no pronounced antimicrobial action for yeast in comparison with the antimicrobial activity of free berberine or chlorhexidine. This was due to the repulsion forces between the anionic microgel and the anionic cell membrane which did not allow the encapsulated berberine or chlorhexidine to be released and diffuse into the cytoplasm causing cell death. In addition to that, the fully anionic charged Carbopol microgel did not allow berberine and chlorhexidine to be released easily at pH 5.5 while the percentage of release increased with pH up to 7.5.The antimicrobial activity of cationic PDAC coated berberine and chlorhexidine loaded-Carbopol microgel was also studied for algae, yeast and E.coli. It was found that cationic PDAC on its own had an acute toxic effect on algae, yeast and E.coli while the toxicity of cationic PDAC reduced upon coating Carbopol microgel with cationic PDAC. Algae and E.coli stayed viable up to 0.0045 wt. % and 0.009 wt. % of PDAC coated Carbopol microgel, respectively. Yeast was resistance to the PDAC coated carbopol for a wide range of concentrations of PDAC coated Carbopol microgel up to 0.018 wt. %. This was due to the different thicknesses of the cell membrane. The Carbopol microgels with encapsulated berberine and chlorhexidine were then coated with cationic PDAC to form PDAC coated particles. The PDAC coated berberine or chlorhexidine loaded carbopol microgel were then incubated with each of algae, yeast, and E.coli. The coating appeared to increase the antimicrobial actions against algae, yeast and E.coli for short incubation times. The increase in the antimicrobial activity was attributed to the electrostatic interaction between the cationic PDAC coated berberine or chlorhexidine loaded carbopol microgel and the anionic cell membrane allowing diffusion of berberine or chlorhexidine easily through cell membrane causing cell death. TEM images showed aggregation of these cationic PDAC coated berberine or chlorhexidine loaded carbopol microgel on the surface of the cell membrane.Chapter seven describes the development of new microfluidics device for cell trapping to achieve a microscreening cell based assay. The idea involved trapping the cells in a micro chamber and then passing over suspensions of the nanomaterials and monitoring the effect. Three design of microfluidic chips were studied with different designs, channel dimensions (depth and width) cell trapping techniques and materials. Initially chemical adhesion was investigated to adhere cells into micro chamber of the microfluidics device using poly-l-lysine bu the cells detached from the surface of microchip because of shear stress forces. Synthesized magnetic yeast cells which were then investigated for trapping other cells into the micro chamber of the chip but the back pressures were too high when liquids were flowed through the system. Magnetic glass beads were then studied to trap the cells, these were synthesized by coating anionic glass beads with cationic and anionic polyelectrolytes such as PAH and PSS, however, they had a low magnetic response towards the magnet. Synthesized magnetic beads were then synthesized using a PDMS based ferrofluid but again a low magnetic response was obtained towards the magnet. Synthesis by flow focusing microfluidics was the tried to generate mono dispersed magnetic beads where SDS with water was the continuous phase and a styrene based ferrofluid was the dispersed phase but the magnetic beads were unstable and they need to be optimized. The continuous phase was then changed to use Hitenol BC20 a polymerisable surfactant, to form hydrophobic magnetic beads and and a mixing serpentine was added to the chip design to give the generated magnetic beads time to be stablilise. Despite these changes the magnetic beads stayed unstable and therefore an emulsification method was used to fabricate poly dispersed magnetic beads which produced 20μm to 50μm magnetic beads. These beads were successfully utilized for trapping cells into the micro chamber of the chip device. A new microfluidic device was designed with suitable channel dimensions which allowed the magnetic beads to move freely inside the micro chamber of the device. These beads were placed into the micro chamber could be controlled using the neodymium magnet easily move the beads
