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This study examined the effects of a microbubble emulsion (ME) combined with sonic or ultrasonic agitation, on irrigation dynamics and reduction of biofilm bacteria. High-speed imaging was used to characterize the bubble dynamics generated in ME by sonic or ultrasonic agitation within polymer teeth. 5.25% NaOCl or ME was sonically or ultrasonically agitated in canals of extracted teeth with 7-day-old Enterococcus faecalis biofilms. Dentinal shavings were sampled and colony-forming units (CFU) enumerated. Mean log CFU/ml values were analyzed with ANOVA and post-hoc tests. Strongly oscillating and vaporizing bubbles were generated within ME during ultrasonic, but not sonic agitation. Post-treatment biofilm CFU were significantly lower in the ultrasonic agitation (P=0.000) of ME group than in the ultrasonic (P=0.009) and sonic agitation (P=0.006) of NaOCl groups. The synergistic effect of ME combined with ultrasonic agitation enhanced bubble dynamics and reduced E. faecalis biofilm bacteria beyond the level achieved by agitation of NaOCl.

This study examined the effects of a microbubble emulsion (ME) combined with sonic or ultrasonic agitation, on irrigation dynamics and reduction of biofilm bacteria. High-speed imaging was used to characterize the bubble dynamics generated in ME by sonic or ultrasonic agitation within polymer teeth. 5.25% NaOCl or ME was sonically or ultrasonically agitated in canals of extracted teeth with 7-day-old Enterococcus faecalis biofilms. Dentinal shavings were sampled and colony-forming units (CFU) enumerated. Mean log CFU/ml values were analyzed with ANOVA and post-hoc tests. Strongly oscillating and vaporizing bubbles were generated within ME during ultrasonic, but not sonic agitation. Post-treatment biofilm CFU were significantly lower in the ultrasonic agitation (P=0.000) of ME group than in the ultrasonic (P=0.009) and sonic agitation (P=0.006) of NaOCl groups. The synergistic effect of ME combined with ultrasonic agitation enhanced bubble dynamics and reduced E. faecalis biofilm bacteria beyond the level achieved by agitation of NaOCl.

This thesis presents the development of a novel, targeted, lipid-based, microbubble ultrasound contrast agent (UCA) for assessment of coronary heart disease (CHD) with high frequency intravascular ultrasound (IVUS). The targeting mechanisms assessed for microbubble attachment include a streptavidin-biotin mechanism, electrostatic mechanism and antibody targeting. The microbubble has been optimized for use with 40MHz IVUS through an investigation into the effect of various production methods on the echogenicity of the agent. Echogenicity has been assessed from quantification of the RF data and determination of the mean ultrasound backscatter. Agitation was found to be the optimal method of production resulting in a 3.94(±1.14)dB increase in the mean backscatter. The stability of the agent has also been assessed over time and optimal storage of the agent determined. A novel flow chamber has been developed for assessment of microbubble detachment under very high WSS. The flow chamber has been calibrated to 50Pa wall shear stress (WSS) using laser Doppler anemometry (LDA). Higher WSS was achieved through the use of higher viscosity fluids. The streptavidin-biotin bond has been assessed within the flow chamber and was found to be 75 times stronger than an electrostatic control. Antibody attachment to the microbubbles via a streptavidin-biotin bridge has been optimised with 91.20(±0.02)% of the microbubbles having antibodies attached. A flow system has also been developed for assessment of microbubble attachment to cells under very low WSS. Microbubbles have been successfully targeted to SK-Hep-1 cells using acoustic radiation force. In addition attachment of the microbubbles to SK-Hep-1 cells has been observed under 0.03Pa WSS in the Ibidi μ-slides.

Droplet-based microfluidic devices have become a preferred versatile platform for various fields in physics, chemistry and biology to manipulate small amounts of liquid samples. In addition to microdroplets, microbubbles are also needed for various pro- cesses in the food, healthcare and cosmetic industries. Polydimethylsiloxane (PDMS) soft lithography, the mainstay for fabricating microfluidic devices, usually requires the usage of expensive apparatus and a complex manufacturing procedure. In ad- dition, current methods have the limited capabilities for fabrication of microfluidic devices within three dimensional (3D) structures. Novel methods for fabrication of droplet-based microfluidic devices for the generation microdroplets and microbubbles are therefore of great interest in current research. In this thesis, we have developed several simple, rapid and low-cost methods for fabrication of microfluidic devices, especially for generation of microdroplets and mi- crobubbles. We first report an inexpensive full-glass microfluidic devices with as- sembly of glass capillaries, for generating monodisperse multiple emulsions. Different types of devices have been designed and tested and the experimental results demon- strated the robust capability of preparing monodisperse single, double, triple and multi-component emulsions. Second, we propose a similar full-glass device for generation of microbubbles, but with assembly of a much smaller nozzle of a glass capillary. Highly monodisperse microbubbles with diameter range from 3.5 to 60 microns have been successfully produced, at rates up to 40 kHz. A simple scaling law based on the capillary number and liquid-to-gas flow rate ratio, successfully predicts the bubble size. Recently, the emergent 3D printing technology provides an attractive fabrication technique, due to its simplicity and low cost. A handful of studies have already demonstrated droplet production through 3D-printed microfluidic devices. However, two-dimensional (2D) flow structures are still used and the advantage of 3D-printing technique has not been fully exploited. Therefore, we apply 3D printing technology to fabricate 3D-miniaturized fluidic device for droplet generation (single emulsion) and droplet-in-droplet (double emulsion) without the need for surface wettability treat- ment of the channel walls, by utilizing 3D geometry design and fabrication. A scaling law is formulated to predict the drop size generated in the device. Furthermore, magnetically responsive microspheres are also produced with our emulsion templates, demonstrating the potential applications of this 3D emulsion generator in chemical and material engineering. Finally, we design and 3D-print a hybrid ?plug-and-play? microfluidic droplet generator, which involves a 3D-printed channel chamber and commercial tubings and fittings. By combination of 3D-printed part and market-available parts, this device can be easily assembled and disassembled, which provides a great flexibility for different demands. A scaling law has been proposed for prediction of drop size generated in the device. Furthermore, a 3D-printed concentration gradient generator and a droplet merging device based on the droplet generator have been developed to demonstrate the great scalability of 3D-printing technology.

Part I: The present work is to calculate dimensionless three-dimensional universal phase and lift force diagrams for a microbubble or pendant drop in a static liquid on a solid surface or orifice. Studying microbubble dynamics is important due to its controlling mass, momentum, energy and concentration transfer rates encountered in micro- and nano-sciences and technologies. In this work, dimensionless phase and force diagrams are presented by applying an equation for microbubble shape to accuracy of the second order of small Bond number provided by O¡¦Brien (1991). Two dimensionless independent parameters, Bond number and contact angle (or base radius), are required to determine dimensionless phase and force diagrams governing static and dynamic states of a microbubble. The phase diagram divides the microbubble surface into three regions, the apex to inflection, inflection to neck, and neck to the edge of microbubble. The growth, collapse, departure and entrapment of a microbubble on a surface thus can be described. The lift forces include hydrostatic buoyancy, difference in gas and hydrostatic pressures at the microbubble base, capillary pressure and surface tension resulted from variation of circumference. The force to attach the microbubble to solid surface is the surface tension resulted from variation of circumference, which is not accounted for in literature. Adjusting the base radius to control static and dynamic behaviors of a microbubble is more effective than Bond number. Part II: Controlling states and growth of a microscale bubble (or pendant drop) in a static liquid on a surface by introducing general phase diagrams is proposed. Microbubbles are often used to affect transport phenomena in micro- and nano-technologies. In this work, a general phase diagram is provided by applying a perturbation solution of Young-Laplace equation for bubble shape with truncation errors of the second power of small Bond number. The three-dimensional phase diagram for a given Bond number is uniquely described by the dimensionless radius of curvature at the apex, contact angle and base radius of the microbubble. Provided that initial and end states are chosen, adjusting two of them gives the desired states and growth, decay and departure of the bubble described by path lines in the phase diagram. A universal three-dimensional phase diagram for a microbubble is also introduced.

Indiana University-Purdue University Indianapolis (IUPUI) / This thesis work aims to make a better knowledge on the insights of physics on microbubble coalescence process, using experimental and numerical approaches. The neck growth and bubble surface wave propagation at the early stage of coalescence, merging preference, as well as a reaction-channel modified microfluidic gas generator are presented in the thesis. Coalescence of unequal-sized microbubbles captive on solid substrate was observed from cross-section view using synchrotron high speed imaging technique and a mi- crofluidic gas generation device. The bridging neck growth and surface wave propaga- tion at the early stage of coalescence were investigated by experimental and numerical methods. The results show that theoretical half power law of neck growth rate is still valid when viscous effect is neglected. However, the inertial-capillary time scale is based on the radius of smaller parent microbubble. The surface wave propagation rate is proportional to the inertial-capillary time scale, which is based on the radius of larger parent microbubble of a coalescence pair. Meanwhile, the relationship of preference distance and size inequality microbub- bles were studied using the same micrfluidic gas generator and observation facilities. The size inequality of parent microbubbles would affect the preference distance of merged bubble in between. The merged bubble gets less closer to the larger parent bubble with an exponent of 1.82 as a reference, which largely affected by shear stress begotten on the solid interface. To express this phenomenon distinguished with free merging bubble pair, we propose the wall shear stress hinders the process of that parent bubbles move towards to each other during coalescence Our hypothesis was confirmed by identical coalescence simulation via ANSYS Fluent. To address the multiple measurement, utilization of Java based photography pro- cessing software ImageJ was applied as a key point to the thesis work. To acquire more microbubble coalescence cases on experiment for study, we enhanced the perfor- mance of microfluidic gas generator with reaction channel optimization. An optimized design on increasing the number of parallel reaction channel from single to triple, was applied to obtain a higher gas generation rate. Also the gas vent shape was modified from triangle to rectangle to provide more information on reaction channel optimiza- tion. The gas generation rate and H2O2 conversion rate were provided to further discuss.

Yes / Most cancer patients receive chemotherapy at some stage of their treatment which makes improving the efficacy of cytotoxic drugs an ongoing and important goal. Despite large numbers of potent anti-cancer agents being developed, a major obstacle to clinical translation remains the inability to deliver therapeutic doses to a tumor without causing intolerable side effects. To address this problem, there has been intense interest in nanoformulations and targeted delivery to improve cancer outcomes. The aim of this work was to demonstrate how vascular endothelial growth factor receptor 2 (VEGFR2)-targeted, ultrasound-triggered delivery with therapeutic microbubbles (thMBs) could improve the therapeutic range of cytotoxic drugs. Methods: Using a microfluidic microbubble production platform, we generated thMBs comprising VEGFR2-targeted microbubbles with attached liposomal payloads for localised ultrasound-triggered delivery of irinotecan and SN38 in mouse models of colorectal cancer. Intravenous injection into tumor-bearing mice was used to examine targeting efficiency and tumor pharmacodynamics. High-frequency ultrasound and bioluminescent imaging were used to visualise microbubbles in real-time. Tandem mass spectrometry (LC-MS/MS) was used to quantitate intratumoral drug delivery and tissue biodistribution. Finally, 89Zr PET radiotracing was used to compare biodistribution and tumor accumulation of ultrasound-triggered SN38 thMBs with VEGFR2 targeted SN38 liposomes alone. Results: ThMBs specifically bound VEGFR2 in vitro and significantly improved tumor responses to low dose irinotecan and SN38 in human colorectal cancer xenografts. An ultrasound trigger was essential to achieve the selective effects of thMBs as without it, thMBs failed to extend intratumoral drug delivery or demonstrate enhanced tumor responses. Sensitive LC-MS/MS quantification of drugs and their metabolites demonstrated that thMBs extended drug exposure in tumors but limited exposure in healthy tissues, not exposed to ultrasound, by persistent encapsulation of drug prior to elimination. 89Zr PET radiotracing showed that the percentage injected dose in tumors achieved with thMBs was twice that of VEGFR2-targeted SN38 liposomes alone. Conclusions: thMBs provide a generic platform for the targeted, ultrasound-triggered delivery of cytotoxic drugs by enhancing tumor responses to low dose drug delivery via combined effects on circulation, tumor drug accumulation and exposure and altered metabolism in normal tissues. / EPSRC funding (EP/I000623/1, EP/K023845/1 and EP/P023266/1) and the MRC for a Confidence in Concept award and MR/L01629X. L.E. McVeigh was funded by an EPSRC PhD Studentship (EP/L504993/1).

An investigation was carried out on the current state of the art in bubble modelling for computational fluid dynamics, and comparisons made between the different methods for both polydisperse and monodisperse multiphase flows. A multigroup method for polydisperse bubbly flows with the bubbles binned in terms of mass was selected from the various alternatives, which included other multigroup models and moment methods. The latter of these involve the integration of moments of the bubble number density function and transport of these quantities. The equations from this multigroup solver were then changed to more accurately and efficiently model cases involving extremely small bubbles over significant amounts of time, as the original model which was subsequently adapted had, as its primary purpose, simulation of larger bubbles over shorter periods of time. This was done by decoupling the gas and liquid momentum equations and adding an empirical rise velocity term for the bubbles. This new model was then partially implemented into OpenFOAM. The functioning of this new solver was confirmed by comparisons between the results and basic analytical solutions to the problems, as well as by means of comparison with another similar multiphase CFD solver (pbeTransportFoam). Following this confirmation of its functionality, the bubble model was implemented into another solver specifically designed for modelling wakes. Finally, the newly created solver was used to run some cases of interest involving a submerged wake. / Master of Science / Bubbles in the ocean are significant for a number of reasons, ranging from mixing of the upper layer of the ocean to scavenging of biological matter, by which means they can also impact the state of the ocean's surface where they are present. They serve as an important mechanism by which air is dissolved in the ocean, and their breaking at the surface can cause particles or droplets to be ejected into the atmosphere. They can be created by a variety of sources, ranging from the movement of ship propellers and hulls to natural processes, both abiotic and from microorganisms or other living things. They can have exceedingly variable sizes, meaning bubbles behave very differently from one another in the same area. For these reasons, their study is both interesting and sometimes challenging. In this research, methods were developed to simulate the movement over a significant amount of time of a wide size variety of very small bubbles within the ocean. First, study was undertaken of preexisting methods of bubble simulation and the different cases they were intended to represent. One of these existing methods was selected for use and then changed to more accurately represent smaller bubbles, as well as including simplifications to allow the simulations to run faster. Lastly, these methods were implemented into OpenFOAM, an open-source set of solvers for computational fluid dynamics (CFD). These new methods for simulation were finally applied to some cases involving submerged bubbles in the ocean and the movement of bubbles in these cases studied.

The growing awareness of global warming potential has internationally aroused interest and demand in reducing greenhouse gas emissions produced by human activity. Each year, the UK consumes a significant amount of energy for residential and industrial space heating and domestic hot water production. At present, gas boilers are mostly installed in the domestic water heating which contributes significantly to excessive CO2 emissions and consumption of primary energy resources. However, air-source heat pump system has higher performance efficiency comparing to the traditional gas boiler, which can reduce the carbon dioxide emission and the usage of primary energy resources. The coefficient of efficiency of the heat pump can be range from 2 to 4.5 in various situations. The market shares of heat pump have been predicted to increase in the coming years to meet the requirement of the European Union Commission. There were about 22,000 heat pumps set up in the UK with 18 percent growth comparing to 2016 as reported by BSRIA. A range from 0.6 to 5.7 million heat pumps are estimated by the National Grid to be set up by 2030 to increase the energy efficiency of the UK. Although the energy efficiency of the heat pump is extremely high, there is still a space for improvement in air-source heat pump water heating system. The performance of the heat pump water heating system can be further enhanced if the dissolved gases in its hot water circuit can be efficiently discharged. The undissolved bubbles can stack in a specific position of the radiator, which would cause the cold spot. This could immensely reduce the efficiency of the heat pump water heating system. To avoid this happening, the bubble behaviors in the heat pump water heating system need to be extensively investigated. The better understanding of the bubble behaviors in an air-source heat pump water heating system can contribute to the design of an air evacuation valve and heat pump piping systems. In this thesis, the effects of various heat pump hot water side parameters on gas microbubble diameters and bubble productions were measured and analyzed by varying different experimental conditions. Correspondingly, a summarized conclusion has been presented to predict the gas microbubble's diameter distributions and volumetric void fraction distributions at different operating conditions. These parameters include various system pressures, water flow rates, and saturation ratios. In this thesis, the main results showed that larger average bubble diameter is at the higher water flow rates at heat pump exit. At 2.2 bar condition, when system water flow rate increased from 800 l/h to 1150 l/h, the average bubble diameter increased from 0.086 mm to 0.108 mm. Moreover, the average bubble diameters increase along with the decrease in system pressures. At 1000 l/h condition, when system pressure increased from 2.2 bar to 2.7 bar, the average bubble diameter decreased from 0.100 mm to 0.087 mm. At 850 l/h condition, when system pressure increased from 1.7 bar to 2.5 bar, the average bubble diameter decreased from 0.101 mm to 0.081 mm. In addition, the average bubble diameters slightly increase along with the increase in saturation ratio. Besides, a prediction equation for the bubble diameter distribution in the water pipe was proposed. At SR 1.15 and 2.5 bar condition, when water flow rate increased from 900 l/h to 1100 l/h, volumetric void fraction decreased from 2.25 E-05 to 4.83 E-06. However, at 1000 l/h and SR 1.15 condition, when system pressure increased from 2.2 bar to 2.7 bar, volumetric void fraction decreased from 2.16 E-05 to 3.78 E-06. It is found that the highest city main saturation ratio was achieved at 1.07 at the specific environmental condition.