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Title: Engineering the surface properties of microbubbles for biomedical applications
Author: Mohamedi, Graciela
ISNI:       0000 0004 5370 1783
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2014
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Surfactant coated microbubbles are widely used as contrast agents (UCA) in medical ultrasound imaging, due to their high echogenicity and non-linear response to acoustic excitation. Controlling the stability of microbubbles in vivo represents a considerable challenge. Understanding the characteristics of the bubble surface and how they change with production method, composition and environment is key to addressing this problem. The aim of this thesis is to investigate viscosity, bubble dissolution, and acoustic response as functions of their composition, manufacturing method and environment. Bubbles were made using combinations of phospholipid and an emulsifier in different molar ratios. Adding the emulsifier decreased both the size and the surface viscosity of the bubbles and caused changes in the scattered pressure amplitude of bubbles under ultrasound. To increase microbubble stability, solid inorganic nanoparticles were adsorbed on to the microbubble surface. These particles behaved as Pickering stabilisers, and deterred Ostwald ripening. The nanoparticles also enhanced the nonlinear behaviour of bubbles at low acoustic pressures. Three manufacturing methods (sonication, cross-flow and flow focusing) were investigated in order to verify stability differences. Sonication produced bubbles with surface viscosities hundreds of centipoise greater than those produced by microfluidics. Both pressure amplitude and harmonic content for sonicated bubbles were found to be much larger due to a higher liposomal adhesion rate at the surface. Solution temperature and bubble age were also investigated. When the solutions were heated above the phospholipid gelling temperature, microfluidic bubbles showed an increased surface viscosity, due to increased liposome adhesion caused by the increased temperature. Bubble composition, manufacturing method and environment were found to vary the surface characteristics of the microbubbles. Further investigations into the affects of the filling gas, in vitro studies, and low temperature TEM characterisation should be conducted to produce a microbubble with the full range of desired characteristics.
Supervisor: Stride, Eleanor Sponsor: Engineering and Physical Sciences Research Council ; Leverhulme Trust ; University of Oxford
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Interfacial fenomena ; Foaming ; Advanced materials ; Surfaces ; bubbles ; ultrasound ; microfluidics ; membranes