Production and characterisation of contrast agent microbubbles

• Main Author: McKendry, Jonathan Edward
• Published: University of Leeds 2011
• Subjects: 530.4275
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.550348

The work in this thesis concentrates on the production and characterisation of microbubbles that are suitable for use' as ultrasound contrast agents. Initially microbubbles were produced using a mechanical agitation technique that forced a gas supernatant into a suspension of shell material. This technique has been demonstrated to be quick and versatile, facilitating the production of high concentrations of microbubbles (-1010 bubbles/nil) with varying shell compositions. However, the majority of microbubbles studied within this thesis have been produced by microfluidic flow focussing as this technique is shown to produce less disperse samples and offer greater control and reproduction of the mean bubble diameter. Microbubbles with lipid, PEG, streptavidin and PEG+streptavidin shell compositions have been produced and were characterised for size, concentration and stability using white light microscopy. A modified Epstein-Plesset model has been fitted to the stability data and used to determine the resistance to gas permeation of each of the shell compositions. AFM Force spectroscopy has been employed to measure the mechanical properties of the microbubbles, providing a measure of the stiffness of the bubble encapsulation. The stiffness values obtained have shown to decrease monotonically with micro bubble radius and have been used in combination with the modified Rayleigh-Plesset to predict the resonance frequency of the microbubbles for each of the shell compositions. The displacement creep and the effect of temperature on the mechanical properties of lipid coated microbubbles have also been investigated. An increase in temperature of 27 QC has been shown to result in a reduction (-3x) of microbubble stiffness. Finally, the standard linear model has been applied to the displacement creep data of a lipid bubble in order to access the visco-elastic properties of the microbubble shell.