Micro Bubble Flow Detachment in a Model Ultrasound Contrast Agent System

  • Douglas Chan, Melbourne University, Australia
  • Stephanie Buttner, Melbourne University, Australia
  • Karina Heemann, Melbourne University, Australia
  • Ben Aldham, CSIRO, Australia
  • Judy Scoble, CSIRO, Australia
  • Anna Raicevic, CSIRO, Australia
  • Luisa Pontes-Braz, CSIRO, Australia
  • Brian Lee, Monash University, Australia
  • The in-vitro detachment of targeted micro-bubbles in both static and continuous flow conditions was investigated to determine if micro-bubbles can be clinically used as targeted ultrasound contrast agents. Ultrasound contrast agents are micro-bubbles coated in a lipid, protein or polymer shell. On intravenous injection they dramatically enhance blood vessels in ultrasound imaging. Targeted micro-bubbles are now being developed, which would adhere to and thus identify microscopic disease tissues. The present work is based on a novel form of protein shelled micro-bubble whose performance has never been assessed. Reynolds number and shear stress are both thought to affect the detachment of micro-bubbles. In particular the links binding bubbles to their targets can easily be broken by fluid flow forces. Pairs of molecules modelling the link between the bubble and target were selected (BSA, Anti-BSA and Streptavidin, Biotin) based on their affinity for each other and their ease of use. Micro-bubbles were prepared and purified. These bubbles were then attached to Petri dishes that had been prepared with the relevant pair and had been blocked to stop any non-specific binding. These dishes were then placed in a flow cell where shear stresses applicable to in-vivo conditions were applied. Flow rates were varied. Data were captured using a microscope with an attached video camera. The images were then processed to quantify the detachment. Preliminary results show that protein based micro-bubbles can be successfully targeted and suggest that they should remain on target under the shear stresses present in human blood vessels.