Probing microbubble adhesion using secondary acoustic radiation force

In this study we investigated the translational dynamics of mutually attracting targeted microbubbles during and after ultrasound (US) insonification in more detail and show this mutual attraction can be used to determine the binding force. In general, similar sized microbubbles are known to attract each other during US application as a result of an acoustic radiation force leading to clustering and coalescence. Targeted microbubbles, however, move back to their initial position after US is turned off, implying the presence of an elastic restoring force, which in turn opposes the net pulling force. From the recoiling curves, a value for the effective spring constant k could be obtained, which was of the order of 2.4 mN/m. For higher acoustic pressures the pulling force exceeded the binding force and the bubbles detached. A threshold force for detachment was calculated with the obtained value of the spring constant. For biotinylated microbubbles (R=2-2.5 μm) targeted to a NeutrAvidin coated surface, the threshold force was between 0.9 nN and 2.0 nN. We also show that the translational dynamics of targeted microbubbles during US application can be modelled accurately using a hydrodynamic model [1], including a value for the spring constant k of the very same order as derived experimentally.