Nonlinear acoustic characterization of the shell and size engineered microbubbles and nanobubbles

Optimization of the bubble performance requires size isolation and accurate shell characterization using models that are not limited by linear assumptions. MBs and NBs with 2 different shell compositions (crosslinked (C) and non-crosslinked (NC)) were made in-house. NC shell is made with 4 different lipids including DBPC, DPPA,DPPE and DSPE-PEG2000. C shell bubbles have additional ingredients that produce a UV polymerized crosslinked shell. Using the method of multiple differential centrifugations, two distinct size populations were separated with mean diameters of 2.9 mu m for NC-MB and 3.3 mu m for C-MB. The attenuation and sound speed of the diluted solutions were measured through transmission and reception method using one pair of PVDF transducers with center frequencies of 10 MHz and 100 % BW at acoustic pressures of approximately 5 to 40 kPa. Our nonlinear model accounting for large amplitude MB oscillations was used to fit the measured attenuation and sound speed data at each pressure. As the pressure increased from 5 kPa to approximate to 50kPa, resonance frequency (f(r)) of the NC-MBs with a mean diameter (MD) of 2.9 mu m decreased from 9.1 to 5.9 MHz and f(r) of the C-MBs with (MD) of 3.3 mu m decreased from 8 to 4.8 MHz. NC-NB solutions did not display any attenuation peak in the frequency range of 210 MHz, additionally; the measured attenuation was 5-10 times smaller than the MBs with the same shell composition. Fitting of the shell parameters suggests that crosslinking the shell results in approximate to 37 % increase in stiffness and 50 % decrease in shell viscosity. The lower attenuation of the NBs even at very high concentrations may explain the enhancement in NB contrast ultrasound.