Pressure-dependent resonance frequency for lipid-coated microbubbles at low acoustic pressures

In this study, a flow-focusing microfluidic device was used to prepare lipid-coated microbubbles with a narrow size distribution. Size-controlled monodisperse microbubbles have been successfully produced with mean diameters ranging from 3.4-12.5 μm. These bubble populations were suspended in an exposure chamber and attenuation coefficients were measured by insonifing with 30-cycle narrow-band acoustic pulses at frequencies ranging from 0.5 to 4.5 MHz, and at four acoustic pressure amplitudes: 10 kPa, 20 kPa, 40 kPa, and 60 kPa. The resonance frequency was defined as the frequency where the peak attenuation coefficient was measured. It was shown that the resonance frequency decreased as the acoustic pressure increased, which was mainly due to the nonlinear behavior of the microbubbles. Compared with linear resonance frequency calculated for lipid-shelled microbubbles, the average changes of the resonance frequency at 10 kPa, 20 kPa, 40 kPa, and 60 kPa were 3.0%, -7.9%, -20.5%, and -27.6%, respectively.