Enhancement and control of acoustic cavitation yield by low-level dual frequency sonication: a subharmonic analysis

Evaluation of inertial cavitation is a significant problem where this mechanism of action is responsible for therapeutic applications such as drug delivery. It has shown that using multiple frequencies one is able to enhance and control induced cavitation. In this study, we used different sonication frequencies as 28 kHz, 130 kHz, 1 MHz, 3 MHz and their dual combinations to enhance acoustic cavitation. At each frequency, two different intensities were used and the subharmonic amplitude of each frequency in combinations was measured. It was observed that in combinations which include 28 kHz, the cavitation activity is enhanced. The 28 kHz subharmonic amplitude was used to compare these protocols in their ability to enhance cavitation. Besides, the area of cavitation damage was determined using an aluminum foil. Our results showed that the inertial cavitation activity increased at higher intensities and there is a significant correlation between the subharmonic amplitude and sonication intensity at each frequency (R>0.90). In addition, simultaneous combined dual-frequency orthogonal sonication at 28 kHz with other frequencies used can significantly increase the inertial cavitation activity as compared to the algebraic sum of the individual ultrasound irradiations in 28 kHz subharmonic frequency. The 28 kHz subharmonic amplitude for 28 kHz (0.04 W/cm(2)) and 3 MHz (2 and 1 W/cm(2)) combined dual frequency were about 4.6 and 1.5 times higher than that obtained from the algebraic sum of 28 kHz and 3 MHz irradiation, respectively. Also the 28 kHz subharmonic amplitude for combination of 28 kHz (0.04 W/cm(2)) and 1 MHz (2 and 1 W/cm(2)) were about 2.4 and 1.6 times higher than that obtained with their algebraic sum. Among different combinations, the continuous mode for two ultrasound sources of 28 kHz (0.04 W/cm(2)) and 3 MHz (2 W/cm(2)) is more effective than other combinations (p-value<0.05). The results of effective irradiation area showed no damaged aluminum foil in MHz sonication alone. However, there is significant difference between the effective irradiation area of combined dual frequency 28 kHz and 3 MHz with other irradiation modes (p-value<0.05) and it is limited locally.