Abstract
Purpose: Although minimally invasive treatment methods based on the thermal and non-thermal effects of ultrasound on microbubbles are being reported, a problematic side effect arises because microbubbles are carried in the flow of the bloodstream. To get around this problem, we developed a method to control the behavior of microbubbles in flow by using an artificial blood vessel with multiple transducers to produce ultrasonic plane waves. Materials and Methods: Microbubbules are propelled in flow by a primary Bjerknes force, a physical phenomenon in which an acoustic wave moves an obstacle in its direction of propagation. These bubbles also aggregate when they enter an ultrasound field because of secondary Bjerknes forces that attract or repel neighboring microbubbles. We thus consider forming bubble aggregations to be an effective way to propel the bubbles before they enter an ultrasound field to receive greater primary Bjerknes force. We have investigated the phenomenon of bubble aggregations and observed variation in diameter and density of aggregations under various conditions of ultrasound exposure. Results: When ultrasound was emitted to cause aggregation, the induction index, which indicates the number of microbubbles induced to the desired path in an artificial blood vessel bifurcation, was confirmed to improve by a factor of 1.3 to 5.5 times greater than the index without forming aggregation. The maximum induction index with aggregation was found to be a central frequency of 2 MHz, where a central frequency of 5 MHz was most effective without aggregation. Conclusion: If a bubble aggregation can be regarded as one large bubble, its propulsion would require less primary Bjerknes force. For further development, we plan to realize active control of bubble aggregations in vivo.
