Active Path Selection of Fluid Microcapsules in Artificial Blood Vessel by Acoustic Radiation Force

Abstract

Micrometer-sized microcapsules collapse upon exposure to ultrasound. Use of this phenomenon for a drug delivery system (DDS), not only for local delivery of medication but also for gene therapy, should be possible. However, enhancing the efficiency of medication is limited because capsules in suspension diffuse in the human body after injection, since the motion of capsules in blood flow cannot be controlled. To control the behavior of microcapsules, acoustic radiation force was introduced. We detected local changes in microcapsule density by producing acoustic radiation force in an artificial blood vessel. Furthermore, we theoretically estimated the conditions required for active path selection of capsules at a bifurcation point in the artificial blood vessel. We observed the difference in capsule density at both in the bifurcation point and in alternative paths downstream of the bifurcation point for different acoustic radiation forces. Comparing the experimental results with those obtained theoretically, the conditions for active path selection were calculated from the acoustic radiation force and fluid resistance of the capsules. The possibility of controlling capsule flow towards a specific point in a blood vessel was demonstrated.

Study to prevent the density of microcapsules from diffusing in blood vessel by local acoustic radiation force

“…We confirmed that the induction index reflects the relative ratio of capsules to pass ROI B versus total amount of capsules through our previously recorded movies [8,9] which calculated shadow index versus capsules density. IV.…”

“…To measure amount of microcapsules, we established two square regions of interest (ROI), which size is 1.8 x 1.2 mm2, in each path (ROIs A and B) and calculated the average brightness. In the previous paper [8,9] we have evaluated amount of capsules by defining shadow index, which reflects brightness change according to existence of capsules in a ROI. However, the value of the shadow index cannot be compared between ROIs if there is initial brightness difference between them.…”

“…If the behavior of capsules could be controlled and constrained the direction, the introduction efficiency would be enhanced. Owing to an acoustic radiation force [5][6][7], which is a physical phenomenon where an acoustic wave pushes an obstacle along its direction of propagation, we have ever reported our attempt to propel microcapsules in water [8,9]. We have elucidated the conditions in sound pressure, flow velocity and diameter of capsules for active path selection of capsules in an artificial blood vessel.…”

Production and Validation of Acoustic Field to Enhance Trapping Efficiency of Microbubbles by Using a Matrix Array Transducer

“…We have ever reported our attempts to control microbubbles using the primary and secondary acoustic forces to elucidate the conditions in sound pressure, central frequency of ultrasound, and flow velocity for active path selection [1,2] and trapping in blood flow [3] of microbubbles using artificial blood vessels. In those experiments we have examined with single element transducers to produce focused or plane acoustic fields, by using concave or flat transducers, respectively.…”

Observation of flow variation in capillaries of artificial blood vessel by producing microbubble aggregations

“…We have ever reported our attempts to control microbubbles using the primary and secondary Bjerknes force to elucidate the conditions in sound pressure, central frequency of ultrasound, and flow velocity for active path selection in water flow [12,13] and trapping in blood flow [14] of microbubbles using artificial blood vessels with a simple shape. In those experiment we have experimentally found that there was an upper limitation of the size of microbubbles aggregations, which were propelled to the wall by primary Bjerknes force, and finally they flaked off the wall and flied to downstream.…”