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

Microbubbles form their aggregations between the neighboring microbubbles by the effect of secondary Bjerknes force under ultrasound exposure. However, because of the difficulty to reproduce a capillary-mimicking artificial blood vessel, the behavior of aggregations in a capillary has not been predicted. Thus we prepared artificial blood vessels including a capillary model, which was made of poly(vinyl alcohol) (PVA) by grayscale lithography method, with minimum diameter of the path of 0.5 mm. By using this model we investigated the possibility of artificial embolization, where the microbubble aggregations might block entire vessels not to penetrate flow in downstream. Confirming that the sizes of flown aggregation were greater than the section area of the minimum path in the capillary model, we investigated the probability of path block in it. As the results we confirmed the probability increased in proportion to sound pressure and inversely to flow velocity. We are going to investigate with more kinds of parameters to enhance the possibility of artificial embolization.

Dependence of aggregate formation of microbubbles upon ultrasound condition and exposure time.

We have previously reported our attempts to control microbubbles (microcapsules) behavior in flow by primary Bjerknes force to increase the local concentration of the bubbles at a diseased part. However, there was a limitation in efficiency to propel bubbles of µm-order size. Thus we consider that forming aggregates of bubbles is effective to be propelled before entering into an ultrasound field by making use of secondary Bjerknes force under continuous ultrasound exposure. In this study, we observed the phenomena of aggregates formation by confirming variation of diameter and density of aggregates under various conditions of ultrasound exposure. Then we elucidated frequency dependence of the size of aggregates of micro-bubbles.

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

We have already reported our attempt to constrain direction of microcapsules in flow owing to an acoustic radiation force. However, the diameter of capsules was too large not to be applied in vivo. Furthermore, acoustic radiation force affected only in focal area because focused ultrasound was used. Thus we have improved our experiment by using microcapsules as small as blood cells and introducing a plane wave of ultrasound. We prepared an artificial blood vessel including a Y-form bifurcation established two observation areas. Then we newly defined the induction index to evaluate the difference of capsule density in two paths of downstream. As the result, optimum angle of ultrasound emission to induce to desired path was derived. And the induction index increased in proportion to the central frequency of ultrasound, which is affected by forming aggregation of capsules to receive more radiation force.