Validation of tracking performance of cell–bubble aggregation versus variation of acoustic field

Abstract

We are now developing an in vivo cell delivery system, which is realized by producing aggregates in which bubbles attach onto the surface of cells with acoustic radiation force. We confirmed the controllability of the aggregation of cells with bubbles compared with those without bubbles. However, because of the destruction of bubbles under continuous ultrasound exposure, there is a compatibility problem between controllability and duration of aggregation. Therefore, we introduced the use of a standing wave of an acoustic field to trap the aggregates in the nodes, in which the aggregates are not directly exposed to a high-pressure sound, and manupilation by varying the acoustic field. We prepared the travelling and oscillation motions of the ultrasound standing wave and investigated the mobility of aggregates that were trapped in the nodes of the standing wave to be translated two-dimensionally. Regarding travelling motion, we found that the node velocities of 10 and 20 µm/s showed better performance than that of 40 µm/s. Regarding oscillation motion, we succeeded in the continuous oscillation of aggregates for 36 s. Also, we found the problem of immobile cells, which was considered to be due to the destruction of bubbles.

Validation of damage on vascular endothelial cells under ultrasound exposure according to adhered situation of bubbles

“…From the results obtained in this research, we elucidated a measure to protect vascular endothelial cells from ultrasound irradiation by varying adhesion situations of LBs. In our preceding studies, [8][9][10][11][12][13][14][15][16][17][18][19][20][21]22) in which we examined active control of micro objects in an artificial blood vessel, we concentrated to irradiate ultrasound to those objects without considering damage on the blood vessels. For the development of therapeutic system including active control of micro objects in blood vessel, the results obtained in this research should be important.…”

“…Since the controllability of BSCs is better for cells with LBs (+) attached onto the cell surfaces than that for cells without LBs according to ultrasound exposure, [10][11][12] we attempted to estimate the degree of adhesion of LBs onto cells by retaining BSCs in flow under ultrasound exposure. Our preceding studies [8][9][10][11][12] suggested that a propelling force to the cell is enhanced by the travelling wave reflected on the surface of the cell because of the boundary in the acoustic impedance. Furthermore, oscillation of the bubbles also enhances the Bjerknes force to propel the cell in the direction of the travelling wave.…”

“…To prevent the diffusion of bubbles after injection into the human body and reduce side effects such as relapse and metastasis inhibitory effects, we have been researching a method to control bubbles [1][2][3][4] using acoustic radiation force. Additionally, we have been researching the manipulation of therapeutic cells to contribute to cellular immunotherapy, [5][6][7] wherein bubble-surrounded cells (BSCs) [8][9][10][11][12][13][14] are produced by attracting bubbles on the cell surfaces to reduce their density. These previous studies have shown that micro objects in blood vessels can be controlled by performing active induction in a bifurcated path using a standing wave 13,14) and active retention in the middle of a path using a travelling wave.…”

Experimental study of ultrasound retention of bubble-surrounded cells under various conditions of acoustic field and flow velocity

“…We have designed the experimental setup 11,12) to observe the behavior of the BSCs in flow under ultrasound exposure.…”

“…As a solution to this problem, StemBells, 7,8) which were developed as a therapeutic application for myocardial infarction, decrease intraplaque inflammation by creating aggregates of microbubbles and stem cells using ultrasound for active induction. We proposed a similar technique involving the formation of bubble-surrounded cells (BSCs), [9][10][11][12] in which lipid bubbles 13) are attached to the surface of cells by making use of the connection between antibodies and their receptors to enhance the controllability of the cells under exposure to ultrasound. We have reported methods for the active control of these cells [9][10][11][12] using acoustic radiation force, which included active induction, [14][15][16][17] trapping, [18][19][20][21][22][23] and the formation of aggregates [24][25][26][27] of microbubbles in artificial blood vessels.…”