A high-speed microscopic system for observation of bubble-cell interaction from a lateral direction

A high-speed observation system for sonoporation study was improved for observation of bubble and cell dynamics under ultrasound exposure from a lateral direction. The effect of the presence of a scaffold mimicking an in vivo situation on the dynamics was investigated to study the mechanisms by which bubbles cause cell membrane damage. Observations showed that the stiffness of the scaffold has a significant effect on bubble dynamics: a microbubble on a hard scaffold remains on its hard surface, but a bubble on a soft scaffold make a translational movement in a direction away from the soft surface. The same movement was observed for bubbles adhering to cell membranes, and bubble-cell interaction was classified into four phenomena. Higher frequencies of cell membrane damage were found in two phenomena: a phenomenon in which a bubble moving in a separating direction drags the cell membrane, resulting in membrane damage, and a phenomenon in which a jet flow generated by bubble-bubble interaction causes local deformation of a cell, resulting in membrane damage. The results suggest that the efficiency of in vivo sonoporation can be improved by utilizing the mechanisms observed in the two phenomena.