|M.Sc Student||Mazzawi Nasma|
|Subject||Bubble-Like Response of Living Cells in an Ultrasound|
|Department||Department of Biomedical Engineering||Supervisor||Professor Emeritus Eitan Kimmel|
|Full Thesis text|
The therapeutic use of ultrasound is investigated extensively in the last two decades for applications such as treating fibroids, tumors and brain disorders or enhancing drug delivery by opening the brain blood barrier. The concept of intra-membrane cavitation, denoted here as the Bilayer Sonophore (BLS), suggests that ultrasound induces a pulsating, flat gas pockets in cell membranes thereby transforming acoustic energy into distortions and strains in the cellular structure. Another aspect of the theory studied here is the hypothesis that as a result of the BLS phenomenon, floating cells in solution will behave as microbubbles under ultrasound. The hypothesis is investigated experimentally using a 2mm diameter transparent tube with flow in the range of 0-1ml/sec, a 15fps camera and a microscope. As cells (ECs and RBCs) flow in the tube, they were exposed to ultrasound field of low intensity and megahertz frequencies. We observed clusters of cells, organized in narrow strips, perpendicular to the tube axis, about one tenth of a wavelength apart. Those shapes turned out to be indicative of a complex pattern of oblique standing waves which are not related to the tube. In addition, ring-like cell clusters were observed in a second experimental setup built to form a circular standing wave pattern only this time cell clusters were about a half of a wavelength apart. Cells were observed to accumulate near the tube walls in clusters like microbubbles under ultrasound do under the influence of inter-bubble secondary radiation forces. An extra objective was to examine micro particles and compare their behavior to cells. Micro bubbles (Ultrasound contrast agents and liposomes) were examined as well. The concluding remark of this work states that in a standing wave field, the bubbly behavior of cells is not expressed since they are not exposed properly to the acoustic pressure needed to develop sonophores while being trapped at free-force spots (nodes/antinodes). In this case a cell is not to be considered a bubble but more as a particle. Therefore, for a future research, applying ultrasound of high enough pressure on cells is needed to ensure the appearance of sonophores within the cell and only then a standing wave field can be used for expressing the cell transition to become a bubble. By then a standing wave field can be used for sorting these 'ultrasound treated' cells of different sizes based on one of their bubbly acquired characteristics such as a resonance frequency.