Engineering a vascular model based on microfluidics for studying microbubbles in an acoustic field
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- Institutt for fysikk 
A major challenge in cancer therapy is the poor and insufficient delivery to tumour sites whichmany chemotherapeutic drugs face. Ultrasound (US) mediated delivery based on cavitating microbubbles(MBs) has emerged as a promising approach to enhance drug delivery to tumours,where several pathways have been proposed. One of the pathways involve the biomechanicaleffects cavitating MBs exert on the endothelial barrier resulting in enhanced endothelialpermeability, with subsequent enhanced drug extravasation from the vascular compartment. Inrelation to this, Acoustic Cluster Therapy (ACT) has been proposed as a novel approach to solvethe limitations of conventional MB formulations including US contrast agents. The mechanismsinvolved when MBs including ACT bubbles present in the endothelial lumen are subject to USmust however be further studied and thoroughly elucidated. This was the motivation for thework that will be presented in this thesis. The goal was to develop a protocol for producing anin vitro system suitable for endothelial cell culture and insonation experiments, allowing interactionsbetween MBs and cells to be studied. Based on experiences from the pre-masterspecialization project, microfluidic devices were designed and fabricated to facilitate seedingof Human Umbilical Vein Endothelial Cells (HUVECs), with optically and acousticallytransparent materials. In addition, human prostatic adenocarcinoma (PC3) cells were seededin microfluidic devices used for insonation experiments to simulate biomechanical interactionsbetween MBs and the endothelial barrier in vivo. Sonoporation, manifested as uptake of the fluorescentdye propidium iodide, could be observed qualitatively (and semi-quantitatively) withboth the commercially available MB SonazoidTM as well as ACT bubbles. Furthermore, the microfluidicdevice enabled evaluation of MB behaviour in microscale channels during insonation,such as the size of ACT bubbles. The goal of this master project was achieved with respect toestablishing an in vitro system that can fulfill its purposes at the proof-of-concept stage.