Micro-scale fluid flows: the application of acoustic streaming to biomedical research

Abstract

Shear stress generated by biological fluid flows in vivo plays an important role in the regulation of numerous cellular processes; these include apoptosis, cellular proliferation and differentiation, regulation of metabolism and of inflammatory responses. The effects of shear stress are particularly prevalent in cells of the cardiovascular and skeletal systems due to the haemodynamic and interstitial fluid flows respectively. The limited scope for controlling in vivo shear stress has required the research to be conducted in vitro. Within the thesis, stable cavitation microstreaming was harnessed as a method for mimicking in vivo shear stress with the aim of developing a generic method for stressing cells. Stable cavitation microstreaming is a steady fluid flow generated by the transfer of acoustic energy into a time averaged steady momentum flux as a result of viscous damping in the boundary layer of an oscillating gas bubble. Microstreaming was generated around Expancel encapsulated microbubbles (EMBs) in purpose built microfluidic devices. The devices provided controlled environments for the generation of microstreaming. Important features of the final device include adherence of microbubbles to an internal surface of the device, the minimisation of primary acoustic radiation forces and the ability to perform high throughput biological experiments on adhered cells in the device. The microstreaming flow was characterized by micro particle image velocimetry (?PIV), showing that flows possess good repeatability and controllability. H9c2 cardiomyocytes, adhered opposite to the microbubbles at a separation distance of approximately 150 ?m, were stressed with microstreaming and their viability was measured. This was carried out in order to assess the applicability of the device to biomedical research. This research is thought to be the first in depth analysis of the controllability and repeatability of microstreaming in the context of stressing cells. Furthermore, it is thought to be the first demonstration of inflicting controlled cell death by stable cavitation microstreaming at a distance of 150 ?m.

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ORCID for M. Hill: orcid.org/0000-0001-6448-9448

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