Applications in acoustic manipulation of biological cells in micro-devices

Abstract

Utilizing ultrasonic standing waves in biocompatible micro-fluidic devices, we are able to acoustically manipulate biological cells for a variety of potentially beneficial pharmaceutical, biomedical and environmental applications. Using a device designed to induce sonoporation in the absence of contrast agent micro-bubbles (CA-free sonoporation) we demonstrate both the uptake and efflux of differently sized, membrane impermeable molecules whilst maintaining high cell viability. Crucially we show that the cytotoxic action of several known pharmaceutical agents is significantly increase in porated cells compare with non-porated control cells, suggesting sonoporation-induced facilitated uptake of these agents. We also report on a device that acoustically excites tethered polymer-shelled micro-bubbles to induce micro-streaming around cardiomyocyte membranes in order to mimic myocardial infarction, ischaemia and induction of apoptosis. Initial results from a levitation culture system that continuously perfuses a pellet of ultrasonically suspended chondrocytes are also presented. The pellet geometry allows large numbers of cells to be cultured without developing a necrotic core. Primary chondrocytes and cell lines demonstrated good viability after more than ten days of levitation. Using low power, continuous ultrasonic excitation we have demonstrated significant reductions in biofilm growth in polymer fluid channels potentially increasing the lifespan of in-situ marine sensors.