Characterization of microbubble-enhanced molecular delivery to cells in acoustofluidic channels

Abstract

Cell therapies are rapidly emerging as a promising approach for treatment of many diseases, such as cancer and cardiovascular diseases. Non-viral methods for molecular delivery are currently in development to increase safety and reduce varability during manufacturing of cell therapies. Ultrasound-mediated microbubble cavitation has been utilized as an effective approach for non-viral molecular delivery via sonoporation or other mechanisms. However, prior ultrasound studies have primarily utilized static sample chambers, which have limited throughput and are generally not practical for cell therapy manufacturing processes. To address these limitations, we are developing novel acoustofluidic platforms to enable intracellular delivery of biomolecules as cells continuously pass through an ultrasound field in a flow chamber. We have investigated a range of fundamental parameters that influence acoustofluidic-mediated molecular delivery to human cells, including microbubble properties, channel geometry, and ultrasound parameters. In addition, we investigated biological factors that influence acoustofluidic-mediated molecular delivery to cells, including cellular properties and extracellular metabolite levels. The results of these studies will be presented to provide new insights into the key parameters and mechanisms that affect the efficiency of molecular delivery to human cells in acoustofluidic channels. Further development of acoustofluidic platforms may enable improved processes for manufacturing of cell therapies.