Shrinking bubbles and dancing cells: combining microfluidics and ultrasound for medical diagnostics and therapy

ROOM 125

Microbubbles are clinically used to enhance the contrast of ultrasound images, for the diagnosis of several heart diseases and cancers. Recently, nanobubbles–bubbles that are orders-of-magnitude smaller than microbubbles–have emerged as even more promising contrast agents for diagnostics applications due to their ability to extravasate from vessels into organ tissue. However, current state-of-the-art techniques to generate nanobubbles are unable to create uniform size nanobubbles, which limits the clinical efficacy of the nanobubbles. In this talk, I describe a microfluidic approach to produce monodisperse–uniform size–nanobubbles. We exploit the differential solubility of gases in aqueous solution to shrink microbubbles into nanobubbles. Namely, we use a two-component gas mixture of water-soluble nitrogen and water-insoluble octafluoropropane as the gas phase. We first generate microbubbles microfluidically, then allow the microbubbles to shrink, due to the dissolution of the water-soluble gas component, to achieve nanobubbles. We find that these nanobubbles show better homogeneity and brightness in both in vitro and in vivo ultrasound imaging experiments, in phantoms and in live mice, respectively, when compared with state-of-the-art bulk-made nanobubbles. These results suggest that the monodisperse nanobubbles may be suitable as ultrasound contrast agents for detecting nanoscale physiological leakages. The second half of this talk focuses on a newly discovered biophysical phenomenon, whereby adherent cells under the perturbation of an acoustic field self-generates microstreaming flows in a microfluidic channel. We find that the velocity of the microstreaming flow is a strong proxy for cellular mechanical properties, and that large molecule drugs can be selectively delivered into the cells via such microstreaming.

Dr. Scott Tsai is an Associate Professor in the Department of Mechanical and Industrial Engineering at Ryerson University, and an Affiliate Scientist at the Li Ka Shing Knowledge Institute of St. Michael’s Hospital. He obtained his BASc degree (2007) in Mechanical Engineering from the University of Toronto, and his SM (2009) and PhD (2012) degrees in Engineering Sciences from Harvard University. Dr. Tsai is the theme lead for Biomedical Delivery Systems at the Institute for Biomedical Engineering, Science, and Technology (iBEST), and he directs the Laboratory of Fields, Flows, and Interfaces (LoFFI). At Ryerson, Dr. Tsai is the interim director of the Biomedical Engineering Graduate Program. Dr. Tsai is a recipient of the United States’ Fulbright Visiting Research Chair Award (2018), Ontario’s Early Career Researcher Award (2016), Canadian Society for Mechanical Engineering’s I. W. Smith Award (2015), and Ryerson University’s Deans’ Teaching Award (2015). 

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