Microfluidic, Multifunctional, Multilayer, Monodisperse Microbubbles

Lee, Abraham ;   Hettiarachchi, Kanaka ;   Bardin, David ;   Shih, Roger

In this talk I will review my lab's development of microfluidic technology for multilayer vesicles (MVs), focusing on gaseous-cored microbubbles. Each of the layers in the MVs can be designed for different in vivo therapeutic functions, including molecular targeting, drug carrying, embolotherapy, and drug releasing. The introduction of a gas phase core in these droplets renders the monodisperse vesicles acoustically responsive and active. This motivated my lab?s first microbubble paper published 7 years ago to generate monodisperse lipid vesicles for ultrasound contrast imaging applications. Ultrasound contrast agents are lipid-shelled microbubbles that improve the imaging accuracy for the detection of functional abnormalities in the body. The optimal size of the microbubble contrast agent is between 2 and 5 μm in diameter since bubbles too small are ineffective as contrast agents and when too large can cause obstruction of the blood vessels. Monodisperse microbubbles, enabled by microfluidics also reduce the volume of contrast agents required per procedure, reducing cost and also complications that can occur when large volumes of reagents are injected. Over the years, our lab has produced a drug carrying gas bubble that is sealed with an outer lipid membrane, enabling the all-in-one multifunctional vesicle. Finally, I will discuss my lab's effort to scale up production of these microfluidic, multilayer, multimodal, monodisperse microbubbles (5M).