Universal Equations for the Coalescence Probability and Long-Term Size Stability of Phospholipid-Coated Monodisperse Microbubbles Formed by Flow Focusing

Resonantly driven monodisperse phospholipid-coated microbubbles are expected to substantially increase the sensitivity and efficiency in contrast-enhanced ultrasound imaging and therapy. They can be produced in a microfluidic flow-focusing device, but questions remain as to the role of the device geometry, the liquid and gas flow, and the phospholipid formulation on bubble stability. Here, we develop a model based on simple continuum mechanics equations that reveals the scaling of the coalescence probability with the key physical parameters. It is used to characterize short-term coalescence behavior and long-term size stability as a function of flow-focusing geometry, bulk viscosity, lipid cosolvent mass fraction, lipid concentration, lipopolymer molecular weight, and lipopolymer molar fraction. All collected data collapse on two master curves given by universal equations for the coalescence probability and the long-term size stability. This work is therefore a route to a more fundamental understanding of the physicochemical monolayer properties of microfluidically formed bubbles and their coalescence behavior in a flow-focusing device.