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The acoustic response of microbubbles (MBs) depends on their resonancefrequency, which is dependent on MB size and shell properties. Monodisperse MBswith tunable shell properties are thus desirable for optimizing and controllingMB behavior in acoustics applications. By utilizing a novel microfluidic methodthat uses lipid concentration to control MB shrinkage, we generate monodisperseMBs of four different initial diameters at three lipid concentrations (5.6,10.0, and 16.0 mg/mL) in the aqueous phase. Following shrinkage, we measure MBresonance frequency and determine its shell stiffness and viscosity. The studydemonstrates that we can generate monodisperse MBs of specific sizes andtunable shell properties by controlling MB initial diameter and aqueous phaselipid concentration. Our results indicate that the resonance frequencyincreases by 180-210% with increasing lipid concentration (from 5.6 to 16.0mg/mL) while bubble diameter is kept constant. Results depict that theresonance frequency increases by ~195% with increasing lipid concentration from5.6 to 16.0 mg/mL, for ~11 um final diameter MBs. Additionally, we find thatthe resonance frequency decreases by ~275% with increasing MB final diameterfrom 5 to 12um, when we use a lipid concentration of 5.6 mg/mL. We alsodetermine that MB shell viscosity and stiffness increase with increasing lipidconcentration and MB final diameter, and the level of change depends on thedegree of shrinkage experienced by MB. Specifically, we find that by increasingthe concentration of lipids from 5.6 to 16.0 mg/mL, the shell stiffness andviscosity of ~11 um final diameter MBs increase by ~400% and ~200 %,respectively. This study demonstrates the feasibility of fine-tuning the MBacoustic response to ultrasound by tailoring MB initial diameter and lipidconcentration.

Controlled tempering of lipid concentration and microbubble shrinkage as a possible mechanism for fine-tuning microbubble size and shell properties