  The acoustic response of microbubbles (MBs) depends on their resonance
frequency, which is dependent on MB size and shell properties. Monodisperse MBs
with tunable shell properties are thus desirable for optimizing and controlling
MB behavior in acoustics applications. By utilizing a novel microfluidic method
that uses lipid concentration to control MB shrinkage, we generate monodisperse
MBs 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 MB
resonance frequency and determine its shell stiffness and viscosity. The study
demonstrates that we can generate monodisperse MBs of specific sizes and
tunable shell properties by controlling MB initial diameter and aqueous phase
lipid concentration. Our results indicate that the resonance frequency
increases by 180-210% with increasing lipid concentration (from 5.6 to 16.0
mg/mL) while bubble diameter is kept constant. Results depict that the
resonance frequency increases by ~195% with increasing lipid concentration from
5.6 to 16.0 mg/mL, for ~11 um final diameter MBs. Additionally, we find that
the resonance frequency decreases by ~275% with increasing MB final diameter
from 5 to 12um, when we use a lipid concentration of 5.6 mg/mL. We also
determine that MB shell viscosity and stiffness increase with increasing lipid
concentration and MB final diameter, and the level of change depends on the
degree of shrinkage experienced by MB. Specifically, we find that by increasing
the concentration of lipids from 5.6 to 16.0 mg/mL, the shell stiffness and
viscosity of ~11 um final diameter MBs increase by ~400% and ~200 %,
respectively. This study demonstrates the feasibility of fine-tuning the MB
acoustic response to ultrasound by tailoring MB initial diameter and lipid
concentration.
