Real-time Control of Microbubble Diameter from a Flow Focusing Microfluidic Device

Microbubbles (MBs), generally of 1 − 4 µm diameter, are useful in contrast ultrasound imaging. MBs can also be used as a therapeutic agent for sonothrombolysis when combined with ultrasound and thrombolytic drugs. Recently, large MBs (10−20 µm diameter) produced by flow focusing microfluidic devices (FFMDs) have been demonstrated to exhibit enhanced bioeffects for sonothrombolysis applications. However, one remaining problem that limits the adoption of this technology is the lack of dynamic monitoring and control of MB diameter. In this study, we demonstrate the regulation of MB diameter in real-time by the incorporation of proportional-integral (PI) feedback control system into an FFMD with an integrated micro Coulter particle counter. With this controller, MB diameters were produced between 14 and 24 µm.