Parallel Output, Liquid Flooded Flow-Focusing Microfluidic Device for Generating Monodisperse Microbubbles within a Catheter

A new method for supplying the liquid phase to a flow focusing microfluidic device (FFMD), designed for the production of monodisperse microbubbles (MBs), is introduced. The FFMD is coupled to a pressurized liquid-filled chamber, avoiding the need for dedicated liquid phase tubing or interconnects from the external field to the microfluidics device. This method significantly reduces the complexity of FFMD fabrication and simplifies the parallelization of FFMDs - an important consideration for increasing MB production rate. Using this new method, flooded FFMDs were fabricated and MB diameter and production rate were measured. The minimum MB size produced was 7.1 +/- 0.5 mu m. The maximum production rate from a single nozzle FFMD was 333,000, MB/s. Production was increased 1.5-fold using a two nozzle, parallelized device, for a maximum production rate of approximately 500,000 MB/s. In addition to increased production, the flooded design allows for miniaturization, with the smallest FFMD measuring 14.5 x 2.8 x 2.3 mm. Finally, B-mode and intravascular ultrasound images were obtained, highlighting the potential for flooded FFMDs to generate microbubbles in situ in a catheter and immediately thereafter image the same MBs in a target blood vessel.