Scaled-Up Production of Monodisperse, Dual Layer Microbubbles Using Multi-Array Microfluidic Module for Medical Imaging and Drug Delivery.

Abstract

The production of uniform-sized and multilayer microbubbles enables promising medical applications that combine ultrasound contrast and targeted delivery of therapeutics, with improvements in the consistency of acoustic response and drug loading relative to non-uniform populations of microbubbles. Microfluidics has shown utility in the generation of such small multi-phase systems, however low production rates from individual devices limit the potential for clinical translation. We present scaled-up production of monodisperse dual-layered microbubbles in a novel multi-array microfluidic module containing four or eight hydrodynamic flow-focusing orifices. Production reached 1.34 × 10(5) Hz in the 8-channel configuration, and microbubble diameters in the high-speed regime (> 5 × 10(4) Hz) ranged between 18.6-22.3 μm with a mean pooled polydispersity index under 9 percent. Results demonstrate that microfluidic scale-up for high-output production of multilayer bubbles is possible while maintaining consistency in size production, suggesting that this method may be appropriate for future clinical applications.