On-chip generation of microbubbles as a practical technology for manufacturing contrast agents for ultrasonic imaging

摘要

This paper presents a new manufacturing method to generate monodisperse microbubble contrast agents with polydispersity index (sigma) values of <2% through microfluidic flow-focusing.Micron-sized lipid shell-based perfiuorocarbon (PFC) gas microbubbles for use as ultrasound contrast agents were produced using this method.The poly(dimethylsiloxane) (PDMS)-based devices feature expanding nozzle geometry with a 7 mu m orifice width,and are robust enough for consistent production of microbubbles with runtimes lasting several hours.With high-speed imaging,we characterized relationships between channel geometry,liquid flow rate Q,and gas pressure P in controlling bubble sizes.By a simple optimization of the channel geometry and Q and P,bubbles with a mean diameter of <5 mu m can be obtained,ideal for various ultrasonic imaging applications.This method demonstrates the potential of microfluidics as an efficient means for custom-designing ultrasound contrast agents with precise size distributions,different gas compositions and new shell materials for stabilization,and for future targeted imaging and therapeutic applications.