Mass Production of Monodisperse Ultrasound Contrast Microbubbles in Integrated Microfluidic Devices

Microbubbles coated by surfactant or polymer have been shown to be the most effective contrast agents for diagnostic ultrasound contrast imaging and targeted molecular imaging probes. The microbubbles produced by flow-focusing units have a narrower size distribution than that of the traditional methods such as sonication or agitation and is nearly monodisperse in size distribution, but with very limited production. This paper investigates the production of monodisperse microbubbles in integrated microfluidic devices in a massive way. The integrated microfluidic devices are composed of three layers: two top layers made from poly(dimethylsiloxane)(PDMS) and one glass slide as the bottom layer. Four and eight FFUs are integrated on a chip sharing the same gas inlet, liquid inlet and outlet channel. Monodisperse microbubbles production efficiency of the three microfluidic devices with one, four and eitht FFUs on a chip are evaluated respectively. It is found that the liquid consumption does not increase linearly with the FFUs number within microfluidic devices while the concentration of the microbubbles increases. The results of this work indicate the potential for mass production of ultrasound contrast agents in large scale integrated microfluidic device for commercial use.