Scaleable production of microbubbles using an ultrasound-modulated microfluidic device

Surfactant-coated gas microbubbles are widely used as contrast agents in ultrasound imaging and increasingly for therapeutic applications. It has been shown that the acoustic response of microbubbles is determined by their size and coating properties and hence depends upon both their chemical composition and the manufacturing technique used to produce them. We have previously presented a hybrid device consisting of a simple microfluidic T-junction with an integrated ultrasound transducer that provides superior production rates and microbubble stability compared with conventional microfluidic systems but with significantly better microbubble uniformity than standard emulsification techniques. The maximum production rate was, however, still limited compared to industrial methods. In the present study a new device was developed that enables production of >108 microbubbles per second using a single device with a mean bubble diameter of 1.4 μm without degrading microbubble uniformity. Production rates of >109 microbubbles per second can be achieved through parallel operation of multiple channels within a single device; comparable with bulk emulsification but without the risk of contamination and/or degradation of sensitive components.