Microfluidic production of ultrasound contrast agents with a capillary gas jet PDMS microchip

Microbubbles have been used as ultrasound contrast agents in medical applications such as imaging, and also for drug/gene delivery, target destruction and so on. Microbubbles are normally made by sonication techniques and the resulting size distribution is very large. Microfluidics provides an alternative way of microbubble fabrication due to recent advances in microfabrication and microfluidics development. The current techniques are capable of making bubbles with a size of several micrometers. However, the throughput for such a size range is very limited. In this study, a new microfluidic bubble generation chip was developed, which incorporates a T-junction PDMS microchannel network with an inserted glass capillary. The flow rate of liquid, gas pressure and the inserted capillary inner diameter are crucial for control of the bubble size. A series of capillaries with different inner diameters have been used. With co-flow focusing liquids and a fine-drawn glass capillary, bubble size could be decreased and bubbles with a size of 13 μm in diameter were generated reliably after the optimizing of liquid flow rate and gas pressure. It was found that a 5 μm capillary inserted microchip produced 11 μm diameter bubbles with a cross-flow rupturing method.