Generation of microbubbles for diagnostic and therapeutic applications using a novel device

Developments in both diagnostic and therapeutic applications of microbubbles have greatly increased the need for more advanced preparation technologies which provide a well-defined, narrow microbubble size-distribution. In this paper, we demonstrate the use of a new device, consisting of a T-junction whose outlet capillary is fitted with an electrohydrodynamic spraying arrangement, to prepare phospholipid-coated air microbubbles, making significant advances in controlling and decreasing the size and size-distribution, and increasing the stability/lifetime of the bubbles prepared. The microbubbles were characterised via optical microscopy to determine the relationship between the size-distribution obtained and the process variables, specifically the flow rates of the phospholipid suspension and air (Q(l) and Q(g)), and the applied voltage (V). The formation of microbubbles in the device was also studied using high-speed photography. For the range of parameters investigated, the bubble diameter was found to scale with the product of the flow rate ratio (Q(l)/Q(g)) and the applied voltage, with a consistent bubble diameter of 5.1 +/- 2 microm being obtained at Q(l)/Q(g) = 1.7 and V = 18 kV. The bubbles prepared using this method were found to be stable for at least 2 h at ambient temperature and pressure.