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

Abstract

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 μm 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.

Keywords: :

• Microbubbles
• T-junction
• electrohydrodynamic phospholipid suspension
• drug delivery
• ultrasound contrast agent