Chirp excitation of polydisperse microbubble populations for increasing sonoporation efficiency

The therapeutic application of microbubbles is a highly active area of research, since they can be used for drug or gene delivery. Phospholipid encapsulated microbubbles typically have a polydisperse size distribution over the 1-10 μm range and can be functionalised for molecular targeting as well as loaded with drug-carrying liposomes. The generation of shear stress on the cell membrane by microbubble oscillations is one mechanism that results in pore formation in the cell membrane. A microbubble oscillating at its resonant frequency would generate maximum shear stress on a membrane. However, due to the polydisperse nature of phospholipid microbubbles, a range of resonant frequencies would exist in a single population. Thus, the use of a linear modulated ultrasound pulse, or “chirp”, to excite a microbubble population could improve the sonoporation efficiency.