Nonlinear oscillation of microbubble in microtubes for ultrasound imaging and drug delivery

Abstract

Ultrasound-assisted microbubble drug delivery is under intensive investigation due to the potential for enhanced local delivery without systemic adverse effects. The efforts in modeling bubble oscillation have been largely focused on using various modified forms of the Rayleigh-Plesset bubble dynamics equation, of which the cornerstone assumption is that a bubble oscillates in an unbounded liquid field and remains spherical until it collapses. Here, nonlinear oscillation of a bubble confined inside a microtube with diameters comparable with capillaries is studied numerically and experimentally. In numerical simulation, the liquid is treated as incompressible viscid fluid and contrast agent is treated as gas bubble obeying the polytropic law. Microbubble oscillation is shown to decrease in a small vessel as compared with oscillation in an infinite fluid or a larger vessel diameter. For the same bubble size, the natural oscillation frequency of a bubble deceases with the decrease of tube size. The natural frequency of a bubble with an equilibrium diameter of 2.5 μm decreases from 3.56 MHz, in unbounded liquid field, to 1.16 MHz in an 8-μm tube. Decreasing the ultrasound center frequency can increase the amplitude of bubble oscillation and thereby produce a higher pressure on the tube.