A microfluidic model of cardiovascular bubble lodging

Embolotherapy involves the occlusion of blood flow to tumors to treat a variety of cancers, including renal carcinoma and hepatocellular carcinoma. The accompanying liver cirrhosis makes the treatment of hepatocellular carcinoma by traditional methods difficult. Previous attempts at embolotherapy have used solid emboli. A major difficulty in embolotherapy is restricting delivery of the emboli to the tumor. We are developing a novel minimally invasive gas embolotherapy technique that uses gas bubbles rather than solid emboli. The bubbles originate as encapsulated liquid droplets that are small enough to pass through capillaries. The droplets can be selectively vaporized in vivo by focused high intensity ultrasound to form gas bubbles which are then sufficiently large to lodge in the tumor vasculature. We investigated the dynamics of bubble lodging in microfluidic model bifurcations made of poly(dimethylsiloxane) and in theoretical analyses. The results show that the critical driving pressure below which a bubble will lodge in a bifurcation is significantly less than the driving pressure required to dislodge it. Based these results, we estimate that gas bubbles from embolotherapy can lodge in vessels 20 μm or smaller in diameter, and conclude that bubbles may potentially be used to reduce blood flow to tumor microcirculation.