Andrés J. Calderón

Microfluidic model of bubble lodging in microvessel bifurcations

The lodging mechanisms and dynamics of cardiovascular gas bubbles are investigated in microfluidic model bifurcations made of poly(dimethylsiloxane). This work is motivated by gas embolotherapy for the potential treatment of cancer by tumor infarction. 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. From the results the authors estimate that gas bubbles from embolotherapy can lodge in vessels 20μm or smaller in diameter, and conclude that bubbles may potentially be used to reduce blood flow to tumor microcirculation.

A boundary element model of the transport of a semi-infinite bubble through a microvessel bifurcation

Motivated by a developmental gas embolotherapy technique for selective occlusion of blood flow to tumors, we examined the transport of a pressure-driven semi-infinite bubble through a liquid-filled bifurcating channel. Homogeneity of bubble splitting as the bubble passes through a vessel bifurcation affects the degree to which the vascular network near the tumor can be uniformly occluded. The homogeneity of bubble splitting was found to increase with bubble driving pressure and to decrease with increased bifurcation angle. Viscous losses at the bifurcation were observed to affect the bubble speed significantly. The potential for oscillating bubble interfaces to induce flow recirculation and impart high stresses on the vessel endothelium was also observed.

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.Copyright

Bubble lodging in bifurcating microvessel networks: a microfluidic model

Lodging of cardiovascular gas bubbles is investigated in a microfluidic model of small arteriole bifurcations. These experiments address the dynamics of the lodging mechanism of gas bubbles in bifurcations. This work is motivated by a novel gas embolotherapy technique for the potential treatment of cancer by tumor infarction. The experimental model arteriole bifurcations were constructed from a transparent elastomer (polydimethylsiloxane). A single air bubble was suspended in water within the parent tube of the bifurcation and a specified driving pressure was imposed via constant elevation reservoirs that were open to atmospheric pressure. The driving pressure and bubble size were varied, and their effects on the bubble lodging were assessed. The results show that the pressure to lodge a bubble in a bifurcation is less than to dislodge it. It was also possible to occlude an entire bifurcation and multiple bifurcation devices with bubbles. Splitting ratios were assessed in the range of lodging to dislodging pressure where we observed an instability in bubble splitting. From the results we estimate that gas bubbles from embolotherapy can lodge in vessels 21 mum or smaller in diameter. These findings may be useful in developing strategies for microbubble delivery in gas embolotherapy

A microfluidic model of microbubble lodging in small arteriole bifurcations

Lodging of cardiovascular gas bubbles is investigated in a microfluidic model of small arteriole bifurcations. This work is motivated by a novel gas embolotherapy technique for the potential treatment of cancer by tumor infarction and by air embolism. The experimental model arteriole bifurcations were constructed from a transparent elastomer, poly(dimethylsiloxane), using soft lithography. A single air bubble was suspended in water within the parent tube of the bifurcation and a specified driving pressure was imposed via constant elevation reservoirs that were open to atmospheric pressure. The driving pressure and bubble size were varied, and their effects on the bubble lodging were assessed. These findings may be useful in developing strategies for microbubble delivery in gas embolotherapy.