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Poster Presentations

PERFLUOROCARBON BUBBLE OCCLUSION MECHANISMS WITHIN AN IN VITRO MICROFLUIDIC MODEL OF THE MICROCIRCULATION.

Stephen, James H.; Wong, Zheng Zheng; Bull, Joseph L.

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The mechanisms by which gas bubbles can occlude blood flow within the microcirculation are clinically relevant to both the treatment of air embolism and the development of gas embolotherapy. Gas embolotherapy is a technique that could be used to occlude blood flow to cancerous tumors. With this technique, albumin-coated liquid perfluorocarbon droplets, about 6μm in diameter, could be introduced into the circulation and acoustically vaporized to form bubbles at precise locations within the tumor vasculature. These bubbles are then large enough to become lodged in the tumor vasculature and occlude blood flow to starve the tumor. The understanding of the interactions between such bubbles and the vascular endothelium is critical to developing successful gas embolotherapy strategies. Circular-lumen microchannels (140 to 800μm in diameter) were constructed from polydimethylsiloxane (PDMS), and dodecafluoropentane (DDFP, C5F12) gas bubbles of various volumes were introduced into the fluid-filled channel to occlude the channel's full diameter. Once the bubble was lodged within the channel, the pressures at the inlet and outlet were slowly adjusted and measured. Bubble motion, including the contact angle, was recorded using a microscope and CCD camera, and the driving pressure required for bubble motion was measured. To simulate the presence of the vascular endothelium in the experiments, human umbilical vein endothelial cells (HUVECs) were cultured on the inner lumen surface of the microchannels. Driving pressures were plotted for various values of the experimental parameters, including bubble volume, microchannel diameter, serum albumin concentration, and endothelialized vs. non-endothelialized channel walls. It was found that increasing serum albumin concentration lowered the surface tension of the fluid/gas interface, thus decreasing the driving pressure required to dislodge the bubble in a non-endothelialized channel. Also, driving pressure does not seem to depend on bubble volume for a given, non-endothelialized channel. Intuitively, smaller diameter microchannels were able to support greater driving pressures with all other variables being equal. These results provide insight into the mechanisms behind bubble occlusion within the circulation and suggest possible treatment strategies for gas embolotherapy. Proteins adsorbed to the bubble surface are important to bubble occlusion and may, in addition to decreasing surface tension, interact with the glycocalyx layer present on endothelial cells. Without bifurcations or possible interactions between adsorbed proteins and cells, the independence of driving pressure on bubble length suggests the dominance of surface tension forces. The effect that an endothelialized microchannel exerts on bubble occlusion is being continually investigated. Lastly, by supporting greater driving pressures, it suggests that smaller vessels will be the most likely sites of occlusion in vivo.

Copyright © 2006 by the American Society for Artificial Internal Organs