(164b) Pressure Effects On Bubble Growth in An Emulsion of Surfactant-Stabilized Perfluoropentane Micro-Droplets

Authors: 
Butterfield, A., University of Utah
Mohan, P., University of Utah
Skliar, M., University of Utah


Perfluorocarbons (PFC) are, in general, volatile compounds that are largely immiscible in water and act as exemplary solvents for gasses. Due to their biocompatibility, gaseous PFC's and PFC's that transition to a gas at body temperature (or under the low and oscillating pressures of ultrasound) have found use as ultrasound imaging contrast agents [1]. PFC's are promising candidates for targeted drug delivery systems and occlusion therapy as well, due to the dramatic change in particle dimensions achievable with their phase shift from liquid to gas [2, 3]. Too little is known, however, regarding the thermodynamics and mass transfer involved in the formation and growth of PFC bubbles from droplets.

In this work we studied the effect of pressure and time on the formation and growth of bubbles within a surfactant-stabilized perfluoropentane (PFP) emulsion. Emulsions of PFP droplets were created by sonicating a solution of water, 2 wt% PFP, and 0.25 mol% Poly (L-lactide-co-ethylene glycol) surfactant. The emulsions were characterized using digital image processing of light microscopy images and dynamic light scattering. Once injected into a 640 µm square flow channel, bubble growth over time was observed at 0, -5, -10, and-15 inHg gauge pressure. Bubbles sizes, locations and numbers were determined by automated digital processing of microscopy images, which were taken over a 30 minute period. Hundreds of bubbles were individually tracked in order to determine what circumstances (e.g. proximity to neighboring bubbles or channel surfaces) affected their appearance, growth or, in some instances, shrinkage. As pressure was decreased, the number of bubbles, average bubble volume, and the average molar flux into each increased. However, after the first 15 min, molar flux for all pressures stabilized near 0.05 nmol/min/mm2. While the boiling-point of PFP is approximately 29° C, bubbles also appeared and grew for several days at atmospheric pressure and 21° C. Furthermore, when low pressure samples were returned to atmospheric pressure, the average volume decreased only slightly more than one would expect if we assumed an ideal gas. It was also observed that bubbles that shrunk or remained at constant volume over time were statistically more likely to be near larger bubble, suggesting Ostwald ripening as a significant factor.

Over time, the emulsion surrounding growing bubbles became less optically dense, suggesting the consumption of nano- and micron-scale pfp droplets. The spatial distribution of bubbles was consistent with nucleation only occurring on the channel surface, and not in the volume. Liquid pfp droplets could remain and be observed at pressures as low as -15 inHg and temperatures as high as 50° C, likely due to the inability of PFP to overcome the pressures of nucleating within a surfactant-stabilized sphere. No bubbles were observed when PFP was omitted from the aqueous surfactant solution at low pressures or elevated temperatures.

As PFP is negligibly soluble in water and liquid droplets were not observed to directly transition to bubbles, a mechanism is proposed where bubble growth occurs through an interplay between accumulation of dissolved gasses, bubble coalescence with and subsequent vaporization of PFP liquid droplets, and Ostwald ripening. The composition of the bubble gas is proposed to be a combination of air, PFP, and water vapor. These finding reveal several important considerations that may be needed in an attempt to predict and control nucleation and bubble growth when using PFC emulsions in vivo for occlusion, drug delivery or as contrast agents.

1. Schutt EGK, D.H., Mattrey RM, Riess JG. Injectable Microbubbles as Contrast Agents for Diagnostic Ultrasound Imaging: The Key Role of Perfluorochemicals. Angewandte Chemie 1996;42(28):3218-3235. 2. Riess JG, Krafft MP. Advanced Fluorocarbon-Based Systems for Oxygen and Drug Delivery, and Diagnosis. Artificial Cells, Blood Substitutes and Biotechnology 1997;25:42-52. 3. Tsutsui JM, Xie F, Porter RT. The use of microbubbles to target drug delivery. Cardiovascular Ultrasound 2004;2(23).

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