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Indirect plasma sterilization of ultrasound contrast agent
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Indirect plasma sterilization of ultrasound contrast agent

Lorenzo Albala
Master of Science (M.S.), Drexel University
Mar 2014
DOI:
https://doi.org/10.17918/etd-7104
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Albala_Lorenzo_20142.39 MBDownloadView

Abstract

Ultrasound contrast media Plasma stability Biomedical Engineering
The ultrasound contrast agent (UCA) SE61 is composed of a sonicated mixture of non-ionic surfactants entrapping perfluorocarbon gas. Formulated with Span60 and water-soluble vitamin E, the microbubbles are a promising UCA, but they require a sterilization method that is unachievable by current solutions. The SE61 manufacturing process was improved in order to achieve safe and effective sterilization by introducing dielectric-barrier discharge non-thermal plasma. Plasma-treating phosphate-buffered saline (PBS) generates ions and reactive oxygen species within the liquid that disrupt microorganismal metabolism. This is currently the only method to obtain a sterilant solution while avoiding direct heat, pressure, chemicals, and radiation, or the expense of aseptic manufacturing methods. 3 minutes plasma treatment of PBS was chosen after preliminary testing, and it effectively sterilized both native and (gramnegative and gram-positive) bacteria-inoculated samples (p = 0.0022). The treated and untreated samples showed no statistical significance in acoustic response (p >0.05 for dose-response and for half-life). Moreover, treated UCA retained appropriate bubble diameter (mean ± SEM: 2.52 ± 0.31[mu]m) with no significant difference compared to untreated (p >0.05). Nile red was used to model the intercalation of drug into the hydrophobic portion of the microbubble shell; this hydrophobic fluorescent solvatochromic probe intercalated successfully into SE61, and was unaffected by plasma treatment. The indirect plasma technique enters the healthcare and device industry as a novel sterilizing option and one that is crucial for SE61 production. Refining the SE61 manufacturing process can lead to enhanced diagnostic US and a potential drug-delivery vehicle, and it paves the way for future experiments and the FDA pipeline.

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