Gas Plasma Sterilization of Surfactant-Based Ultrasound Contrast Agents

Contrast agents in ultrasound imaging have made a substantial impact on account of the physical similarities between tissues and fluids in the human body.
Perfluorocarbon gas-filled microbubbles have been shown to possess great viability as both ultrasound contrast agents (UCA) and as therapeutic targeted drug-delivery vehicles. PFC gas has extremely low solubility (in blood), the bubbles are safe in concordance with the human body and are small enough (<6µm) to pass through the smallest vessels; most importantly, contrast is greatly enhanced by their acoustic impedance.
As for all substances injected into the human body, sterility is mandated by clinical needs and industry requirements. Unfortunately, short of production in a “clean” facility, microbubbles are far from sterile.

The focus of this experiment is to employ gas plasma to sterilize bubbles freeze-dried for storage with a goal of identifying the ideal plasma setting. The sterility was tested with microscopy analysis of sample in media after applying various combinations of intensity and duration of plasma gas (Harrick Plasma Cleaner PDC-32G) on freeze-dried microbubbles. The echogenicity post-sterilization was tested with ultrasounds.

Sterility was inconsistently achieved in our surfactant-based microbubbles: maximum 50% of culture batches uncontaminated (based on 48-hour standard).
Though polylactic acid bubbles can be sterilized with similar setup, surfactant MBs may require sterilization in other stages or even different plasma equipment.
The results, while not consistently sterile, are encouraging because it marks the possibility of a cost-effective way to sterilize surfactant-based bubbles. More studies are being conducted with different plasma equipment.