Method for continuous large-scale mass production of therapeutic phospholipid-shell oxygen microbubbles

This technology is an all-in-one apparatus that allows for the continuous generation of stable microbubbles with a gas volume of at least 50%.

Unmet Need: Efficient production, concentration, storage, and evaluation of phospholipid-shell microbubbles

Delivering oxygen locally to tissue is important for promoting wound healing, treating stroke, enhancing the therapeutic index of radiation therapy and many other applications. Microbubbles—gas spheres encapsulated by stabilizing phospholipid shells—are an attractive alternative for fast, non-invasive, intravenous delivery of oxygen. Current microbubble production techniques, however, do not operate continuously or at sufficient scale. This technology may significantly reduce the dollar and time costs of using microbubbles in several relevant therapeutic applications.

The Technology: Continuous process for the efficient production of phospholipid-shell microbubbles

This technology is an apparatus and procedure for continuously generating and accumulating a diverse variety of microbubbles. The microbubbles are selectively removed by syringe and then concentrated by centrifuge. Finally, they are transferred into oxygenated glass bottles via a three-needle system. This technology can operate continuously and yields higher throughput than existing microbubble production, concentration, storage, and evaluation methodologies.

A prototype of the technology has been shown to create concentrated phospholipid-shell microbubbles of over 50% gas by volume that remain stable over a 3-week period and demonstrate rapid payload release.

Applications:

• Efficient, large-scale production of microbubbles
• Mass production of different types of microbubbles (e.g., different sizes, gas content, etc.) as required for different biomedical uses
• Methods to concentrate and store microbubbles
• Evaluation of microbubble stability
• Microbubble oxygenation for treating hypoxia and hypoxemia

Advantages:

• Effective method of continuously producing and storing microbubbles at a large scale
• Saves time during periods of high demand
• Produces microbubbles that are predominantly 2-5 microns in diameter, a size range favorable for biomedical use
• High gas content
• Rapid payload release

Lead Inventor:

Mark Borden, Ph.D.

Patent Information:

Patent Status

Related Publications:

• Legband, ND, Feshitan, JA, Borden MA, Terry BS. “Evaluation of peritoneal microbubble oxygenation therapy in a rabbit model of hypoxemia” IEEE Trans Biomed Eng. 2015 May; 62(5): 1376-1382.

• Feshitan JA, Legband ND, Borden MA, Terry BS. “Systemic oxygen delivery by peritoneal perfusion of oxygen microbubbles.” Biomaterials. 2014 March; 35(9): 2600-2606.

• Kwan JJ, Borden MA. “Lipid monolayer dilational mechanics during microbubble gas exchange.” Soft Matter. 2012 March 13; 8(17): 4756-4766.

• Swanson EJ, Mohan V, Kheir J, Borden MA. “Phospholipid-stabilized microbubble foam for injectable oxygen delivery.” Langmuir. 2010 Sept 28; 26(20): 15726-15729.

Tech Ventures Reference:

• IR M10-021

• Licensing Contact: Dovina Qu