Microfluidic manufacturing of uniform nano and microbubbles for ultrasound based imaging and therapeutics applications

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This NSERC Strategic Projects grant is funding the development of a microfluidics-based manufacturing technology that achieves uniform size and high-throughput production of nano and microbubbles in the diameter range of 50 nm - 10 µm. (We simply refer to these bubbles as microbubbles.) The strategy we employ achieves highly uniform microbubbles that overcome the large size distribution limitations of existing commercially available microbubbles that are used as clinical ultrasound contrast agents and also increasingly as therapeutic delivery agents. Specifically, despite the significant potential utility of microbubbles in ultrasound imaging and therapeutics, commercially available microbubbles have a large distribution of sizes, which result in sub-optimal imaging conditions and therapeutic effects. Our advanced manufacturing approach overcomes these issues by enabling precise user-control of microbubble sizes. One key novelty of our technique is the application of vacuum-shrinkage of microbubbles after the bubbles are generated microfluidically. Our goals in this Project are to 1) model and achieve precise control of bubble sizes from 50 nm - 10 µm, 2) scale-up the production of the microbubbles to clinically relevant levels by integrating an edge emulsification microfluidic microbubble generation scheme to our manufacturing technology, and 3) embed in-line quality control of the microbubbles by ultrasound inspection. The microbubbles we are making are safe: commercially available microbubbles have been approved for clinical use in many countries, including in Canada and the United States. The microbubble ultrasound contrast agents also have a growing global market, from $4.46B USD in 2016 to a projected $5.44B USD in 2021 at a compounded annual growth rate (CAGR) of 4.1%. Thus, we anticipate that the development of our technology will help the Canadian micro and nanotechnology manufacturing industry gain access into this potentially highly lucrative market, and improve Canada's employment in the manufacturing technology sector.