On-chip generation of microbubbles as a practical technology for manufacturing contrast agents for ultrasonic imaging |
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Authors: | Hettiarachchi Kanaka Talu Esra Longo Marjorie L Dayton Paul A Lee Abraham P |
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Institution: | Department of Biomedical Engineering, University of California at Irvine, Irvine, CA 92697, USA. |
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Abstract: | This paper presents a new manufacturing method to generate monodisperse microbubble contrast agents with polydispersity index (sigma) values of <2% through microfluidic flow-focusing. Micron-sized lipid shell-based perfluorocarbon (PFC) gas microbubbles for use as ultrasound contrast agents were produced using this method. The poly(dimethylsiloxane) (PDMS)-based devices feature expanding nozzle geometry with a 7 microm orifice width, and are robust enough for consistent production of microbubbles with runtimes lasting several hours. With high-speed imaging, we characterized relationships between channel geometry, liquid flow rate Q, and gas pressure P in controlling bubble sizes. By a simple optimization of the channel geometry and Q and P, bubbles with a mean diameter of <5 microm can be obtained, ideal for various ultrasonic imaging applications. This method demonstrates the potential of microfluidics as an efficient means for custom-designing ultrasound contrast agents with precise size distributions, different gas compositions and new shell materials for stabilization, and for future targeted imaging and therapeutic applications. |
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