On-chip generation of microbubbles as a practical technology for manufacturing contrast agents for ultrasonic imaging.
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.
Hettiarachchi
Kanaka
K
Department of Biomedical Engineering, University of California at Irvine, Irvine, CA 92697, USA.
Talu
Esra
E
Longo
Marjorie L
ML
Dayton
Paul A
PA
Lee
Abraham P
AP
D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003287:Contrast Media / Q000494:pharmacology*; D004058:Diffusion; D004129:Dimethylpolysiloxanes / Q000737:chemistry; D016503:Drug Delivery Systems; D005466:Fluorocarbons / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry; D046228:Microarray Analysis / Q000379:methods*; D045423:Microbubbles; D046210:Microfluidic Analytical Techniques; D044085:Microfluidics; D008856:Microscopy, Fluorescence; D008956:Models, Chemical; D011312:Pressure; D012828:Silicones / Q000737:chemistry; D014463:Ultrasonography / Q000295:instrumentation*
D003287:Contrast Media; D004129:Dimethylpolysiloxanes; D005466:Fluorocarbons; D008055:Lipids; D012828:Silicones; C013830:baysilon