Ultrasound contrast agents are stabilized microbubbles with diameters on the order of 1-10 microns. Because the compressibility of the gas core of these microbubbles, they are substantially more echogenic than the interfaces between different types of tissue that ultrasound is traditionally used to detect. To this date, available microbubble contrast agents are produced with techniques which result in a polydisperse size distribution. Since the resonance frequency of the contrast agent depends on its diameter, an aliquot of current contrast agents has a wide range of resonance frequencies. This variance limits the sensitivity of current ultrasound imaging systems, which have bandwidth limits which permit detection of only a narrow range of resonance frequencies. With this research, we will produce a new type of contrast agent with a small size distribution. Significantly decreasing the polydispersity of the contrast agent will result in an increase in the sensitivity of the imaging system. Through simulations, we have estimated that by reducing the standard deviation in the size distribution from the current average of 1.5 microns to 0.2 microns would increase sensitivity of the imaging system over 500%. ? Recently, our research group has demonstrated that nearly monodisperse contrast agents can be produced using a technique known as flow-focusing. In this proposal, support is requested for manufacture and testing of a novel type of microfluidic system designed to produce monodisperse, micron-sized, contrast agents. Preliminary studies have demonstrated feasibility of using microfluidic technology for achieving the desired goal. We are able to produce bubbles on the order of 8 microns using a flow-focusing microfluidic device. The further development of this microfluidic system, and resulting production of monodisperse contrast agents, will open several new avenues for high sensitivity targeted ultrasound imaging. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Small Research Grants (R03)
Project #
5R03EB006846-02
Application #
7342404
Study Section
Enabling Bioanalytical and Biophysical Technologies Study Section (EBT)
Program Officer
Zhang, Yantian
Project Start
2007-02-01
Project End
2009-01-31
Budget Start
2008-02-01
Budget End
2009-01-31
Support Year
2
Fiscal Year
2008
Total Cost
$67,887
Indirect Cost
Name
University of California Irvine
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92697
Kaya, Mehmet; Feingold, Steven; Hettiarachchi, Kanaka et al. (2010) Acoustic responses of monodisperse lipid-encapsulated microbubble contrast agents produced by flow focusing. Bubble Sci Eng Technol 2:33-40
Hettiarachchi, Kanaka; Zhang, Shirley; Feingold, Steven et al. (2009) Controllable microfluidic synthesis of multiphase drug-carrying lipospheres for site-targeted therapy. Biotechnol Prog 25:938-45