Microfluidics systems for formulation of contrast agents for molecular imaging

用于配制分子成像造影剂的微流体系统

• 批准号: 7342404
• 负责人: Abraham P. Lee
• 金额: $ 6.79万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-01 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7342404
• 关键词: 3-Dimensional; Acoustics; Adhesions; Aliquot; Animal Model; Caliber; Contrast Media; Date Available; Detection; Development; Devices; Drug Formulations; Frequencies; Gases; Goals; Histocompatibility Testing; Histology; Image; Investigation; Ligands; Methods; Microbubbles; Microfluidic Microchips; Microfluidics; Numbers; Optics; Population; Production; Property; Range; Rate; Research; Research Personnel; Signal Transduction; Site; Stabilizing Agents; Standards of Weights and Measures; System; Techniques; Technology; Testing; Time; Tissues; Ultrasonic Transducer; Ultrasonography; Work; base; concept; design; desire; improved; in vivo; lithography; manufacturing process; molecular imaging; novel; poly(dimethylsiloxane); prototype; scale up; simulation; size; two-dimensional

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：超声对比剂是稳定的微泡，直径为1-10微米。由于这些微泡的气体芯的可压缩性，它们比传统上用于检测的不同类型的组织之间的接口要大得多。到目前为止，可用的微泡对比剂是通过技术产生多分散尺寸分布的技术。由于造影剂的共振频率取决于其直径，因此当前对比度的等分试样具有广泛的共振频率。这种差异限制了当前的超声成像系统的灵敏度，后宽限制仅允许检测狭窄的共振频率。通过这项研究，我们将生产一种具有较小尺寸分布的新型对比剂。显着降低对比剂的多分散性将导致成像系统的灵敏度提高。通过模拟，我们估计，通过将尺寸分布的标准偏差从当前平均值减少到1.5微米为0.2微米，将使成像系统的灵敏度超过500％。 最近，我们的研究小组表明，几乎可以使用称为流动的技术来生产几乎单分散的对比剂。在此提案中，请求支持用于制造和测试一种新型的微流体系统，旨在生产单分散，微米大小的对比剂。初步研究表明，使用微流体技术实现所需目标的可行性。我们能够使用流动的微流体设备在8微米的阶数产生气泡。该微流体系统的进一步发展，以及产生的单分散造影剂，将为高灵敏度靶向超声成像开放几种新途径。

项目成果

Controllable microfluidic synthesis of multiphase drug-carrying lipospheres for site-targeted therapy.

• DOI: 10.1002/btpr.214
• 发表时间: 2009-07
• 期刊: BIOTECHNOLOGY PROGRESS
• 影响因子: 2.9
• 作者: Hettiarachchi, Kanaka;Lee, Abraham P.;Zhang, Shirley;Feingold, Steven;Dayton, Paul A.
• 通讯作者: Dayton, Paul A.

Acoustic responses of monodisperse lipid-encapsulated microbubble contrast agents produced by flow focusing.

• DOI: 10.1179/175889610x12779105661532
• 发表时间: 2010-12-01
• 期刊: Bubble science engineering and technology
• 作者: Kaya, Mehmet;Feingold, Steven;Dayton, Paul A
• 通讯作者: Dayton, Paul A