Microfluidics systems for formulation of contrast agents for molecular imaging

描述（由申请人提供）：超声造影剂是直径约为1-10微米的稳定微泡。由于这些微泡的气核的可压缩性，它们比超声传统上用于检测的不同类型的组织之间的界面实质上更具回声。迄今为止，可用的微泡造影剂是用导致多分散尺寸分布的技术生产的。由于造影剂的共振频率取决于其直径，所以当前造影剂的等分试样具有宽范围的共振频率。这种变化限制了当前超声成像系统的灵敏度，其具有仅允许检测窄范围的谐振频率的带宽限制。通过这项研究，我们将生产一种新型的造影剂与小尺寸分布。显着降低造影剂的多分散性将导致成像系统的灵敏度增加。通过模拟，我们估计，通过将尺寸分布的标准偏差从当前的平均1.5微米减小到0.2微米，将使成像系统的灵敏度增加超过500%。 最近，我们的研究小组已经证明，几乎单分散的造影剂可以使用称为流动聚焦技术生产。在这项提案中，要求支持制造和测试一种新型的微流控系统，旨在生产单分散，微米级，造影剂。初步研究已经证明了使用微流体技术实现预期目标的可行性。我们能够使用流动聚焦微流体装置产生8微米量级的气泡。这种微流体系统的进一步发展，以及由此产生的单分散造影剂的生产，将为高灵敏度靶向超声成像开辟几条新途径。

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.