Microfluidics systems for formulation of contrast agents for molecular imaging

描述（由申请人提供）：超声造影剂是直径在1-10微米量级的稳定微泡。由于这些微泡气体核心的可压缩性，它们比传统超声检测的不同类型组织之间的界面具有更强的回声。到目前为止，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它的直径，所以当前的造影剂具有很宽的共振频率范围。这种差异限制了当前超声成像系统的灵敏度，这些系统的带宽限制只允许检测一个狭窄的共振频率范围。通过这项研究，我们将生产出一种新型的粒径分布较小的造影剂。显着降低造影剂的多分散性将导致成像系统灵敏度的增加。通过模拟，我们估计通过减小尺寸分布的标准偏差，从目前的平均1.5微米到0.2微米，将使成像系统的灵敏度提高500%以上。

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.