EAGER: Nanoparticle-Based Integrated Microsystem for Selective Targeting of Bio-Species in Flowing Suspensions

本研究的目的是开发一种高性能的系统，以显著提高特异性和敏感性针对单个生物物种。该方法基于利用智能纳米粒子，封装各种化学物质并配备归航功能，提供了一种高效的纳米级精确递送有效载荷的载体。目前的系统使用特异性非常低的药物，导致严重的副作用和较差的系统反应。有机-无机纳米颗粒将与抗体功能化，以特异性结合循环肿瘤细胞，以改善系统的性能。智力上的优点在于有选择地捕获罕见的移动生物目标，这仍然是一个巨大的工程挑战。血液循环中的转移性癌细胞将成为目标。为了应对这一挑战，独特的跨膜细胞-细胞粘附分子被用作受体。混合纳米颗粒上的抗体具有脂质体双层结构和硅酸盐表面，用作选择性结合靶细胞受体的归巢配体。该项目可以通过将拟议的方法不仅应用于疾病的检测，而且应用于疾病的诊断、监测和治疗，产生重大影响。在护理点采用具有增强特异性的自动免疫测定将提高患者治疗的疗效，帮助根除癌症等疾病。拟议的项目直接支持目前正在开发的Bio-MEMS教育计划；它通过为学生提供进行先进跨学科研究的机会，将劳动力发展纳入其中。还将安排对K-12和普通社区的科学教育外展。

The objective of this research is to develop a high-performance system to target individual bio-species with dramatically enhanced specificity and sensitivity. The approach is based on utilizing smart nanoparticles, encapsulating various chemicals and equipped with homing features, to provide a vehicle for pin-point delivery of payloads at a nanoscale with high efficiency. Current systems utilize drugs with very low specificity resulting in serious side effects and poor system response. Organic-inorganic nanoparticles will be functionalized with antibodies for specific binding to circulating tumor cells flowing in complex mixtures to improve the system performance.The intellectual merit lies in the goal of selectively capturing a rare moving bio target that is still a tremendous engineering challenge. Metastatic cancer cells circulating in the blood stream will be targeted. To meet this challenge, unique trans-membrane cell-cell adhesion molecules are used as receptors. The antibodies on the hybrid nanoparticles, having a liposomal bilayer structure and a silicate surface, are used as homing ligands for selective binding to the target cell receptors.The project could have a major impact by applying the proposed methodologies not only to detection but also diagnosis, monitoring and treatment of diseases. An automated immunoassay employed at the point-of-care with enhanced specificity will increase the efficacy of patient treatment helping eradicate diseases such as cancer. The proposed project directly supports the Bio-MEMS educational program currently under development; it incorporates workforce development by providing an opportunity for students to carry out advanced interdisciplinary research. Science education outreach for K-12 and general communities will also be arranged.