MAGNETIC NANOSENSORS FOR BIOMEDICAL ANALYSES OF MICROVESICLES

描述（由申请人提供）：微囊泡（mv）是细胞释放到循环中的磷脂囊泡，最近作为一种新的诊断生物标志物出现。据报道，在各种恶性肿瘤中，包括心血管疾病、糖尿病和炎症，MVs水平升高；MVs似乎在红细胞衰老过程中也起着不可或缺的作用。然而，一个主要的障碍，推进我们的中压生物学知识，从而充分利用其临床潜力，一直缺乏准确和标准化的中压分析方法。我们最近开发了一种新的基于纳米技术的诊断平台，称为“DMR”（诊断磁共振）。通过采用核磁共振（NMR）原理，DMR设备测量样品的横向弛豫，从而用分子特异性磁性纳米颗粒（MNPs）标记生物靶标。通过系统地开发优化的MNPs和基于芯片的微型核磁共振系统，DMR技术现在已经显著进步，可以提供敏感的、即时的细胞分子分析。在这些成就的基础上，本提案的总体目标是适应并进一步推进DMR平台，用于直接从全血中快速检测和多路分析mv。我们将特别关注以下几点

DESCRIPTION (provided by applicant): Microvesicles (MVs) are phospholipid vesicles released into the circulation by cells, which have recently emerged as a new diagnostic biomarker. Elevated level of MVs has been reported in various malignancies, including cardiovascular diseases, diabetes, and inflammation; MVs also appear to play an integral role in the erythrocyte aging process. However, a major barrier to advancing our knowledge of MV biology, and thus fully harnessing their clinical potential, has been the lack of accurate and standardized methods for MV analysis. We have recently developed a new, nanotechnology-based diagnostic platform termed "DMR" (diagnostic magnetic resonance). By employing principles of nuclear magnetic resonance (NMR), the DMR device measures the transverse relaxation of samples, whereby biological targets are labeled with molecular-specific magnetic nanoparticles (MNPs). By systematically developing optimized MNPs and chip-based miniature NMR systems, the DMR technology has now significantly advanced so as to provide sensitive, point-of-care molecular analyses of cells. Building upon these achievements, the overall goal of this proposal is to adapt and further advance the DMR platform for rapid detection and multiplexed profiling of MVs directly from whole blood. We will specifically focus on the following aims. In Aim 1, we will synthesize new magnetic nanoagents and assay methods that will allow highly efficient and selective MNP-labeling of MV targets. In Aim 2, we will implement a miniaturized NMR system integrated with sophisticated microfluidics. This system will be designed to enable MV analysis to be performed entirely on a single chip; it will isolate MVs directly from whole blood, label MVs with MNPs, and perform NMR measurements on the targeted MVs. In Aim 3, both the optimized nanoagents and device will be applied to the detection and comprehensive profiling of erythrocyte-derived MVs in blood products. This study will advance our understanding of the biology of blood aging, which could lead to improved blood product quality and transfusion safety. We envision a broad diagnostic potential for the proposed DMR-MV technology in both the life sciences and in clinical practice. By facilitating the rapid and quantitative molecular analysis of MVs from different cellular origins, this technology could enable early disease detection and treatment monitoring. In turn, this could expedite advances in creating personalized treatment by providing valuable information on the cellular/molecular signatures of individual patients.