MAGNETIC NANOSENSORS FOR BIOMEDICAL ANALYSES OF MICROVESICLES

用于微泡生物医学分析的磁性纳米传感器

• 批准号: 8458935
• 负责人: Hakho Lee
• 金额: $ 41.41万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-16 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8458935
• 关键词: Achievement; Adopted; Aging; Aging-Related Process; Biological; Biological Assay; Biological Markers; Biological Sciences; Biology; Blood; Blood Banks; Blood Circulation; Blood Platelets; Blood Preservation; CD47 gene; CD8B1 gene; Cardiovascular Diseases; Cells; Chemistry; Clinical; Consultations; Detection; Devices; Diabetes Mellitus; Diagnosis; Diagnostic; Disease; Endothelial Cells; Enzyme-Linked Immunosorbent Assay; Erythrocyte Aging; Erythrocytes; Flow Cytometry; Glioma; Glycophorin A; Goals; Gold; Hand; Health; Hematological Disease; Individual; Inflammation; Knowledge; Label; Lead; Leukocytes; Light; Literature; Lymphocyte; MS4A1 gene; Magnetic Resonance; Magnetic Resonance Imaging; Magnetism; Malignant Neoplasms; Measurement; Measures; Medical; Medicine; Methods; Microfluidic Microchips; Microfluidics; Molecular; Molecular Analysis; Molecular Profiling; Molecular Target; Monitor; Nanotechnology; National Heart, Lung, and Blood Institute; Natural History; Nuclear Magnetic Resonance; One-Step dentin bonding system; PTPRC gene; Patients; Phosphatidylserines; Phospholipids; Play; Population; Proteins; Protocols documentation; Quality Control; Reagent; Relaxation; Reporting; Research; Role; Safety; Sampling; Sensitivity and Specificity; Signal Transduction; Surveys; System; Technology; Time; Transfusion; Variant; Vascular Diseases; Vesicle; Whole Blood; Work; base; blood product; cell type; clinical practice; cohort; crosslink; design; flotillin; improved; in vivo; iron oxide; mathematical model; miniaturize; nanomaterials; nanoparticle; nanoscience; nanosensors; novel; novel diagnostics; point of care; rapid detection; response

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.

描述（由申请人提供）：微泡（MVS）是细胞释放到循环中的磷脂囊泡，这些囊泡最近已成为一种新的诊断生物标志物。已经报道了各种恶性肿瘤的MV水平升高，包括心血管疾病，糖尿病和炎症。 MV在红细胞衰老过程中似乎也起着不可或缺的作用。但是，提高我们对MV生物学知识并因此充分利用其临床潜力的主要障碍是缺乏准确和标准化的MV分析方法。我们最近开发了一个新的，基于纳米技术的诊断平台，称为“ DMR”（诊断磁共振）。通过采用核磁共振原理（NMR），DMR设备测量样品的横向松弛，从而用分子特异性磁性纳米颗粒（MNP）标记生物学靶标。通过系统地开发优化的MNP和基于芯片的微型NMR系统，DMR技术现已显着提高，以提供敏感的细胞分子分析。在这些成就的基础上，该提案的总体目标是适应并进一步推进DMR平台，以直接从全血中直接从全血中对MV进行快速检测和多重分析。我们将特别关注以下 目标。在AIM 1中，我们将综合新的磁性纳米器和测定方法，这些方法将允许MV靶标的高效和选择性MNP标记。在AIM 2中，我们将实施与复杂的微流体集成的小型NMR系统。该系统将旨在使MV分析完全在单个芯片上执行；它将直接从全血中分离MV，用MNPS标记MV，并在靶向的MV上进行NMR测量。在AIM 3中，优化的纳米器和设备都将应用于血液产品中红细胞衍生的MV的检测和全面分析。这项研究将提高我们对血液衰老的生物学的理解，这可能会改善血液产物质量和输血安全性。我们设想在生命科学和临床实践中提出的DMR-MV技术具有广泛的诊断潜力。通过促进来自不同细胞起源的MV的快速和定量分子分析，该技术可以实现早期疾病检测和治疗监测。反过来，这可以通过提供有关个别患者的细胞/分子特征的有价值的信息来加快创造个性化治疗的进步。