Clinical platform for high-throughput analyses of extracellular vesicles

细胞外囊泡高通量分析的临床平台

基本信息

  • 批准号:
    9906460
  • 负责人:
  • 金额:
    $ 11.07万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2018
  • 资助国家:
    美国
  • 起止时间:
    2018-08-02 至 2023-07-31
  • 项目状态:
    已结题

项目摘要

Extracellular vesicles (EVs) have emerged as a promising surrogate for the tissue biopsy, potentially enabling non-invasive, real-time cancer monitoring. Most cancer cells release large numbers of EVs into circulation that carry molecular constituents of the parent tumor. Analyzing EVs could thus offer new avenues to assess tumor burden and tumor heterogeneity. Adoption of EV analyses into a clinical workflow, however, is impeded by the lack of standardized, practical methods. Conventional assay tools (e.g., ultracentrifugation, Western blotting, ELISA) require large sample volumes and extensive processing; they are impractical for clinical applications. Variations in sample handling and testing protocols often lead to inconsistent and variable findings. The goal of this proposal is i) to address such technical challenges by advancing a robust platform for EV protein analyses, and ii) to rigorously evaluate EVs' clinical value as cancer biomarkers. We formed a strategic academic-industry partnership to achieve this goal: Exosome Diagnostics, an industry leader in EV-based cancer diagnostics, offering ready capacity to develop and manufacture in-vitro diagnostic medical devices; and the Center for Systems Biology at Massachusetts General Hospital, a pioneer in developing novel analytical technologies for EV analyses. These teams will bring in their multidisciplinary expertise, innovative technologies and complementary resources to carry out the following translational projects: First, we will build a sensitive, high-throughput platform for EV protein screening. The system will adopt our recently developed nPLEX (nano-plasmonic exosome) technology that is based on novel surface plasmon resonance (SPR) through nanohole structures. Our initial study showed that nPLEX achieved >1000-fold higher sensitivity than conventional methods and yet consumed scant sample volumes (0.1 μL). The new nPLEX system will have expanded analytical capacity and scalability for commercial production. We will design a new SPR chip and a detection instrument for massively parallel EV screening, and also establish standardized assay protocols. Leveraging the developmental and regulatory expertise of Exosome Diagnostics, the resulting platform will be ready for translation into clinical diagnostic laboratories. Second, we will perform a targeted clinical study, particularly testing whether EV protein signatures can be used as a biomarker for cancer detection and treatment monitoring. We will collect circulating EVs from ovarian cancer patients undergoing therapies, and track serial changes of EV protein levels. We will ensure assay reliability and reproducibility to deliver clinically translatable EV diagnostics. We will follow stringent quality control on device design and sample processing, accrue well-annotated patient and control samples, and perform multisite testing. The technical and scientific outcomes of this research could have a significant translational impact in cancer, establishing a robust, highly specific assay to guide treatment decision and assess therapeutic efficacy. Exosome Diagnostics will provide regulatory guidance as well as channels to market new tests and devices.
细胞外囊泡(EV)已成为组织活检的一种有前途的替代品, 实现非侵入性的实时癌症监测。大多数癌细胞释放大量的EV进入 携带母体肿瘤分子成分的血液循环。因此,分析电动汽车可以提供新的途径 以评估肿瘤负荷和肿瘤异质性。然而,在临床工作流程中采用EV分析, 由于缺乏标准化、实用化的方法,常规的化验工具(例如,超离心, 蛋白质印迹,ELISA)需要大的样品体积和广泛的处理;它们对于 临床应用。样品处理和测试方案的变化通常导致不一致和可变的结果。 发现。该提案的目标是:i)通过推进一个强大的平台来应对这些技术挑战, EV蛋白分析,和ii)严格评估EV作为癌症生物标志物的临床价值。我们成立了一个 战略性学术-产业合作伙伴关系,以实现这一目标:外泌体诊断,行业领导者, 基于EV的癌症诊断,提供开发和制造体外诊断医疗器械的现成能力 马萨诸塞州总医院的系统生物学中心,开发新型 用于EV分析的分析技术。这些团队将带来他们的多学科专业知识,创新 技术和互补资源,开展以下转化项目:首先,我们将建立 用于EV蛋白筛选的灵敏、高通量平台。该系统将采用我们最近开发的 基于新型表面等离子体共振(SPR)的nPLEX(纳米等离子体外泌体)技术 通过纳米孔结构。我们的初步研究表明,nPLEX的灵敏度比 常规方法,但消耗少量样品体积(0.1 μL)。新的nPLEX系统将具有 扩大分析能力和商业生产的可扩展性。我们将设计一个新的SPR芯片和一个 检测仪器,用于大规模平行EV筛查,并建立标准化的检测方案。 利用外泌体诊断的开发和监管专业知识,由此产生的平台将 准备转化为临床诊断实验室。第二,我们将进行有针对性的临床研究, 特别是测试EV蛋白特征是否可以用作癌症检测的生物标志物, 治疗监测。我们将从接受治疗的卵巢癌患者中收集循环EV, 跟踪EV蛋白水平的连续变化。我们将确保检测的可靠性和重现性, 临床上可翻译的EV诊断。我们将遵循严格的质量控制的设备设计和样品 处理、累积注释良好的患者和对照样本,并执行多点测试。技术 这项研究的科学成果可能对癌症产生重大的转化影响, 一个强大的,高度特异性的检测,以指导治疗决策和评估治疗效果。外来体 诊断将提供监管指导以及市场新测试和设备的渠道。

项目成果

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Hakho Lee其他文献

Hakho Lee的其他文献

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{{ truncateString('Hakho Lee', 18)}}的其他基金

High-throughput Phenotyping of iPSC-derived Airway Epithelium by Multiscale Machine Learning Microscopy
通过多尺度机器学习显微镜对 iPSC 衍生的气道上皮进行高通量表型分析
  • 批准号:
    10659397
  • 财政年份:
    2023
  • 资助金额:
    $ 11.07万
  • 项目类别:
3D Fourier Imaging System for High Throughput Analyses of Cancer Organoids
用于癌症类器官高通量分析的 3D 傅里叶成像系统
  • 批准号:
    10577796
  • 财政年份:
    2022
  • 资助金额:
    $ 11.07万
  • 项目类别:
3D Fourier Imaging System for High Throughput Analyses of Cancer Organoids
用于癌症类器官高通量分析的 3D 傅里叶成像系统
  • 批准号:
    10358186
  • 财政年份:
    2022
  • 资助金额:
    $ 11.07万
  • 项目类别:
High-throughput Integrated Magneto-electrochemical Exosome (HiMEX) platform to identify neurodevelopmental markers associated with pre and postnatal oxycodone exposure
高通量集成磁电化学外泌体 (HiMEX) 平台,用于识别与产前和产后羟考酮暴露相关的神经发育标志物
  • 批准号:
    10017043
  • 财政年份:
    2019
  • 资助金额:
    $ 11.07万
  • 项目类别:
Clinical platform for high-throughput analyses of extracellular vesicles
细胞外囊泡高通量分析的临床平台
  • 批准号:
    10462501
  • 财政年份:
    2018
  • 资助金额:
    $ 11.07万
  • 项目类别:
Clinical platform for high-throughput analyses of extracellular vesicles
细胞外囊泡高通量分析的临床平台
  • 批准号:
    9754806
  • 财政年份:
    2018
  • 资助金额:
    $ 11.07万
  • 项目类别:
Clinical platform for high-throughput analyses of extracellular vesicles
细胞外囊泡高通量分析的临床平台
  • 批准号:
    10224771
  • 财政年份:
    2018
  • 资助金额:
    $ 11.07万
  • 项目类别:
Multiplexed exosome analyses with DNA barcoding
使用 DNA 条形码进行多重外泌体分析
  • 批准号:
    9266748
  • 财政年份:
    2016
  • 资助金额:
    $ 11.07万
  • 项目类别:
Multiplexed exosome analyses with DNA barcoding
使用 DNA 条形码进行多重外泌体分析
  • 批准号:
    9099367
  • 财政年份:
    2016
  • 资助金额:
    $ 11.07万
  • 项目类别:
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
  • 财政年份:
    2012
  • 资助金额:
    $ 11.07万
  • 项目类别:

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