Nano-plasmonic technology for high-throughput single exosome analyses

用于高通量单一外泌体分析的纳米等离子体技术

• 批准号: 10224113
• 负责人: Hyungsoon Im
• 金额: $ 18.27万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-08 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10224113
• 关键词: Adoption; Affinity; Age; Ascites; Biological; Biological Assay; Biological Models; Blood; Body Fluids; Cancer Diagnostics; Cancer Patient; Cancer cell line; Cells; Clinical; Clinical Research; Detection; Dimensions; Emerging Technologies; Engineering; Exhibits; Fluorescence; Genetic Materials; Glass; Goals; Gold; Heterogeneity; Human; Immobilization; Individual; Label; Ligands; Lipids; Liquid substance; Malignant Neoplasms; Malignant neoplasm of ovary; Measurement; Membrane; Messenger RNA; Modality; Molecular; Molecular Analysis; Molecular Probes; Molecular Profiling; Monitor; Nanostructures; Periodicity; Pharmaceutical Preparations; Phospholipids; Plasma; Primary Neoplasm; Process; Protein Analysis; Proteins; RNA analysis; RNA marker; Resistance; Resolution; Sampling; Sensitivity and Specificity; Signal Transduction; Slide; Specificity; Specimen; Structure; Surface; Surface Plasmon Resonance; System; Techniques; Technology; Testing; Tumor-Derived; Urine; Vesicle; base; cancer care; cancer cell; cancer diagnosis; cancer invasiveness; cancer therapy; circulating biomarkers; detection assay; detection sensitivity; exosome; experience; extracellular vesicles; high throughput analysis; high throughput technology; innovation; insight; lithography; minimally invasive; multiplex detection; nanoplasmonic; nanorod; nanoscale; neoplastic cell; next generation; personalized cancer therapy; plasmonics; protein biomarkers; prototype; response; routine screening; screening; sensor; sex; targeted biomarker; tool; transmission process; treatment response; tumor; validation studies

Extracellular vesicles (EVs) present new opportunities for cancer diagnoses and treatment monitoring as circulating biomarkers. These cell-derived membrane-bound vesicles are abundantly present in biological fluids and carry cell-specific cargos, such as lipids, proteins and genetic materials, which can be harnessed as a minimally invasive means to probe the molecular status of tumors. EV analyses, however, poses unique technical challenges due to EVs' nanometer size, heterogeneity, and presence in vast biological background. We have previously developed nanoplasmonic sensing platforms that can rapidly and sensitively detect tumor EVs directly from clinical samples. Drawing upon our previous experiences with the prototypes, the goal of this application is to further advance the cutting-edge nanoplasmonics technology for comprehensive molecular analyses at single EV resolution. Specifically, we will 1) adapt gold nanorod structures that provides higher sensitivity down to a single molecular level and 2) integrate plasmon-enhanced fluorescence detection for multiplexed EV protein and RNA analyses in single EVs. We hypothesize that the approach will be more sensitive and comprehensive in profiling EV protein and mRNA markers than is currently possible. Using an ovarian cancer as a model system, we will evaluate 1) system implementation for high-throughput single EV detection; 2) reliable detection of tumor-derived EVs in clinical samples; and 3) multiplexed EV marker screening on tumor-derived EVs. If successful, the developed platform would render a more accessible tool to significantly accelerate the clinical adoption of EV analyses as routine screening tests for cancer care in clinical settings.

细胞外小泡(EVS)为癌症诊断和治疗监测提供了新的机会 循环中的生物标志物。这些细胞衍生的膜结合囊泡大量存在于生物体液中。 并携带细胞特有的货物，如脂质、蛋白质和遗传物质，这些可以作为一种 微创意味着探测肿瘤的分子状态。然而，电动汽车分析提出了独特的 由于电动汽车的纳米尺寸、异质性以及存在于广泛的生物背景中的技术挑战。 我们之前已经开发了纳米等离子传感平台，可以快速而灵敏地检测肿瘤 EVS直接从临床样本中提取。根据我们之前关于原型的经验，这一目标是 应用是进一步推进合成分子的前沿纳米等离子体技术 在单一电动汽车分辨率下进行分析。具体地说，我们将1)采用金纳米棒结构，以提供更高的 灵敏度降至单分子水平和2)集成等离子体增强荧光检测 在单个EVS中进行多路EV蛋白质和RNA分析。我们假设这种方法将会有更多 在分析EV蛋白和mRNA标记物方面比目前可能的更灵敏和全面。使用 以卵巢癌为模型系统，我们将评估1)系统实现的高通量单EV 检测；2)在临床样本中可靠地检测肿瘤来源的EV；以及3)多重EV标志物 肿瘤来源的EVS的筛选。如果成功，开发的平台将提供一个更易于访问的工具 显著加快EV分析作为临床癌症治疗常规筛查试验的临床采用 设置。