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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

基本信息

批准号：
9795485
负责人：
Hyungsoon Im
金额：
$ 21.92万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
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/9795485
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 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 protein profiling prototype response routine screening screening sensor sex targeted biomarker tool transmission process treatment response tumor validation studies

项目摘要

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.

细胞外囊泡（EV）为癌症诊断和治疗监测提供了新的机会，循环生物标志物。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异性的货物，如脂质，蛋白质和遗传物质，可以作为一种微创手段来探测肿瘤的分子状态。然而，EV分析提出了独特的由于EV的纳米尺寸、异质性和存在于广泛的生物背景中，因此存在技术挑战。我们之前已经开发了纳米等离子体传感平台，可以快速灵敏地检测肿瘤直接来自临床样本的EV。利用我们以前的原型经验，应用是为了进一步推进尖端的纳米等离子体技术，以单一EV分辨率进行分析。具体来说，我们将1）适应金纳米棒结构，提供更高的灵敏度低至单个分子水平，和2）集成等离子体增强荧光检测，在单个EV中进行多重EV蛋白和RNA分析。我们假设，这种方法将更加在分析EV蛋白和mRNA标志物方面比目前可能的更敏感和全面。使用卵巢癌作为一个模型系统，我们将评估1）高通量单EV的系统实现检测; 2）可靠地检测临床样品中的肿瘤来源的EV;和3）多重EV标志物筛选肿瘤来源的EV。如果成功，开发的平台将提供一个更容易使用的工具，显著加速EV分析作为临床癌症护理常规筛查试验的临床采用设置.