Streamlined and comprehensive circulating tumor exosome profiling by microfluidic arrayed nanoplasmonic sensors and actuators

通过微流体阵列纳米等离子体传感器和执行器进行简化和全面的循环肿瘤外泌体分析

• 批准号: 10426030
• 负责人: Wei-Chuan Shih
• 金额: $ 66.33万
• 依托单位: UNIVERSITY OF HOUSTON
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-15 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10426030
• 关键词: Address; Animals; Antibodies; Area; Benchmarking; Binding; Biological Markers; Biomedical Research; Biosensing Techniques; Blood; Blood Circulation; Blood Volume; Blood specimen; Cancer Center; Cancer Detection; Cancer Diagnostics; Cancer Patient; Cancer cell line; Cancerous; Cell Membrane Permeability; Cells; Characteristics; Collaborations; Complement; DNA; Data; Detection; Detection of Minimal Residual Disease; Devices; Diagnostic; Disease; Doctor of Medicine; Electroporation; Event; Fluorescence; Fluorescent Probes; Gastroenterology; Genetic Markers; Genetic Materials; Genomics; Goals; Gold; Harvest; Image; Imaging technology; In Situ Hybridization; Individual; Label; Liposomes; Liquid substance; Malignant Neoplasms; Malignant neoplasm of esophagus; Malignant neoplasm of lung; Maps; Measures; Membrane Proteins; MicroRNAs; Microbubbles; Microfluidics; Microscopic; Microscopy; Mission; Molecular; Molecular Profiling; Monitor; Nature; Needles; Neoplasm Circulating Cells; Outcome; PET/CT scan; Paper; Performance; Positioning Attribute; Process; Protocols documentation; RNA; Recurrence; Research; Research Personnel; Residual Neoplasm; Resolution; Sampling; Sensitivity and Specificity; Signal Transduction; Specificity; Surface; Surface Antigens; Surface Plasmon Resonance; Technology; United States National Institutes of Health; Ursidae Family; Validation; Withdrawal; Work; base; biochip; cancer biomarkers; cancer cell; cancer diagnosis; cancer therapy; cancer type; care outcomes; cost; cost effective; density; differential expression; digital; exosome; extracellular vesicles; genetic profiling; imaging system; improved; innovation; insight; liquid biopsy; nano; nano-exosomes; nanobubble; nanodisk; nanoplasmonic; nanovesicle; novel; novel strategies; operation; point of care; prognostic; protein biomarkers; prototype; sensor; spectroscopic imaging; technology development; tool; transcriptomics; tumor; tumor DNA

PROJECT SUMMARY Detection of cancer biomarkers in the blood, known as “liquid biopsy”, can in principle improve the accuracy of measuring nearly invisible “minimal residual disease (MRD)”. Exosomes are cell- excreted extracellular vesicles that contain surface proteins and genetic materials (DNA and RNA) that reflect the characteristics and make-up of the parental cell. Analyzing exosomes would therefore provide direct insight into the state of the cancerous cell. For cancer diagnostics in particular, recent evidences have shown that several micro-RNAs are differentially expressed in CTE. Therefore, unlocking the wealth of information in CTE can potentially cause a paradigm shift. However, current barriers for profiling CTE are the following: (1) all existing technologies require blood withdrawal; (2) involve sophisticated protocols; (3) label-free sizing/counting lacks molecular specificity; (4) provide highly averaged results with high background from normal exosomes, thus leading to poor sensitivity. (5) provide “partial” information: either surface antigen or cargo DNA/RNA, but not both. All of the above has led to a simplistic binary outcome that lacks dynamic range and cannot be used frequently with high sensitivity. We propose a multi-pronged solution on a microfluidic arrayed nanoplasmonic sensor & actuator (MANSA) platform for: (1) streamlined isolation, concentration, and profiling. (2) improve sensitivity by monitoring individual unlabeled exosome binding events with dynamic imaging technology complemented by spectroscopic imaging. (3) improve specificity by profiling both surface antigen and internal D/RNA biomarkers at single exosome level. (4) eliminate blood withdrawal using an integrated needle device. (5) benchmark performance with various sample complexity from cancer cell line extracts to cancer patient blood samples. Our goal is to obtain a high-resolution, digital exosome map with both multiplex surface protein and cargo D/RNA biomarker profiles to facilitate high dynamic range enumeration and boost sensitivity. The proposed technology will become a cost- effective, point-of-care-friendly, translational platform that will address a critical need in early cancer and MRD detection to improve cancer healthcare outcomes. The technology can also be broadly applied to exosome-based diagnostics of non-cancer diseases and basic biomedical research.

项目概要 检测血液中的癌症生物标志物（称为“液体活检”）原则上可以改善 测量几乎看不见的“微小残留病（MRD）”的准确性。外泌体是细胞 排出的细胞外囊泡含有表面蛋白和遗传物质（DNA和RNA） 反映亲本细胞的特征和组成。分析外泌体将 因此可以直接了解癌细胞的状态。用于癌症诊断 特别是，最近的证据表明，几种 micro-RNA 在 热膨胀系数。因此，解锁 CTE 中的丰富信息可能会引发一种范式 转移。然而，目前分析 CTE 的障碍如下：(1) 所有现有技术 需要抽血； (2)涉及复杂的协议； (3) 缺乏无标签尺寸/计数 分子特异性； (4) 提供高度平均的结果，且背景高于正常值 外泌体，从而导致敏感性差。 (5) 提供“部分”信息：任一表面抗原 或货物 DNA/RNA，但不能两者兼而有之。所有上述都导致了一个简单的二元结果，缺乏 动态范围大，不能频繁高灵敏度使用。我们建议多管齐下 微流体阵列纳米等离子体传感器和执行器 (MANSA) 平台上的解决方案用于：(1) 简化隔离、浓缩和分析。 (2)通过监测提高灵敏度 采用动态成像技术辅以单个未标记的外泌体结合事件 光谱成像。 (3) 通过分析表面抗原和内部抗原来提高特异性 单个外泌体水平的 D/RNA 生物标志物。 (4) 使用集成消除抽血 针装置。 (5) 癌细胞系各种样本复杂性的基准性能 提取到癌症患者的血液样本中。我们的目标是获得高分辨率的数字外泌体 具有多重表面蛋白和货物 D/RNA 生物标志物图谱，以促进高 动态范围枚举并提高灵敏度。所提出的技术将成为一种成本- 有效的、护理点友好的转化平台，将满足早期的关键需求 癌症和 MRD 检测可改善癌症医疗保健结果。该技术还可以 广泛应用于基于外泌体的非癌症疾病诊断和基础生物医学 研究。