Integrated Microfluidic Exosome Profiling for Early Detection of Cancer

用于癌症早期检测的集成微流控外泌体分析

• 批准号: 9114066
• 负责人: Yong Zeng
• 金额: $ 21.23万
• 依托单位: UNIVERSITY OF KANSAS LAWRENCE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9114066
• 关键词: Address; Area; Benign; Biological; Biological Assay; Biological Markers; Biological Process; Biology; Biomedical Technology; Blood; Blood Plasma Volume; Blood specimen; Cancer Diagnostics; Cancer Patient; Characteristics; Chemicals; Classification; Clinical; Consumption; Cytolysis; Detection; Development; Diagnostic; Diagnostic Neoplasm Staging; Disease; Disease model; Early Diagnosis; Enzyme-Linked Immunosorbent Assay; Enzymes; Exhibits; Goals; Gold; Health; Human; Immunoassay; Immunosuppressive Agents; In Situ; Liquid substance; Malignant Neoplasms; Malignant neoplasm of ovary; Manuals; Measurement; Membrane Proteins; Messenger RNA; Methods; MicroRNAs; Microfluidics; Molecular; Molecular Analysis; Monitor; Operative Surgical Procedures; Ovarian Serous Adenocarcinoma; Performance; Play; Process; Proteins; Protocols documentation; Research; Role; Sample Size; Sampling; Screening for cancer; Sensitivity and Specificity; Signaling Protein; Staging; Survival Rate; System; Techniques; Technology; Testing; Time; Tumor Antigens; Tumor Markers; Tumor-Derived; Ultracentrifugation; Unresectable; Vesicle; Western Blotting; anticancer research; base; biomarker panel; blood-based biomarker; cancer biomarkers; cancer diagnosis; cancer type; cell type; clinical investigation; effective therapy; exosome; extracellular vesicles; improved; innovation; micro-total analysis system; microsystems; minimally invasive; nanoparticle; neoplastic cell; new technology; novel; novel marker; personalized cancer therapy; point of care; protein profiling; response; scale up; screening; treatment response; tumor; tumorigenesis

DESCRIPTION (provided by applicant): Detection of asymptomatic early-stage disease is critical for effective treatment of most cancer types. For instance, when detected at Stage I, the 5-year survival rate for ovarian cancer patients is greater than 90%, versus 20% for advanced-stage disease. However, currently most cancers are diagnosed at late stages, which underscore the pressing need of novel biomarkers, strategies and technologies. Probing circulating exosomes is emerging as a new paradigm for non-invasive cancer diagnosis and monitoring of treatment response, because of growing evidences of their biological functions and clinical implications in tumorigenesis and progression. Tumor-derived exosomes accumulate in human blood and are enriched in a selective repertoire of biomolecules, including signaling proteins, enzymes, tumor antigens, miRNAs, and mRNAs. The constitutive release and exosome enrichment of certain tumor markers present distinctive opportunities for early cancer diagnosis. Despite the potential for cancer diagnosis, biology and clinical value of exosomes remain largely unknown, due to the challenges in efficient isolation, molecular classification and comprehensive characterization of exosomes. Here we propose to tackle this major roadblock by developing an innovative microfluidic technology that enables selective isolation, subpopulation classification by surface protein topography, and in situ multiplexed barcode protein profiling of exosomes, all streamlined in a "sample-in-answer-out" system. The project consists of two specific aims: 1) Develop an integrated Microfluidic Exosome Profiling Assay (MEPA) for molecular analysis of circulating exosomes in microliter volumes of plasma; and 2) Characterize and validate MEPA for potential use in early detection of cancer using ovarian cancer as the disease model. This research, if successful, will yield a transformative technology that can substantially improve the analytical performance for molecular characterization of tumor-derived exosomes while overcoming the constraints of exosome loss/damage during isolation, analysis throughput, and sample consumption in conventional protocols. Thus the technology should offer an unprecedented ability to accelerate the exosome research, opening new opportunities to probing the biology of a tumor noninvasively and to developing novel reliable biomarkers for screening and early detection of cancer.

描述（由申请人提供）：无症状早期疾病的检测对于大多数癌症类型的有效治疗至关重要。例如，当在I期检测时，卵巢癌患者的5年生存率大于90%，而晚期疾病为20%。然而，目前大多数癌症都是在晚期才被诊断出来的，这突出了对新的生物标志物、策略和技术的迫切需求。由于越来越多的证据表明其在肿瘤发生和发展中的生物学功能和临床意义，探测循环外泌体正在成为非侵入性癌症诊断和监测治疗反应的新范式。肿瘤来源的外泌体在人血液中积累，并富含生物分子的选择性库，包括信号传导蛋白、酶、肿瘤抗原、miRNA和mRNA。某些肿瘤标志物的组成性释放和外泌体富集为早期癌症诊断提供了独特的机会。尽管外泌体具有癌症诊断的潜力，但由于外泌体的有效分离、分子分类和综合表征方面的挑战，外泌体的生物学和临床价值在很大程度上仍然未知。在这里，我们建议通过开发一种创新的微流体技术来解决这一主要障碍，该技术能够通过表面蛋白质形貌进行选择性分离，亚群分类，以及外泌体的原位多重条形码蛋白质分析，所有这些都在“样品输入-回答”系统中进行了简化。该项目包括两个具体目标：1）开发一种集成的微流体外泌体分析测定（MEPA），用于微升体积血浆中循环外泌体的分子分析; 2）表征和验证MEPA，以卵巢癌作为疾病模型，用于早期检测癌症的潜在用途。这项研究如果成功，将产生一种变革性的技术，可以大大提高肿瘤源性外泌体分子表征的分析性能，同时克服传统方案中分离期间外泌体损失/损伤、分析通量和样品消耗的限制。因此，该技术应该提供前所未有的能力来加速外泌体研究，为非侵入性地探索肿瘤生物学和开发用于癌症筛查和早期检测的新型可靠生物标志物提供新的机会。