Meso-plex miRNA and protein profiling for cancer diagnostics using chip-integrate

使用芯片集成进行癌症诊断的中观复合体 miRNA 和蛋白质分析

• 批准号: 8547294
• 负责人: Ryan C Bailey
• 金额: $ 34.77万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8547294
• 关键词: Accounting; Address; American; Behavior; Biological Assay; Biological Markers; Biopsy Specimen; Cancer Diagnostics; Cause of Death; Cell Line; Clinic; Clinical; Clinical Oncology; Clinical Treatment; Complex; DNA; Detection; Diagnosis; Diagnostic; Disease; Disease Progression; Disease remission; Elements; Employee Strikes; Enzyme-Linked Immunosorbent Assay; Freezing; Genomics; Glioblastoma; Gold; Individual; Laboratories; Life; Malignant Neoplasms; Malignant neoplasm of brain; Measurement; Medicine; Messenger RNA; Methodology; Methods; MicroRNAs; Microscopic; Modeling; Molecular; Molecular Profiling; Mutate; Nucleic Acids; Onset of illness; PTEN gene; Pathology; Pathway interactions; Patients; Physicians; Predictive Value; Process; Production; Protein Microchips; Proteins; Proteomics; RNA; Research Personnel; Sampling; Semiconductors; Signal Pathway; Silicon; Specimen; Staging; Surgical Models; Systems Biology; Technology; Time; Translations; Treatment Protocols; United States; Virion; Visual; War; Western Blotting; analytical tool; arm; base; clinically relevant; cost; cost effective; effective therapy; empowered; fighting; improved; insight; photonics; prevent; prognostic; protein expression; protein profiling; public health relevance; sensor; technology validation; theranostics; tool; tool development; tumor; tumor progression

DESCRIPTION (provided by applicant): Armed with an increasingly clear picture of the complex biomolecular mechanisms of disease onset and progression, clinical oncology is poised to realize the promise of personalized medicine by applying multiplexed analytical tools for improved diagnostic, prognostic, and theranostic capabilities. However, there are, in general, a lack of suitable technologies to support multiplexed analyses in the clinic-particularly with respect to the analysis of disease-relevant miRNA and protein panels, despite their clearly established utility. Complex and aberrant mechanisms underlying cancer onset and progression can only be unraveled through the measurement of multiple biomarker signatures and at both the miRNA and protein level, a wealth of putative biomarkers have been identified that show enhanced predictive value when considered together with panels of other markers. However, many discovery technologies are not amenable to the clinic. For miRNAs, qRT-PCR assays are incredibly sensitive, relatively rapid, and cost effective, yet are only able to quantitte expression of a single target per assay. Conversely, microarrays are readily multiplexable, yet quite slow and expensive. Thus, there exists a pressing need for meso-plex diagnostic capabilities whereby focused panels of 10s of miRNAs can be simultaneously interrogated using rapid, cost effective, and highly scalable technologies. Again, there is a striking gap in analyticl capabilities that limit the translation of multiplexed proteomics into the clinic. The gold standar enzyme-linked immunosorbent assay (ELISA), is typically very sensitive, selective, and cost effective, though most often single-plex. Protein microarrays are highly multiplexable, but generally far less sensitive, less selective, and not amenable to the clinical setting. Emerging multiplexed analysis methodologies offer some improvements but have yet to find widespread clinical utility. Chip-integrated silicon photonic sensor arrays have recently emerged as an inherently scalable and multiplexable biomolecular analysis technology, and this application aims to robustly validate this powerful technology for meso-plex cancer diagnostics. Silicon photonic microring resonator arrays, having up to 128 uniquely address-able sensor elements, have been previously utilized to quantitatively detect nucleic acid and protein signatures in multiplexed assay formats and from within complex, clinically-relevant sample matrices. Importantly, the technology has its origin in well-established methods of semiconductor processing and sensor array chips can be scalably fabricated to allow low cost assays (<$1/measurement). Furthermore, the molecular generality of this methodology will be utilized to simultaneous profile micro-RNA (miRNA) and protein expression from the same clinical sample-a transformative capability. Although applicable to any cancer, the lethal brain cancer glioblastoma multiforme will be the laboratory and clinical model. Well-established miRNA and protein biomarkers exist for glioblastoma, thus keeping the proposed efforts entirely on technology validation.

描述（由申请人提供）：随着对疾病发生和进展的复杂生物分子机制越来越清晰的了解，临床肿瘤学有望通过应用多重分析工具来提高诊断、预后和治疗诊断能力，从而实现个性化医疗的前景。然而，总体而言，缺乏合适的技术来支持临床中的多重分析，特别是在疾病相关 miRNA 和蛋白质组的分析方面，尽管它们具有明确的用途。 癌症发病和进展背后的复杂和异常机制只能通过测量多种生物标志物特征来揭示，并且在 miRNA 和蛋白质水平上，已经鉴定出大量假定的生物标志物，当与其他标志物组一起考虑时，这些生物标志物显示出增强的预测价值。然而，许多发现技术并不适合临床。对于 miRNA，qRT-PCR 检测非常灵敏、相对快速且具有成本效益，但每次检测只能定量单个靶标的表达。相反，微阵列很容易进行多路复用，但速度相当慢且昂贵。因此，迫切需要介观复合体诊断能力，从而可以使用快速、成本有效且高度可扩展的技术同时询问 10 个 miRNA 的集中组。同样，分析能力存在显着差距，限制了多重蛋白质组学向临床的转化。金标准酶联免疫吸附测定 (ELISA) 通常非常灵敏、选择性强且成本效益高，但通常是单重测定。蛋白质微阵列具有高度的多重性，但通常灵敏度较低，选择性较低，并且不适合临床环境。新兴的多重分析方法提供了一些改进，但尚未找到广泛的临床实用性。 芯片集成硅光子传感器阵列最近已成为一种本质上可扩展和可复用的生物分子分析技术，该应用旨在稳健地验证这种用于介观复合癌症诊断的强大技术。硅光子微环谐振器阵列具有多达 128 个独特可寻址的传感器元件，之前已被用于以多重分析格式以及复杂的临床相关样品基质中定量检测核酸和蛋白质特征。重要的是，该技术起源于成熟的半导体加工方法，并且传感器阵列芯片可以大规模制造，以实现低成本检测（<1 美元/测量）。此外，该方法的分子通用性将用于同时分析同一临床样本中的微小 RNA (miRNA) 和蛋白质表达——这是一种变革性的能力。尽管适用于任何癌症，致命的脑癌多形性胶质母细胞瘤将成为实验室和临床模型。胶质母细胞瘤存在成熟的 miRNA 和蛋白质生物标志物，因此所提出的努力完全依赖于技术验证。