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Nanoplasmonics-based molecular analysis tool for molecular biomarkers of cancer

基于纳米等离子体的癌症分子生物标志物分子分析工具

基本信息

批准号：
9321908
负责人：
Tuan Vo-Dinh
金额：
$ 23.7万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-08 至 2018-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9321908
关键词：
Adopted Area Barrett Esophagus Biological Assay Biological Markers Biological Models Biosensing Techniques Blood Blood specimen Clinic Clinical Competitive Binding Consumption DNA Detection Development Diagnosis Diagnostic Diagnostic tests Early Diagnosis Early Intervention Endoscopy Enrollment Esophageal Esophageal Adenocarcinoma Excision Future Goals Gold Human Incidence Investigation Label Malignant Neoplasms Malignant neoplasm of esophagus Malignant neoplasm of gastrointestinal tract Methods MicroRNAs Molecular Molecular Analysis Molecular Conformation Nanotechnology Northern Blotting Patients Polymerase Chain Reaction Process Research Resources Reverse Transcriptase Polymerase Chain Reaction Reverse Transcription Risk Risk Factors Sampling Scheme Screening for cancer Sentinel Shapes Signal Transduction Specificity Surface System Systems Analysis Techniques Technology Testing Time Tissues Translating accurate diagnosis anticancer research base cancer biomarkers cancer diagnosis cancer type clinical Diagnosis clinical diagnostics clinical practice clinical risk clinical translation cohort cost cost effective design diagnosis standard diagnostic accuracy diagnostic screening gastrointestinal improved innovation interest laboratory equipment microRNA biomarkers minimally invasive molecular marker multiplex detection nanoplasmonic nanoprobe new technology new therapeutic target novel novel diagnostics novel strategies peripheral blood plasmonics point of care public health relevance repository screening small molecule stem surveillance strategy tool

项目摘要

DESCRIPTION (provided by applicant): MicroRNAs (miRNAs) have demonstrated great promise as biomarkers for investigation of cancer development and progression and for early detection, yet these small molecules have not been adopted into early diagnostics for clinical practice because of challenging analytical aspects in the lab. Microarray-based technology, Northern blotting, sequencing, and qRT-PCR analyses are often employed, involving elaborate, time-consuming and expensive processes that require special laboratory equipment. There is a need to develop alternative molecular assay strategies that may offer more advantages over conventional methods and have the potential to enhance research in the areas of early detection and screening, and clinical diagnosis. Although miRNAs related to gastrointestinal (GI) cancer will be used as the model system, the proposed molecular analysis technology will be applicable generally to other types of cancers and other miRNA probes. We will develop a novel molecular analysis technology based on the "Inverse Molecular Sentinel" (iMS) scheme using surface-enhanced Raman scattering (SERS) detection that will move miRNA testing from an RT-PCR lab-based based assay scheme to a molecular analysis and testing technology that is simpler, faster and more cost effective. The specific aims of this project are: (1) Develop the new iMS molecular analysis method for multiplex detection of molecular biomarkers, miRNAs. Due to the highly specific and narrow SERS peaks, we will use the iMS technique to simultaneously detect multiple microRNA sequences as a simple and rapid multiplex screening tool for esophageal cancer. The analytical features of merit (specificity, sensitivity, probe stability) of the new molecular analysis technology will be investigated in detail. (2) Apply and evaluate the iMS molecular analysis method for diagnosis and investigation of GI cancer development and progression using clinical samples. We will demonstrate the usefulness of the iMS technique to detect miRNAs in peripheral blood samples from patients with known cancer diagnosis and from controls. In the clinical cohort, RT-PCR will be used as the gold standard for diagnosis, and nanoprobes will be tested against RT-PCR for diagnostic accuracy. The iMS biosensing system has the potential to be faster and more efficient than currently available systems, and is capable of providing great sensitivity with higher levels of specificity and multiplexing capabilities to screen microRNAs associated with Barrett's esophagus and esophageal cancer. In conclusion, the proposed molecular analysis technology represents a major innovation that has great transformative potential in cancer research, diagnostics and screening. The iMS approach is a `homogenous' assay (i.e., requiring no sample removal, and thus no microfluids). Also, the targets do not need to be labeled, thus reducing cost and complexity. The advantages of the novel molecular analysis technology would allow detection of multiple miRNA biotargets for research on cancer development and progression, and ultimately enable its future clinical translation to render a faster and more accurate diagnosis at point-of-care settings.

描述(申请人提供)：microRNAs(MiRNAs)已显示出作为研究癌症发展和进展以及早期检测的生物标志物的巨大前景，但由于实验室中具有挑战性的分析方面的原因，这些小分子尚未被用于临床实践的早期诊断。基于微阵列的技术、Northern杂交、测序和qRT-PCR分析经常被使用，涉及需要特殊实验室设备的复杂、耗时和昂贵的过程。有必要开发替代的分子检测策略，这种策略可以提供比传统方法更多的优势，并有可能加强在早期检测和筛查以及临床诊断领域的研究。虽然与胃肠道(GI)癌相关的miRNAs将被用作模型系统，但拟议的分子分析技术将普遍适用于其他类型的癌症和其他miRNA探针。我们将开发一种新的分子分析技术，该技术基于使用表面增强拉曼散射(SERS)检测的“反向分子哨兵”(IMS)方案，将miRNA检测从基于RT-PCR实验室的分析方案转变为更简单、更快速和更具成本效益的分子分析和测试技术。本项目的具体目标是：(1)发展新的IMS分子分析方法，用于分子生物标志物miRNAs的多重检测。由于SERS峰高度特异和窄，我们将使用IMS技术同时检测多个microRNA序列，作为一种简单快速的食道癌多重筛查工具。将详细研究新的分子分析技术的优点(特异性、灵敏度、探针稳定性)的分析特征。(2)利用临床标本对IMS分子分析方法在胃肠道肿瘤诊断和研究中的应用进行评价。我们将展示IMS技术在检测已知癌症诊断患者和对照患者外周血样本中miRNAs的有效性。在临床队列中，RT-PCR将被用作诊断的金标准，纳米探针将与RT-PCR进行诊断准确性的测试。IMS生物传感系统有可能比目前可用的系统更快、更高效，并能够提供极高的灵敏度、更高水平的特异性和多路复用能力来筛选与Barrett‘s食道和食道癌相关的microRNA。总之，提出的分子分析技术是一项重大创新，在癌症研究、诊断和筛查方面具有巨大的变革潜力。IMS方法是一种“均质”分析方法(即不需要去除样品，因此不需要微流体)。此外，不需要对目标进行标记，从而降低了成本和复杂性。新的分子分析技术的优势将允许检测用于癌症发展和进展研究的多个miRNA生物靶点，并最终使其未来的临床翻译能够在护理地点环境中提供更快和更准确的诊断。