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（由申请人提供）：MicroRNA (miRNA) 作为研究癌症发生和进展以及早期检测的生物标志物已展现出巨大的前景，但由于分析方面具有挑战性，这些小分子尚未被采用到临床实践的早期诊断中。实验室经常采用基于微阵列的技术、Northern 印迹、测序和 qRT-PCR 分析，涉及复杂、耗时且昂贵的过程，需要特殊的实验室设备，因此需要开发可提供更多信息的替代分子检测策略。。尽管与胃肠道（GI）癌症相关的 miRNA 将被用作模型系统，但所提出的分子分析技术将具有普遍适用性。我们将开发一种基于“反向分子哨兵”(iMS) 方案的新型分子分析技术，使用表面增强拉曼散射 (SERS) 检测，将 miRNA 测试从传统的检测转移到其他类型的癌症和其他 miRNA 探针。基于 RT-PCR 实验室检测方案的分子分析和检测技术更简单、更快速、更具成本效益该项目的具体目标是： (1) 开发新的 iMS 分子分析方法，用于分子生物标志物的多重检测。由于具有高特异性和窄的SERS峰，我们将使用iMS技术同时检测多个microRNA序列作为食管癌的简单快速的多重筛查工具的优点（特异性、灵敏度、探针稳定性）。的(2) 应用和评估 iMS 分子分析方法，利用临床样本诊断和研究胃肠道癌症的发生和进展。在临床队列中，RT-PCR 将用作诊断的金标准，纳米探针将针对 RT-PCR 进行测试，以确保诊断准确性。更快、更高效与现有系统相比，它能够提供更高水平的灵敏度和更高水平的特异性和多重分析能力，以筛选与巴雷特食管和食管癌相关的 microRNA。总之，所提出的分子分析技术代表了一项重大创新，在癌症领域具有巨大的变革潜力。 iMS 方法是一种“同质”测定（即不需要去除样品，因此不需要微流体）。此外，目标不需要标记，从而降低了成本。新型分子分析技术的优势将允许检测多个 miRNA 生物靶标，用于癌症发展和进展的研究，并最终使其未来的临床转化能够在护理点提供更快、更准确的诊断。