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Cancer molecular analysis using quantum dots

使用量子点进行癌症分子分析

基本信息

批准号：
9076630
负责人：
Xiaohu Gao
金额：
$ 23.52万
依托单位：
UNIVERSITY OF WASHINGTON
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：
2015-06-01 至 2018-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9076630
关键词：
Address Affect Antibodies Antigens Biological Markers Biomedical Research Buffers Cells Chemicals Clinical Communication Complex Consumption Cultured Cells Custom DNA DNA Probes Development Diagnosis Diagnostic Diagnostic Procedure Disease Emerging Technologies Ensure Evaluation Event Functional disorder Gene Chips Generations Goals Health Heterogeneity Human Human body Image Imaging technology Immune Immunofluorescence Immunologic In Situ Individual Kinetics Label Libraries Malignant Neoplasms Masks Mass Spectrum Analysis Mediating Medicine Methodology Methods Microscopy Modification Molecular Molecular Analysis Molecular Profiling Molecular Target Mutation Optics Pathologic Processes Performance Phenotype Portraits Preparation Process Production Property Protein Microchips Proteomics Protocols documentation Quantum Dots Reagent Reporter Reporting Research Resolution Reverse Transcriptase Polymerase Chain Reaction Route Sampling Semiconductors Signal Pathway Signal Transduction Specificity Specimen Staging Staining method Stains Systems Biology Technical Expertise Techniques Technology Time Tissues Translations Tumor Biology Tumor Markers Two-Dimensional Gel Electrophoresis Work accurate diagnosis antibody engineering anticancer research antigen antibody binding base body system cancer biomarkers cancer cell cell fixing clinical Diagnosis clinical practice cost effective flexibility hybrid antibody imaging biomarker innovation instrumentation neoplastic cell next generation novel optical imaging outcome forecast prognostic protein expression response screening self assembly success targeted treatment technology development therapy development tool tumor heterogeneity weapons

项目摘要

DESCRIPTION (provided by applicant): Comprehensive molecular characterization of individual cells is instrumental for understanding cell pathophysiology and our ability to diagnose and control the progression of complex pathological processes, such as cancer. In principle, tagging each biomolecule with a unique reporter probe and detecting its localization with high sensitivity at sub-cellular resolution can achieve this goal. Yet, none of the conventional biomedical techniques can stand up to the challenge, suffering from a limitation in the number of molecular targets that can be analyzed simultaneously, providing limited single cell information, and often utilizing qualitative rather than quantitative analysis. Translation of novel nanoparticl-based imaging technologies into biomedical research and clinical diagnostics promises to provide powerful tools for addressing phenotypic heterogeneity of tumors, opening access to studying low-abundance events often masked or completely erased by batch processing, and elucidating cancer biomarker signatures for accurate diagnosis and targeted therapy. To deliver on this promise, we recently invented a multicolor multicycle molecular profiling technology based on cyclic imaging of tens to hundreds of tumor biomarkers in single cells with optical imaging resolution (Nat. Commun. 2013 & Nat. Protocols 2013). Built on this work and another advance we made on DNA strand mediated displacement for fast and multicycle analysis (JACS 2011), we propose to explore and develop a new generation of multicolor multicycle proteomic technology with fast yet mild destaining condition. Our approach takes advantage of simple bioconjugation and self-assembly mechanisms for straightforward probe preparation, hybrid antibody-DNA probes for encoding of molecular targets, the unique optical properties of quantum dots for quantitative and multicolor imaging, and the mildness and fast kinetics of DNA toehold- mediated displacement. Unique combination of these features (which are supported by our recent preliminary results) yields simple, but powerful technology that should enable molecular characterization of individual cancer cells in situ, while requiring no specialized technical skills or significant modifications to common staining methodology and imaging instrumentation. As a result, if successful, the proposed QD technology should be readily applicable for a wide range of applications, in particular examination of molecular signaling pathways in cancer cells, evaluation of response to therapy, and development of multiplexed diagnostic and prognostic panels, thus promising to produce a substantial impact in cancer research and clinical practice.