Charge sensitive optical detection for high-throughput study of small molecules

用于小分子高通量研究的电荷敏感光学检测

基本信息

批准号：
9147498
负责人：
NONGJIAN TAO
金额：
$ 38.14万
依托单位：
ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-08-01 至 2019-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9147498
关键词：
Address Affinity Antineoplastic Agents Automation Binding Biochemical Reaction Biological Markers Biomedical Research Biosensing Techniques Cell physiology Charge Collaborations Detection Diagnosis Drug Targeting Drug resistance Electrons Fiber Fluorescence Fluorescent Dyes Geometry Grant Kinetics Label Lead Malignant Neoplasms Manufacturer Name Measures Mechanics Membrane Proteins Methods Molecular Analysis Molecular Weight Mutate Noise Optics Output Peptide Library Performance Pharmaceutical Preparations Pharmacologic Substance Phosphotransferases Post-Translational Protein Processing Preclinical Drug Evaluation Procedures Process Proteins Reaction Reading Research Screening for cancer Serum Signal Transduction Surface System Techniques Technology Testing Time Translations United States National Institutes of Health Validation Work anticancer research biomarker discovery cancer biomarkers cancer initiation cancer therapy commercialization computerized data processing cost data acquisition design drug candidate drug development electric field electronic data high throughput screening innovation instrument molecular mass new technology novel strategies optical fiber receptor screening small molecule success tool tumor progression

项目摘要

PROJECT SUMMARY A technology that can detect and quantify the kinetics of small molecule binding and biochemical reactions, such as post-translational protein modifications, is critical for understanding the mechanisms underlying cancer initiation and progression, for discovering cancer biomarkers, and for screening cancer drug candidates. Currently, the most widely used technology uses fluorescence labels, which is difficult for small molecules with sizes comparable to the fluorescent dyes, especially for quantitative kinetic information. Various label-free techniques have been developed, but their sensitivity diminishes with the molecular mass, making it extremely challenging to detect small molecules and biochemical reactions that involve small mass changes. To address this need, a charge sensitive optical detection (CSOD) technology will be developed in this project. CSOD is compatible with the standard microplate technology, making it attractive for high-throughput screening and analysis of molecular interactions and reactions. The basic principle was established with the support of an IMAT (Innovative Molecular Analysis Technologies for cancer research) R21 grant. In the present R33 project, the team will work closely with collaborators in academic research labs and pharmaceutical companies, and a bioanalytical instrument company to develop and validate the technology for the unmet need. The success of the project will lead to a new label-free high-throughput screening technology for measuring molecular interactions, particularly small molecule interactions and post-translational modifications. These processes are highly important for the research, diagnosis and treatment of cancer.

项目概要一种可以检测和量化小分子结合和生化反应动力学的技术，例如翻译后蛋白质修饰对于理解癌症的机制至关重要启动和进展，发现癌症生物标志物，以及筛选癌症候选药物。目前，应用最广泛的技术是荧光标记，这对于具有小分子特征的小分子来说是困难的。尺寸与荧光染料相当，特别是对于定量动力学信息。各种无标签技术已经开发出来，但它们的灵敏度随着分子质量的增加而降低，使其极其检测涉及小质量变化的小分子和生化反应具有挑战性。致地址为此，本项目将开发一种电荷敏感光学检测（CSOD）技术。 CSOD 是与标准微孔板技术兼容，使其对高通量筛选和分子相互作用和反应的分析。基本原则是在一个组织的支持下制定的 IMAT（癌症研究创新分子分析技术）R21 拨款。在目前的R33项目中，该团队将与学术研究实验室和制药公司的合作者密切合作，生物分析仪器公司开发和验证未满足需求的技术。该项目的成功将带来一种新的无标记高通量筛选技术测量分子相互作用，特别是小分子相互作用和翻译后修饰。这些过程对于癌症的研究、诊断和治疗非常重要。