Imaging Polarimeter for Simultaneous Determination of Luminescence Polarization

用于同时测定发光偏振的成像旋光仪

基本信息

批准号：
8904027
负责人：
Bart E Kahr
金额：
$ 18.87万
依托单位：
NEW YORK UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-01 至 2017-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8904027
关键词：
Address Affect Anisotropy Benchmarking Beryllium Binding Biological Biological Assay Biological Monitoring Biopolymers Birefringence Characteristics Chromatin Circular Dichroism Circular Dichroism Spectroscopy Collection Complex DNA Devices Disease Elements Ensure Event Fluorescence Fluorescence Polarization Fourier Analysis Hand Health Heart Image In Situ Lead Left Ligands Light Lighting Measurement Measures Methods Microscope Molecular Conformation Morphologic artifacts Nucleic Acids Optical Methods Optics Organism Pharmaceutical Preparations Pharmacologic Substance Phase Plastics Poison Positioning Attribute Premalignant Property Proteins Quartz Research Personnel Residual state Sampling Scanning Scheme Science Signal Transduction Solutions Source Speed Staining method Stains Study models Techniques Time Tissues absorption analog analytical tool base charge coupled device camera chiral molecule design detector dichroism drug development drug use screening efficacy testing expectation experience fluorescence imaging high throughput screening instrument instrumentation light emission luminescence novel polarimeter polarimetry polarized light receptor response screening small molecule small molecule libraries stereochemistry transmission process

项目摘要

DESCRIPTION (provided by applicant): Circular dichroism (CD) is an important analytical tool for the analysis of drugs and their binding to biopolymers. It is based on the differential absorption of left and right helical light by chiral molecules such as many small molecule drugs, as well as proteins and nucleic acids for examples. Unfortunately, CD, and related phenomena that are related to luminescence -- the emission of light -- fluorescence detected circular dichroism (FDCD) and circularly polarized emission (CPE) of light, are not amenable to high-throughput discovery platforms in which a drug is screened against a variety of conditions of synthesis, or in its interactions with a variety of biological active receptors. This is because th plastic multi-well plates commonly used in optical analysis have residual strain and associated refraction anisotropy that corrupts comparisons of transmission of left and right circularly polarized light. Here, we aim to build an instrument that can be used for screening drugs with CD analysis even in multi-well plates. The instrument requires a vertical design adapted to well plates. It also relies on more than one modulator of the polarization state of light before and after the sample and the necessary experience with analyzing the complex signal that is produced during such an arrangement. (Typically CD spectrometers use a single modulator). The instrument will be significant because CD, FDCD, and CPE are all powerful probes of drug-biomolecule interactions. Thus, high-throughput screening assays based on the simultaneous acquisition of these parameters will broadly impact the biomedical field. It will be powerful because the simultaneous collections of a variety of distinct but related physical phenomena will increase the accuracy of our assays and obviate the need for counter-screening to further differentiate positive hits. We further devise a strategy for imaging each of these parameters, even though their measurement is based on polarization modulators that are faster than imaging cameras. At the heart of this strategy is a stroboscopic LED array that also serves to compute the Fourier analysis necessary for deriving the requisite optical properties. Drugs are increasing discovered in serial fashion through synthesis of via chemical libraries, screening of existing compounds, or via assays of efficacy with respect to the binding to a particular target. Our instrument with be of public benefit in speeding up the pipeline from discovery of active compounds to active pharmaceuticals associated with all manner of disease and illness. We will test the efficacy of our so-called Mueller matrix fluorimeter by examining DNA and chromatin in solution, and in organisms, and their responses in the presence of agents known to affect conformational changes in nucleic acids.