DEVELOPMENT OF OPTICAL DEVICE FOR USE IN DRUG DISCOVERY

说明(调查人员摘要)：本提案涉及 NINDS的分子神经生物学研究进展 引诱。一种高通量、基于荧光的技术 提出了测量受体介导的细胞反应。我们的目标是 一种可测量细胞内钙离子的光学探针的研制 由荧光染料报告的信号用于大容量应用 作为筛选一些合成或天然化合物。一批 报告染料现在可以用来测量细胞内的钙信号 存在以下表膜受体激活和检测的方法 如果这些信号是由变力或代谢性机制传递的。 光学探头设计将结合高效的光吞吐量， 细胞灌流和快速数据采集。商业应用 一种快速、廉价和定量的分析方法 将成为接受者提供的合同服务 向制药公司、政府和大学提供生物 在搜索中筛选新的合成和自然存在的化合物 新的神经活性药物。它的主要优势是 方法包括：1)独立于放射性同位素；2)独立 来自实验动物；3)快速、简单和低成本；4)高 容量吞吐量；5)受体占有率的定量测量 功效；6)适应数百种受体和亚型。 建议的商业应用：不可用

DESCRIPTION (Investigator's Abstract): This proposal addresses the Molecular Neurobiology interest of NINDS from the latest Omnibus solicitation. A high throughput, fluorescence based technique to measure receptor mediated cellular responses is proposed. The goal is to develop an optical probe capable of measuring intracellular Ca2+ signals reported by fluorescent dyes for high volume application such as screening a number of synthetic or natural compounds. A number of reporter dyes are now available to measure intracellular Ca2+ signals following surface membrane receptor activation and methods exist to test if these signals are transduced by inotropic or metabotropic mechanisms. The optical probe design will incorporate efficient light throughput, cell perfusion and fast data acquisition. The commercial application of the development is that a rapid, inexpensive and quantitative assay will become available to be offered as a contract service by Receptor Biology to pharmaceutical companies, government and universities to screen novel synthetic and naturally occurring compounds in the search for novel neuro-active pharmaceuticals. The major advantage of the method include: 1) independence from radioisotopes; 2) independence from laboratory animals; 3) rapidity, simplicity and low cost; 4) high volume throughput; 5) quantitative measure of receptor occupancy and efficacy; 6) adaptable to hundreds of receptors and subtypes. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE