Novel Europium Based Time-Resolve Fluorophore with Exceptional Intensity and Stab

新型铕基时间分辨荧光团，具有卓越的强度和稳定性

• 批准号: 8000276
• 负责人: Darren J Magda
• 金额: $ 18.94万
• 依托单位: LUMIPHORE, INC.
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-20 至 2011-09-19
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8000276
• 关键词: Arts; Benchmarking; Binding; Biological; Biological Assay; Biological Sciences; Biomedical Research; Biotin; Buffers; Businesses; California; Characteristics; Chelating Agents; Chemistry; Clinical; Code; Color; Complex; Computer Systems Development; Coupled; DNA Sequence; Detection; Development; Diagnosis; Diagnostic; Divalent Cations; Dyes; Elements; Energy Transfer; Ensure; Environment; Equipment; Europium; Exhibits; Extinction (Psychology); Family; Flow Cytometry; Fluorescence; Fluorescence Microscopy; Fluorescence Resonance Energy Transfer; Fluorescent Dyes; France; Gamma globulin; Generations; Genomics; Germany; Healthcare; Image; Immune; Immunoassay; Industry; International; Ions; Kinetics; Label; Lanthanoid Series Elements; Lasers; Lead; Licensing; Life; Ligands; Light; Link; Marketing; Modeling; Nature; Noise; Patient Care; Phase; Play; Property; Proteins; Public Health; Reading; Reagent; Reporter; Research; Research Personnel; Research Proposals; Role; Route; Sampling; Screening procedure; Signal Transduction; Solutions; Source; Speed; Streptavidin; System; Technology; Terbium; Time; Universities; Utah; Vertebral column; absorption; aqueous; arm; base; commercialization; cost; cyanine dye 5; diagnostic accuracy; drug discovery; fluorophore; high throughput screening; improved; innovation; instrument; luminescence; macromolecule; next generation; novel; novel diagnostics; physical property; practical application; prevent; protein protein interaction; public health relevance; quantum; research and development; sound; usability

DESCRIPTION (provided by applicant): Due to their favorable photophysical and spectral properties, complexes of lanthanide ions (particularly Terbium and Europium) offer significant advantages over organic fluorescent dyes. Compared with traditional organic fluorescent materials, the lanthanide coordination compounds have the following properties - long life-time, a large Stokes shift, and sharp fluorescent peak profiles. Due to these attractive properties, time-resolved reagents based on lanthanide fluorescence have been created. However, existing lanthanide products have not been fully successful in producing products with sufficient stability and brightness to compete with conventional organic fluorophores. Under this Phase I SBIR, Lumiphore will develop a Europium (Eu) fluorescent reporter based on the novel 1,2-HOPO sensitizing unit. The proposed reporter (Lumi4-Eu) will have exceptional photophysical and stability characteristics that will set a new benchmark for Eu reporters in a wide range of drug discovery, diagnostic, rapid sequencing and array applications. This research will result in a fluorescence reagent with exceptional stability, usability, and fluorescent properties that will expand the capabilities of time resolved fluorescent diagnostics by offering the second color of a duplex set of compatible, but complementary lanthanide reporters (the other being Lumiphore's terbium-based fluorescence reporter - Lumi4-Tb). Combining Lumi4- Eu and Lumi4-Tb will enable a new generation of time resolved fluorescence or time resolved Fvrster resonant energy transfer (TR-FRET) based multiplex applications. Lumiphore will use this technology to develop a rapid, multiplexed immunoassay diagnostic platform. This platform holds the promise of exquisite sensitivities, speed, and versatility for the increasing demands of 21st century healthcare. PUBLIC HEALTH RELEVANCE: The proposed research when combines with Lumiphore's existing terbium-based fluorescence reporter (Lumi4-Tb) will impact public health by enabling highly multiplexed diagnostic assay formats that combine fast turnaround times and high assay throughput efficiency. These assays will be used in high throughput screening (HTS) drug discovery, genomic screening, rapid DNA sequencing, clinical diagnostics and fluorescence microscopy applications for both basic and applied biomedical research.

描述（由申请人提供）：由于其良好的光物理和光谱特性，镧系离子（特别是铽和铕）的络合物比有机荧光染料具有显着的优势。与传统的有机荧光材料相比，镧系配位化合物具有寿命长、斯托克斯位移大、荧光峰轮廓尖锐等特点。由于这些吸引人的特性，基于镧系元素荧光的时间分辨试剂已被创建。然而，现有的镧系元素产品尚未完全成功地生产出具有足够稳定性和亮度以与传统有机荧光团竞争的产品。在第一阶段 SBIR 下，Lumiphore 将开发基于新型 1,2-HOPO 敏化单元的铕 (Eu) 荧光报告基因。拟议的报告基因（Lumi4-Eu）将具有卓越的光物理和稳定性特性，这将为欧盟报告基因在广泛的药物发现、诊断、快速测序和阵列应用中树立新的基准。这项研究将产生一种具有卓越稳定性、可用性和荧光特性的荧光试剂，通过提供一组兼容但互补的镧系元素报告基因组的第二种颜色（另一个是 Lumiphore 的铽基荧光报告基因 - Lumi4-Tb），扩展时间分辨荧光诊断的能力。 Lumi4-Eu 和 Lumi4-Tb 的结合将实现新一代基于时间分辨荧光或时间分辨 Fvrster 共振能量转移 (TR-FRET) 的多重应用。 Lumiphore 将利用这项技术开发一个快速、多重免疫分析诊断平台。该平台具有极高的灵敏度、速度和多功能性，可满足 21 世纪医疗保健日益增长的需求。 公共健康相关性：拟议的研究与 Lumiphore 现有的铽基荧光报告基因 (Lumi4-Tb) 相结合，将通过实现高度多重诊断检测格式（结合快速周转时间和高检测通量效率）来影响公众健康。这些检测方法将用于基础和应用生物医学研究的高通量筛选 (HTS) 药物发现、基因组筛选、快速 DNA 测序、临床诊断和荧光显微镜应用。