Nano-Oscillator Arrays for Sensitive Plasmonic Detection of Molecular Interactions and Reactions

用于分子相互作用和反应的灵敏等离激元检测的纳米振荡器阵列

• 批准号: 9812346
• 负责人: Nguyen Ly
• 金额: $ 70.15万
• 依托单位: BIOSENSING INSTRUMENT, INC.
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-05-01 至 2020-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9812346
• 关键词: Address; Affinity; Algorithms; Arizona; Binding; Biochemical Process; Biochemical Reaction; Biochemistry; Biological Markers; Biological Process; Biosensing Techniques; Case Study; Charge; Computer software; Data; Data Collection; Detection; Disease; Electrons; FDA approved; Feasibility Studies; Hormones; Kinetics; Label; Ligands; Mainstreaming; Measures; Methods; Molecular; Nanoarray Analytical Device; Neurotransmitters; Optics; Organism; Peptides; Performance; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Phosphorylation; Phosphotransferases; Post-Translational Protein Processing; Process; Production; Proteins; Protocols documentation; Reaction; Reaction Time; Reporting; Resolution; Signal Transduction; Small Business Innovation Research Grant; Speed; Surface; Surface Plasmon Resonance; System; Technology; Testing; Time; Universities; Validation; Work; base; commercialization; data acquisition; data management; design; detector; drug development; electric field; flexibility; image processing; imager; imaging modality; innovation; instrument; instrumentation; manufacturability; nano; nanoparticle; new technology; plasmonics; protein distribution; prototype; receptor; screening; sensor; signal processing; small molecule; success; tool

ABSTRACT Detecting molecular interactions and reactions are basic tasks to understand biochemical processes in living organisms, discover biomarkers and develop drugs. Today's mainstream commercial detection technologies are based on measuring mass changes, which struggle to detect small molecules (e.g., metabolites, hormones, and neurotransmitters), and biochemical reactions involving small mass changes (e.g., protein phosphorylation and other post-translational modifications). However, these molecules and reactions are critical to biological functions, and disease initiation and progression. Small molecules also count for over 90% of FDA approved drugs. To address this unmet need, this project aims to develop a nano-oscillator array (NOA) detection technology. Each nano-oscillator consists of a nanoparticle tethered to a surface plasmon resonance (SPR) sensor surface with a flexible molecular linker. The nanoparticle is pre-functionalized with target proteins. When applying an alternating electric field normal to the sensor surface, the nanoparticle is forced to oscillate, and the oscillation amplitude is measured with a SPR imaging method with sub-nm resolution. This resolution corresponds to a fraction of electron charge, making NOA particularly sensitive to the binding of molecules to the proteins on the nanoparticle, or post-translational modification of the proteins via a change in the net charge or charge distribution of the proteins. Collaborative efforts among Biosensing Instrument, Inc., Arizona State University, and pharmaceutical companies have resulted in substantial preliminary data that demonstrates the powerful potential of NOA. In this fast track project, the team will work together to prepare NOA for commercialization by I) expanding on preliminary and feasibility studies of NOA as a new commercial technology for quantifying small molecule binding and biochemical reactions, II) developing a commercial prototype NOA system, including optical instrumentation, signal processing algorithms, NOA sensor production methods, workflow processes, and application specific tools, and III) carrying out both validation tests and show case studies on NOA enabled applications (i.e. killer applications). The success of this project will lead to a new technology to address the unmet need for quantifying small molecule binding kinetics and biochemical reactions kinetics.

抽象的 检测分子相互作用和反应是了解生活中生化过程的基本任务 有机体，发现生物标志物并开发药物。今天的主流商业检测技术 基于测量质量变化，这些变化难以检测小分子（例如代谢产物，激素， 和神经递质），以及涉及质量较小的变化的生化反应（例如蛋白质磷酸化 和其他翻译后修改）。但是，这些分子和反应对生物学至关重要 功能以及疾病的启动和进展。小分子还计算了超过90％的FDA批准 毒品。 为了满足这种未满足的需求，该项目旨在开发纳米振荡器阵列（NOA）检测技术。 每个纳米振荡器都由一个纳米颗粒束缚在表面等离子体共振（SPR）传感器表面 具有柔性分子接头。纳米颗粒用靶蛋白预先官能化。应用 与传感器表面的正常电场交替，纳米颗粒被迫振荡，振荡 振幅是用带有子NM分辨率的SPR成像方法测量的。该分辨率对应于 电子电荷的一部分，使NOA对分子与蛋白质的结合特别敏感 纳米颗粒或通过净电荷的变化对蛋白质的翻译后修饰 蛋白质的分布。亚利桑那州立大学生物传感仪器，Inc。的合作努力， 制药公司产生了大量的初步数据，证明了强大的 NOA的潜力。 在这个快速轨道项目中，团队将共同努力为NOA做准备，以通过i）扩展 NOA作为量化小分子的新商业技术的初步和可行性研究 结合和生化反应，ii）开发商业原型NOA系统，包括光学 仪器，信号处理算法，NOA传感器生产方法，工作流程和 以及特定于应用程序的工具，以及iii）执行验证测试并显示有关启用NOA的案例研究 申请（即杀手申请）。该项目的成功将导致一项新技术来解决 量化小分子结合动力学和生化反应动力学的需求未满足。