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命体生化过程的基本任务 有机体，发现生物标志物并开发药物。当今主流商业检测技术 基于测量质量变化，难以检测小分子（例如代谢物、激素、 和神经递质），以及涉及小质量变化的生化反应（例如，蛋白质磷酸化 和其他翻译后修饰）。然而，这些分子和反应对于生物至关重要 功能以及疾病的发生和进展。小分子也占 FDA 批准的 90% 以上 药物。 为了解决这一未满足的需求，该项目旨在开发纳米振荡器阵列（NOA）检测技术。 每个纳米振荡器均由束缚在表面等离子共振 (SPR) 传感器表面的纳米粒子组成 具有灵活的分子连接体。纳米粒子用目标蛋白进行预功能化。当申请 垂直于传感器表面的交变电场，纳米颗粒被迫振荡，并且振荡 振幅采用亚纳米分辨率的 SPR 成像方法进行测量。该决议对应于 电子电荷的一部分，使得 NOA 对分子与蛋白质上的结合特别敏感 纳米颗粒，或通过净电荷或电荷变化对蛋白质进行翻译后修饰 蛋白质的分布。 Biosensing Instrument, Inc.、亚利桑那州立大学、 和制药公司已经得出了大量的初步数据，证明了强大的 NOA 的潜力。 在这个快速通道项目中，团队将共同努力为 NOA 的商业化做准备，方法是 I) 扩展 NOA 作为定量小分子的新型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 仪器仪表、信号处理算法、NOA 传感器生产方法、工作流程以及 应用特定工具，以及 III) 执行验证测试并展示启用 NOA 的案例研究 应用程序（即杀手级应用程序）。该项目的成功将带来一种新技术来解决这个问题 量化小分子结合动力学和生化反应动力学的需求尚未得到满足。