Development of closely-coupled nanostructures for advanced sensing and imaging

开发用于先进传感和成像的紧密耦合纳米结构

• 批准号: RGPIN-2020-06073
• 负责人: Chen, Jennifer
• 金额: $ 3.5万
• 依托单位: York University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=747817
• 关键词: Development; closely; coupled; nanostructures; advanced

The proposed research program aims to develop closely-coupled nanoparticle assemblies as optical sensors for the unmet needs in biomedical research, healthcare and security. Sensing based on single plasmonic nanostructure is shown to be invaluable for elucidating biomolecular interactions in the microenvironment; however demonstrations have thus far been limited to proof-of-concept studies because of the inaccessibility of the customized research-grade instrumentation setups. The proposed work aims to overcome this drawback by designing bioprogrammable bottom-up self-assembled nanoparticle clusters. These plasmonic assemblies exhibit enhanced light scattering to enable the extrapolation of the optical response of thousands of sensors in parallel from darkfield microscopy images. The objectives are to develop and evaluate the sensing platform for bioanalysis down to the single-cell level, and to establish the capability of spatial mapping of molecular distribution and chemical gradient in the microenvironment. Specifically, the proposed research aims to develop new biomolecular linkers, novel multifunctional nanoparticles and large-area multiplexed sensing patch to reach the goals. In the first research area, we will design new biomolecular linkers based on nucleic acids and their hybrid conjugates with peptides for imparting responsivity of the plasmonic assemblies to biomarkers such as microRNA and proteins. The detection of biomolecules from single cells will be pursued to verify the applicability of the technology in analyzing the cellular distribution of biomarkers. In the second research area, we will develop a new class of nanoparticle assemblies comprising orthogonal optical properties of fluorescence and localized surface plasmon resonance. In combination with the newly developed biomolecular linkers, the multifunctional assemblies will be integrated into a robust large-area flexible sensing patch to enable multiplexed detection for field or point-of-care applications. The proposed sensing platform contrasts existing single-cell analytical technologies and molecular imaging techniques which require large instrumentations, centralized laboratory and sample preparation that is laborious and costly. By developing portable, economical and user-friendly sensing platform for analyses that otherwise could only be carried out in research settings, our work will help bridge the gap of fundamental research and practical applications.

拟议的研究计划旨在开发紧密耦合的纳米颗粒组件，作为生物医学研究，医疗保健和安全性未满足需求的光学传感器。基于单等离子体纳米结构的传感对于阐明微环境中的二分子相互作用是无价的。然而，迄今为止，由于定制的研究级仪器设置的无法访问，迄今为止的演示仅限于概念验证研究。拟议的工作旨在通过设计可生物编程的自下而上的自组装纳米颗粒簇来克服这一缺点。这些等离子体组件表现出增强的光散射，以使数千个传感器的光学响应与黑暗显微镜图像平行。这些目标是开发和评估生物分析的传感平台，以便至单细胞水平，并确定在微环境中分子分布和化学梯度的空间映射的能力。 具体而言，拟议的研究旨在开发新的生物分子接头，新型的多功能纳米颗粒和大区域多路复用感应贴片以达到目标。在第一个研究领域，我们将基于核酸及其杂化偶联物与肽的杂化物设计新的生物分子接头，以赋予等离子组件对生物标志物（如microRNA和蛋白质）的响应性。将追求对单个细胞的生物分子的检测，以验证该技术在分析生物标志物细胞分布时的适用性。在第二个研究领域，我们将开发一种新的纳米颗粒组件，其中包括荧光和局部表面等离子体共振的正交光学特性。结合新开发的生物分子接头，多功能组件将集成到健壮的大区块柔性感应贴片中，以实现用于现场或护理点应用的多路复用检测。提出的传感平台对比了现有的单细胞分析技术和分子成像技术，这些技术需要大型仪器，集中的实验室和样品制备，这些仪器和样品制备费用繁琐且昂贵。通过开发可移植，经济和用户友好的传感平台进行分析，否则只能在研究环境中进行，我们的工作将有助于弥合基本研究和实际应用的差距。