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Activatable Fluorescent Protein/Metal Hybrid Raman Nano-Probes for Biosensing

用于生物传感的可激活荧光蛋白/金属混合拉曼纳米探针

基本信息

批准号：
1406812
负责人：
Fabien Pinaud
金额：
$ 45万
依托单位：
University of Southern California
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2014
资助国家：
美国
起止时间：
2014-07-15 至 2018-01-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1406812&HistoricalAwards=false
关键词：
Activatable Fluorescent Protein Metal Hybrid

项目摘要

Non-technical:This award by the Biomaterials Program in the Division of Materials Research to the University of Southern California is to develop probes that are activatable fluorescent protein/metal hybrids that will be useful in Surface Enhanced Raman Spectroscopy (SERS) for biosensing. Detecting individual pathogenic cells and eliminating them is crucial for early cancer detection and treatments. Raman nanoprobes are among a handful of probes that could provide such high detection sensitivity. Yet, current formulations are molecularly bulky and lacking in specificity and sensitivity, which ultimately limits their efficacy in research and medical settings. This project offers a novel design and implementation of Raman nanoprobes for biosensing, with the goal of achieving highly sensitive but specific detection of cancer cells. Educational and outreach components are an integral part of the project. The proposed activities engage participating researchers and students in highly interdisciplinary research to prepare the next generation of scientists to face the growing demands for interdisciplinary skills at the interface between physics, chemistry and biology. The program also integrates modern technology and interdisciplinary science for young students. Mentoring and cross-disciplinary training of traditionally underrepresented undergraduate and high-school students on emerging nanotechnology methods and on the use of advanced photonic instrumentations will be realized through established programs at the University of Southern California, through partnership with non-profit organizations and through outreach to high-schools in the Greater Los Angeles area. Technical:Plasmonic Raman nanoprobes are highly promising agents for the next generation of biomedical imaging and treatment but current limitations in their design, including large sizes (100 nm) and poor Raman signals, significantly impede their potential for major breakthroughs in molecular imaging and theranostics. This project will investigate the use of split-fluorescent proteins as both molecular glue and Raman reporters for cell-directed assembly of small and activatable surface enhanced Raman scattering (SERS) metal nanoprobes, with the aim of achieving highly sensitive and specific Raman detection of cancer cells. The project offers a novel approach to SERS biosensing and detection and may allow significant advances in the basic understanding of (i) photonic properties emerging at natural chromophore/metal nanoparticle interfaces, (ii) Raman enhancement processes in well-defined nanostructures and (iii) molecular factors affecting the assembly of nanomaterials into controlled nanoclusters in live cells. The studies are expected to contribute knowledge and techniques that will be broadly useful for the directed assembly of nanoparticles into metamaterials and into catalytic/electronic nanostructures to be used in biomedical, prosthetics, therapeutics and fundamental research applications. An integral part of this project is the training and mentoring of underrepresented students in interdisciplinary research in nanotechnology, biomaterials and photonics, through the integration of research findings and instrumentation into classroom teaching, outreach programs to local high-schools, and general public presentations. Significant enhancement of the infrastructure for research and education at the University of Southern California is also provided by the implementation of an optical set-up for single molecule SERS measurements.

非技术性：这项由南加州大学材料研究部生物材料项目授予的奖项旨在开发可激活的荧光蛋白/金属混合物探针，这些探针将用于生物传感的表面增强拉曼光谱（Sers）。检测单个致病细胞并消除它们对于早期癌症检测和治疗至关重要。拉曼纳米探针是少数可以提供如此高检测灵敏度的探针之一。然而，目前的制剂分子体积庞大，缺乏特异性和敏感性，这最终限制了它们在研究和医疗环境中的功效。该项目提供了一种新颖的设计和实施的拉曼纳米探针的生物传感，实现高度敏感，但具体的检测癌细胞的目标。教育和外联部分是该项目的一个组成部分。拟议的活动使参与的研究人员和学生参与高度跨学科的研究，以培养下一代科学家，使他们能够在物理、化学和生物学之间的界面上应对日益增长的跨学科技能需求。该计划还为年轻学生整合了现代技术和跨学科科学。指导和传统上代表性不足的本科生和高中学生新兴的纳米技术方法和先进的光子仪器的使用将通过在南加州大学的既定方案，通过与非营利组织的合作伙伴关系，并通过推广到大洛杉矶地区的高中实现跨学科的培训。技术：等离子体拉曼纳米探针是下一代生物医学成像和治疗的非常有前途的试剂，但目前其设计的限制，包括大尺寸（100 nm）和差的拉曼信号，显着阻碍了其在分子成像和治疗诊断学方面取得重大突破的潜力。本项目将研究使用分裂荧光蛋白作为分子胶和拉曼报告分子，用于细胞定向组装小型可活化的表面增强拉曼散射（Sers）金属纳米探针，目的是实现癌细胞的高灵敏度和特异性拉曼检测。该项目为Sers生物传感和检测提供了一种新的方法，并可能在以下基本理解方面取得重大进展：（i）天然发色团/金属纳米颗粒界面处出现的光子特性，（ii）定义明确的纳米结构中的拉曼增强过程，以及（iii）影响纳米材料组装成活细胞中受控纳米团簇的分子因素。这些研究预计将有助于知识和技术，将广泛用于定向组装纳米粒子到超材料和催化/电子纳米结构，用于生物医学，修复学，治疗学和基础研究应用。该项目的一个组成部分是在纳米技术，生物材料和光子学的跨学科研究的代表性不足的学生的培训和指导，通过研究成果和仪器到课堂教学，推广计划到当地高中的整合，和一般公众介绍。南加州大学的研究和教育基础设施的显着增强也提供了单分子Sers测量的光学设置的实施。