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

非技术：该奖项由南加州大学材料研究部生物材料项目颁发，旨在开发可激活的荧光蛋白/金属杂交探针，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灭它们对于癌症的早期发现和治疗至关重要。拉曼纳米探针是少数几种可以提供如此高检测灵敏度的探针之一。然而，目前的配方分子体积庞大，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。该项目为生物传感提供了一种新颖的拉曼纳米探针设计和实现，其目标是实现对癌细胞的高灵敏度和特异性检测。教育和外联部分是该项目的一个组成部分。提议的活动让参与的研究人员和学生参与高度跨学科的研究，为下一代科学家做好准备，以面对物理、化学和生物学之间对跨学科技能日益增长的需求。该项目还将现代技术与跨学科科学相结合，为青年学生提供服务。在新兴纳米技术方法和先进光子仪器的使用方面，对传统上代表性不足的本科生和高中生的指导和跨学科培训将通过南加州大学的既定项目、与非营利组织的合作以及与大洛杉矶地区高中的联系来实现。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极具前景的试剂，但目前其设计的局限性，包括大尺寸（100纳米）和较差的拉曼信号，严重阻碍了它们在分子成像和治疗方面取得重大突破的潜力。该项目将研究分裂荧光蛋白作为分子胶和拉曼报告蛋白的使用，用于细胞定向组装小型和可激活的表面增强拉曼散射（SERS）金属纳米探针，目的是实现对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方法，并可能在以下方面的基本理解方面取得重大进展：(1)天然发色团/金属纳米颗粒界面上出现的光子特性，(2)定义良好的纳米结构中的拉曼增强过程，以及(3)影响纳米材料在活细胞中组装成受控纳米团簇的分子因素。这些研究预计将为纳米颗粒定向组装成超材料和催化/电子纳米结构提供广泛有用的知识和技术，用于生物医学、假肢、治疗和基础研究应用。该项目的一个组成部分是培训和指导代表性不足的学生在纳米技术、生物材料和光子学的跨学科研究中，通过将研究成果和仪器整合到课堂教学中，向当地高中推广计划，并向公众展示。南加州大学的研究和教育基础设施的显著增强也通过实施单分子SERS测量的光学装置提供。

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.