Viral Detection Using Fluorescent Nanocrystals

描述（由申请人提供）：本提案的目的是证明荧光半导体纳米晶体作为临床环境中快速检测传染病的探针的可行性。然而，这项技术将广泛适用于诊断许多类型的传染病，包括新出现的传染病和具有生物恐怖主义潜力的病原体。集合的研究合作利用了三个具有所需不同专业领域的小组之间独特的合作努力，包括物理和材料化学，病毒学和免疫学。为实现这一目标，本文提出了三个具体目标：设计、合成和表征新型纳米偶联探针检测呼吸道合胞病毒（RSV）。具体目标2。为RSV的快速、早期检测开发纳米晶体染色和成像策略。具体目标3。评估基于荧光纳米晶体的RSV检测方案与现有诊断方式在呼吸道病毒感染儿童临床鼻洗样本中的效用。这项资助的完成将导致基于高荧光抗体或RNA共轭CdSe/ZnS核壳纳米晶体的新型纳米偶联物的开发。优化这些探针将需要更深入地了解外壳生长过程和CdSe/ZnS界面的性质。跨学科的研究团队将综合使用掺杂纳米晶体结构的合成方法、分析方法和强大的表面化学来靶向探针，提供迄今为止最详细的核壳界面分子描述。预计这一结果将直接影响合成荧光效率更高的量子点的方法，并扩大其在生物学研究中的应用。由此产生的探针将在临床环境中作为RSV感染的早期快速诊断进行评估。这种早期发现对于适当治疗患者至关重要，因为目前抗病毒药物在感染的早期阶段有效。来自单一激发源的这些材料的新型大小依赖荧光也为这些探针的多路复用检测各种感染提供了途径。除了临床应用外，预计这些探针最终将使研究人员能够研究病毒贩运的基本问题。

DESCRIPTION (provided by applicant): The purpose of this proposal is to demonstrate the feasibility of fluorescent semiconductor nanocrystals as probes for the rapid detection of infectious diseases in a clinical setting. The technology will be broadly applicable, however, to diagnosis of many types of infectious diseases including emerging infections and agents with bioterrorist potential. The assembled research collaboration capitalizes on a unique cooperative effort between three groups with the required diverse areas of expertise, including physical and materials chemistry, virology and immunology. To obtain this goal, three specific aims are proposed: SPECIFIC AIM 1. Design, synthesize, and characterize novel nanoconjugate probes to detect respiratory syncytial virus (RSV). SPECIFIC AIM 2. Develop nanocrystal staining and imaging strategies for the rapid, early detection of RSV. SPECIFIC AIM 3. Evaluate the utility of the fluorescent nanocrystal-based RSV detection scheme compared to existing diagnostic modalities in clinical nasal wash samples from children with respiratory viral infection. Completion of this grant will result in the development of a novel class of nanoconjugates based on highly fluorescent antibody or RNA conjugated CdSe/ZnS core shell nanocrystals. Optimizing these probes will require a deeper understanding of the shell growth process and the nature of the CdSe/ZnS interface. Combining an integrated approach using synthetic methods for doped nanocrystal structures, analytical methods and powerful surface chemistries to target the probes, the interdisciplinary research team will provide the most detailed molecular description to date of the core shell interface. It is expected that such results will directly impact methods to synthesize quantum dots with higher fluorescence efficiencies and expand their applications in biological research. The resulting probes will be evaluated as an early, rapid diagnostic for RSV infection in a clinical setting. Such early detection is critical for proper treatment of patients, since anti-viral drugs are currently effective during the early stages of the infection. The novel size dependent fluorescence of these materials from a single source of excitation also provides a route for the multiplexing of these probes to detect a variety of infections. In addition to clinical applications, it is expected that these probes will ultimately allow researchers to investigate fundamental questions in viral trafficking.