Viral Detection Using Fluorescent Nanocrystals

描述(申请人提供)：这项建议的目的是证明荧光半导体纳米晶作为探针在临床环境中快速检测传染病的可行性。然而，这项技术将广泛适用于许多类型的传染病的诊断，包括新出现的感染和具有生物恐怖潜力的病原体。这一集合的研究合作利用了三个小组之间独特的合作努力，这些小组拥有所需的不同领域的专业知识，包括物理和材料化学、病毒学和免疫学。为了实现这一目标，提出了三个具体的目标：特异性目的1.设计、合成和表征用于检测呼吸道合胞病毒(RSV)的新型纳米共轭探针。特定目的2.开发纳米晶染色和成像策略，以快速、早期地检测RSV。具体目的3.评价基于荧光纳米晶体的呼吸道合胞病毒检测方案与现有诊断方法在呼吸道病毒感染儿童的临床鼻腔冲洗样本中的实用性。这笔赠款的完成将导致开发一类基于高荧光抗体或RNA连接的CdSe/ZnS核壳纳米晶的新型纳米结合物。优化这些探针将需要对壳层生长过程和CdSe/ZnS界面的性质有更深入的了解。结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针对探针的综合方法，跨学科研究团队将提供迄今为止最详细的核壳界面分子描述。预计这些结果将直接影响合成具有更高荧光效率的量子点的方法，并扩大其在生物研究中的应用。由此产生的探针将在临床环境中被评估为RSV感染的早期、快速诊断。这种早期检测对患者的适当治疗至关重要，因为抗病毒药物目前在感染的早期阶段有效。这些材料来自单一激发源的新的大小依赖荧光也为这些探针的多路复用提供了一条检测各种感染的途径。除了临床应用，预计这些探测器最终将使研究人员能够调查病毒贩运中的基本问题。

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.