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. ? ? ?
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| Halfpenny, Kristin C; Wright, David W (2010) Nanoparticle detection of respiratory infection. Wiley Interdiscip Rev Nanomed Nanobiotechnol 2:277-90 |
