Advanced Microarray Technology for Pathogen Surveillance

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DESCRIPTION (provided by applicant): This proposal is in response to NIAID's call for Cooperative Research Partnerships for Biodefense (RFAAI-05-019). Consistent with the stated objectives of this RFA, our established team of chemists, biologists and engineers from the commercial sector, academia and government, proposes to conduct the research necessary to advance three potential products that are anticipated to significantly enhance the utility of microarrays for pathogen surveillance and biodefense. Influenza surveillance will be targeted as the first specific application of the technology. Because human-adapted influenza virus is a readily transmitted, primarily airborne pathogen, and because the potential exists for the virus to be genetically engineered into novel forms, influenza A represents a serious public health and biodefense concern. The Centers for Disease Control and Prevention and the World Health Organization have strongly emphasized the importance of global influenza surveillance because of its critical role in determination of viral strain identification (required for vaccine production) and disease distribution. While there are 112 institutions in 83 countries that serve as National Influenza Centers for surveillance, coverage of the world's population remains quite limited, and significant efforts are needed to enhance influenza surveillance. A major factor in this dearth of coverage is the current expensive and labor-intensive (days) method for strain analysis. In order to realize the tremendous potential of the microarray platform for rapid disease diagnosis and pathogen identification, it is essential that alternative, inexpensive and easy-to-use detection technologies be developed. Use of microarrays as effective monitoring systems in biodefense also requires field portability for prompt and widespread deployment. Our vision is a diagnostic kit that would enable field application of microarrays with an analysis time of hours instead of days and at a cost consistent with the need for world-wide distribution. The kit would provide the means for rapid target extraction from the sample, on-chip signal amplification resulting in a polymer detectable by eye, and a hand-held reader to be used for interpretation of multi-pathogen microarrays. The proposed Specific Aims are to develop the following three products: a) a simple sample handling kit for virus pre-concentration, b) an innovative non-enzymatic technology for amplifying signals from bio-recognition events (both nucleic acids and proteins) directly on microarrays, and c) a robust, inexpensive field-portable microarray reader.