The long-term objective of the proposed work is the development of a field portable microchip assay that will serve as a rapid diagnostic for influenza A. Annual influenza A virus infections have a significant impact on humanity both in terms of death, between 500,000 and 1,000,000 people worldwide each year, and economic impact resulting from direct and indirect loss of productivity during infection. Because influenza A is an easily transmitted, primarily airborne pathogen, and because the potential exists for the virus to be genetically engineered into novel forms, it represents a serious biodefense concern. We have chosen to work with influenza A virus for three significant reasons: 1) the virus' impact on human health and the importance of worldwide surveillance, 2) influenza A's potential as a bioterrorism agent, and 3) this virus can serve as an excellent model system for development and thorough testing of general methodologies and technologies for rapid, field portable diagnostics. We will take advantage of functional genomics by developing a DNA microarray, the """"""""Flu Chip,"""""""" that will provide information as to whether or not an individual is infected with influenza as well as provide both type and antigenic sub-type characterization of the virus. As envisioned, this Flu Chip could play a key role in a rapid defensive response to a genetically engineered influenza virus. In addition, the technology to be developed in this work could be quickly extended to screen for multiple biological pathogens simultaneously.
The specific aims of this application are 1) selection of appropriate genetic targets for typing, sub-typing and strain analysis for influenza A, 2) optimization of sample handling and RNA capture onto microarrays, 3) development of new approaches for on-chip signal amplification, 4) development of a field-portable microarray reader, and 5) independent evaluation and validation of the Flu Chip. To accomplish our objectives, we have assembled a well-coordinated group of scientists and engineers from academia (University of Colorado), government (Centers for Disease Control), and the commercial sector (TeleChem/Arrayit.com).
| Townsend, Michael B; Smagala, James A; Dawson, Erica D et al. (2008) Detection of adamantane-resistant influenza on a microarray. J Clin Virol 42:117-23 |
| Mehlmann, Martin; Bonner, Aleta B; Williams, John V et al. (2007) Comparison of the MChip to viral culture, reverse transcription-PCR, and the QuickVue influenza A+B test for rapid diagnosis of influenza. J Clin Microbiol 45:1234-7 |
| Moore, Chad L; Smagala, James A; Smith, Catherine B et al. (2007) Evaluation of MChip with historic subtype H1N1 influenza A viruses, including the 1918 ""Spanish Flu"" strain. J Clin Microbiol 45:3807-10 |
| Dankbar, Daniela M; Dawson, Erica D; Mehlmann, Martin et al. (2007) Diagnostic microarray for influenza B viruses. Anal Chem 79:2084-90 |
| Dawson, Erica D; Moore, Chad L; Dankbar, Daniela M et al. (2007) Identification of A/H5N1 influenza viruses using a single gene diagnostic microarray. Anal Chem 79:378-84 |
| Mehlmann, Martin; Dawson, Erica D; Townsend, Michael B et al. (2006) Robust sequence selection method used to develop the FluChip diagnostic microarray for influenza virus. J Clin Microbiol 44:2857-62 |
| Townsend, Michael B; Dawson, Erica D; Mehlmann, Martin et al. (2006) Experimental evaluation of the FluChip diagnostic microarray for influenza virus surveillance. J Clin Microbiol 44:2863-71 |
| Dawson, Erica D; Moore, Chad L; Smagala, James A et al. (2006) MChip: a tool for influenza surveillance. Anal Chem 78:7610-5 |
| Mehlmann, Martin; Townsend, Michael B; Stears, Robin L et al. (2005) Optimization of fragmentation conditions for microarray analysis of viral RNA. Anal Biochem 347:316-23 |
| Dawson, Erica D; Reppert, Amy E; Rowlen, Kathy L et al. (2005) Spotting optimization for oligo microarrays on aldehyde-glass. Anal Biochem 341:352-60 |
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