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Molecular & Cellular Analysis Technologies
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This grant brings together two innovative technologies: a novel fluid transfer device and a novel technique for detecting Single Nucleotide Polymorphisms (SNPs) on cDNA arrays. Integrated together, these two technologies will have an immediate and significant impact on the molecular analysis of cancer. Actuated by piezo-electric elements, the fluid transfer technology enables the pipetting of sub-nanoliter volumes of fluid. Additionally, novel sensing technology allows the operational state of the device to be continuously monitored. The sensing technology is indispensable for massively parallel DNA analysis applications requiring thousands of different samples to be reliably aspirated and dispensed. The ultimate goal is to integrate the fluid transfer and sensor technology into an automated pipetting instrument for cancer research and general laboratory applications. Initially the instrument will be applied to a novel technology making it possible for the first time to detect SNPs, deletions and insertions on readily available and relatively inexpensive, spotted cDNA arrays. An Invention Disclosure has been filed by the Collaborating Investigator with the Fred Hutchinson Cancer Research Center (F.H.C.R.C.), Seattle, WA for this exciting new technology. The detection of SNPs on DNA microarrays has heretofore only been possible using allele specific hybridization on oligonucleotide arrays (GeneChips) produced by Affymetrix. Limited access to these GeneChips and their prohibitive costs will make it difficult to apply this technology to large numbers of DNA samples. A major goal of the proposed study is to develop and demonstrate the feasibility of the new SNP detection methodology for high throughput detection of polymorphisms at multiple loci using the high-density cDNA arrays produced by the novel arrayer to be developed in this grant. These highly reproducible, high-density arrays are also expected to provide improved sensitivity and specificity in the analysis of mRNA expression. Experiments will be performed to demonstrate the advantages of the proposed technology over existing pin based mechanical arrayers for gene expression analysis. PROPOSED COMMERCIAL APPLICATIONS: Fueled by emerging technologies like bio-chips, micro-arrays and high throughput screening and the high costs of reagents in general, the bio- medical industry is going towards assays using smaller fluid sample volumes. The proposed research directly addresses this growing market by developing a general purpose automated laboratory pipetting instrument for these applications. By keeping development costs down, the new technology will make high quality, high density DNA arrays accessible to a much broader segment of the cancer research community.