The overall goal of this proposal is to develop and implement an integrated suite of technologies for enabling microarray-based diagnostic assays and the cGMP manufacturing processes and procedures necessary to manufacture these products. Microarrays have found widespread use in biology and medicine as important tools for evaluating gene expression and genomics. Using these tools, clinical researchers are driving the characterization of the molecular signatures of disease as they relate to both prognosis and therapy. By resolving the detection of complex analyte mixtures, microarray technology offers tremendous promise to improve patient care in situations in which clinical decisions must be informed by classifiers based on inputs from large sets of features. Broader implementation of diagnostic microarrays will require the development and manufacture of enabling technologies that are robust and reproducible and can be performed reliably and efficiently in the clinical diagnostic laboratory setting. Rigorous control of design and manufacturing processes of these products is essential to achieving inter-lot, inter-laboratory consistency and obtaining regulatory approval and reimbursement. The solutions to these issues should enable much more widespread implementation of diagnostic microarrays and the corresponding advances in human healthcare that are promised by molecular diagnostics. Phase I activities have resulted in the development of a cGMP manufactured, single-tube, streamlined amplification format that shows excellent correlation with industry- standard research-grade amplification reagents. This Phase II application outlines the steps we will take to expand features of this product to be the most comprehensive amplification format. The investigations in this grant will be directed toward the development of a thorough set of quality control features and assays that will give information suitability of the reagents for microarray outcomes.
As understanding of human disease progresses and new methods for high throughput analyses continue to be developed, molecular diagnostics testing is becoming more accurate but more complicated. Our investigations will provide quality and control tools to ensure that these diagnostic tests can be used in clinical laboratories.
