SBIR Phase II: Novel Microarray Platforms For Detection Of Rare Molecules In Complex Mixtures

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This Small Business Innovation Research (SBIR) Phase II project will provide an optimized composite polymer protein binding surface for proteomics applications. The new surface will be specifically designed for reverse phase protein microarrays to enable detection of rare molecules in complex biological mixtures. Discovery and quantification of rare molecules in complex mixtures is essential to improve the understanding of disease mechanism and progression, and responses to treatment regimes. Current surfaces used in these applications have properties that exhibit limited sensitivity of detection due to optical interferences, low protein binding and accumulation of nonspecific interactions. This project will optimize and introduce the application of a new track etched , nitrocellulose composite membrane for protein array applications. Manufacturing processes for the new composite will be developed to generate multiple forms of the composite to allow it to be incorporated into a variety of binding assay formats. This effort will also shed light on important properties for generating ultrasensitive binding surfaces. The result of this project will be an optimized composite membrane with characteristics and manufacturability suited for the most sensitive binding applications, such as reverse phase protein arrays. The platform initially will be optimized for fluorescent detection of rare molecules in complex cell lysates. The broader impact/commercial potential of this project will be to provide a family of discovery and diagnostic tools that will expand the understanding, detection and treatment of human disease. The current focus in translational medicine for therapies in clinical trials is to identify expression patterns of proteins (biomarkers) in individual patients. These measurements allow the monitoring and understanding of individualized disease progression and responses to treatment. They will provide the data necessary to create targeted, personalized treatment regimens. Protein arrays have found utility over the past decade as research tools that provide multiplexed detection and quantification of protein expression. However, the full potential of these tools as diagnostic platforms that provide patient-specific information and guide drug treatment has not been realized due to insufficient binding capacity, limited dynamic range and poor sensitivity. This project defines a new composite surface that has a significant increase in both binding capacity and sensitivity when incorporated into multiplexed immunoassay systems. The composite can be included in a variety of platforms to enhance discovery and quantification of important markers on an individual scale as well as high throughput systems for broad diagnostic application.