SBIR Phase II: Mass Spectrometry Imaging for High-Throughput Discovery of Enzyme Activity

This Small Business Innovation Research (SBIR) Phase II project will further develop and commercialize a groundbreaking technology for high-throughput cost-effective screening and analysis. This technology addresses the growing disparity between the ability to generate high-complexity chemical libraries with molecular genetics and combinatorial chemistry approaches, versus the ability to rapidly screen these libraries for high-value molecules. This new high-throughput screening product is a novel integration of an acoustic ejection device with chip-based mass spectrometry to produce mass readout microarrays that are analyzed in high-throughput with mass spectrometry imaging and computational algorithms. Phase II efforts will focus on a high-throughput screening product for cellulase enzyme discovery, a critical enzyme in the production of alternative fuels that is limited by optically based screens which often generate false leads. Importantly, this integrated high-throughput platform does not require sample labeling, is applicable to a broad range of chemical activities, and provides much more information from a single readout than current approaches. Phase II development will produce a commercial screening technology with these advantages and analysis throughput of 250,000 samples/week, while maintaining the flexibility for future applications in the industrial, pharmaceutical and diagnostic markets. The broader impact/commercial potential of this project are cost-effective high-throughput discovery of new enzymes and molecules with enhanced or novel activities in the industrial, environmental, pharmaceutical or diagnostic markets. Also, the proposed technology enables entirely new types of high-throughput screens that are currently inaccessible with existing technologies. Most immediately this high-throughput screening product will be commercialized for application in the $1 billion industrial enzyme market with specific focus on one of the largest fractions of this market, the enzymes important for efficient and economically viable production of second-generation alternative fuels. Beyond the application to alternative fuels, Phase II development will produce a flexible discovery platform that can be expanded to numerous commercial markets. For example, the Phase II developments can also help develop new lower-cost therapeutics by reducing false leads and enable higher specificity diagnostics and testing by providing much more chemical information.