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

这个小企业创新研究（SBIR）二期项目将进一步开发和商业化一项突破性的高通量、高成本效益的筛选和分析技术。该技术解决了利用分子遗传学和组合化学方法生成高复杂性化学文库的能力与快速筛选高价值分子文库的能力之间日益增长的差距。这种新的高通量筛选产品是一种声学弹射装置与基于芯片的质谱法的新型集成，可以产生质量读出微阵列，并用质谱成像和计算算法进行高通量分析。第二阶段的工作将集中在纤维素酶发现的高通量筛选产品上，纤维素酶是生产替代燃料的关键酶，受到光学筛选的限制，通常会产生错误的线索。重要的是，这种集成的高通量平台不需要样品标记，适用于广泛的化学活动，并且从单个读数提供比当前方法更多的信息。二期开发将产生具有这些优势的商业筛选技术，分析吞吐量为250,000个样品/周，同时保持未来在工业，制药和诊断市场应用的灵活性。该项目更广泛的影响/商业潜力是具有成本效益的高通量新酶和分子的发现，这些酶和分子在工业、环境、制药或诊断市场上具有增强或新颖的活性。此外，所提出的技术可以实现目前现有技术无法实现的全新类型的高通量屏幕。这种高通量筛选产品将立即商业化，应用于价值10亿美元的工业酶市场，特别关注这个市场的最大组成部分之一，对第二代替代燃料的高效和经济可行的生产至关重要的酶。除了替代燃料的应用之外，第二阶段的开发将产生一个灵活的发现平台，可以扩展到许多商业市场。例如，II期的发展还可以通过减少假导联来帮助开发新的低成本治疗方法，并通过提供更多的化学信息来实现更高特异性的诊断和测试。

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.