Quantitative Microfluidic Molecular Evolution

描述(申请人提供)：在随机序列空间中搜索基于核酸的疗法、生物催化剂和分子诊断学从根本上受到现代人工样品制备和分析技术的限制。新兴的微流控技术允许将稀释、混合和反应等集成、自动化和快速的样品处理过程与快速电泳或层析分析相结合。现在，基本微流控组件可用于构建自动分子进化微芯片，该芯片由许多独立的混合器/分析器电路并行工作，以通过随机序列空间进化候选疗法、催化剂或配体，以寻找具有显著增强的分子特性的变体，如催化效率或结合常数。这项研究将使用新型微流控仪器：1)自动化和加速分子进化，2)高通量并行探索序列空间，3)量化进化生物学和分子进化的基本属性，如重复、收敛和适应。

DESCRIPTION (provided by applicant): The search through random sequence space for nucleic acid-based therapeutics, biocatalysts, and molecular diagnostics is fundamentally limited by modern manual sample preparation and analytical technologies. Emergent microfluidic technologies allow the union of integrated, automated and rapid sample handling procedures such as dilution, mixing, and reaction with rapid electrophoretic or chromatographic analysis. The basic microfluidic components are now available to construct an automated molecular evolution microchip consisting of many independent mixer/analyzer circuits working in parallel to evolve candidate therapeutics, catalysts, or ligands through random sequence space in the search for variants with dramatically enhanced molecular properties such as catalytic efficiency or binding constants. This research will employ novel microfluidic instrumentation for: 1) automating and expediting molecular evolution, 2) high throughput parallel explorations of sequence space, and 3) quantitating fundamental properties in evolutionary biology and molecular evolution such as reccurrence, convergence, and adaptation.