Quantitative Microfluidic Molecular Evolution

描述（由申请人提供）：通过随机序列空间寻找基于核酸的疗法、生物催化剂和分子诊断，从根本上受到现代手工样品制备和分析技术的限制。新兴的微流体技术允许集成，自动化和快速的样品处理程序，如稀释，混合，反应与快速电泳或色谱分析的结合。基本的微流控组件现在可用于构建自动分子进化微芯片，该芯片由许多独立的混频器/分析仪电路组成，并行工作，通过随机序列空间进化候选疗法，催化剂或配体，以寻找具有显着增强的分子特性（如催化效率或结合常数）的变体。本研究将采用新型微流控仪器：1)自动化和加速分子进化；2)高通量序列空间并行探索；3)定量进化生物学和分子进化的基本特性，如递归、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.