A universal droplet microfluidic platform for ultrahigh-throughput biocatalyst evolution

摘要 生物技术的进步依赖于通过基因工程快速迭代的方法 酶和途径。虽然计算和基因合成技术已经看到了相当多的 在过去几十年的创新中，筛选所需活性的变体已经落后， 预付款。事实上，微孔板，一种近60年的技术，仍然是主要的工具。客观 流体发现的目的是通过引入一种基于精确度的新型筛选模式来改变这一领域 纳升流体处理;这种开创性的方法将增加屏幕的规模，可以执行 100倍，同时降低成本除了全新的硬件架构， 筛选，我们的方法实现了无标记质谱和计算技术， 发现意想不到的酶活性和增强。Fluid Discovery由以下发明者创立： 关键技术，因此，处于推进这一领域并成为商业 成功这笔赠款将推动第一个alpha原型的开发，该原型可以由抢先体验运行 客户，以说明该技术的实用性，其适用于工业研究和 发展，以及市场的成熟;所有这些都是筹集私人资金所必需的， 商业规模扩大。我们的团队包括药物开发专家（Prince博士）， 商业化（Sunkara博士）和科学与技术（Abate博士）。这支队伍有一条展示的赛道 商业成功的记录，建立了当前价值超过10亿美元的公司。Fluid Discovery 技术将使工程活动不可行与今天的技术在一个价格点访问， 生物技术初创企业和学术研究实验室，以及对大型制药公司有吸引力的变革效率。

Abstract The advance of biotechnology is dependent on approaches for rapidly iterating through genetically engineered enzymes and pathways. While computational and gene synthesis techniques have seen considerable innovation in the last few decades, screening variants for desired activities has lagged behind, with few notable advances. Indeed, microwell plates, a nearly 60-year-old technology, remain the dominant tool. The objective of Fluid Discovery is to transform this field by introducing a novel screening paradigm based on precision nanoliter fluid handling; this groundbreaking approach will increase the scale of screens that can be performed by 100x while driving down costs. In addition to a fundamentally new hardware architecture for scalable screening, our approach implements label-free mass spectrometry and computational techniques to enable discovery of unanticipated enzyme activities and enhancements. Fluid Discovery is founded by the inventor of the key technologies and, thus, is in a prime position to advance this space and become a commercial success. This grant will fuel the development of the first alpha prototype that can be run by early access customers, to illustrate the utility of the technology, its appropriateness for industrial research and development, and its maturity for the market; all of which will be necessary to raise private funding for commercial scale up. Our team includes experts in pharmaceutical development (Dr. Prince), commercialization (Dr. Sunkara), and science and technology (Dr. Abate). This team has a demonstrated track record of commercial success, having built companies with current value >$1 billion. Fluid Discovery’s technology will allow engineering campaigns infeasible with today’s technology at a price point accessible to biotech startups and academic research labs, and with transformative efficiencies attractive to Big Pharma.