A universal droplet microfluidic platform for ultrahigh-throughput biocatalyst evolution

用于超高通量生物催化剂进化的通用液滴微流控平台

• 批准号: 10705725
• 负责人: Adam R. Abate
• 金额: $ 81.71万
• 依托单位: FLUID DISCOVERY INC
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-25 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10705725
• 关键词: Abate; Active Sites; Amino Acids; Architecture; Automobile Driving; Biological; Biological Assay; Biosensing Techniques; Biotechnology; Cannabinoids; Capital; Cells; Chemicals; Collaborations; Complex; Computational Technique; Computer software; Contracts; Data; Development; Directed Molecular Evolution; Engineering; Environment; Enzymes; Evolution; Feedback; Funding; Future; Genetic Engineering; Grant; Health; Human; Industrialization; Industry; Label; Laboratories; Letters; Libraries; Liquid substance; Manufacturer; Marketing; Mass Spectrum Analysis; Materials Testing; Mediation; Metabolic; Microfluidics; Mission; Mutagenesis; Mutation; Natural Products; Nature; Organism; Outsourcing; Pathway interactions; Pharmacologic Substance; Phase; Phenotype; Plastics; Positioning Attribute; Price; Printing; Privatization; Production; Property; Recombinants; Reporter; Research; Route; Running; Scheme; Science; Software Design; Source; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Structure; Synthesis Chemistry; Techniques; Technology; Testing; Translating; Variant; Yarrowia lipolytica; combinatorial; commercialization; computerized data processing; cost; cost effective; design; drug discovery; enzyme activity; gene synthesis; innovation; instrument; manufacture; manufacturing organization; mutant; nanolitre; novel; prototype; research and development; scale up; screening; success; synthetic biology; tool; trend

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.

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大的 在过去几十年的创新中，为期望的活动筛选变种一直落后，几乎没有什么值得注意的 预付款。事实上，有近60年历史的微孔板技术仍然是占主导地位的工具。目标是 流体发现的目的是通过引入一种基于精确度的新的筛选范式来改变这一领域 纳升液体处理；这种突破性的方法将增加可以进行的筛分规模 降低100倍，同时降低成本。除了可扩展的全新硬件体系结构之外 筛选，我们的方法实现了无标记质谱学和计算技术，以使 发现意想不到的酶活性和增强作用。流体发现由发明人创立 关键技术，因此处于推动这一空间并成为商业的首要地位 成功。这笔赠款将推动第一个阿尔法原型的开发，该原型可以由Elear Access运行 客户，以说明该技术的实用性、其对工业研究的适用性和 发展及其对市场的成熟度；所有这些都将是筹集私人资金用于 扩大商业规模。我们的团队包括药物开发专家(普林斯博士)， 商业化(Sunkara博士)和科学技术(Abate博士)。这支队伍有一条示范赛道 商业成功的记录，建立了价值10亿美元的现值公司。流体发现号 技术将允许以可获得的价格点进行工程活动，而目前的技术是不可行的 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性效率。