EAGER: Coacervate Protocell Microdrops for Downstream Processing Applications

EAGER：用于下游加工应用的凝聚 Protocell 微滴

• 批准号: 1744459
• 负责人: Nicole Zacharia
• 金额: $ 20万
• 依托单位: University of Akron
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2019-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1744459&HistoricalAwards=false
• 关键词: EAGER; Coacervate; Protocell; Microdrops; Downstream

The manufacture of pharmaceuticals requires isolation of a bioactive compound of interest from a complex multi-component solution. The components within the solution often have similar chemical and physical properties, making isolation and purification of a specific desired component difficult, resource intensive, and expensive. Undesirable biological side effects of impurities necessitate a robust and reliable separation process. This project will explore a fundamentally new approach to separate pharmaceuticals, using engineered polymers to create microscopic drops that concentrate the compound of interest into a second phase, in a process known as coacervation. Concentration within a coacervate drop mimics the process by which bacteria selectively transfer compounds of interest across the cell wall. The coacervate drops thus acts as a membrane-less "protocell" to concentrate and partition compounds of interest into the interior. This project focuses on designing the polymers with a controlled trigger for coacervation to isolate biological compounds of interest with molecular-level specificity. This project will concentrate and partition representative biological compounds from dilute aqueous solutions via complex coacervation using polymer macromolecules. The polymer macromolecules will be molecularly designed with oppositely charged, or hydrogen bonding, functional groups that trigger coacervation via strong intermolecular interactions. Coacervation will lead to a liquid-liquid separation that concentrates the species of interest into a dense, polymer rich liquid. Partitioning into this phase then facilities recovery and/or disposal. This early-concept grant for exploratory research (EAGER) project will test the primary hypothesis that the coacervate drop will stabilize select model biological molecules from dilute, yet complex, aqueous media. The interaction between model proteins and various coacervate environments will be examined. It is anticipated that this concept will lead to the use of coacervate drops as protocells to isolate and recover compounds of interest. It is anticipated that successful demonstration of this early-concept will lead to use of coacervate drops for increasingly complex tasks, such as use as cell-like microreactors for waste degradation.

药物的制造需要从复杂的多组分溶液中分离感兴趣的生物活性化合物。 溶液中的组分通常具有相似的化学和物理性质，使得特定所需组分的分离和纯化困难、资源密集且昂贵。杂质的不良生物学副作用需要稳健和可靠的分离过程。该项目将探索一种从根本上分离药物的新方法，使用工程聚合物制造微观液滴，将感兴趣的化合物浓缩到第二阶段，这一过程称为凝聚。 凝聚层液滴内的浓度模拟细菌选择性地将感兴趣的化合物转移穿过细胞壁的过程。凝聚液滴因此充当无膜的“原始细胞”，以将感兴趣的化合物浓缩并分配到内部。 该项目的重点是设计具有可控凝聚触发器的聚合物，以分离具有分子水平特异性的生物化合物。该项目将使用聚合物大分子通过复凝聚从稀水溶液中浓缩和分配代表性的生物化合物。 聚合物大分子将在分子上设计有带相反电荷或氢键的官能团，这些官能团通过强分子间相互作用触发凝聚。 凝聚将导致液-液分离，其将感兴趣的物质浓缩成致密的富含聚合物的液体。 划分到这一阶段，然后设施回收和/或处置。 这个探索性研究（EAGER）项目的早期概念资助将测试主要假设，即凝聚层下降将稳定稀释但复杂的水介质中的选定模型生物分子。模型蛋白质和各种凝聚环境之间的相互作用将被检查。预计这一概念将导致使用凝聚液滴作为原始细胞来分离和回收感兴趣的化合物。 预计这一早期概念的成功演示将导致凝聚液滴用于越来越复杂的任务，例如用作废物降解的细胞状微反应器。