SBIR Phase I: Hierarchically Porous Membrane Media for Affinity-based Separations

SBIR 第一阶段：用于基于亲和力的分离的分级多孔膜介质

• 批准号: 1447969
• 负责人: Rachel Dorin
• 金额: $ 15万
• 依托单位: TeraPore Technologies, Inc.
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1447969&HistoricalAwards=false
• 关键词: SBIR; Phase; Hierarchically; Porous; Membrane

The broader impact/commercial potential of this Small Business Innovation Research Phase I project is the development of a polymeric material that dramatically improves protein purification. This project will focus on creating a material based on block-copolymers that specifically addresses the high purity needs of therapeutic proteins manufactured by the biopharmaceutical industry. Therapeutic proteins are utilized in the treatment of an array of diseases and the market for such products continues to grow. Proteins currently represent the majority of top revenue generating therapeutic pharmaceuticals, and their dominance in the industry is expected to increase as new therapeutic applications are discovered. While the need for therapeutic proteins is evident, materials and methods for their manufacture and processing have not kept up with demand. The structures generated through this project have unique physical and chemical properties that enable the rapid and selective purification of therapeutic proteins, resulting in lower production costs and higher production capacities for end-users. This novel and highly selective purification material has the potential to address pressing commercial needs in the biopharmaceutical industry, increase the availability of therapeutic proteins to individuals, and further our scientific understanding of block copolymer structures and their applicability to bioseparations. The objectives of this Phase I research project are the development of a hierarchically porous membrane chromatography material and its application to the purification of therapeutic proteins. The use of affinity-based chromatographic resins for the purification of proteins is widespread but suffers from low throughput, which leads to high costs. An alternative to affinity resins are membrane chromatography units that utilize both diffusive and convective flow to increase throughput, however, typical media for membrane chromatography has limited functionality and capacity. For this project, a block copolymer that can be functionalized with highly selective ligands will be synthesized and processed into a membrane structure containing porosity on multiple length-scales. Using a facile and scalable process that leads to the spinodal decomposition of the block copolymer and a sacrificial polymer, this membrane chromatography material is expected to have macro-scale pores offering convective flow for separation applications as well as high surface areas offering high capacity for target proteins. After functionalizing with the appropriate chemical moiety, this new material will be investigated as a separation media using feed streams containing the target protein. Static and dynamic binding capacities of the block-copolymer membrane chromatography material will be investigated and benchmarked against competitive performance metrics.

这个小型企业创新研究阶段I项目的更广泛的影响/商业潜力是开发一种可显着改善蛋白质纯化的聚合物材料。该项目将着重于创建基于块聚合物的材料，该材料专门满足生物制药行业生产的治疗蛋白的高纯度需求。治疗蛋白用于治疗一系列疾病，这种产品的市场持续增长。目前，蛋白质代表了产生治疗性药物的大部分最高收入，随着发现新的治疗应用，预计其在行业中的优势将增加。尽管对治疗蛋白的需求显而易见，但其制造和加工的材料和方法并没有跟上需求。通过该项目产生的结构具有独特的物理和化学特性，可快速和选择性地纯化治疗蛋白，从而导致最终用户的生产成本较低和较高的生产能力。这种新颖的高度选择性纯化材料有可能满足生物制药行业中的迫切商业需求，增加对个体的治疗蛋白的可用性，并进一步我们对块共聚物结构的科学理解及其对生物释放的适用性。该阶段研究项目的目标是开发分层多孔膜色谱材料及其在纯化治疗蛋白上的应用。基于亲和力的色谱树脂用于纯化蛋白质的纯化是广泛的，但吞吐量很低，这导致了高成本。亲和力树脂的一种替代方法是膜色谱单元，它们利用扩散和对流流以增加吞吐量，但是，膜色谱法的典型培养基的功能和容量有限。对于此项目，可以合成可以与高度选择性配体功能化的块共聚物，并将其处理成包含多个长度尺度上的孔隙率的膜结构。使用可简化且可扩展的过程，该过程导致块共聚物和牺牲聚合物的旋律分解，该膜色谱材料有望具有宏观孔，可为分离应用提供对流流以及高表面积，提供高表面积的靶标蛋白。用适当的化学部分功能化后，将使用含有靶蛋白的进料流将该新材料作为分离培养基进行研究。将研究并根据竞争性能指标对块聚合物膜色谱材料的静态和动态结合能力进行研究。