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.

这个小企业创新研究第一阶段项目的更广泛的影响/商业潜力是开发一种聚合物材料，大大提高蛋白质纯化。该项目将专注于创建一种基于嵌段共聚物的材料，专门解决生物制药行业生产的治疗性蛋白质的高纯度需求。治疗性蛋白质用于治疗一系列疾病，并且此类产品的市场持续增长。蛋白质目前代表了大部分最高收入的治疗药物，随着新的治疗应用的发现，它们在行业中的主导地位预计将增加。虽然对治疗性蛋白质的需求是显而易见的，但其制造和加工的材料和方法却没有跟上需求。通过该项目产生的结构具有独特的物理和化学性质，能够快速和选择性地纯化治疗性蛋白质，从而降低生产成本，提高最终用户的生产能力。这种新型的高选择性纯化材料有可能解决生物制药行业迫切的商业需求，增加个人治疗蛋白质的可用性，并进一步加深我们对嵌段共聚物结构及其在生物分离中的适用性的科学理解。该I期研究项目的目标是开发分级多孔膜色谱材料及其在治疗性蛋白质纯化中的应用。使用基于亲和性的色谱树脂纯化蛋白质是普遍的，但具有低通量的缺点，这导致高成本。亲和树脂的替代物是利用扩散流和对流流两者来增加通量的膜色谱单元，然而，用于膜色谱的典型介质具有有限的功能和容量。在这个项目中，将合成一种可以用高选择性配体官能化的嵌段共聚物，并将其加工成在多个长度尺度上具有多孔性的膜结构。使用导致嵌段共聚物和牺牲聚合物的亚稳分解的简易且可扩展的工艺，预期该膜色谱材料具有为分离应用提供对流流动的宏观尺度孔以及为靶蛋白提供高容量的高表面积。在用适当的化学部分官能化后，将使用含有靶蛋白的进料流研究这种新材料作为分离介质。将研究嵌段共聚物膜色谱材料的静态和动态结合能力，并根据竞争性性能指标进行基准测试。