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

这个小型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，极大地改善蛋白质的纯化。该项目将专注于创造一种基于嵌段共聚物的材料，专门满足生物制药行业生产的治疗蛋白的高纯度需求。治疗性蛋白质被用于治疗一系列疾病，而且此类产品的市场持续增长。蛋白质目前占治疗药物收入的大部分，随着新的治疗应用的发现，它们在该行业的主导地位预计将增加。尽管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还跟不上需求。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，从而为最终用户带来更低的生产成本和更高的生产能力。这种新型的高选择性纯化材料有可能满足生物制药行业迫切的商业需求，增加个人获得治疗性蛋白质的可能性，并促进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。这一阶段研究项目的目标是开发一种分级多孔膜层析材料，并将其应用于治疗性蛋白质的纯化。亲和层析树脂广泛应用于蛋白质的纯化，但产量低，成本高。亲和树脂的另一种选择是膜层析单元，它利用扩散和对流来增加通量，然而，典型的膜层析介质的功能和容量有限。在这个项目中，将合成一种可以用高选择性配体功能化的嵌段共聚物，并将其加工成具有多个长度尺度的孔隙率的膜结构。这种膜层析材料使用一种简单且可扩展的过程，导致嵌段共聚物和牺牲聚合物的旋节分解，预计这种膜层析材料将具有宏观尺度的孔，为分离应用提供对流流动，以及高比表面积，提供高容量的目标蛋白质。在用适当的化学部分功能化后，这种新材料将作为分离介质使用包含目标蛋白的饲料流进行研究。将研究嵌段共聚物膜层析材料的静态和动态结合能力，并以竞争性性能指标为基准进行基准测试。

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.