New Generation Tailored Adsorptive Membranes

摘要提案标题：新一代定制吸附膜提案编号：CTS-0456831主要研究者：Ranil Wickramasingh机构： 科罗拉多州立大学本项目的目标是开发一种新型的、高效的单元操作的吸附膜，用于回收和纯化现代分子生物学的产物，如质粒DNA、大蛋白质、病毒和病毒载体。新型高通量膜将被开发作为替代色谱支持。 由于进料被泵送通过膜孔，因此可以消除孔扩散，从而产生与流速无关的结合能力。由于吸附膜的容量等于或大于色谱树脂的容量，因此所需的膜体积将远小于当前填充床体积。 研究重点是用于基因治疗和疫苗生产的病毒和病毒载体纯化，以及病毒清除，这对于从细胞培养物中生产抗体和生物药物至关重要。将追求五个目标：1）市售膜和功能化膜的特点，以确定其孔隙率，孔径分布和表面化学。将确定病毒吸附和结合病毒洗脱的优化条件。 2)非径迹蚀刻膜将通过膜表面的接枝聚合来改性。 3)径迹蚀刻膜将通过膜表面的接枝聚合进行改性。 比较径迹蚀刻和非径迹蚀刻膜的病毒吸附将提供关于病毒吸附的最佳膜形态的有用信息。 4)包含离子交换单体和“间隔物”共聚单体的共聚物接枝物将从膜表面生长，以检查离子交换位点的空间分布如何影响病毒结合。 5)将开发一个具有实用价值的病毒清除预测模型。该模型将提供对此处未检测的病毒吸附的深入了解，并将包括膜孔径分布的影响。就更广泛的影响而言，PI将与其机构的项目主管合作，重点是增加代表性不足群体的本科生参与研究。NSF的补充奖励机制，如REU，RET和国际补充将寻求支持夏季本科研究人员和教师居住，并加强国际合作。 这项研究的应用可以通过提供生物净化的突破性技术来造福社会。

AbstractProposal Title: New Generation Tailored Adsorptive MembranesProposal Number: CTS-0456831Principal Investigator: Ranil WickramasingheInstitution: Colorado State UniversityThe objective of this project is to develop adsorptive membranes as a new, high efficiency unit operation for the recovery and purification of the products of modern molecular biology, such as plasmid DNA, large proteins, and viruses and viral vectors. Novel, high-throughput membranes will be developed as alternative chromatographic supports. Since the feed is pumped through the membrane pores, pore diffusion can be eliminated, leading to binding capacities that are independent of flow rate. As the capacities of adsorptive membranes are equivalent to or greater than those of chromatographic resins, the membrane volume required will be much less than current packed-bed volumes. The research focuses on virus and viral vector purification for gene therapy and vaccine production, as well as virus clearance, which is essential in the production of antibodies and biopharmaceuticals from cell cultures. Five objectives will be pursued: 1) Commercially available membranes and functionalized membranes will be characterized to determine their porosities, pore-size distributions and surface chemistries. Optimized conditions for virus adsorption and the elution of bound viruses will be determined. 2) Non-track-etched membranes will be modified by graft polymerization from the membrane surface. 3) Track-etched membranes will be modified by graft polymerization from the membrane surface. Comparing virus adsorption by track-etched and non-track-etched membranes will provide useful information on the optimum membrane morphology for virus adsorption. 4) Copolymer grafts comprising an ion-exchange monomer and a "spacer" co-monomer will be grown from the membrane surfaces to examine how spatial distribution of ion-exchange sites affects virus binding. 5) A predictive model of practical value for virus clearance will be developed. This model will provide insights into adsorption of viruses not tested here and will include the effects of membrane pore-size distribution. In terms of the broader impacts, the PIs will work with the directors of programs at their institutions that focus on increasing participation in research by undergraduates from underrepresented groups. NSF supplemental award mechanisms such as REU, RET, and international supplements will be sought to support summer undergraduate researchers and teachers in residence and to strengthen the international collaboration. Applications of this research could benefit society by providing breakthrough technologies in bio-purifications.