New Generation Tailored Adsorptive Membranes

建议标题：新一代定制吸附膜建议编号：CTS-0456831首席研究员：Ranil Wickramasinghe研究所：科罗拉多州立大学这个项目的目标是开发一种新的、高效的单元操作，用于回收和纯化现代分子生物学的产物，如质粒DNA、大蛋白、病毒和病毒载体。新型的高通量膜将被开发作为替代的层析载体。由于进料是通过膜孔泵送的，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层析树脂的容量，所需的膜体积将远远小于目前的填充床体积。这项研究的重点是用于基因治疗和疫苗生产的病毒和病毒载体的纯化，以及病毒清除，这是从细胞培养中生产抗体和生物制药所必需的。将追求五个目标：1)对商用膜和功能化膜进行表征，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最佳条件。2)对非刻蚀膜进行表面接枝聚合改性。3)采用表面接枝聚合的方法对径迹刻蚀膜进行改性。比较径迹蚀刻膜和非径迹蚀刻膜对病毒的吸附，将为病毒吸附的最佳膜形态提供有用的信息。4)由一个离子交换单体和一个“间隔基”共单体组成的共聚接枝将从膜表面生长出来，以研究离子交换位置的空间分布如何影响病毒结合。5)建立具有实用价值的病毒清除预测模型。这个模型将提供对这里没有测试的病毒的吸附的洞察力，并将包括膜孔径分布的影响。在更广泛的影响方面，私人投资机构将与其机构的项目主任合作，这些项目的重点是增加来自代表性不足群体的本科生对研究的参与。NSF将寻求补充奖励机制，如REU、RET和国际补充资金，以支持夏季本科生研究人员和常驻教师，并加强国际合作。这项研究的应用可以通过在生物净化方面提供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.