Protein Transport in Charged Gels for Chromatography and Membrane Applications

摘要提案标题：用于色谱和膜应用的荷电凝胶中的蛋白质转运提案编号：CTS-0414143主要研究者：Georgio Carta机构： 该项目的目的是发展一个基本的了解蛋白质分配和运输的带电水凝胶。 了解带电大分子在这类材料中的输运性质是其开发和优化设计的关键。 最近通过微观研究获得了新的见解，这可以为发展对运输的机械理解提供基础。 该项目将扩大目前在这一领域的努力，最终目标是开发用于蛋白质分离的新吸附剂和膜，以及预测其过程性能的模型。 蛋白质分配和运输带电葡聚糖凝胶和琼脂糖-葡聚糖复合材料将在微观尺度上研究，重点是凝胶性质和蛋白质分子量和电荷对平衡吸收和传质动力学的影响。 将使用放射性示踪技术研究带电聚丙烯酰胺凝胶和带电琼脂糖-葡聚糖复合物中的蛋白质离子交换动力学，以阐明梯度和示踪扩散条件下的蛋白质转运。 将进行离子凝胶中单一和多组分蛋白质转运的建模以及这些模型在预测柱色谱在处理条件下的行为方面的应用。 这项研究将提供一个更高层次的了解在这些复杂的介质中的传输现象，以及模型，以帮助设计和优化色谱过程。 这项研究将产生多方面的广泛影响。 它将指导介质制造商开发优化的固定相。 它还将为速率模型的制定提供基础，以预测和优化色谱分离，从而使制药公司能够改进生物工艺的设计和效率。由于分离和纯化通常是生物加工中成本最高的步骤，因此迫切需要经过培训的分离科学家和工程师开发和实施新型分离介质，将广泛的实验和建模方法整合在一起，以提高工业生物分离的有效性。

AbstractProposal Title: Protein Transport in Charged Gels for Chromatography and Membrane ApplicationsProposal Number: CTS-0414143Principal Investigator: Georgio CartaInstitution: University of VirginiaThe objective of this project is to develop a fundamental understanding of protein partitioning and transport in charged hydrogels. Understanding the transport properties of charged macromolecules in such materials is a key to their development and optimum design. New insights have recently been obtained through microscopic studies, which can provide the basis to develop a mechanistic understanding of transport. This project will expand current efforts in this area with the ultimate goal of developing new adsorbents and membranes for protein separations as well as models to predict their process performance. Protein partitioning and transport in charged dextran gels and agarose-dextran composites will be studied on a microscopic scale focusing on the effects of gel properties and protein molecular weight and charge on equilibrium uptake and mass transfer kinetics. Kinetics of protein ion-exchange in charged poly(acrylamide) gels and charged agarose-dextran composites will be studied using radiotracer techniques to elucidate protein transport under both gradient and tracer diffusion conditions. Modeling single and multicomponent protein transport in ionic gels and application of these models to predict the behavior of column chromatography under processing conditions will be performed. This research will provide a higher level of understanding of transport phenomena in these complex media as well as models to aid the design and optimization of chromatographic processes. The research will have multiple broader impacts. It will guide the development of optimized stationary phases by media manufacturers. It will also provide a basis for the formulation of rate models to predict and optimize chromatographic separations permitting pharmaceutical companies to improve the design and efficiency of bioprocesses. Since separation and purification are often the costliest steps in bioprocessing, there is a critical need for separation scientists and engineers who are trained to develop and implement novel separation media integrating a broad spectrum of experimental and modeling approaches to improve the effectiveness of industrial bioseparations.