Protein Transport in Charged Gels for Chromatography and Membrane Applications

摘要提案题目：用于色谱和膜应用的带电凝胶中的蛋白质运输提案号：cts -0414143首席研究员：乔治·卡特机构：弗吉尼亚大学该项目的目的是对带电凝胶中的蛋白质分配和运输有一个基本的了解。了解这些材料中带电大分子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制理解提供基础。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。蛋白质在带电荷的葡聚糖凝胶和琼脂糖-葡聚糖复合物中的分配和运输将在微观尺度上进行研究，重点关注凝胶性质、蛋白质分子量和电荷对平衡摄取和传质动力学的影响。在带电荷的聚丙烯酰胺凝胶和带电荷的琼脂糖-葡聚糖复合材料中，蛋白质离子交换动力学将使用放射性示踪技术来阐明梯度和示踪扩散条件下的蛋白质运输。模拟离子凝胶中的单组分和多组分蛋白质运输，并应用这些模型来预测处理条件下柱层析的行为。这项研究将提供对这些复杂介质中的输运现象的更高层次的理解，以及帮助设计和优化色谱过程的模型。这项研究将产生多重更广泛的影响。它将指导介质制造商开发优化的固定相。它还将为预测和优化色谱分离的速率模型的制定提供基础，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处理中成本最高的步骤，因此迫切需要经过培训的分离科学家和工程师来开发和实施整合广泛的实验和建模方法的新型分离介质，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.