Protein Adsorption and Transport in Chromatographic Bioprocessing

色谱生物加工中的蛋白质吸附和运输

• 批准号: 0828590
• 负责人: Abraham Lenhoff
• 金额: $ 30万
• 依托单位: University of Delaware
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0828590&HistoricalAwards=false
• 关键词: Protein; Adsorption; Transport; Chromatographic; Bioprocessing

CBET-0828590LenhoffThis NSF award by the Chemical and Biological Separations program supports work by Professor Abraham Lenhoff at the University of Delaware to characterize quantitatively the structure-performance relationship in ion-exchange chromatography of proteins. The results of such analyses will then be used to develop systematic approaches for predicting chromatographic behavior on the basis of a small number of relevant experimental measurements. Ion-exchange chromatography is a major unit operation in industrial bioprocessing, and the prevalence of empirical screening methods can make efficient methods for reducing the scope of trial-and-error methods of optimization particularly valuable. The proposed research will distinguish between traditional adsorbents on consolidated polymeric or gel-like base matrices, and polymer-modified phases in which additional flexible inclusions of various kinds have been shown to offer some performance improvements. For the traditional adsorbents, prior work has produced approaches to predict adsorption isotherms and transport properties to a degree that should allow effective prediction of overall chromatographic behavior. Such capabilities are still lacking for the polymer-modified adsorbents, however. We will therefore measure retention and transport properties for the polymer-modified adsorbents and seek to correlate them with structural characteristics of the materials. In addition, starting with traditional media and moving on to polymer-modified ones, mechanistic methods will be used to develop predictive models of protein loading and elution in packed columns.The proposed research should have an impact in several areas. First, it should contribute significantly to improving the efficiency of conceptual and detailed design of chromatographic steps in bioprocessing. A complementary contribution will be to stationary-phase design, where suitable use of our results can allow desirable characteristics to be designed into such materials. Second, the research will be an effective educational vehicle for training of graduate and undergraduate students; numerous such students who have worked on previous projects of this kind are employed in the biotech and pharma industries. Finally, the proposed research will include a component to disseminate the findings to the larger community interested in chromatographic research and practice by making computational packages for column modeling available as both Matlab routines and as applets that can be run in any web browser.

CBET-0828590 Lenhoff化学和生物分离项目的NSF奖项支持特拉华州大学Abraham Lenhoff教授的工作，以定量表征蛋白质离子交换色谱中的结构-性能关系。 这些分析的结果将被用来开发系统的方法，预测色谱行为的基础上，少量的相关实验测量。 离子交换色谱是工业生物处理中的主要单元操作，经验筛选方法的流行可以使用于减少优化的试错法的范围的有效方法特别有价值。 拟议的研究将区分传统的吸附剂在巩固的聚合物或凝胶状的基础矩阵，和聚合物改性相，其中额外的各种灵活的夹杂物已被证明提供一些性能改进。 对于传统的吸附剂，以前的工作已经产生的方法来预测吸附等温线和运输性能的程度，应该允许有效预测的整体色谱行为。然而，聚合物改性的吸附剂仍然缺乏这种能力。因此，我们将测量聚合物改性的吸附剂的保留和传输性能，并试图将它们与材料的结构特征相关联。 此外，从传统介质开始，到聚合物改性介质，机械方法将用于开发填充柱中蛋白质加载和洗脱的预测模型。 首先，它应该有助于显着提高效率的概念和详细设计的色谱步骤在生物加工。一个互补的贡献将是静止相的设计，在适当使用我们的结果可以允许理想的特性被设计成这样的材料。 其次，这项研究将成为培养研究生和本科生的有效教育工具;许多从事过此类项目的学生都在生物技术和制药行业工作。 最后，拟议的研究将包括一个组件，通过使柱建模计算包既作为Matlab例程又作为可在任何网络浏览器中运行的小程序，将研究结果传播给对色谱研究和实践感兴趣的更大社区。