Multimodal Membranes for High-throughput Bioseparations

用于高通量生物分离的多模式膜

• 批准号: 1159622
• 负责人: Scott Husson
• 金额: $ 26.21万
• 依托单位: Clemson University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-15 至 2016-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1159622&HistoricalAwards=false
• 关键词: Multimodal; Membranes; throughput; Bioseparations

1159622HussonMultimodal ligands bind proteins by a combination of ionic interactions, hydrophobic interactions and/or hydrogen bonding. Multimodal resin chromatography is gaining popularity as a purification tool for biologics, as it can accommodate purification needs for challenging feedstocks where single mode methods fail. The novelty of the proposed concept is that multimodal ligands are used to develop advanced membrane adsorbers. Using a membrane support is appealing because dynamic protein binding capacities of these materials will not depend on throughput. Thus, volumetric productivity can be very high compared to more traditional chromatography materials. This will help to alleviate the tradeoff that manufacturers must now make between load processing time and dynamic binding capacity. Performance testing will demonstrate that the multimodal functionality can expand the loading operating space for chromatographic separations beyond what is possible with single mode materials. The program will employ and further advance the strategies developed in our lab to design membrane adsorbers with dynamic binding capacities that exceed traditional materials. Specifically, the multimodal membrane adsorbers will be prepared using an advancement called surface-initiated AGET (activators generated by electron transfer) ATRP (atom transfer radical polymerization), which simplifies the modification procedure and enhances membrane manufacturability. This method of polymerization is unique for this application because it gives us molecular-level control over the nanostructure of the modification layer. Fundamental studies on multimodal polymer nanolayers will be done in parallel to understand how the structural properties of these modification layers impact protein binding capacities, adsorption isotherms, and adsorption kinetics. Adsorption data will be used to build a predictive model for protein breakthrough on multimodal membrane adsorbers and compare predictions to experimental breakthrough curves for various proteins under a range of operating conditions. Finally, performance parameters will be compared to commercial products, which currently are limited to resin-based materials. Development of efficient bioseparation processes is recognized as an urgent need facing the pharmaceutical and biotechnology industries, particularly for high dose chronic therapies. The proposed use-inspired basic research program will develop multimodal membranes for high productivity protein chromatography. The integration of advanced multimodal functionality and a membrane adsorber platform will provide a new class of chromatography materials to accomplish selective separations with minimal load conditioning at high volumetric throughput. Considering that a high percentage of the total cost of bioprocesses is due to downstream recovery and purification, our membrane materials are a potentially transformative new purification tool to help the pharmaceutical and biotechnology industries provide lower cost therapeutic products for the US consumer. Societal benefits from research require dissemination to potential users in formats beyond the scholarly journal article. Thus, in addition to disseminating findings through publications and presentations, our program will test a new virtual platform for timely dissemination of research findings. The virtual poster conference will allow face-to-face discussions among researchers in the US and internationally without the associated time and cost for travel to a common physical location.

1159622 HussonMultimodal配体通过离子相互作用、疏水相互作用和/或氢键结合蛋白质。多模式树脂色谱作为生物制品的纯化工具越来越受欢迎，因为它可以适应单一模式方法失败的具有挑战性的原料的纯化需求。所提出的概念的新奇是，多峰配体用于开发先进的膜吸附器。使用膜支持物是有吸引力的，因为这些材料的动态蛋白质结合能力将不依赖于通量。因此，与更传统的色谱材料相比，体积生产率可以非常高。这将有助于减轻制造商现在必须在负载处理时间和动态绑定容量之间做出的权衡。性能测试将证明，多峰功能可以扩展色谱分离的加载操作空间，超出单峰材料的可能范围。该计划将采用并进一步推进我们实验室开发的策略，以设计具有超过传统材料的动态结合能力的膜吸附器。具体而言，将使用称为表面引发的AGET（由电子转移产生的活化剂）ATRP（原子转移自由基聚合）的进步来制备多模态膜吸附器，这简化了改性程序并提高了膜的可制造性。这种聚合方法对于该应用是独特的，因为它使我们对改性层的纳米结构进行分子水平的控制。多峰聚合物纳米层的基础研究将平行进行，以了解这些改性层的结构特性如何影响蛋白质结合能力，吸附等温线和吸附动力学。 吸附数据将用于建立多模式膜吸附器上蛋白质穿透的预测模型，并将预测结果与各种蛋白质在一系列操作条件下的实验穿透曲线进行比较。最后，将性能参数与商业产品进行比较，目前商业产品仅限于树脂基材料。开发有效的生物分离方法被认为是制药和生物技术工业面临的迫切需要，特别是对于高剂量慢性治疗。拟议的使用启发的基础研究计划将开发用于高生产率蛋白质色谱的多模态膜。先进的多模式功能和膜吸附器平台的集成将提供一种新的色谱材料，以实现选择性分离，最小的负载调节，高体积通量。考虑到生物工艺总成本的很大一部分是由于下游回收和纯化，我们的膜材料是一种潜在的变革性新纯化工具，可帮助制药和生物技术行业为美国消费者提供更低成本的治疗产品。研究的社会效益要求以学术期刊文章以外的形式向潜在用户传播。因此，除了通过出版物和演示文稿传播研究结果外，我们的计划还将测试一个新的虚拟平台，以及时传播研究结果。虚拟海报会议将允许美国和国际研究人员之间进行面对面的讨论，而无需花费相关的时间和费用前往共同的物理位置。