Multimodal Membranes for High-throughput Bioseparations

1159622 Husson多模式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。多模式树脂层析作为生物制品的一种纯化工具越来越受欢迎，因为它可以满足具有挑战性的原料的纯化需求，在单模式方法失败的情况下。这一概念的新颖之处在于，多模式配体被用来开发先进的膜吸附器。使用膜载体是很有吸引力的，因为这些材料的动态蛋白质结合能力将不依赖于吞吐量。因此，与更传统的层析材料相比，体积生产率可以非常高。这将有助于缓解制造商现在必须在加载处理时间和动态结合能力之间进行权衡。性能测试将证明，多模式功能可以扩展色层分离的加载操作空间，超出单模式材料的可能。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。具体地说，多模膜吸附器将使用一种名为表面引发的电子转移激活剂(ATRP)的先进技术来制备，它简化了修饰过程并提高了膜的可制造性。这种聚合方法对于这种应用是独一无二的，因为它使我们能够在分子水平上控制改性层的纳米结构。多模式聚合物纳米层的基础研究将并行进行，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。吸附数据将被用来建立多模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。开发高效的生物分离工艺被认为是制药和生物技术行业面临的迫切需要，特别是大剂量慢性疗法。拟议的受使用启发的基础研究计划将开发用于高生产率蛋白质层析的多模膜。先进的多模式功能和膜吸附平台的集成将提供一种新的层析材料，以最小的负载条件在高容量吞吐量下实现选择性分离。考虑到生物工艺总成本的很高比例是由于下游回收和提纯，我们的膜材料是一种潜在的变革性新净化工具，可以帮助制药和生物技术行业为美国消费者提供成本更低的治疗产品。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成果外，我们的计划还将测试一个新的虚拟平台，用于及时传播研究成果。虚拟海报会议将允许美国和国际研究人员进行面对面的讨论，而不需要前往共同的物理地点旅行的相关时间和成本。

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.