Multimodal Membranes for High-throughput Bioseparations

多模态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。多模态树脂色谱法作为生物制品的纯化工具越来越受欢迎，因为它可以适应单模方法失败的具有挑战性的原料的纯化需求。提出的概念的新颖之处在于多模态配体用于开发先进的膜吸附剂。使用膜支持是有吸引力的，因为这些材料的动态蛋白质结合能力将不依赖于吞吐量。因此，与更传统的色谱材料相比，体积效率可以非常高。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，多模态功能可以扩大色谱分离的加载操作空间，超出单模态材料的可能范围。该项目将采用并进一步推进我们实验室开发的策略，设计具有超越传统材料的动态结合能力的膜吸附剂。具体来说，多模态膜吸附剂将使用一种称为表面启动AGET（由电子转移产生的活化剂）ATRP（原子转移自由基聚合）的进展来制备，这简化了改性过程并提高了膜的可制造性。这种聚合方法在这种应用中是独一无二的，因为它使我们能够在分子水平上控制修饰层的纳米结构。多模态聚合物纳米层的基础研究将同时进行，以了解这些修饰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态膜吸附器上蛋白质突破的预测模型，并将预测结果与各种蛋白质在一系列操作条件下的实验突破曲线进行比较。最后，性能参数将与商业产品进行比较，目前仅限于树脂基材料。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，特别是对于高剂量慢性疗法。提出的用途启发的基础研究计划将开发用于高效蛋白质色谱的多模态膜。先进的多模态功能和膜吸附平台的集成将提供一类新的色谱材料，以最小的负载调节在高容量吞吐量下完成选择性分离。考虑到生物工艺总成本的很大一部分是由于下游的回收和净化，我们的膜材料是一种潜在的革命性的新型净化工具，可以帮助制药和生物技术行业为美国消费者提供更低成本的治疗产品。研究的社会效益需要以学术期刊文章以外的形式传播给潜在用户。因此，除了通过出版物和演讲传播研究成果外，我们的项目还将测试一个新的虚拟平台，以便及时传播研究成果。虚拟海报会议将允许美国和国际上的研究人员进行面对面的讨论，而无需花费相关的时间和费用前往一个共同的物理地点。

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.