Capillary-Channeled Polymer Fibers: Chemistries and Structures for Protein Separations and Analytics

毛细管通道聚合物纤维：蛋白质分离和分析的化学和结构

• 批准号: 1307078
• 负责人: Richard Marcus
• 金额: $ 43.43万
• 依托单位: Clemson University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-15 至 2017-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1307078&HistoricalAwards=false
• 关键词: Capillary; Channeled; Polymer; Fibers; Chemistries

With support from the Chemical Measurement and Imaging Program (Division of Chemistry), Professor R. Kenneth Marcus, his collaborators and their students at Clemson University are developing and characterizing capillary-channeled polymer (C-CP) fibers as stationary phases for rapid processing of biomacromolecules. C-CP materials are amenable to a wide range of column formats (microbore to preparative) and offer advantages for macromolecular separations relative to traditional porous-bead, membrane, and monolithic stationary phases, including low flow resistance, minimization of size-exclusion effects, much higher mass transfer rates, and high mobile phase velocities (not necessarily volume flow rates) and gradient rates without sacrificing chromatographic performance. Proposed studies are directed at exploiting the basic characteristics of C-CP fiber columns to affect highly productive and selective separations in the realm of protein analytics. This work is necessarily interdisciplinary, involving cooperation between analytical and biochemistries, chemical engineering, and textile science researchers. A two-pronged approach will be taken. The first research area will focus on modification of surface chemistries to affect high levels of selectivity. The modifications will be evaluated not only for their chemical selectivity, but also the ligand utilization efficiency, susceptibility to non-specific binding, and robustness in terms of process cycling (including caustic clean in place procedures). In all cases, performance metrics will be directly compared to columns packed with commercially available stationary phases. The second research area looks beyond chromatographic column structures, involving the characterization and optimization of the hydrodynamic aspects of depletion/capture columns and micropipette tip constructs and how they affect performance of in-line and discrete sample protein processing, respectively.Just as scientists catalog all the genes in an organism's DNA to study its biological function, they are also developing protein analytics to eventually be able to catalog the varying collections of proteins an organism uses to carry out its functions. Complete, accurate protein catalogs are critical to the development of more effective pharmaceuticals, diagnostic tools and the advance of molecular medicine. They rely heavily on efficient separations technology because biological samples are so complex. This work conducted by Prof. Marcus will advance protein analytics by developing separations technology that can analyze more complex samples more accurately in less time. The studies involve a collaborative effort between research groups from the Department of Chemistry and the School of Materials Science and Engineering, both of which are affiliated with the Clemson University Center for Advanced Engineering of Fibers and Films (CAEFF). Collaborations with federal laboratories are also planned. Successful completion of the work may lead to new commercial ventures in the textile and pharmaceutical industries in South Carolina and elsewhere. CAEFF programs expose graduate students to science and research philosophies across the science/engineering interface. The low cost and simplicity of constructing C-CP fiber columns will allow their use in newly designed undergraduate and graduate laboratory experiments illustrating the basic principles of protein chromatography.

在化学测量和成像计划(化学系)的支持下，R.Kenneth Marcus教授和他的合作者以及他们在克莱姆森大学的学生正在开发和表征毛细管通道聚合物(C-CP)纤维作为生物大分子快速处理的固定相。C-CP材料适用于多种柱型(从微孔到制备)，与传统的多孔珠、膜和整体固定相相比，C-CP材料在大分子分离方面具有优势，包括低流动阻力、最大限度地减少尺寸排斥效应、更高的传质速率、以及高流动相速度(不一定是体积流速)和梯度速率，而不会牺牲色谱性能。拟议的研究旨在开发C-CP纤维柱的基本特性，以影响蛋白质分析领域的高效和选择性分离。这项工作必须是跨学科的，涉及分析和生物化学、化学工程和纺织科学研究人员之间的合作。我们将采取双管齐下的方法。第一个研究领域将集中在表面化学修饰以影响高水平的选择性。将不仅评估这些修饰的化学选择性，还将评估配体利用效率、对非特异性结合的敏感性以及过程循环(包括腐蚀性现场清洗过程)方面的稳健性。在所有情况下，性能指标都将直接与填充有商业用途的固定相的色谱柱进行比较。第二个研究领域超越了色谱柱结构，涉及耗尽/捕获柱和微吸管尖端结构的流体动力学方面的表征和优化，以及它们分别如何影响在线和离散样本蛋白质处理的性能。就像科学家对生物体DNA中的所有基因进行编目以研究其生物功能一样，他们也在开发蛋白质分析，以最终能够对生物体用于执行其功能的不同蛋白质集合进行编目。完整、准确的蛋白质目录对于开发更有效的药物、诊断工具和分子医学的进步至关重要。他们严重依赖高效的分离技术，因为生物样本非常复杂。马库斯教授的这项工作将通过开发分离技术来推动蛋白质分析，这种技术可以在更短的时间内更准确地分析更复杂的样品。这些研究涉及化学系和材料科学与工程学院的研究小组之间的合作，这两个学院都隶属于克莱姆森大学纤维和薄膜高级工程中心(CAEFF)。与联邦实验室的合作也在计划之中。这项工作的成功完成可能会在南卡罗来纳州和其他地方的纺织和制药行业带来新的商业冒险。CAEFF项目让研究生在科学/工程界面上接触到科学和研究哲学。构建C-CP纤维柱的低成本和简单性将使它们能够用于新设计的本科生和研究生实验室实验，说明蛋白质层析的基本原理。