EAGER: IMPRESS-U: High-throughput agile interfaces for cell sorting

该IMPRESS-U项目将由NSF、美国国家科学院和波兰国家科学中心共同支持。这项研究将在合作伙伴关系，团结在美国的格鲁吉亚大学进行;乌克兰凝聚态物理研究所和波兰热舒夫大学医学院。IMPRESS-U项目的美国部分由国际科学与工程办公室和ENG/CBET计划共同资助。第1部分本项目解决了最近出现的问题，可规模化生产的活细胞用于生物医学用途;特别是，该项目的重点是高质量的细胞分选和分离。细胞治疗领域的革命性进展是通过成体细胞重编程来诱导多能干细胞（iPS），这些细胞可以发育成各种细胞类型并形成器官。具有愈合特性的靶细胞应该使用负担得起的方法以足够的量快速生长。有效地将治疗性细胞与潜在危险的、受损的或转化的（致瘤的）细胞分离是至关重要的。所有现有的基于抗体的细胞分选程序也产生机械细胞损伤和损失的重大风险。在这个项目中，研究人员的目标是开发一种替代的变革性的，可扩展的，廉价的，微妙的细胞和无抗体的细胞分选方法，基于细胞与特别设计的动态聚合物材料（智能表面）的相互作用。这种细胞分选的新方法直接涉及基于其表面组成分选微观颗粒的基本问题的解决方案。协同，跨学科，国际团队将通过结合化学，化学工程，材料科学和微制造方面的独特专业知识进行这项研究。该项目的研究计划提供了充足的机会，培养一个多元化的团队的科学和工程专业的学生和早期的职业研究人员。第2部分本项目的目的是开发新的方法，分选哺乳动物细胞的基础上，他们的亲和力吸附剂，而不使用特定的抗体。这些新方法类似于色谱法，即基于分子间力的组合实现高效率的分子分离，分子间力通常对每个分子都是独特的。色谱法不能应用于细胞分选，因为细胞-吸附剂相互作用的高能量是由于增加的接触表面积导致准不可逆的细胞吸附。研究人员提出了一个高风险高回报的项目，开发一种使用聚合物刷或网络的动态界面来促进细胞解吸的方法。通过在水介质中经历相变的界面处的渗透将产生足以使细胞解吸的力。研究小组选择了接近最佳细胞培养温度的最低临界溶解温度（LCST）附近的相行为的热诱导变化。通过在低于和高于LCST的温度下进行多次振荡循环，可以使聚合物材料在其溶胀状态和凝聚状态之间交替。界面设计是一个纳米结构的薄聚合物层制成的粘合剂静态和动态热敏补丁。粘合剂贴片将具有提供基于亲和力的相互作用的主要官能团的组合。动态贴片将周期性地推开具有较低亲和力的细胞，以释放表面官能团，用于随后具有较高亲和力的细胞的附着，引导系统朝向基于亲和力的化学平衡。这些接口将基于原子分子动力学模拟和粗粒度建模的结合进行设计。分离机制，其效率，和区分细胞的质量将与模型细胞mixed.This奖项反映了NSF的法定使命，并已被认为是值得的支持，通过使用基金会的智力价值和更广泛的影响审查标准进行评估。

This IMPRESS-U project will be jointly supported by NSF, US National Academy of Sciences, and National Science Centre of Poland. The research will be conducted in collaborative partnership that unites the University of Georgia in the U.S.; the Institute for Condensed Matter Physics in Ukraine; and the Medical College, Rzeszow University in Poland. The U.S. portion of this IMPRESS-U project is co-funded by the Office of International Science and Engineering and ENG/CBET program. Part 1This project addresses recently emerged problems of scalable manufacturing of live cells for biomedical use; specifically, the project focuses on high-quality cell sorting and separation. Revolutionary progress in the field of cell therapy was made by adult cell reprogramming to induce pluripotent stem (iPS) cells, which can potentially develop into every cell type and form organs. The target cells with healing properties should be quickly grown in sufficient amounts using affordable methods. It is critical to effectively separate therapeutic cells from potentially dangerous, damaged, or transformed (tumorigenic) cells. All existing antibody-based cell sorting procedures also generate a significant risk for mechanical cell damage and loss. In this project, the researchers aim to develop an alternative transformative, scalable, inexpensive, delicate for the cells, and antibody-free cell sorting method based on the interactions of cells with specially engineered dynamic polymeric materials (smart surfaces). This new method of cell sorting relates directly to the solution of the fundamental problem of sorting microscopic particles based on their surface composition. The synergistic, interdisciplinary, international team will conduct this research by combining unique expertise in chemistry, chemical engineering, materials science, and micromanufacturing. The project research program provides ample opportunities for training a diverse team of science and engineering students and early-career researchers.Part 2This project aims to develop new methods for sorting mammalian cells based on their affinity to adsorbents without the use of specific antibodies. These new methods resemble chromatography when the high efficiency of molecular separation is achieved based on a combination of intermolecular forces, which are generally unique for each individual molecule. Chromatography cannot be applied for cell sorting because of the high energy of cell-adsorbent interactions due to an increased contact surface area that results in quasi-irreversible cell adsorption. The researchers propose a high-risk – high-payoff project to develop a method to boost cell desorption using dynamic interfaces of polymer brushes or networks. The force sufficient for cell desorption will be generated by osmosis at the interface that undergoes phase transition in aqueous media. The research team selects the thermo-induced changes in the phase behavior around the lower critical solution temperature (LCST) close to the optimal cell culture temperature. By multiple oscillating cycles for temperatures below and above LCST, one can alternate the polymer material between its swollen and condensed states. The interface design is a nanostructured thin polymer layer made of adhesive static and dynamic thermosensitive patches. The adhesive patches will have a combination of major functional groups providing affinity-based interactions. The dynamic patches will periodically push off cells with a lower affinity to liberate the surface functional groups for the following attachment of the cells with a higher affinity, guiding the system towards affinity-based chemical equilibrium. The interfaces will be engineered based on the combination of atomistic molecular dynamic simulations and coarse-grained modeling. The separation mechanism, its efficiency, and the quality of the discriminated cells will be verified with model cellular mixes.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.