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

IMPRESS-U项目将由美国国家科学基金会、美国国家科学院和波兰国家科学中心联合支持。这项研究将在合作伙伴关系下进行，联合美国佐治亚大学；乌克兰凝聚态物理研究所；以及波兰热索夫大学医学院。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。第一部分：该项目解决了最近出现的生物医学用活细胞的可扩展制造问题；具体来说，该项目侧重于高质量的细胞分选和分离。成体细胞重编程诱导多能干细胞（iPS）是细胞治疗领域的革命性进展，iPS细胞有可能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快速生长到足够数量。有效地将治疗细胞与潜在危险、受损或转化（致瘤）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会产生机械细胞损伤和丢失的重大风险。在这个项目中，研究人员的目标是开发一种可替代的、可扩展的、廉价的、精致的细胞和基于细胞与特殊工程动态聚合物材料（智能表面）相互作用的无抗体细胞分选方法。这种新的细胞分选方法直接关系到根据表面组成对微观颗粒进行分选的基本问题的解决。这个协同的、跨学科的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来开展这项研究。项目研究计划为培养由理工科学生和早期职业研究人员组成的多元化团队提供了充足的机会。本项目旨在开发不使用特异性抗体的基于吸附剂亲和力的哺乳动物细胞分选新方法。这些新方法类似于色谱法，基于分子间力的组合实现高效率的分子分离，而分子间力通常对每个单独的分子都是独特的。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，由于增加的接触表面积，导致准不可逆细胞吸附。研究人员提出了一个高风险高回报的项目，即开发一种利用聚合物刷或网络的动态界面来促进细胞脱附的方法。在水介质中发生相变的界面处的渗透作用将产生足够的细胞解吸力。研究小组选择了接近最佳细胞培养温度的低临界溶液温度（LCST）附近的热诱导相行为变化。通过在低于和高于最低温度的温度下进行多次振荡循环，人们可以在聚合物材料的膨胀状态和冷凝状态之间交替。界面设计是由粘接的静态和动态热敏贴片组成的纳米结构薄聚合物层。粘接贴片将具有主要功能基团的组合，提供基于亲和力的相互作用。动态贴片会周期性地推开亲和力较低的细胞，释放表面官能团，供亲和力较高的细胞后续附着，引导系统走向基于亲和力的化学平衡。接口的设计将基于原子分子动力学模拟和粗粒度建模的结合。分离机制、效率和鉴别细胞的质量将通过模型细胞混合物进行验证。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.