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

EAGER：IMPRESS-U：用于细胞分选的高通量敏捷接口

• 批准号: 2401713
• 负责人: Sergiy Minko
• 金额: $ 30万
• 依托单位: University of Georgia Research Foundation Inc
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2024
• 资助国家: 美国
• 起止时间: 2024-01-01 至 2025-12-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2401713&HistoricalAwards=false
• 关键词: EAGER; IMPRESS; throughput; agile; interfaces

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.

这个印象深刻的项目将由NSF，美国国家科学院和波兰国家科学中心共同支持。这项研究将以合作伙伴关系进行，该合作伙伴关系将美国佐治亚大学统治；乌克兰冷凝物理学研究所；和波兰的Rzeszow大学医学院。该印象-U项目的美国部分是由国际科学与工程与英语/CBET计划共同资助的。第1部分这个项目最近出现了用于生物医学使用的活细胞可扩展生产的问题；具体而言，该项目着重于高质量的细胞分类和分离。成人细胞重编程以诱导多能茎（IPS）细胞而进行了细胞治疗领域的革命性进步，这些细胞可能会发展为每种细胞类型和形成器官。具有愈合特性的靶细胞有效地将治疗细胞与潜在危险，受损或转化的（肿瘤）细胞分开。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损失的重大风险。在这个项目中，研究人员旨在基于细胞与特殊工程动态聚合物材料（智能表面）的相互作用，开发一种替代性变革，可扩展，廉价，细胞和无抗体细胞分选方法。这种新的细胞分选方法直接与基于其表面组成分类微观颗粒的基本问题的解决方案有关。协同，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进行这项研究。该项目研究计划为培训科学和工程专业学生和早期研究人员的潜水团队提供了足够的机会。第2部分项目旨在开发新的方法，以基于对吸附剂的亲和力而无需使用特定抗体，以对吸附剂的亲和力进行分类。当基于分子间力的组合实现分子分离的高效率时，这些新方法类似于色谱法，这对于每个分子通常是独特的。由于接触表面积增加，因此色谱法不能用于细胞吸附剂相互作用的高能量，从而导致准反式细胞吸附。研究人员提出了一个高风险 - 高付款项目，以开发一种使用聚合物刷或网络的动态接口来增强细胞解吸的方法。足以使细胞解吸的力是通过在水性培养基中发生相变的界面上的渗透而产生的。研究小组选择了接近最佳细胞培养温度的较低临界溶液温度（LCST）周围的热诱导的相行为变化。通过在LCST以下和更高的温度下进行多个振荡循环，可以在其肿胀和凝结状态之间替代聚合物材料。界面设计是由粘合剂静态和动态热敏贴片制成的纳米结构的薄聚合物层。粘合剂斑块将与提供基于亲和力相互作用的主要功能组的组合。动态贴片将定期推出具有较低亲和力的细胞，以解放表面官能团以较高亲和力的以下连接，从而引导系统达到基于亲和力的化学平衡。界面将根据原子分子动态模拟和粗粒化建模的组合进行设计。分离机制，其效率和歧视细胞的质量将通过模型的细胞组合进行验证。该奖项反映了NSF的法定任务，并使用基金会的知识分子优点和更广泛的影响审查标准，通过评估被认为是宝贵的支持。