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.

该 IMPRESS-U 项目将得到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的共同支持，该研究将与美国佐治亚大学凝聚态物理研究所合作进行。 IMPRESS-U 项目的美国部分由国际科学与工程办公室和 ENG/CBET 项目共同资助。 1该项目解决了最近出现的生物医学用途活细胞可扩展制造的问题；具体而言，该项目重点关注高质量细胞分选和分离，通过成体细胞重编程诱导多能干细胞 (iPS) 取得了革命性进展。 ）细胞，这些细胞有可能发育成各种细胞类型并形成器官，应该使用经济实惠的方法快速生长足够数量的治疗细胞与潜在危险的、受损的或转化的（致瘤的）细胞。 ）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，研究人员的目标是开发一种可替代的、可扩展的、廉价的、对细胞敏感的、无抗体的细胞分选方法。这种新的细胞分选方法基于细胞与特殊设计的动态聚合物材料（智能表面）的相互作用，直接关系到根据表面成分分选微观颗粒这一基本问题的解决方案。将进行此通过独特地结合化学、化学工程、材料科学和微制造方面的专业知识进行研究。该项目研究计划为培训由科学和工程专业的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。第二部分该项目旨在开发新的分类方法。这些新方法类似于色谱法，基于分子间力的组合实现分子分离，而分子间力通常对每个单独的分子都是独特的。色谱法无法应用于细胞分选，因为接触表面积增加导致细胞与吸附剂相互作用的能量较高，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来开发一种方法来分选细胞。使用聚合物刷或网络的动态界面促进细胞解吸，该力将通过在水介质中经历相变的界面产生。在接近最佳细胞培养温度的较低临界溶液温度 (LCST) 附近的相行为 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膨胀状态和凝聚状态之间交替。界面设计是一种纳米结构薄层。由粘性静态和动态热敏贴片制成的聚合物层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以进行后续附着。具有更高亲和力的细胞，引导系统实现基于亲和力的化学平衡，该界面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。被区分的细胞将通过模型细胞混合物进行验证。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力优点和更广泛的影响审查标准进行评估，被认为值得支持。