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

这个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。这项研究将与美国佐治亚大学、乌克兰凝聚态物理研究所和波兰Rzeszow大学医学院合作进行。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。第1部分这个项目解决了最近出现的生物医学用活细胞可扩展制造的问题；具体地说，该项目专注于高质量的细胞分类和分离。在细胞治疗领域取得了革命性的进展，成体细胞重新编程诱导多能干细胞(IPS)，这种细胞有可能发育成各种类型的细胞并形成器官。应该使用负担得起的方法快速培养出足够数量的具有愈合能力的靶细胞。有效地将治疗性细胞与潜在危险、受损或转化的(致瘤)细胞分开是至关重要的。所有现有的基于抗体的细胞分选程序也会产生很大的细胞机械性损伤和丢失风险。在这个项目中，研究人员的目标是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，开发一种替代的、可转化的、可扩展的、廉价的、针对细胞的精细的、无抗体的细胞分选方法。这种新的细胞分选方法直接关系到根据微观颗粒的表面组成对其进行分选这一根本问题的解决。协同的、跨学科的国际团队将结合化学、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。项目研究计划为培养不同的理工科学生和早期研究人员提供了充足的机会。本项目旨在开发新的方法，根据哺乳动物细胞对吸附剂的亲和力，在不使用特定抗体的情况下对其进行分选。这些新方法类似于基于分子间力的组合实现分子分离的高效率的层析，分子间力通常对每个单独的分子是唯一的。由于细胞-吸附剂相互作用的高能，增加了接触表面积，导致准不可逆的细胞吸附，因此层析不能用于细胞分选。研究人员提出了一个高风险-高回报的项目，以开发一种使用聚合物刷子或网络的动态界面来促进细胞解吸的方法。在水介质中，足够的细胞脱附力将通过在经历相变的界面上的渗透作用产生。研究小组选择接近最佳细胞培养温度的较低临界溶液温度(LCST)附近的热诱导相态变化。通过在低于和高于LCST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和凝聚状态之间交替。界面设计是由粘合的静态和动态热敏贴片组成的纳米结构薄聚合物层。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。动态贴片会周期性地将亲和力较低的细胞推开，释放表面官能团，以便随后与亲和力较高的细胞附着，引导系统走向基于亲和力的化学平衡。界面将基于原子分子动力学模拟和粗粒度建模的组合进行设计。分离机制、效率和被区分细胞的质量将通过模型细胞混合物进行验证。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.