Reversible Cell Capture and Release for Cell Separation

化学和生物分离计划的NSF奖项支持Yong Wang教授应用核酸适体创建细胞分离方法的工作。细胞分离不仅在基础生物学研究中，而且在临床诊断中发挥着重要作用。目前的细胞分离方法主要依赖于抗体介导的细胞识别。然而，抗体或抗体功能化系统由于其容易丧失功能和难以逆转抗体-细胞相互作用而经常表现出限制。这些缺点会显著限制下游细胞分析和应用。因此，显然需要发现和工程化用于细胞分离应用的替代生物分子配体。由于核酸适体不同于抗体，具有许多优点，如高亲和力和特异性，对苛刻条件的极大耐受性，以及易于用标准化学方法合成，因此我们假设核酸适体可以用于开发新的细胞分离方法。为了验证这一假设，我们将系统地研究适体和细胞受体之间的生物分子相互作用，了解多组分系统中的分子间识别，并探索适体介导的细胞捕获和释放用于细胞分离。 该研究项目的成功不仅可以开发一种新的、通用的细胞分离方法，而且可以丰富现有的生物分子识别知识，并为核酸研究提供资源信息。除了这些技术影响外，该计划还将对人力资源和教育产生影响。首先，这个项目将为学生提供一个跨学科的环境，学习生物分子工程，动力学分析，材料开发和细胞分离。学生将不仅能够获得动手研究技能，还可以学习分析，沟通，协作和创新技能。其次，PI将通过与当地高中合作启动一项新的推广计划，并不断招收K-12学生和教师到实验室学习尖端技术。第三，学生的研究成果将通过在同行评审的期刊上发表文章和在国家/国际会议上发表演讲而广泛传播。

This NSF award by the Chemical and Biological Separations program supports work by Professor Yong Wang to apply nucleic acid aptamers to create a cell separation method. Cell separation has played an essential role not only in basic biological research, but in clinical diagnosis. Current methods for cell separation are mostly dependent on antibody-mediated cell recognition. However, antibodies or antibody-functionalized systems often exhibit limitations due to their easiness of losing functions and difficulty of reversing antibody-cell interactions. These shortcomings can significantly limit downstream cell analysis and applications. Thus, there is a clear need to discover and engineer alternative biomolecular ligands for cell separation applications. Because nucleic acid aptamers are different from antibodies and have numerous merits such as high affinity and specificity, great tolerance of harsh conditions, and easy synthesis with a standard chemical procedure, we hypothesize that nucleic acid aptamers can be used to develop a new method for cell separation. To test this hypothesis, we will systematically investigate biomolecular interactions between aptamers and cell receptors, understand intermolecular recognition in a multicomponent system, and explore the aptamer-mediated cell capture and release for cell separation. The success of this research project will not only enable the development of a novel, universal cell separation method, but also enrich the current knowledge of biomolecular recognition and provide resourceful information for nucleic acid research. In addition to these technological impacts, this program will make impacts on human resource and education. First, this project will provide students with an interdisciplinary environment to learn biomolecular engineering, kinetic analysis, material development, and cell separation. The students will be able not only to acquire hands-on research skills, but also to learn analytical, communication, collaboration, and innovation skills. Second, the PI will initiate a new outreach program by collaborating with local high schools and continuously enroll K-12 students and teachers to the lab to learn cutting-edge techniques. Third, the students' research findings will be widely disseminated through publications in peer-refereed journals and presentations at national/international conferences.