Development of Nanowire Needle/Electrode for Site-Specific Delivery of Bio-Probes for Intracellular Living Cell Studies

这个由生物传感/CBET计划授予的NSF奖项支持伊利诺伊大学香槟分校Yu教授的工作，他开发了一套坚固、功能强大且易于应用的纳米线针/电极，以及一种新颖而强大的方法，将微量但可控数量的探针，如量子点、纳米颗粒和分子探针，直接输送到同一细胞或不同细胞中的特定隔间，以最小的侵入性绕过细胞内吞路径。更具体地说，一种新的纳米制造策略将被应用于纳米线针/电极的实用和经济制造，使其与生物科学实验室的一般实践相兼容，并易于广泛使用。基于硫醇的偶联化学用于将探针连接到纳米线针/电极表面，随后将被开发用于实现附着的探针在细胞或亚细胞结构内的近瞬时和靶向释放。我们将进一步展示磁性纳米颗粒的位置特异性传递和细胞内的力学研究，以确定应力传播的异质性，这对于了解细胞的机械转导路径非常重要。因此，这一发展代表着对现有方法的潜在变革性改进，并可以开辟新的场所，为活细胞的高级生物学研究提供创新策略，否则这些策略是不切实际的，甚至是不可能的。在这项建议中开发的新工具将可供研究界成员使用，以大大有利于对细胞生物学中多样化和基本问题的扩展研究。该项目开发的方法和技术也是吸引学生和公众教育的主题。

0933223YuThis NSF award by the Biosensing /CBET program supports work by Professor Yu at University of Illinois at Urbana-Champaign to develop a set of robust, functional and readily-applicable nanowire needles/electrodes and a novel and powerful method for direct delivery of a trace but controlled amount of probes, such as QDs, nanoparticles and molecular probes, into the specific compartments in the same cell or different cells with minimal intrusiveness, bypassing the endocytic pathways.More specifically, a new nanofabrication strategy will be applied for the practical and economical fabrication of the nanowire needle/electrode so to make it compatible with the general practice in bioscience laboratory and readily adaptable for broad use. Thiol-based conjugation chemistry for attaching probes onto nanowire needle/electrode surfaces will be designed and later exploited for realizing near instantaneous and targeted release of the attached probes inside cells or sub-cellular structures. We will further demonstrate the site specific delivery of magnetic nanoparticles and the intracellular mechanical studies with magnetic twisting cytometry to determine heterogeneity of stress propagation, important for understanding mechanotransduction pathways of cells. The development represents thus a potentially transformational improvement over the existing methods, and can open up novel venues to conjure innovative strategies, which otherwise would be impractical or even impossible, for the advanced biological studies of living cells. New tools developed in this proposal will be made available for members in the research community to significantly benefit the expanded studies of diversified and fundamental problems in cell biology. The method and technology developed in this project are also appealing subjects for the education of students and the public.