Mechanical manipulation and characterization of biological cells - a micro/nanorobotics and microelectromechanical systems (MEMS) approach

生物学和医学的进步需要能够高速机械操纵细胞和表征细胞特性的技术。缺乏这些技术是利用正常细胞和恶性细胞之间的生物物理差异进行遗传研究、分子筛选和疾病诊断等领域的障碍。与生物化学技术相比，用于操纵和表征生物细胞的机械技术在很大程度上处于探索之中。该研究计划将开发用于机械操纵和表征单细胞的创新工具，系统和技术，追求三个主要战略方向，即：（1）用于分子/基因筛选的高速微机器人细胞注射;（2）用于癌症基因定位的扫描电子显微镜内亚细胞结构的纳米机器人操纵;（3）用于癌症基因定位的纳米机器人操纵。以及（3）用于疾病诊断的正常和恶性细胞的高速机械表征。该研究将涉及来自光学和电子显微镜的视觉反馈的处理，多种传感模式（视觉，力和位置）的同化和亚微米和亚纳牛顿水平的自动化，以及皮升细胞成分的操纵。我们将开发新的设计和制造工艺，以构建新型的微纳器件。我们将创建集成微纳工具的微纳机器人系统，并开发智能操作策略，用于在光学和电子显微镜下自动操作和表征单细胞和亚细胞内容物。这项研究所带来的新技术和系统将使我们能够解决一系列难以用现有方法完成的单细胞研究，特别是在遗传学，生殖生物学，癌症研究和疾病诊断方面。除了MEMS和微纳米机器人领域的创新外，该研究计划还将改变细胞的机械操作方式，并通过实现对单细胞的准确，自动和有效操作来表征。

Advances in biology and medicine require enabling techniques for mechanically manipulating cells and characterizing cellular properties at a high speed. The lack of these techniques is a barrier to areas such as genetic research, molecule screening, and disease diagnosis utilizing biophysical differences between normal and malignant cells. Compared with biochemical techniques, mechanical techniques for manipulating and characterizing biological cells are largely under explored. This research program will develop innovative tools, systems, and techniques for mechanically manipulating and characterizing single cells, pursuing three major strategic directions, namely: (1) high-speed microrobotic cell injection for molecule/gene screening; (2) nanorobotic manipulation of sub-cellular structures within scanning electron microsopes for cancer gene mapping; and (3) high-speed mechanical characterization of normal and malignant cells for disease diagnosis. The research will involve the processing of visual feedback from optical and electron microscopy, assimilation of multiple sensing modalities (vision, force, and position) and automation at the sub-micrometer and sub-nanoNewton levels, and the manipulation of pico-liter cellular components. We will develop new designs and fabrication processes to construct new types of micro-nano devices. We will create micro-nanorobotic systems integrating micro-nano tools, and develop intelligent manipulation strategies for automated manipulation and characterization of single cells and sub-cellular contents under optical and electron microscopy. New techniques and systems made possible by this research will allow us to address a range of single-cell studies that are difficult to fulfill with existing methods, particularly in genetics, reproductive biology, cancer research, and disease diagnostics. Besides innovations in the fields of MEMS and micro-nanorobotics, this research program will change the way cells are mechanically manipulated and characterized by enabling accurate, automatic, and efficient manipulation of single cells.