Mechanical Manipulation and Characterization of Biological Cells

Mechanical manipulation and characterization of an individual biological cell is currently one of the most exciting research areas in the field of medical robotics. Single cell manipulation is an important process in intracytoplasmic sperm injection (ICSI), pro-nuclei DNA injection, gene therapy, and other biomedical areas. However, conventional cell manipulation requires long training and the success rate depends on the experience of the operator. The goal of this research is to address the drawbacks of conventional cell manipulation by using force and vision feedback for cell manipulation tasks. We hypothesize that force feedback plays an important role in cell manipulation and possibly helps in cell characterization. This dissertation will summarize our research on: 1) the development of force and vision feedback interface for cell manipulation, 2) human subject studies to evaluate the addition of force feedback for cell injection tasks, 3) the development of haptics-enabled atomic force microscope system for cell indentation tasks, 4) appropriate analytical model for characterizing the mechanical property of mouse embryonic stem cells (mESC) and 5) several indentation studies on mESC to determine the mechanical property of undifferentiated and early differentiating (6 days under differentiation conditions) mESC. Our experimental results on zebrafish egg cells show that a system with force feedback capability when combined with vision feedback can lead to potentially higher success rates in cell injection tasks. Using this information, we performed experiments on mESC using the AFM to understand their characteristics in the undifferentiated pluripotent state as well as early differentiating state. These experiments were done on both live as well as fixed cells to understand the correlation between the two during cell indentation studies. Our results show that the mechanical property of undifferentiated mESC differs from early differentiating (6th day) mESC in both live and fixed cells. Thus, we hypothesize that mechanical characterization studies will potentially pave the way for developing a high throughput system with force feedback capability, to understand and predict the differentiation path a particular pluripotent cell will follow. This finding could also be used to develop improved methods of targeted cellular differentiation of stem cells for therapeutic and regenerative medicine