Cell Manipulation and Characterization
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Motivation: 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, therapeutic and regenerative medicine, 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.
Project Highlights:
- Force and Vision Feedback Interface for Cell Injection: We have developed a cell injection system which has the capability to measure forces in ¦ĚN range and provide a haptic display of the cell injection forces in real time. Using this system, we conducted human factors studies to evaluate the role of force feedback in cell injection tasks. The experiments were performed on zebrafish egg cells (diameter: 600 uN - 1 mm), since it is an excellent model for vertebrate studies. We observed that subjects had a higher degree of success in injecting the desired material (trepan blue dye) into the cell with simultaneous vision + force feedback compared with vision feedback alone. Thus, our findings confirm that a system with force feedback capability when combined with vision feedback can lead to potentially higher success rates in transgenesis, specifically where mechanical manipulation techniques are involved.
- Haptics-enabled Atomic Force Microscopy (AFM) System: We have developed a haptics-enabled atomic force microscope system which has the capability to qualitatively characterize an individual cell. The system comprises of an AFM which measures forces in nN-pN range and a PHANToM haptic feedback device to obtain force feedback response in real time when the AFM probe contacts the cell. We have performed experiments on mouse embryonic stem cells (mESC) with diameter in the range of 10 - 15 um, since it has potential application in therapeutic and regenerative medicine. Specifically, we conducted indentation studies on undifferentiated and early differentiating mESC. The haptics-enabled AFM monitoring provided real time force information when the AFM cantilever contacts the mESC. This information can be used to detect the state of mESC (undifferentiated/early differentiating) in real time.
- Mechanical Characterization of Mouse Embryonic Stem cells (mESC): We conducted several indentation studies on undifferentiated and early differentiating (6 days under differentiation conditions) mESC using the atomic force microscope (AFM) system. The experimental data was analyzed by various contact models that can be used to accurately model the geometry of the AFM tip and mESC interaction. With the choice of appropriate contact model, we can determine the accurate stiffness of the cell membrane and hence provide accurate force feedback to the user. Further, our results confirm that the mechanical property of undifferentiated mESC is different from differentiating (6th day) mESC.
Relevant Publications:
- Anand Pillarisetti, Carol Keefer, and Jaydev P. Desai, “Mechanical Characterization of Fixed Undifferentiated and Differentiating mESC”, Second biennial IEEE/RAS-EMBS International Conference on Biomedical Robotics and Biomechatronics - BioRob, October 2008.
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- Anand Pillarisetti, Carol Keefer, and Jaydev P. Desai, “Mechanical Response of Embryonic Stem Cells using Haptics-enabled Atomic Force Microscopy”, 11th International Symposium on Experimental Robotics, Athens, Greece, 2008.
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- Anand Pillarisetti, Maxim Pekarev, Ari D. Brooks, and Jaydev P. Desai, “Evaluating the Effect of Force Feedback in Cell Injection”. IEEE Transactions on Automation Science and Engineering, 4(3): pp. 322-331, 2007. [PDF
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