Development of Cell-based Biochip for Cytotoxic Study of Human Natural Killer Cells against Leukemic Cells

• Main Authors: Yu-Hung Wang, 王宇宏
• Other Authors: Long-Sun Huang
• Format: Others
• Language: zh-TW
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/67901671699550039939

碩士 === 國立臺灣大學 === 應用力學研究所 === 99 === Leukemia that occurs due to accumulation of abnormal white blood cells causes damage to the human immune system. A common treatment for Leukemia is used with bone marrow transplantation. Full Human Leukocyte Antigen(HLA) matched donor is required prior to bone marrow transplantation in order to prevent graft-versus-host disease (GvHD). The study reported that patients had only a limited chance of 25% finding the same HLA haplotypes from their own parents. Studies also have shown that natural killer cell transplantation with no need of HLA match is feasible for patients with leukemia. Natural killer cells are able to identify a wide range of tumor cells ,and to discriminate unhealthy cells efficiently. As a result, natural killer cell transplantation is considered as a promising treatment for leukemia. However, natural killer cells from healthy donors exhibit various levels of cytotoxicity to tumor cells. Effective investigation of cytotoxicity of natural killer cells to tumor cells remains a great challenge. 　　We have developed cell-based micro-channel biosensors which are capable of forming various effector-to-target ratios, and of investigating the cytotoxicity of natural killer cells against leukemic cells. The cell-base biosensor with micro-channels was able to trap micro particles with 20 μm and 10 μm in diameter for simulation of leukemic cells (K562) and natural killer cells (NK92). It was found that the number of micro particles trapped in micro channel was proportional to the gap length. For real cells, the numbers of K562 trapped in micro channel with the gap length of 180 μm and 720 μm gap length were 10 and 36, respectively (sample=4). In the case of a gap length of 100 μm, the device was found to trap 14 natural killer cells in average(sample=4). By use of micro-particle simulation, this study shows similar tendency of real cells of tumor cells (K562) and natural killer cells (NK92) in this device. The cell-based biosensor device achieved the effector (NK92) - to - target (K562) ratio of 17 /10 in this study, and allowed the real-time monitoring microscopic system for cytotoxic process and effective investigation. 　　Unlike conventional cell culture experiments in a dish of a huge amount of cells, the present device simply allows very few hybrid cells for manipulation, cytotoxic interaction, and significantly reduced consumption of culture medium. The cell-based micro device exhibits the capability and potential of effective investigation for tumor cells (K562) and natural killer cells(NK92).