Methodological Research of the Fuzzy Control in Insulin Production

研究的目的是开发一种模糊控制系统，该系统包含了酿酒酵母生产胰岛素的先进发酵技术。胰岛素是治疗糖尿病的重要药物，主要在国外生产，例如Novo。然而，我们不难想象，在生产过程中存在着严重的技术问题，因为酵母会产生酒精，严重影响细胞的生长和生产。因此，为了开发模糊控制算法和在线控制系统，我们需要进行大量的培养实验。为了保证模糊控制系统的有效性，我们尝试将模糊控制系统应用于酿酒酵母生产酒精。我们成功地控制了葡萄糖的投料，提高了生长速度，缩短了生产酒精的培养时间。本文提出的模糊控制结构简单，与日本清酒酿造公司开发的普通模糊控制相比，具有更多的模糊规则和隶属函数。将该方法应用于固定化生产乙醇的细胞体系，成功地将葡萄糖浓度保持在适宜的水平。在模糊控制中，隶属函数的人工整定和生产规则的人工调整是一个严重的问题，因为这些步骤耗费了大量的精力，严重影响了模糊控制的效率。然后，我们尝试制作一个显示隶属度函数的显示系统，造成模糊推理误差。考虑到显示系统的建议，我们对隶属函数进行了修改。如果修改量很小，模糊控制通常会稍微改进一点。但是，如果对模糊控制进行较大的修改，则会对模糊控制造成损害，因为修改会影响到许多未考虑到修改效果的规则。我们还研究了蛋白质组分析技术在模糊控制开发中的应用。目前，二维电泳凝胶图像不稳定，但我们成功地利用人工神经网络来区分培养状态。因此，我们可以将蛋白质组分析的信息用于模糊控制系统的开发。少

The objective of the research is the development of Fuzzy control system, which include the know-how of the superior fermentation technique, and is suitable for the production of Insulin by Saccharomyces cerevisiae. Insulin is important pharmaceuticals for diabetes, and produced mainly abroad, for example, Novo. Co. Ltd in Denmark has been producing Insulin using yeast However, we can easily imagine the severe technical problems in the production, because yeast produce alcohol, which seriously effect on the cell growth and the production. There fore, we need to perform many culture experiment in order to develop the fuzzy control algorithm and the on-line control system.In order to make sure the validity of the fuzzy control system, we tried to use the control system in the alcohol production by Saccharomyces cerevisiae. We succeeded to control the glucose feeding and to increase the growth rate and shorten culture time for the alcohol production. Our fuzzy control has a simple structu … More re of fuzzy rules and membership functions compared with the normal fuzzy control, which has been developed in Japanese sake brewery company. Our approach applied to the immobilized cell system for alcohol production, and we can keep the glucose concentration at suitable level for the ethanol production successfully. In the fuzzy control, we have a severe problem which is the manual tuning of membership functions and manual adjustment of production rules, because we spend a lot of trouble for the procedures and they influence the efficiency of the fuzzy control serious ly. Then we tried to make the display system which shows the membership functions causing the fuzzy reasoning error. Taking into consideration of the suggestion from the display system, we modified the membership function. If the modification is small, the fuzzy control usually improved a little bit. But, if modified largely, the fuzzy control is damaged, because the many rule, which is not considered into the modification effect was effected by the modification. We also investigate the use of the proteome analysis technique for the fuzzy control development. Now, 2-D electrophoresis gel image is not stable but we succeed it to distinguish the culture state with the aid on ANN. Therefore we will be able to use the information from proteome analysis for the development of fuzzy control system. Less