Methodological Research of the Fuzzy Control in Insulin Production

本课题的研究目的是开发一种适用于酿酒酵母生产胰岛素的模糊控制系统，该系统包含了上级发酵工艺的知识。胰岛素是治疗糖尿病的重要药物，主要在国外生产，如Novo。丹麦的一家生物制药公司利用酵母菌生产胰岛素，但由于酵母菌产生酒精，严重影响细胞生长和产量，因此生产过程中存在的技术问题是可想而知的。为了验证模糊控制系统的有效性，本文将模糊控制系统应用于酿酒酵母酒精发酵过程中，并对酿酒酵母酒精发酵过程进行了实验研究。我们成功地控制了葡萄糖补料，提高了生长速度，缩短了酒精生产的培养时间。该模糊控制器结构简单， ...更多信息 与日本清酒公司开发的常规模糊控制相比，模糊规则和隶属度函数都有很大的改进。将该方法应用于固定化细胞发酵生产乙醇，成功地将葡萄糖浓度控制在适宜的水平。在模糊控制中，存在着一个严重的问题，即隶属度函数的人工整定和产生式规则的人工调整，这是因为人工调整过程耗费了大量的人力物力，严重影响了模糊控制的效率。然后，我们尝试制作了显示系统，显示模糊推理错误的隶属函数。考虑到显示系统的建议，我们修改了隶属函数。如果修改较小，模糊控制通常会有所改善。但是，如果对模糊控制器进行较大的修改，则会对模糊控制器造成损害，因为许多未被考虑到修改效果的规则会受到修改的影响。我们还研究了使用蛋白质组分析技术的模糊控制的发展。目前，二维电泳凝胶图像并不稳定，但我们成功地利用人工神经网络来区分培养状态，因此我们将能够利用蛋白质组分析的信息来开发模糊控制系统。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