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published_at 2021
Creators : 小野 文也 Dissertation Number : 創科博甲第45号 Degree Names : 博士(工学) Date Granted : 2021-01-06 Degree Grantors : Yamaguchi University
published_at 2021
Creators : 須内 寿男 Dissertation Number : 創科博乙第3号 Degree Names : 博士(理学) Date Granted : 2021-03-04 Degree Grantors : Yamaguchi University
published_at 2021
Creators : 山崎 ちひろ Dissertation Number : 創科博乙第4号 Degree Names : 博士(学術) Date Granted : 2021-03-04 Degree Grantors : Yamaguchi University
published_at 2021-03
Creators : 村岡 和満 Dissertation Number : 理工博乙第146号 Degree Names : 博士(工学) Date Granted : 2021-03-03 Degree Grantors : Yamaguchi University
published_at 2021
Creators : 佐々木 嶺 Dissertation Number : 医博甲第1590号 Degree Names : 博士(医学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
published_at 2021
Creators : 藤本 祐子 Dissertation Number : 医博甲第1591号 Degree Names : 博士(医学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
published_at 2021
Creators : 松田 まどか Dissertation Number : 医博甲第1592号 Degree Names : 博士(医学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
published_at 2021
Creators : 山内 由里佳 Dissertation Number : 医博甲第1593号 Degree Names : 博士(医学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
published_at 2021
Creators : 梶井 俊郎 Dissertation Number : 医博甲第1594号 Degree Names : 博士(医学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
published_at 2021
Creators : 河野 通暁 Dissertation Number : 医博甲第1595号 Degree Names : 博士(医学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
published_at 2021
Creators : 民谷 正輝 Dissertation Number : 医博甲第1596号 Degree Names : 博士(医学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
published_at 2021
Creators : 永瀨 隆 Dissertation Number : 医博甲第1597号 Degree Names : 博士(医学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
published_at 2021
Creators : 有吉 平 Dissertation Number : 医博甲第1598号 Degree Names : 博士(医学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
published_at 2021
Creators : 坂田 恭史 Dissertation Number : 医博甲第1599号 Degree Names : 博士(医学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
published_at 2021
Creators : 山田 健介 Dissertation Number : 医博甲第1600号 Degree Names : 博士(医学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
published_at 2021
Creators : 中山 祐起 Dissertation Number : 医博甲第1601号 Degree Names : 博士(医学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
published_at 2021
Creators : 有吉 彰子 Dissertation Number : 医博甲第1602号 Degree Names : 博士(医学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
published_at 2021
Creators : 亀田 ふみ Dissertation Number : 医博甲第1603号 Degree Names : 博士(医学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
published_at 2021
Creators : 清平 美和 Dissertation Number : 医博甲第1604号 Degree Names : 博士(医学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
published_at 2021
Creators : 尾﨑 正和 Dissertation Number : 医博甲第1605号 Degree Names : 博士(医学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
published_at 2021
Creators : 藤山 雄一 Dissertation Number : 医博甲第1606号 Degree Names : 博士(医学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
published_at 2021
Creators : 安部 希 Dissertation Number : 医博甲第1607号 Degree Names : 博士(医学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
published_at 2021
Creators : 清水 宏輔 Dissertation Number : 医博甲第1608号 Degree Names : 博士(医学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
published_at 2021
Creators : 三好 啓介 Dissertation Number : 医博甲第1609号 Degree Names : 博士(医学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
published_at 2021
Creators : 三原 由実子 Dissertation Number : 医博甲第1610号 Degree Names : 博士(医学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
published_at 2021
Creators : Zhang Min Dissertation Number : 医博甲第1611号 Degree Names : 博士(医工学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
published_at 2021
Creators : 宇都宮 利彰 Dissertation Number : 医博甲第1612号 Degree Names : 博士(医工学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
published_at 2021
Creators : 松村 卓郎 Dissertation Number : 医博甲第1613号 Degree Names : 博士(医工学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
published_at 2021
Creators : 仁志 麻衣子 Dissertation Number : 医博甲第1614号 Degree Names : 博士(生命科学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
published_at 2021
Creators : 安田 真弓 Dissertation Number : 医博甲第1615号 Degree Names : 博士(生命科学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
published_at 2021
Creators : 藤本 拓也 Dissertation Number : 医博甲第1616号 Degree Names : 博士(生命科学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
published_at 2021
Creators : 礒村 由美 Dissertation Number : 医博甲第1617号 Degree Names : 博士(保健学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
published_at 2021
Creators : 金森 弓枝 Dissertation Number : 医博甲第1618号 Degree Names : 博士(保健学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
published_at 2021
Creators : 伊藤 秀幸 Dissertation Number : 医博甲第1619号 Degree Names : 博士(保健学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
published_at 2021
Creators : 金重 里沙 Dissertation Number : 医博甲第1620号 Degree Names : 博士(保健学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
published_at 2021
Creators : 宮成 健司 Dissertation Number : 医博乙第1097号 Degree Names : 博士(医学) Date Granted : 2021-03-10 Degree Grantors : Yamaguchi University
published_at 2021
Creators : 福田 謙 Dissertation Number : 医博乙第1098号 Degree Names : 博士(医学) Date Granted : 2021-03-10 Degree Grantors : Yamaguchi University
published_at 2021
Creators : 水谷 誠 Dissertation Number : 医博乙第1099号 Degree Names : 博士(医学) Date Granted : 2021-03-10 Degree Grantors : Yamaguchi University
published_at 2021
Creators : 呂 博超 Dissertation Number : 医博乙第1100号 Degree Names : 博士(医工学) Date Granted : 2021-03-10 Degree Grantors : Yamaguchi University
published_at 2021
Creators : 野村 基惟 Dissertation Number : 獣博乙第71号 Degree Names : 博士(獣医学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
published_at 2021
Creators : 田島 茂行 Dissertation Number : 獣博乙第72号 Degree Names : 博士(獣医学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
published_at 2021
Creators : 平山 祐理 Dissertation Number : 獣博乙第73号 Degree Names : 博士(獣医学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
published_at 2021
Creators : 一二三 達郎 Dissertation Number : 獣博乙第74号 Degree Names : 博士(獣医学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
published_at 2021
Creators : 網本 宏和 Dissertation Number : 獣博甲第433号 Degree Names : 博士(獣医学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
published_at 2021
Creators : 小林 俊夫 Dissertation Number : 獣博甲第434号 Degree Names : 博士(獣医学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
published_at 2021
Creators : 松下 有美 Dissertation Number : 獣博甲第435号 Degree Names : 博士(獣医学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
published_at 2021
Creators : Vu Minh Duc Dissertation Number : 獣博甲第436号 Degree Names : 博士(獣医学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
published_at 2021
Creators : 松川 拓哉 Dissertation Number : 獣博甲第437号 Degree Names : 博士(獣医学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
published_at 2021
Creators : 藏前 哲郎 Dissertation Number : 獣博甲第438号 Degree Names : 博士(獣医学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
published_at 2021
Creators : 朱 夏希 Dissertation Number : 獣博甲第439号 Degree Names : 博士(獣医学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
published_at 2021
Creators : Kereilwe Onalenna Dissertation Number : 獣博甲第440号 Degree Names : 博士(獣医学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
published_at 2021
Creators : 酒井 治 Dissertation Number : 獣博甲第441号 Degree Names : 博士(獣医学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
published_at 2021
Creators : 児玉 省吾 Dissertation Number : 創科博甲第46号 Degree Names : 博士(理学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
Creators : 潟岡 陽 Dissertation Number : 創科博甲第47号 Degree Names : 博士(工学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
Creators : 黒川 陽太 Dissertation Number : 創科博甲第48号 Degree Names : 博士(工学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
Creators : 池田 茜 Dissertation Number : 創科博甲第49号 Degree Names : 博士(工学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
Creators : 川波 敏博 Dissertation Number : 創科博甲第50号 Degree Names : 博士(工学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
Creators : Fukushima Kuniharu Dissertation Number : 創科博甲第51号 Degree Names : 博士(工学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
Creators : Mihara Takafumi Dissertation Number : 創科博甲第52号 Degree Names : 博士(工学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
Creators : Liu Yongsheng Dissertation Number : 創科博甲第53号 Degree Names : 博士(工学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
Creators : Xu Zhisong Dissertation Number : 創科博甲第54号 Degree Names : 博士(工学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
Creators : Hasegawa Hiroaki Dissertation Number : 創科博甲第55号 Degree Names : 博士(工学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
Creators : Warunyuwong Passaworn Dissertation Number : 創科博甲第56号 Degree Names : 博士(工学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
Creators : Jiang Junzhe Dissertation Number : 創科博甲第57号 Degree Names : 博士(工学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
Creators : Han Jihae Dissertation Number : 創科博甲第58号 Degree Names : 博士(工学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
Creators : 吉田 圭志朗 Dissertation Number : 創科博甲第59号 Degree Names : 博士(工学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
Chromatography is considered as a key operation in the downstream process (DSP) of biopharmaceuticals, including proteins. Therapeutic proteins such as monoclonal antibodies (mAbs) with high economic values in the global market require immediate innovation in the purification step to adapt to the increased throughput from upstream. Authorities have also initiated changes toward a more modernized pharmaceutical manufacturing platform which is agile and flexible without extensive oversight. Instead of the conventional batch operation and empirical models, the design and application of in silico modeling and simulation for integrated multi-column processes to improve their performance in capture chromatography steps have been explored in the dissertation. Due to the fact that mechanistic models can reveal adsorption and mass transfer behaviors better in the chromatography compared to statistical models, mechanistic frameworks were applied in the study. Ion-exchange and protein A chromatography, the main categories of therapeutic protein chromatography were examined. With an example of oligonucleotides, the mass transfer phenomenon of biomolecules in different types of ion-exchange resins was explored by mechanistic models. The results demonstrate the effectiveness of modeling approaches to understand the chromatography process of biopharmaceuticals. By focusing on the DSP of mAbs, multi-column continuous chromatography was examined with IgG samples. The study covered the repeating batch to 4-column settings in the continuous periodic counter-current (PCC) chromatography, with development in modeling and simulation tools for process quantification and evaluation. Process performances including productivity, capacity utilization, and buffer consumption were investigated by simulations with the aim to increase productivities and lower buffer consumptions, which are the main bottleneck in the current DSP. The critical operation parameter, breakthrough percent (BT%) for column switching in PCC processes, requires the information from binding capacity, mass transfer, and non-loading operations. To obtain the optimal BT% under synchronized conditions, numerical solvers developed from mechanistic models were employed. It was found that over 20% improvement in buffer consumption and resin utilization can be observed in PCC processes while the same productivity as batch operation is maintained. Furthermore, regressive relations were developed for predictions of process performances and BT% based on the findings from PCC simulations. With high coherence in R2 over 0.95, the linear regression function can act as an accelerated method in the PCC process design. Finally, a new strategy of linear flow-velocity gradient (LFG) in the loading step was explored as a supplement to increase process efficiency. The method controls the total column capacity and the loaded amount as functions of time. Based on the relationship between the dynamic binding capacity and residence time, the gradient time of LFG was obtained. The optimal flow velocities and time gradients were examined by scanning through the range of applicable residence times. A case study of the 4-column PCC process is presented. By integrating a linear decreasing flow gradient in the PCC loading operation, the productivity has 1.4 times enhancement along with a 13% reduction in the cost of resin per amount of processed mAbs compared to constant flows. Undoubtedly, the next generation of DSP platform technology is directed toward continuous and integrated systems. Regarding the advantages in process performances and regulation perspectives, continuous manufacturing can advance development and manufacturing while assuring the product quality. The evolution in modeling and simulation enables faster development of in silico process prediction and evaluation. With the support from models, process design and optimization in chromatography can rise to the challenge.
Creators : Chen Chyi Shin Dissertation Number : 創科博甲第60号 Degree Names : 博士(学術) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
Creators : 太田 茂徳 Dissertation Number : 創科博甲第61号 Degree Names : 博士(生命科学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
Creators : 寺田 直樹 Dissertation Number : 創科博甲第62号 Degree Names : 博士(学術) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
Creators : Nguyen Minh Thuy Dissertation Number : 創科博甲第63号 Degree Names : 博士(生命科学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
Creators : Feronika Heppy Sriherfyna Dissertation Number : 創科博甲第64号 Degree Names : 博士(生命科学) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
Creators : Jiang Yuxuan Dissertation Number : 東アジア博甲第141号 Degree Names : 博士(学術) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
Creators : Meng Fanhong Dissertation Number : 東アジア博甲第142号 Degree Names : 博士(学術) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
Creators : Liu Chuanxia Dissertation Number : 東アジア博甲第143号 Degree Names : 博士(学術) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
Creators : Guo Ruiqi Dissertation Number : 東アジア博甲第144号 Degree Names : 博士(学術) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
Creators : Nyoman Satyayudha Dananjaya Dissertation Number : 東アジア博甲第145号 Degree Names : 博士(学術) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
Creators : Putu Ayu Asty Senja Pratiwi Dissertation Number : 東アジア博甲第146号 Degree Names : 博士(学術) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
Creators : Wu Biao Dissertation Number : 東アジア博甲第147号 Degree Names : 博士(学術) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
Creators : Yin Guopeng Dissertation Number : 東アジア博甲第148号 Degree Names : 博士(学術) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
Creators : 若杉 祥太 Dissertation Number : 東アジア博甲第149号 Degree Names : 博士(学術) Date Granted : 2021-03-16 Degree Grantors : Yamaguchi University
Creators : 柳井 章江 Dissertation Number : 医博乙第1101号 Degree Names : 博士(医学) Date Granted : 2021-04-14 Degree Grantors : Yamaguchi University
Creators : 松本 奈実 Dissertation Number : 創科博乙第5号 Degree Names : 博士(生命科学) Date Granted : 2021-06-16 Degree Grantors : Yamaguchi University
Creators : Srivastava Pratibha Dissertation Number : 医博甲第1621号 Degree Names : 博士(医学) Date Granted : 2021-09-27 Degree Grantors : Yamaguchi University
Creators : 小室 拓也 Dissertation Number : 医博甲第1622号 Degree Names : 博士(医学) Date Granted : 2021-09-27 Degree Grantors : Yamaguchi University
Creators : 藤原 康弘 Dissertation Number : 医博甲第1623号 Degree Names : 博士(医学) Date Granted : 2021-09-27 Degree Grantors : Yamaguchi University
Creators : 森 純一 Dissertation Number : 医博甲第1624号 Degree Names : 博士(医学) Date Granted : 2021-09-27 Degree Grantors : Yamaguchi University
Creators : 小林 由佳 Dissertation Number : 医博甲第1625号 Degree Names : 博士(医学) Date Granted : 2021-09-27 Degree Grantors : Yamaguchi University
Creators : 小林 利彦 Dissertation Number : 医博甲第1626号 Degree Names : 博士(医学) Date Granted : 2021-09-27 Degree Grantors : Yamaguchi University
Creators : Tsuchida Katsuhiko Dissertation Number : 獣博乙第75号 Degree Names : 博士(獣医学) Date Granted : 2021-09-27 Degree Grantors : Yamaguchi University
Creators : Masuda Yasumitsu Dissertation Number : 獣博乙第76号 Degree Names : 博士(獣医学) Date Granted : 2021-09-27 Degree Grantors : Yamaguchi University
Creators : Iwanaga Tomoko Dissertation Number : 獣博乙第77号 Degree Names : 博士(獣医学) Date Granted : 2021-09-27 Degree Grantors : Yamaguchi University
Creators : Aya Takahiro Dissertation Number : 獣博甲第442号 Degree Names : 博士(獣医学) Date Granted : 2021-09-27 Degree Grantors : Yamaguchi University
Creators : Ahmed Magdy Ahmed Khalil Dissertation Number : 獣博甲第443号 Degree Names : 博士(獣医学) Date Granted : 2021-09-27 Degree Grantors : Yamaguchi University
Creators : 横江 祈 Dissertation Number : 獣博甲第444号 Degree Names : 博士(獣医学) Date Granted : 2021-09-27 Degree Grantors : Yamaguchi University
Creators : 山口 文 Dissertation Number : 獣博甲第445号 Degree Names : 博士(獣医学) Date Granted : 2021-09-27 Degree Grantors : Yamaguchi University
Creators : Abdul Haris Setiawan Dissertation Number : 東アジア博甲第150号 Degree Names : 博士(学術) Date Granted : 2021-09-27 Degree Grantors : Yamaguchi University
Creators : Do Thi Van Dissertation Number : 東アジア博甲第151号 Degree Names : 博士(学術) Date Granted : 2021-09-27 Degree Grantors : Yamaguchi University
Creators : 原田 美冬 Dissertation Number : 創科博甲第65号 Degree Names : 博士(工学) Date Granted : 2021-09-27 Degree Grantors : Yamaguchi University
Creators : 福島 聖人 Dissertation Number : 創科博甲第66号 Degree Names : 博士(工学) Date Granted : 2021-09-27 Degree Grantors : Yamaguchi University
Creators : Katiyar Vaibhav Dissertation Number : 創科博甲第67号 Degree Names : 博士(工学) Date Granted : 2021-09-27 Degree Grantors : Yamaguchi University