Linear flow‐velocity gradient chromatography—An efficient method for increasing the process efficiency of batch and continuous capture chromatography of proteins
| Autor: | Shuichi Yamamoto, Chyi-Shin Chen, Kosei Ando, Noriko Yoshimoto |
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| Rok vydání: | 2021 |
| Předmět: |
0106 biological sciences
0301 basic medicine Materials science Bioengineering Residence time (fluid dynamics) 01 natural sciences Applied Microbiology and Biotechnology Chromatography Affinity Article ARTICLES 03 medical and health sciences 010608 biotechnology Animals flow velocity programming Computer Simulation Staphylococcal Protein A Chromatography Velocity gradient capture chromatography linear flow‐velocity gradient Antibodies Monoclonal dBc continuous chromatography Linear flow Bioseparations and Downstream Processing 030104 developmental biology Models Chemical Volume (thermodynamics) Flow velocity Scientific method Process efficiency monoclonal antibodies Biotechnology |
| Zdroj: | Biotechnology and Bioengineering |
| ISSN: | 1097-0290 0006-3592 |
| DOI: | 10.1002/bit.27649 |
| Popis: | A new method was proposed for increasing the capture chromatography process efficiency, linear flow‐velocity gradient (LFG). The method uses a linear decreasing flow‐velocity gradient with time during the sample loading. The initial flow velocity, the final flow velocity and the gradient time are the parameters to be tuned. We have developed a method for determining these parameters by using the total column capacity and the total loaded amount as a function of time. The capacity can be calculated by using the relationships between dynamic binding capacity (DBC) and residence time. By leveraging the capacity, loading amount, and the required conditions, the optimum LFG can be designed. The method was verified by ion‐exchange and protein A chromatography of monoclonal antibodies (mAbs). A two‐fold increase in the productivity during the sample loading was possible by LFG compared with the constant flow‐velocity (CF) operation. LFG was also applied to a 4‐column continuous process. The simulation showed that the cost of resin per unit amount of processed mAbs can be reduced by 13% while 1.4 times enhancement in productivity was preserved after optimization by LFG compared to CF. The process efficiency improvement is more pronounced when the isotherm is highly favorable and the loading volume is large. Linear flow‐velocity gradient (LFG) is developed to increase the efficiency of the capture chromatography process for proteins (mAbs). By applying a decreasing LFG to the loading step, dynamic binding capacity increases with time. The optimal LFG can be determined by achieving the maximum capacity utilization. Although LFG is effective for the batch operation, it can be applied to the continuous process. A 1.4 fold increase in productivity and a 13% reduction in resin cost are shown by comparing LFG with the constant flow‐velocity operation in a 4‐column continuous chromatography process of mAbs. |
| Databáze: | OpenAIRE |
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