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Linear flow‐velocity gradient chromatography—An efficient method for increasing the process efficiency of batch and continuous capture chromatography of proteins
Author(s) -
Chen ChyiShin,
Ando Kosei,
Yoshimoto Noriko,
Yamamoto Shuichi
Publication year - 2021
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.27649
Subject(s) - chromatography , volumetric flow rate , chemistry , residence time (fluid dynamics) , simulated moving bed , analytical chemistry (journal) , flow velocity , flow (mathematics) , packed bed , materials science , mechanics , engineering , adsorption , physics , geotechnical engineering , organic chemistry
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.