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        Optimization and Mathematical Modeling of the Transtubular Bioreactor for the Production of Monoclonal Antibodies from a Hybridoma Cell Line

        CraigR.Halberstadt,BernhardO.Palsson,A.ReesMidgley 한국생물공학회 2002 Biotechnology and Bioprocess Engineering Vol.7 No.3

        This report describes the use of a transtubular bioreactor to study the relative efectsof diffusion versus perfusion of medium on antibody production by a hybridoma cel line. The study was performed with a high-density cel culture maintained in a serum-fre, low-protein me-dium for 77 days. It was determined that the reactor possessed a macro-mixing pattern residence rangement of the medium lines in the reactor, the flow paterns for nutrient distribution consist of largely independent medium path lengths ranging from short to long. When operated with cy-clic, reversing, transtubular medium flow, some regions of the reactor (with short residence times) are more accesible to medium than others (with long residence times). From this standpoint, the reactor can be divided into three regions: a captive volume, which consists of medium primarily delivered via diffusion; a laped volume, which provides nutrients through unilateral convection; volumes were modified experimentally by changing the period over which the direction of me-dium flow was reversed from 15 min (larger captive volume) to 9 h (larger swept volume). The re-sults suggest that antibody concentration increases as the size of the diffusion-limited (captive) volume is increased to a maximum at around 30 min with a sharp decrease thereafter. As reflected by changes in measured consumption of glucose and production of lactate, no significant difer-ence in celular metabolism occured as the reactor was moved betwen these diferent states. tibody productivity under serum-free, low-protein conditions with minimal effects on celular me-tabolism.

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