The Experts below are selected from a list of 244596 Experts worldwide ranked by ideXlab platform
Lewis C Cantley - One of the best experts on this subject based on the ideXlab platform.
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metabolic flux and the regulation of Mammalian Cell growth
Cell Metabolism, 2011Co-Authors: Jason W Locasale, Lewis C CantleyAbstract:The study of normal Mammalian Cell growth and the defects that contribute to disease pathogenesis links metabolism to Cell growth. Here, we visit several aspects of growth-promoting metabolism, emphasizing recent advances in our understanding of how alterations in glucose metabolism affect cytosolic and mitochondrial redox potential and ATP generation. These alterations drive Cell proliferation not only through supporting biosynthesis, energy metabolism, and maintaining redox potential but also through initiating signaling mechanisms that are still poorly characterized. The evolutionary basis of these additional layers of growth control is also discussed.
Brian Glennon - One of the best experts on this subject based on the ideXlab platform.
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glucose concentration control of a fed batch Mammalian Cell bioprocess using a nonlinear model predictive controller
Journal of Process Control, 2014Co-Authors: Stephen Craven, Jessica Whelan, Brian GlennonAbstract:Abstract A non-linear model predictive controller (NMPC) was investigated as a route to delivering improved product quality, batch to batch reproducibility and significant cost reductions by providing a means for better controlling the bioreactor environment in a Chinese hamster ovary (CHO) Mammalian Cell fed-batch process. A nonlinear fundamental bioprocess model was developed to represent the CHO Mammalian Cell fed-batch bioprocess under study. This developed nonlinear model aided in the configuration and tuning of a NMPC through off-line simulation. The tuned NMPC was applied to a 15 L pilot-plant bioreactor for glucose concentration fixed set-point control. Traditionally, bioprocesses are characterized by long critical process parameter (CPP) measurement intervals (24 h). However, advances in PAT have helped increase CPP measurement frequency. An in situ Kaiser RXN2 Raman spectroscopy instrument was used to monitor the glucose concentration at 6 min intervals. Glucose concentration control of a bioreactor is not a trivial task due to high process variability, measurement noise and long measurement intervals. Nevertheless, NMPC proved successful in achieving closed loop fixed set-point control in the presence of these common bioprocess operation attributes.
Thomas Ryll - One of the best experts on this subject based on the ideXlab platform.
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performance of high intensity fed batch Mammalian Cell cultures in disposable bioreactor systems
Biotechnology Progress, 2011Co-Authors: John Smelko, Kelly Wiltberger, Eric Francis Hickman, Beverly Janey Morris, Tobias James Blackburn, Thomas RyllAbstract:The adoption of disposable bioreactor technology as an alternate to traditional nondisposable technology is gaining momentum in the biotechnology industry. Evaluation of current disposable bioreactors systems to sustain high intensity fed-batch Mammalian Cell culture processes needs to be explored. In this study, an assessment was performed comparing single-use bioreactors (SUBs) systems of 50-, 250-, and 1,000-L operating scales with traditional stainless steel (SS) and glass vessels using four distinct Mammalian Cell culture processes. This comparison focuses on expansion and production stage performance. The SUB performance was evaluated based on three main areas: operability, process scalability, and process performance. The process performance and operability aspects were assessed over time and product quality performance was compared at the day of harvest. Expansion stage results showed disposable bioreactors mirror traditional bioreactors in terms of Cellular growth and metabolism. Set-up and disposal times were dramatically reduced using the SUB systems when compared with traditional systems. Production stage runs for both Chinese hamster ovary and NS0 Cell lines in the SUB system were able to model SS bioreactors runs at 100-, 200-, 2,000-, and 15,000-L scales. A single 1,000-L SUB run applying a high intensity fed-batch process was able to generate 7.5 kg of antibody with comparable product quality. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011
John Smelko - One of the best experts on this subject based on the ideXlab platform.
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performance of high intensity fed batch Mammalian Cell cultures in disposable bioreactor systems
Biotechnology Progress, 2011Co-Authors: John Smelko, Kelly Wiltberger, Eric Francis Hickman, Beverly Janey Morris, Tobias James Blackburn, Thomas RyllAbstract:The adoption of disposable bioreactor technology as an alternate to traditional nondisposable technology is gaining momentum in the biotechnology industry. Evaluation of current disposable bioreactors systems to sustain high intensity fed-batch Mammalian Cell culture processes needs to be explored. In this study, an assessment was performed comparing single-use bioreactors (SUBs) systems of 50-, 250-, and 1,000-L operating scales with traditional stainless steel (SS) and glass vessels using four distinct Mammalian Cell culture processes. This comparison focuses on expansion and production stage performance. The SUB performance was evaluated based on three main areas: operability, process scalability, and process performance. The process performance and operability aspects were assessed over time and product quality performance was compared at the day of harvest. Expansion stage results showed disposable bioreactors mirror traditional bioreactors in terms of Cellular growth and metabolism. Set-up and disposal times were dramatically reduced using the SUB systems when compared with traditional systems. Production stage runs for both Chinese hamster ovary and NS0 Cell lines in the SUB system were able to model SS bioreactors runs at 100-, 200-, 2,000-, and 15,000-L scales. A single 1,000-L SUB run applying a high intensity fed-batch process was able to generate 7.5 kg of antibody with comparable product quality. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011
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effects of solution environment on Mammalian Cell fermentation broth properties enhanced impurity removal and clarification performance
Biotechnology and Bioengineering, 2011Co-Authors: Matthew Westoby, John Smelko, James Chrostowski, Philippe De Vilmorin, Jonathan RomeroAbstract:The processing of recombinant proteins from high Cell density, high product titer Cell cultures containing Mammalian Cells is commonly performed using tangential flow microfiltration (MF). However, the increased Cellular debris present in these complex feed streams can prematurely foul the membrane, adversely impacting MF capacity and throughput. In addition, high Cell density Cell culture streams introduce elevated levels of process-related impurities, which increase the burden on subsequent purification operations to remove these complex media components and impurities. To address this challenge, an evaluation of Mammalian Cell culture broth buffer properties was examined to determine if enhanced impurity removal and clarification performance could be achieved. A framework is presented here for establishing optimized Mammalian Cell culture buffer conditions, involving trade-offs between product recovery and purification and improved clarification at manufacturing-scale production. A reduction in Cell culture broth pH to 4.7-5.0 induced flocculation and impurity precipitation which increased the average feed particle-size. These conditions led to enhanced impurity removal and improved MF throughput and filter capacity for several Mammalian systems. Feed conditions were further optimized by controlling ionic composition along with pH to improve product recovery from high Cell density/high product titer Cell cultures.
Jason W Locasale - One of the best experts on this subject based on the ideXlab platform.
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metabolic flux and the regulation of Mammalian Cell growth
Cell Metabolism, 2011Co-Authors: Jason W Locasale, Lewis C CantleyAbstract:The study of normal Mammalian Cell growth and the defects that contribute to disease pathogenesis links metabolism to Cell growth. Here, we visit several aspects of growth-promoting metabolism, emphasizing recent advances in our understanding of how alterations in glucose metabolism affect cytosolic and mitochondrial redox potential and ATP generation. These alterations drive Cell proliferation not only through supporting biosynthesis, energy metabolism, and maintaining redox potential but also through initiating signaling mechanisms that are still poorly characterized. The evolutionary basis of these additional layers of growth control is also discussed.
