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Suspension Culture of Mammalian Cells
Published in Anthony S. Lubiniecki, Large-Scale Mammalian Cell Culture Technology, 2018
John R. Birch, Robert Arathoon
Culture medium is fed to the reactor at a predetermined and constant rate which maintains the dilution rate of the culture at a value less than the maximum specific growth rate of the cells (to avoid washout of cells from the fermenter). Culture fluid containing cells and cell products is removed at the same rate. Steady-state conditions are achieved in the chemostat in which specific growth rate is determined by the dilution rate and maximum cell density is regulated by deliberately controlling the concentration of a selected essential nutrient or inhibitory catabolite. Hence by appropriate selection of dilution rate and by design of the culture medium one can independently manipulate growth rate, cell density, and the nature of the limiting nutrient. Steady-state conditions are achieved in which cell growth is truly exponential and any measured cellular or environmental parameter will remain constant with time, provided genetic stability is maintained. The major use of the chemostat has been to study the physiology of microbial cells but now there are examples of its application to mammalian cell studies. Tovey (1985) described the use of the chemostat to study mouse L1210 cells and Boraston et al. (1984) described its use with mouse hybridoma cells to investigate the effect of growth rate on respiration rate. Antibody synthesis was studied in chemostat culture of a hybridoma cell synthesizing an IgM by Birch et al. (1985) and was shown to be stable over prolonged culture periods and under a variety of nutrient limitations.
Competition in a Modified Gradostat
Published in Ovide Arino, David E. Axelrod, Marek Kimmel, Mathematical population dynamics, 2020
The chemostat or continuous culture vessel is a classical environment in which to study the growth and competition between species of microorganisms for growth-limiting nutrients. It has also spawned a large amount of mathematical modeling efforts. Basically, the chemostat is a well-stirred vessel that receives a constant inflow of material, growth medium, and essential nutrient, from a reservoir and suffers a compensating runoff or overflow, thus maintaining constant volume.
Ordinary Differential Equations
Published in Niket S. Kaisare, Computational Techniques for Process Simulation and Analysis Using MATLAB®, 2017
A chemostat is a continuous stirred biological reactor, where a growth medium is continuously added to the reactor containing unconverted substrates, metabolic products, and microorganisms. The inlet to the chemostat usually contains only the substrate(s); it typically does not contain microorganisms. The microorganisms consume the substrate to grow, and in the process, make useful products. Since the chemostat is essentially a CSTR, the product stream from the reactor consists of the same components as the chemostat itself. The concentrations of all the important species: substrate(s), intermediates (if any), metabolites and products, and biomass are modeled as a transient ODE system. The growth rate of the microorganisms can often be complex. The simplest model that captures the essential features of microorganism grown is given by Monod. The growth rate is given by rg=μmaxSKS+SXwhere [S] and [X] are substrate and biomass concentrations, respectively. The rate constant μmax is the maximum growth rate and KS is the saturation constant. At large substrate concentration, when [S] ≫ KS, the growth rate is zero-order in substrate concentration; whereas when [S] falls substantially, the growth rate becomes first-order in substrate concentration.
A critical process variable-regulated, parameter-balancing auxostat, performed using disposed COVID-19 personal protective equipment-based substrate mixture, yields sustained and improved endoglucanase titers
Published in Preparative Biochemistry & Biotechnology, 2023
Navnit Kumar Ramamoorthy, Revanth Babu Pallam, Kabilan Subash Chandrabose, Renganathan Sahadevan, Venkateswara Sarma Vemuri
The present work aspires to address the missing gaps and unexplored facets of the enzyme-production bio-process in continuous culture-based operational runs. A chemostat is a continuous-culture operation, where a steady-state is attempted to be maintained in a bio-reactor[31] operated for extended periods of time.[32] A steady-state is considered attained, when the culture broth’s volume, the microbe’s specific growth rate, the microbial concentration, and the substrate’s concentration are maintained constant.[33] Using a pre-designed dilution rate, the culture volume is maintained constant; the influx of fresh feed is balanced by the harvest of an equal volume of the product-containing culture medium.[32] Substrate feeding, based on feed-back from a measured, prevailing process variable of the fermentation (such as pH, or dissolved oxygen) is called an indirect feedback loop-based feeding strategy.[6] If such a loop-based feeding strategy[34] is applied to continuous-cultures, the process is termed: an auxostat operation.[35] In the present study, the choice of the feed-back loop to be monitored was based on our previous observations during cellulase production SMFs.[7,8,24]