Death, phase

The production of secondaiy metabohtes has often been characterized using the classical equations of Leudeldng and Piret. However, the complexities of plant cell and tissue cultures have led to revisions to this equation to include fresh cell weight and viability, cell expansion, and culture death phase. Therefore, the production model is written as the following ... 

During the stationary phase, the growth rate is zero as a result of the depletion of nutrients and essential metabolites. Several important fermentation produets (ineluding most antibioties) are produeed in the stationary phase. The stationary phase is followed by a phase where eells die or sporulate. During the death phase, there is a deerease in live eell eoneentration, whieh results from the toxie byproduets eoupled with the depletion of the nutrient. The number of viable eells usually follows an exponential deeay eurve during this period. 

The death phase where some cells are lysed (after 25 hours not obvious in Figure 85). 

Without renewal of the food supply, or adequate waste removal, the colony will enter the logarithmic death phase. The number of cells will decline as rapidly as it initially increased. Ultimately, the entire culture expires and the cycle is complete. 

Death phase After nutrients available for the cells are depleted, cells will start to die and the number of viable cells will decrease. 

The stationary phase is usually followed by a death phase in which the organisms in the population die. Death occurs either because of the depletion of the cellular reserves of energy, or the accumulation of toxic products. Like growth, death is an exponential function. In some cases, the organisms not only die but also disintegrate, a process called lysis. 

The stationary phase can be represented by X = const, whereas the death phase can be modeled according to Eq. (8.7) with kd as the death rate constant lime 1 or upon integration based on Xma.. as the cell density after the stationary phase [Eqs. (8.8a) and (8.8b)]. 

Cell growth phases comprise lag phase, exponential or log growth phase, stationary or plateau phase, and senescence or death phase, as shown in Figure 2.5. Cell growth can be mathematically represented by the following general equation ... 

The final phase. Phase IV, is the death phase where a decrease in live ( concentration occurs. This decline is a result of either the toxic by-product and/or the depletion of nutrient supply. 

Before the hydrodynamic and mass-transport properties of the systems of interest are discussed, it is advantageous to outline first the sequence of events that occur at the metal/solution interface that leads to the development of damage. This is done so that the reader will have a greater appreciation of the role that fluid flow plays in each phase and how those parameters that are affected by fluid flow impact the nucleation, growth, and death phases of the damaging processes. 

Equation 4.2.10 is valid for small k, which is normally the case until the culture reaches the late stationary or death phase. 

Cell lysis generally becomes important when viability is low. Examples include continuous culture (with or without cell retention) at low dilution rates and the late stationary and death phases of batch culture. Cell lysis is also important in stirred reactors with very high agitation rates. In order to quantify cell growth parameters under these conditions, the lysed cells must be accounted for. One way to do this is to measure the amount of the cytosolic enzyme lactate dehydrogenase (LDH) released into the medium (see Chapter 2, section 2.5). A procedure for measuring LDH activity is described in Chapter 4, section 4.7. 

Eq.(13)-(14) take into accormt the production of MAb by each cell cycle phase, where v(%) is viability, QMAb.oi, Qmm,s, QMAb,a2/tA g cell" h" ] are specific MAb production rates of the corresponding cell-cycle phases, [MAb] is the concentration of monoclonal-antibody [mg L" ], KMAbV M is an inhibition constant for MAb production with respect to cell viability. The introduction of viability in Qmm was based on the results of Glacken et al. (1988) which demonstrated that cell culture productivity was affected by low viability these findings were also observed in our experiments that specific productivity decreased for CRL-1606 during death phase. 

Cells growth is described as an autocatalytic reaction. All growth requires an initial seed or inoculum of cells. As the cells are given nutrients, they metabolize this food to make more cells. The nutrient requirements vary considerably with cell type, but all cells undergo the growth phases shown in Fig. 1—stationary, exponential, deceleration, stationary, and death phases. 

The death phase (involving exponential/logarith-mic decline) begins when cell deaths exceed births (i.e. the viable-cell count declines). 

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