Growth Phases of Cells

Since mass transfer and mixing are related to cell growth, a brief discussion on the stages of cell growth is as follows—all cell lines exhibit the following four phases in their growth (Fig. 7B.14)  

Lag phase (a-b) In this phase, the bioactive species acclimatize to the environment constituting the food available. The growth rate is therefore relatively low. 

Log phase (b-c) After acclimating, the species are ready for growth. They start multiplying relatively fast. 

Stationary phase (c-d) As the population of the species grows, there is a competition among them for the available nutrient supply. The exponential growth of the previous period cannot be sustained under such competition. There is a virtual stoppage of growth that stabilizes the population of the species. 

Death phase (d-e) In aU biological processes, growth of the cells is accompanied by formation of toxic species. The accumulation of these species increases the toxic effects. In a batch process, the food supply also diminishes because of consumption during the first three phases. The combined effect of toxicity and malnutrition causes cell death. 

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For the identical experimental conditions, electroporation efficiency depends on the type of cells the composition of the membrane, shape, and size of cells strongly influences the electroporation efficiency [40-42]. In electroporation of bacteria, the growth phase of cell has significant influence on transformation efficiency, which is higher for cells harvested and electroporated from mid-log phase. However, cells from stationary phase can also be transected with reasonably good efficiency. Mammalian cell can be electroporated at relatively lower fields but pulse length controls the entry of external molecules into cells. 

Interestingly several authors noted an increased production of alkaloids in the presence of 2,4-D (763,781,796), whereas with other auxins in the media no production at all could be observed (763,781). The production of alkaloids is not restricted to a certain growth phase of cell suspension cultures (786,787,792). 

Exponential growth The phase of cell growth in which the number of cells or the cell mass increases exponentially. 

Figure 3. Growth phases of short-term cultures. Upon initiation of short-term cultures, growth rapidly increases (Phase 1). A stable growth rate is maintained for a defined number of passages (Phase 2). Finally, most cells undergo a crisis of senescence and ultimately die (Phase 3). In some cases immortal cell lines are established.

Charette and Moran 1999 Charette et al. 1999 Amid et al. 2002). Such observations often coincide with the collection of significant quantities of large phytoplankton during the growth phase of a bloom such that the volume-to-surface area ratio of the cells is increasing and the POC/ Th ratio, representing the ratio of an assimilated element to an adsorbed one, follows. 

Cultivation. The cells are transferred from the cryogenic cell bank to a liquid nutrient medium, where they are allowed to reproduce. Mammalian cells such as CHO divide about once every 24 h (bacterial cells, such as Escherichia coli, usually divide once every 20 min, and thus a sufficient number of cells are obtained in a much shorter time than in traditional fermentation processes). During the growth phase the cell culture is transferred to progressively larger culture vessels. 

Leflunomide undergoes rapid conversion, both in the intestine and in the plasma, to its active metabolite, A77-1726. This metabolite inhibits dihydroorotate dehydrogenase, leading to a decrease in ribonucleotide synthesis and the arrest of stimulated cells in the Gi phase of cell growth. Consequently, leflunomide inhibits T-cell proliferation and production of autoantibodies by cells. Secondary effects include increases of interleukin-10 receptor mRNA, decreased interleukin-8 receptor type A mRNA, and decreased TNF-a-dependent nuclear factor kappa (NF- ) activation. 

If liquid medium is inoculated with a seed culture, the cell will start to grow exponentially after the lag phase. The change of the cell concentration in a batch fermenter is equal to the growth rate of cells in it ... 

Based on total DNA content the E. coli genome could code for 3000 to 4000 individual proteins (14), and a total of perhaps 1500 have been visualized by two-dimensional electrophoresis during different growth conditions (15,16). Further, the proteins produced vary with the growth phase of the cell and the composition of the growth medium (6,15,16). These numbers are larger and the potential distribution more complex for mammalian host cell systems. From this complex mixture a process specific subset will be enriched, and therefore the distribution reference impurities must be refined to represent that population. 

An additional advantage of this DO control system is the possibility of having a real-time estimation of the cells respiration rate. As can be observed in Equation 1, if C is constant, the term of the transfer kLa.(Cs-C) is equivalent to the consumption Q02 X. With the actuation value of the controller, the transfer rate can be calculated, and also the consumption at each moment (Kamen et al., 1996). There are several reports in the literature dealing with the use of respiration measurements to estimate cell concentration online, based on the assumption that, during the growth phase, each cell consumes a constant amount of oxygen (Yoon and Konstantinov, 1994 Ruffieux et al., 1998 Jorjani and Ozturk, 1999). 

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