Bioreactors volume

These techniques are of particular interest in that they provide a means of separating molecular species which are difficult to separate by other techniques and which may be present in very low concentrations. Such species include large molecules, sub-micrometre size particles, stereo-isomers and the products from bioreactors (Volume 3). The separations can be highly specific and may depend on molecular size and shape, and the configuration of the constituent chemical groups of the molecules. 

The terminal settling velocity v, can be obtained by Eq. (1) and, in a perfusion system, the overflow rate Q is equal to the product between the specific perfusion rate D and the bioreactor volume V. Hence ... 

Batch cultivation is perhaps the simplest way to operate a fermentor or bioreactor. It is easy to scale up, easy to operate, quick to turn around, and reliable for scale-up. Batch sizes of 15,000 L have been reported for animal cell cultivation [2], and vessels of over 100,000 L for fermentation are also available. Continuous processes can be classified into cell retention and non-cell retention. The devices typically used for cell retention are spin filters, hollow fibers, and decanters. Large-scale operation of continuous processes can reach up to 2,000 L of bioreactor volume. Typically, the process is operated at 1-2 bioreactor volumes... 

Continuous cultivation is used mainly in research and development activities, at small scales. It is characterized by a continuous feed of fresh medium and a continuous removal of cell suspension, both at the same flow rate, and at constant bioreactor volume. 

As mentioned in Chapter 9, since production scale-up is related to the increase of cell culture surface for adherent cells, consideration must be given to the relationship between the surface area available for cell growth and the bioreactor volume (Kent and Mutharasani, 1992). 

Table 18.1 compares the relationship between cell culture surface area and bioreactor volume in many different culture systems usually used with adherent cells. For microcarriers, this coefficient might reach 60 cm2/ml of medium for culture area prepared with 10 mg of microcarriers per milliliter. For Roux bottles, this coefficient is around 3 cm2/ml. In cultures initiated with 2 mg of microcarriers per milliliter of medium, high cell densities of even 3 X 106 cells/ml are often reached, compared with smaller cell densities from 2 to 3 X 105 cells/ml usually observed in Roux bottle systems. Another great advantage of the use of microcarrier culture systems is the possibility of preparing cell cultures with hundreds or even thousands of liters (Montagnon et al., 1984). 

Table 18.1 Relationship between cell culture surface area and bioreactor volume used with animal adherent cells...

In perfusion bioreactors, supernatant is removed from the bioreactor at certain times, the cells are separated from the supernatant, the supernatant is harvested, and the cells are returned to the bioreactor. Perfusion bioreactors can be operated in a variety of modes. The simplest mode is to consistently remove a certain amount of broth each day (i.e., one bioreactor volume/day) and replace with fresh media. This mode is relatively easy to control. However, as the cell density increases, the required nutrient level may not be met. Also,... 

Some work has been done on photoreactor concepts that would collect sunlight using dish solar concentrators that direct concentrated sunlight onto the aperture of a light pipe or optical fiber system. An optical fiber system would then carry light into the reactor and disperse it evenly throughout the bioreactor volume. Such a... 

Often the coupling of the membrane unit with the bioreactor results in significant synergy as in the study of O Brien et al. [6.15] on the application of PVMBR to ethanol production, which we discussed in Chapter 3. The required bioreactor volume for the PVMBR system was smaller than that of the conventional system by a factor of 12. Nevertheless, it turns out that the PVMBR-based process is still 25 % more expensive than the classical batch fermentation process in terms of capital costs despite the substantial reduction in the required reactor volume. This cost differential is not only due to the membrane costs, which are, themselves, substantial, but also due to the cost of the additional hardware associated with membrane operation. The application of MBR for the ethanol production by fermentation faces marginal economics, since ethanol is a relatively cheap commodity chemical. 

The use of values of p ax for A. latus and R. eutropha and a maximum biomass concentration of 30 gL in Eq. 1 gives a productivity ratio of 8.2 with A. latus and 5.25 with R. eutropha if to is set to a low 10 h. This means that for a fixed desired amount of product per unit of time, the bioreactor volume can be substantially reduced if a continuous culture is chosen over a batch process. From an engineering point of view, the reactor performance would also be easier to control, as lower fermentor volumes lead to less segregation through better mixing at inferior energy expenditure. ... 

The area ratio effects on the liquid-phase mass transfer coefficient are more difficult to predict. Area ratio effects are usually studied by keeping the bioreactor volume equal, which requires the effective bioreactor height to be adjusted. As the height is increased, the interfacial solute gas concentration increases as well, which decreases the gas solubility and, in turn, the liquid-phase mass transfer coefficient. In addition, an increase in the area ratio decreases the liquid circulation rate, which increases gas holdup, but may decrease surface renewal. The greater height also raises the pressure drop and power consumption, which increases surface renewal and the liquid-phase mass transfer coefficient. The extent of these effects is dependent on the operational scale and power level, and it is hard to predict which will dominate. 

---