Bioreactor operating parameters

In this paper the fundamental aspects of process development for the production of core and virus-like particles with baculovirus infected insect cells are reviewed. The issues addressed include particle formation and monomer composition, chemical and physical conditions for optimal cell growth, baculovirus replication and product expression, multiplicity of infection strategy, and scale-up of the process. Study of the differences in the metabolic requirements of infected and non-infected cells is necessary for high cell density processes. In the bioreactor, the specific oxygen uptake rate (OURsp) plays a central role in process scale-up, leading to the specification of the bioreactor operational parameters. Shear stress can also be an important variable for bioreactor operation due to its influence on cell growth and product expression. 

In this part the determination of critical variables for bioreactor operation and scale-up are reviewed. Special focus is put on the specific oxygen uptake rate (OURsp) and its influence upon the specification of bioreactor operational parameters. Shear stress can also be an important variable for process design and its importance in cell growth and product expression is discussed. 

The Bioreactor is the major equipment used in biochemical processes. It differs totally from a simple chemical reaction vessel. To control physical operating parameters and microbial environmental conditions, there are several influential variables ... 

Fluidization Regime. As for traditional fluidization applications, the fluidization regime—dispersed bubble, coalesced bubble, or slugging—in which a three-phase fluidized bioreactor operates depends strongly on the system parameters and operating conditions. Generally, desirable fluidization is considered to be characterized by stable operation with uniform phase holdups, typical of the dispersed bubble regime. It would be useful to be able to predict what conditions will produce such behavior. 

Parameter Stirred-tank bioreactors operated in batch and fed-batch mode Stirred-tank bioreactors operated in perfusion mode Heterogeneous bioreactors (packed-bed or hollow-fiber) operated in perfusion mode... 

This type of separator has been used basically for cell retention in perfusion processes. It operates directly coupled to the top of a bioreactor. To maximize retention efficiency and cell viability when using it, different operational parameters should be optimized, such as cycle duration, perfusion and recirculation flow rates, acoustic force intensity, and the separator backwash frequency (Shirgaonkar et al., 2004). 

Various adsorbents have been examined for their potential to increase in situ product separation in plant cell culture. Suspended solid adsorbents were popular, and the use of immobilized adsorbent has been investigated recently [17-20]. The advantages of immobilized adsorbent are that it is easy to use in a bioreactor operation and that it allows adsorbents to be easily separated from culture broth for the repeated use of cells and adsorbents [21, 22]. The design and optimization of in situ separation process for phytochemicals using immobilized adsorbent required a detailed mathematical model. It was difficult to achieve an optimal design based on purely empirical correlations, because the effects of various design parameters and process variables were coupled. 

The objective of the experiments carried out in this pilot plant was to determine the optimal values of some operational parameters, such as biomass concentration, transmembrane pressure, flow rate, and hydrauhc retention time, the last defined as the relationship between the volume of the bioreactor and the daily flow discharge of permeate. The working plan was as follows ... 

Even though the bioreactor itself may not be the most costly piece of process equipment, it determines the technical feasibility of the entire process. The attention paid to bioreactor design, scale-up, and operating parameters reflects its central role in successful commercial ventures. 

Small-scale fermentation here refers to cultivation in bioreactors that can rigorously control the growth and production environment. These fermenters may range in size from 2 1 to 201. There exist a handful of operating parameters that should be optimized near the beginning of the development process, including... 

Enzyme thermal inactivation during bioreactor operation is of paramount importance and must be considered for proper bioreactor design, as shown in Fig. 3.1. To do so, a mathematical model must be developed based on experimentally calculated and validated parameters. Mechanistic models to describe enzyme inactivation were presented in sections 5.4.1 and 5.4.2. 

Temperature is a variable of paramount importance in any bioprocess. Temperature optimization of bioreactor operation is a complicated task since many variables and parameters are involved that are strongly dependent on temperature. Besides, temperature exerts opposite effects on enzyme activity and stability. Then, thermal optimization of enzyme reactor operation requires that temperature explicit functions for all parameters involved be determined and validated. Optimization wifi... 

The fundamental gas-liquid mass transfer models lack the ability to obtain and process all necessary information and factors integral to bioreactor operation. Gas-liquid systems are simply too complex. Therefore, a theoretical equation, which is widely applicable, does not exist (Garcia-Ochoa and Gomez, 2004). Empirical correlations have been developed to simplify analysis and design and have become exclusive in the literature and practice (Kawase and Moo-Young, 1988). Model parameters are chosen that are thought to influence the operation, and their powers and constants are fltted to the experimental data. The correlations are used for design and scale-up while theoretical mass transfer models are used to explain the influence of various operational inputs. 

Parameter Estimation of Kinetic Models with Bioreactors 157 Table 4.5. Bioreactor operation techniques and biological behavior. 

During operation of the bioreactors, samples were collected for the analysis of key operating parameters, such as dissolved oxygen, nutrient levels, total organic carbon and suspended solids. Microbial analysis was performed to assess the cell concentration of the specialized bacteria being added. All cultures were prepared in advance and added to the bioreactors. Additional samples were collected to measure the contaminant concentration across the bioreactor, as well as in the various portions of the treatment system, in order to calculate a mass balance. 

The aim of this chapter is to give a detailed overview of the characterization of biocatalysts and the development of membrane bioreactors, in particular, the main aspects of biocatalyst kinetics and their immobilization/ entrapment, either within the porous membrane structure, or on its surface. Thansport models that can help to predict the behaviour of membrane bioreactors, as well as the most relevant theoretical models and operating parameters, are presented below. This data is then analysed in order to ascertain how to improve effectiveness and productivity of the membrane bioreactors. Some relevant fields of application are also discussed in order to show the potential of such systems. 

Reactor II. In this 750 L stirred-tank bioreactor (also with a propeller), the consortium grown on Reactor I served as seed for this system. The final volume of medium was 550 L. Operational parameters such as pH (no NaOH was utilized) and temperature were the same. Agitation velocity was decreased to 60 rpm. Sodium lactate was fed continuously... 

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