Mass transfer bioreactor design

Naruse et al. proposed another bioreactor design [22,23], in which porcine hepatocyte spheroids are immobilized on non-woven polyester fabric. This device allows more direct contact between hepatocytes and perfused medium and improves, therefore, the mass transfer capacity. The non-woven fabric module expressed better metabohc and synthetic functions at 24 hours than a hollow fiber module containing spheroids in suspension culture. Longer term results are not yet available and the immunoexclusion properties of this fabric have not been addressed. 

This chapter describes the different types of batch and continuous bioreactors. The basic reactor concepts are described as well as the respective basic bioreactors design equations. The comparison of enzyme reactors is performed taking into account the enzyme kinetics. The modelhng and design of real reactors is discussed based on the several factors which influence their performance the immobilized biocatalyst kinetics, the external and internal mass transfer effects, the axial dispersion effects, and the operational stabihty of the immobilized biocatalyst. 

It should be noted here that the bioartificial fiver device is not only a bioreactor but also a mass transfer device. The mass transfer of various nutrients from the blood into the liver cells, and also the transfer of many products of biochemical reactions from the cells into the bloodstream, should be efficient processes. In human fiver, the oxygen-rich blood is delivered via the hepatic artery, and bioartificial devices should be so designed that the oxygen can be easily delivered to the cells. 

Gemeiner et al. (1993) presented a similar method for the direct determination of catalytic properties of immobilized cells. Cephalosporin C transforming Trigonopsis variabilis were immobilized by three different methods, filled into a column and set into the ET. After thermal equilibration, Cephalosporin C solutions (0.1-50 mmol/1) were continously pumped through the ET until steady-state heat production was obtained. Again, the ET was shown to be suitable for a rapid and simple estimation of the kinetic properties of immobilized cells. Microkinetic factors such as mass transfer were taken into account (Stefuca et al. 1994). Thus, ET measurements allow us to obtain intrinsic data, even from immobilized cells. Moreover, the data can be applied to optimize biocatalyst design and bioreactor models (Gemeiner et al. 1996). 

Mass transfer limitations can be relevant in heterogeneous biocatalysis. If the enzyme is immobilized in the surface or inside a solid matrix, external (EDR) or internal (IDR) diffusional restrictions may be significant and have to be considered for proper bioreactor design. As shown in Fig. 3.1, this effect can be conveniently incorporated into the model that describes enzyme reactor operation in terms of the effectiveness factor, defined as the ratio between the effective (or observed) and inherent (in the absence of diffusional restrictions) reaction rates. Expressions for the effectiveness factor (rj), in the case of EDR, and the global effectiveness factor (t ) for different particle geometries, in the case of IDR, were developed in sections 4.4.1 and 4.4.2 (see Eqs. 4.39-4.42,4.53,4.54,4.71 and 4.72). Such functions can be generically written as ... 

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. 

A significant difficulty in characterizing and quantifying gas-liquid, liquid-solid, and gas-liquid-solid mixtures commonly found in bioreactor flows is that the systems are typically opaque (e.g., even an air-water system becomes opaque at fairly low volumetric gas fractions) this necessitates the use of specially designed invasive measurement probes or noninvasive techniques when determining internal flow and transport characteristics. Many of these probes or techniques were developed for a particular type of gas-liquid flow or bioreactor. This chapter first introduces experimental techniques to gauge bioreactor hydrodynamics and then summarizes gas-liquid mass transfer measurement techniques used in bioreactors. 

The gas-liquid interfacial area (a) is a fundamental parameter in designing bioreactors because the knowledge of this parameter is required to calculate individual gas-liquid mass transfer rates (Vasquez et al., 2000). The interfacial area is a challenge to quantify because it is influenced by the bioreactor geometry and operating conditions, as well as the physical and chemical properties of the gas-liquid system. In some cases, the interfacial area is estimated by assuming a uniform bubble diameter and measuring the overall gas holdup e. In this case, the gas-liquid interfacial area is estimated from Chisti (1989) ... 

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