Modeling of the Performance of Industrial Bioreactors with a Dynamic Microenvironmental Approach: A Critical Review

Abstract

In industrial fed-batch bioreactors, imperfect mixing coupled with the biological consumption of nutrients causes temporal and spatial concentration gradients leading to the formation of zones very rich in substrate close to the feed port and low or even depleted regions further from it. The direct consequence is that cells experience a changing environment during the cultivation process and, thus, respond differently from laboratory cultivation, where a degree of homogeneity is assumed throughout the reactor. A drastic decline in the performance of the bioprocess is often observed in large-scale reactors due to this nonhomogeneity.The literature on substrate concentration gradient formation in production-scale bioreactors and their effects on the biological material has been evaluated, and the findings are reported in the present critical review. The need to combine mixing models and biokinetics for the successful modeling of the performance of industrial bioreactors is pointed out. The microenvironmental approach is discussed from a bioengineering point of view, i.e., giving biological and engineering factors the same importance. The lack of dynamic biological models in this respect is pointed out. Three advanced methods for the quantitative description of the mixing process in stirred, aerated tanks of industrial size are presented and commented on in terms of adequacy and reliability with regard to the microenvironmental approach.

Applicability of GFP Microbial Whole Cell Biosensors to Bioreactor Operations - Mathematical Modeling and Related Experimental Tools

“…The characterization of these gradients in function of the bioreactor design modification and the up-scaling procedures is of particular importance and is generally achieved by the aim of structured hydrodynamic models that can be classified into three distinct classes with increasing level of complexity (Guillard F., 1999). The simplest structured hydrodynamic model is based on a rough compartimentalisation of the bioreactor in a few virtual fluid zones.…”

Quantitative measures of disorder in biological oscillations and their implications for bioreactor operation

“…The filter can provide estimations of past, present, and future states of a system even when a precise model is not known. This feature is useful for microbial processes under nonideal (realistic) conditions because models developed on laboratory data may become inapplicable or imprecise under the influence of disturbances and spatial gradients (Gillard and Tragardh, 1999;Liden, 2002).…”

“…Previous studies (Montague and Morris, 1994;Rohner and Meyer, 1995;Gillard and Tragardh, 1999) show that w k and v k may be represented as white noise with normal probability distributions:…”

Fractal Analysis of the Attenuation of Noise Inflow to Bioreactors under Monotonic, Oscillating and Chaotic Conditions

“…Therefore, industrial-scale fermentations are often subject to noise from the environment, carried mainly by inflow streams (Gillard and Tragardh, 1999;Rohner and Meyer, 1995). However, such ideal conditions are difficult to obtain in large-scale operations, owing to both practical difficulties and high costs.…”

“…Observations from real fermentation processes (Gillard and Tragardh, 1999;Rohner and Meyer, 1995) indicate that the noise contains a spectrum of disturbances with different variances. To analyze the behavior of such processes, a lumped approximation as a generalized noise with a spectral density 1/f β is incorporated into a deterministic model.…”