Time-Delayed Bioreactor Model of Phenol and Cresol Mixture Degradation with Interaction Kinetics

This paper is devoted to a mathematical model for phenol and p-cresol mixture degradation in a continuously stirred bioreactor. The biomass specific growth rate is presented as sum kinetics with interaction parameters (SKIP). A discrete time delay is introduced and incorporated into the biomass growth response. These two aspects—the mutual influence of the two substrates and the natural biological time delay in the biomass growth rate—are new in the scientific literature concerning bioreactor (chemostat) models. The equilibrium points of the model are determined and their local asymptotic stability as well as the occurrence of local Hopf bifurcations are studied in dependence on the delay parameter. The existence and uniqueness of positive solutions are established, and the global stabilizability of the model dynamics is proved for certain values of the delay. Numerical simulations illustrate the global behavior of the model solutions as well as the transient oscillations as a result of the Hopf bifurcation. The performed theoretical analysis and computer simulations can be successfully used to better understand the biodegradation dynamics of the chemical compounds in the bioreactor and to predict and control the system behavior in real life conditions.

Optimization of Conditions For Increasing of Saffron Cell Biomass And Crocin Production In Stirred Bioreactor

Bioreactors provide suitable conditions for the growth of cells and production of secondary metabolites by regulating physical and chemical factors. In this study, first, sucrose, 2-(N-morpholino) ethanesulfonic acid (MES) as a buffering agent and medium pH was optimized in the Erlenmeyer flask. This aim was then pursued in a stirred bioreactor through aeration and pH medium adjustment. Results of the first step showed that Schenk and Hildebrandt (SH) basal medium with naphthalene acetic acid (2 mg.l-1) and 6-benzylaminopurine (1 mg.l-1) supplemented with 2.5 mM of MES and gradually increment of sucrose from 3 to 6% caused to catch the highest cell biomass and crocin production. The spectrophotometry measurement showed that the highest crocin content of the cells was 0.8 mg/g after five weeks. The results of the second part revealed that in the stirred bioreactor, constant pH (5.8) during the growth period is a limited factor for the cell growth and crocin production. Although aeration initially found to be an inhibited factor for the production of crocin, results showed that, if the evaporated volume of water caused by aeration is constituted, it can be an effective factor to increase cell growth rate around 2 folds. In addition, total crocin content of the cells, based on the HPLC could be raised up to 2 mg/g. Based on this study, it can be concluded that MES and gradual increment of sucrose could increasing the cell growth and crocin production. Aeration in bioreactor can increase cell biomass, if the medium volume will be kept constant.

Large-Scale Microcarrier Culture of Chinese Perch Brain Cell for Viral Vaccine Production in a Stirred Bioreactor

Mandarin fish (Siniperca chuatsi) is one of the important cultured fish species in China. Infectious spleen and kidney necrosis virus (ISKNV) and Siniperca Chuatsi rhabdovirus (SCRV) have hindered the development of mandarin fish farming industry. Vaccination is the most effective method for control of viral diseases, however viral vaccine production requires the large-scale culture of cells. Herein, a suspension culture system of Chinese perch brain cell (CPB) was developed on Cytodex 1 microcarrier in a stirred bioreactor. Firstly, CPB cells were cultured using Cytodex 1 microcarrier in 125 mL stirring flasks. With the optimum operational parameters, CPB cells grew well, distributed uniformly, and could fully cover the microcarriers. Then, CPB cells were digested with trypsin and expanded step-by-step with different expansion ratios from the 125 mL stirring bottle to a 500 mL stirring bottle, and finally to a 3-L bioreactor. Results showed that with an expansion ratio of 1:3, we achieved a high cell density level (2.25 × 106 cells/mL) with an efficient use of the microcarriers, which also confirmed the data obtained from the 125 mL stirring flask. Moreover, obvious cytopathic effects (CPE) were observed in the suspended CPB cells post-infection with ISKNV and SCRV. This study provided a large-scale culture system of CPB cells for virus vaccine production.

Alginate-chitosan core-shell microcapsule cultures of hepatic cells in a small scale stirred bioreactor: impact of shear forces and microcapsule core composition

A small scale stirred bioreactor was designed and the effect of different agitation rates (30, 60 and 100 rpm) was investigated on HepG2 cells cultured in alginate-chitosan (AC) core-shell microcapsule in terms of the cell proliferation and liver-specific function. The microencapsulated hepatic cells could proliferate well when they were cultured for 10 days at 30 rpm while the cell-laden microcapsules showed no cell proliferation at 100 rpm in the bioreactor system. Albumin production rate, as an important liver function, increased also 1.8- and 1.5- fold under stirring rate of 30 rpm compared to the static culture and 60 rpm of agitation, respectively. Moreover, In comparison with the static culture, about 1.5-fold increment in urea production was observed at 30 rpm. Similarly, the highest expressions of albumin and P450 genes were found at 30 rpm stirring rate, which were 4.9- and 19.2-fold of the static culture. Addition of collagen to the microcapsule core composition (ACol/C) could improve the cell proliferation and functionality at 60 rpm in comparison with the cell-laden microcapsules without collagen. The study demonstrated the hepatic cell-laden ACol/C microcapsule hydrogel cultured in the small scale stirred bioreactor at low mixing rate has a great potential for mass production of the hepatic cells while maintaining liver-specific functions.

Core–shell hydrogel microcapsules enable formation of human pluripotent stem cell spheroids and their cultivation in a stirred bioreactor

Cellular therapies based on human pluripotent stem cells (hPSCs) offer considerable promise for treating numerous diseases including diabetes and end stage liver failure. Stem cell spheroids may be cultured in stirred bioreactors to scale up cell production to cell numbers relevant for use in humans. Despite significant progress in bioreactor culture of stem cells, areas for improvement remain. In this study, we demonstrate that microfluidic encapsulation of hPSCs and formation of spheroids. A co-axial droplet microfluidic device was used to fabricate 400 μm diameter capsules with a poly(ethylene glycol) hydrogel shell and an aqueous core. Spheroid formation was demonstrated for three hPSC lines to highlight broad utility of this encapsulation technology. In-capsule differentiation of stem cell spheroids into pancreatic β-cells in suspension culture was also demonstrated.

An overview of drive systems and sealing types in stirred bioreactors used in biotechnological processes

No matter the scale, stirred tank bioreactors are the most commonly used systems in biotechnological production processes. Single-use and reusable systems are supplied by several manufacturers. The type, size, and number of impellers used in these systems have a significant influence on the characteristics and designs of bioreactors. Depending on the desired application, classic shaft-driven systems, bearing-mounted drives, or stirring elements that levitate freely in the vessel may be employed. In systems with drive shafts, process hygiene requirements also affect the type of seal used. For sensitive processes with high hygienic requirements, magnetic-driven stirring systems, which have been the focus of much research in recent years, are recommended. This review provides the reader with an overview of the most common agitation and seal types implemented in stirred bioreactor systems, highlights their advantages and disadvantages, and explains their possible fields of application. Special attention is paid to the development of magnetically driven agitators, which are widely used in reusable systems and are also becoming more and more important in their single-use counterparts.Key Points• Basic design of the most frequently used bioreactor type: the stirred tank bioreactor• Differences in most common seal types in stirred systems and fields of application• Comprehensive overview of commercially available bioreactor seal types• Increased use of magnetically driven agitation systems in single-use bioreactors

Global Stability Analysis of a Bioreactor Model for Phenol and Cresol Mixture Degradation

We propose a mathematical model for phenol and p-cresol mixture degradation in a continuously stirred bioreactor. The model is described by three nonlinear ordinary differential equations. The novel idea in the model design is the biomass specific growth rate, known as sum kinetics with interaction parameters (SKIP) and involving inhibition effects. We determine the equilibrium points of the model and study their local asymptotic stability and bifurcations with respect to a practically important parameter. Existence and uniqueness of positive solutions are proved. Global stabilizability of the model dynamics towards equilibrium points is established. The dynamic behavior of the solutions is demonstrated on some numerical examples.