Multilateral approach on enhancing economic viability of lipid production from microalgae: A review.

The effects of temperature, agitation and aeration on glycoprotein GP-1 production by Streptomyces kanasenisi ZX01 in bench-scale fermentors were systematically investigated. The maximum final GP-1 production was achieved at an agitation speed of 200 rpm, aeration rate of 2.0 vvm and temperature of 30 °C. By using a dynamic gassing out method, the effects of agitation and aeration on volumetric oxygen transfer coefficient (kLa) were also studied. The values of volumetric oxygen transfer coefficient in the logarithmic phase increased with increase of agitation speed (from 14.53 to 32.82 h−1) and aeration rate (from 13.21 to 22.43 h−1). In addition, a successful scale-up from bench-scale to pilot-scale was performed based on volumetric oxygen transfer coefficient, resulting in final GP-1 production of 3.92, 4.03, 3.82 and 4.20 mg/L in 5 L, 15 L, 70 L and 500 L fermentors, respectively. These results indicated that constant volumetric oxygen transfer coefficient was appropriate for the scale-up of batch fermentation of glycoprotein GP-1 by Streptomyces kanasenisi ZX01, and this scale-up strategy successfully achieved 100-fold scale-up from bench-scale to pilot-scale fermentor.

Effects of Agitation, Aeration and Temperature on Production of a Novel Glycoprotein GP-1 by Streptomyces kanasenisi ZX01 and Scale-Up Based on Volumetric Oxygen Transfer Coefficient

This study presents a full operation and optimisation of a mixing unit; an innovative approach is developed to address the behaviour of gas-liquid mixing by using Electrical Resistance Tomography (ERT). The validity of the method is investigated by developing the tomographic images using different numbers of baffles in a mixing unit. This technique provided clear visual evidence of better mixing that took place inside the gasliquid system and the effect of a different number of baffles on mixing characteristics. For optimum gas flow rate (m3/s) and power input (kW), the oxygen absorption rate in water was measured. Dynamic gassingout method was applied for five different gas flow rates and four different power inputs to find out mass transfer coefficient (KLa). The rest of the experiments with one up to four baffles were carried out at these optimum values of power input (2.0 kW) and gas flow rate (8.5×10-4 m3/s). The experimental results and tomography visualisations showed that the gasliquid mixing with standard baffling provided near the optimal process performance and good mechanical stability, as higher mass transfer rates were obtained using a greater number of baffles. The addition of single baffle had a striking effect on mixing efficiency and additions of further baffles significantly decrease mixing time. The energy required for complete mixing was remarkably reduced in the case of four baffles as compared to without any baffle. The process economics study showed that the increased cost of baffles installation accounts for less cost of energy input for agitation. The process economics have also revealed that the optimum numbers of baffles are four in the present mixing unit and the use of an optimum number of baffles reduced the energy input cost by 54%.

Study of gas–liquid mixing in stirred vessel using electrical resistance tomography

The production of monoclonal antibodies by mammalian cell culture in bioreactors up to 25,000 L is state of the art technology in the biotech industry. During the lifecycle of a product, several scale up activities and technology transfers are typically executed to enable the supply chain strategy of a global pharmaceutical company. Given the sensitivity of mammalian cells to physicochemical culture conditions, process and equipment knowledge are critical to avoid impacts on timelines, product quantity and quality. Especially, the fluid dynamics of large scale bioreactors versus small scale models need to be described, and similarity demonstrated, in light of the Quality by Design approach promoted by the FDA. This approach comprises an associated design space which is established during process characterization and validation in bench scale bioreactors. Therefore the establishment of predictive models and simulation tools for major operating conditions of stirred vessels (mixing, mass transfer, and shear force.), based on fundamental engineering principles, have experienced a renaissance in the recent years. This work illustrates the systematic characterization of a large variety of bioreactor designs deployed in a global manufacturing network ranging from small bench scale equipment to large scale production equipment (25,000 L). Several traditional methods to determine power input, mixing, mass transfer and shear force have been used to create a data base and identify differences for various impeller types and configurations in operating ranges typically applied in cell culture processes at manufacturing scale. In addition, extrapolation of different empirical models, e.g. Cooke et al. (Paper presented at the proceedings of the 2nd international conference of bioreactor fluid dynamics, Cranfield, UK, 1988), have been assessed for their validity in these operational ranges. Results for selected designs are shown and serve as examples of structured characterization to enable fast and agile process transfers, scale up and troubleshooting.

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Equipment characterization to mitigate risks during transfers of cell culture manufacturing processes

Towards improved accuracy in modeling aeration efficiency through understanding bubble size distribution dynamics.

The volumetric mass transfer coefficient (k L a) is often used in order to compare the efficiency of bioreactors and as an important scale-up factor. In bioreactors, a number of methods are available for estimation the overall volumetric oxygen mass transfer coefficient: the dynamic method, the steady-state method based on a preliminary determination of the oxygen uptake rate, the gaseous oxygen balance, the carbon dioxide balance. Each method provides a different estimation of the value of k L a. We examined the sensitivity of the various methods and compare the k L a values obtained in order to select the most suitable method as a function of the type of bioreactor used. In this work we applied dynamic gassing-out method for measuring the volumetric mass transfer coefficient k L a in three type gas-liquid reactors (stirred tanks, bubble columns and airlift). Тhe aim of this work is on the basis of our experimental data to obtain several correlations for evaluation of k L a.

D. Popova

Papers

Experimental determination of the volumetric mass transfer coefficient