scholarly journals Towards the development of automated fed-batch cell culture processes at microscale

BioTechniques ◽  
2019 ◽  
Vol 67 (5) ◽  
pp. 238-241
Author(s):  
Vincent Wiegmann ◽  
Maria Giaka ◽  
Cristina Bernal Martinez ◽  
Frank Baganz
Keyword(s):  
Feeding Strategy ◽  
Viable Cell ◽  
Feeding Strategies ◽  
Fed Batch ◽  
Cho Cell ◽  
Feed Medium ◽  
Cell Densities ◽  
The Impact ◽  
Batch Cell ◽  
Selection Of

Aim: To investigate the impact of various feeding strategies on the growth and productivity of a GS-CHO cell line. Methods: Feed additions were conducted at fixed volumes or linked to a marker such as cell growth or metabolism and added as bolus or near-continuously using the automated feeding module of the micro-Matrix (Applikon). Results: The selected feeding regimens supported maximum viable cell densities of up to 1.9 × 107 cells ml−1 and final titers of up to 1.13 g l−1. Differences in growth and titer between feeding strategies were insignificant, with the exception of one feeding strategy. Conclusion: As the more complex feeding strategies did not create an advantage, the selection of a simple feeding strategy such as bolus or continuous addition of feed medium is preferred.

The impact of pH inhomogeneities on CHO cell physiology and fed-batch process performance - two-compartment scale-down modelling and intracellular pH excursion

2017 ◽  
Vol 12 (7) ◽  
pp. 1600633 ◽  
Author(s):  
Matthias Brunner ◽  
Philipp Braun ◽  
Philipp Doppler ◽  
Christoph Posch ◽  
Dirk Behrens ◽  
...  
Keyword(s):  
Intracellular Ph ◽  
Batch Process ◽  
Cell Physiology ◽  
Process Performance ◽  
Fed Batch ◽  
Cho Cell ◽  
Scale Down ◽  
The Impact

scholarly journals Selection of chemically defined media for CHO cell fed-batch culture processes

2016 ◽  
Vol 69 (1) ◽  
pp. 39-56 ◽  
Author(s):  
Xiao Pan ◽  
Mathieu Streefland ◽  
Ciska Dalm ◽  
René H. Wijffels ◽  
Dirk E. Martens
Keyword(s):  
Batch Culture ◽  
Fed Batch ◽  
Cho Cell ◽  
Chemically Defined Media ◽  
Defined Media ◽  
Fed Batch Culture ◽  
Selection Of

Principle of Express Selection of Leading Producing Clones of Monoclonal Antibodies in the Development of Stable CHO-Based Cell Lines

2019 ◽  
Vol 35 (4) ◽  
pp. 65-72
Author(s):  
V.I. Pavelko ◽  
I.A. Kirik ◽  
V.N. Bade ◽  
T.O. Malygina ◽  
R.A. Khamitov ◽  
...  
Keyword(s):  
Cell Culture ◽  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Parallel Processing ◽  
Cell Lines ◽  
Cho Cells ◽  
Fed Batch ◽  
Cho Cell ◽  
Recombinant Monoclonal Antibody ◽  
Selection Of

Growth and productive characteristics of monoclonal cell lines based on CHO cells and producing a therapeutic protein have been monitored using the robot Ambr Tap Biosystems, which permitted to identify the leading line. Twenty four clones producing a recombinant monoclonal antibody were studied under the close to industrial conditions in a fed-batch culturing mode. The ambr®15 cell culture workstation controls 24 disposable mini bioreactors, and offers parallel processing and evaluation of multiple (24) experiments in an automated bench-top system. The volumetric productivity of 24 clones determined by ELISA was 120-450 mg /L. A protocol was shown to select a leader among producing clones for further research. producing clones, mini bioreactor; Ambr Tap Biosystems, fed-batch, monoclonal antibodies, CHO cell culture

scholarly journals The Joint Effect of pH Gradient and Glucose Feeding on the Growth Kinetics of Lactococcus lactis CECT 539 in Glucose-Limited Fed-Batch Cultures

2019 ◽  
Vol 68 (2) ◽  
pp. 269-280
Author(s):  
MÓNICA COSTAS MALVIDO ◽  
ELISA ALONSO GONZÁLEZ ◽  
RICARDO J. BENDAÑA JÁCOME ◽  
NELSON PÉREZ GUERRA
Keyword(s):  
Lactococcus Lactis ◽  
Viable Cell ◽  
Product Formation ◽  
Ph Gradient ◽  
Feeding Strategies ◽  
Fed Batch ◽  
Batch Cultures ◽  
Cell Counts ◽  
First Time ◽  
Kinetics Of

Two glucose-limited realkalized fed-batch cultures of Lactococcus lactis CECT 539 were carried out in a diluted whey medium (DW) using two different feeding media. The cultures were fed a mixture of a 400 g/l concentrated lactose and a concentrated mussel processing waste (CMPW, 101.72 g glucose/l) medium (fermentation I) or a CMPW medium supplemented with glucose and KH2PO4 up to concentrations of 400 g glucose/l and 3.21 g total phosphorus/l, respectively (fermentation II). For an accurate description and a better understanding of the kinetics of both cultures, the growth and product formation by L. lactis CECT 539 were both modelled, for the first time, as a function of the amounts of glucose (G) added and the pH gradient (VpH) generated in every realkalization and feeding cycle, by using an empirical polynomial model. With this modeling procedure, the kinetics of biomass, viable cell counts, nisin, lactic acid, acetic acid and butane-2,3-diol production in both cultures were successfully described (R2 values > 0.970) and interpreted for the first time. In addition, the optimum VpH and G values for each product were accurately calculated in the two realkalized fed-batch cultures. This approach appears to be useful for designing feeding strategies to enhance the productions of biomass, bacteriocin, and metabolites by the nisin-producing strain in wastes from the food industry.

scholarly journals Experimental investigation of polyvinyl alcohol degradation in UV/H202 photochemical reactors using different hydrogen peroxide feeding strategies

2021 ◽  
Author(s):  
Dina Hamad
Keyword(s):  
Hydrogen Peroxide ◽  
Polyvinyl Alcohol ◽  
Operating Conditions ◽  
Continuous Treatment ◽  
Experimental Result ◽  
Feeding Strategies ◽  
Process Performance ◽  
Fed Batch ◽  
Batch System ◽  
The Impact

Synthetic water-soluble polymers are popular in industry and they are produced in large scale owing to their wide spectrum of applications. In particular, the polyvinyl alcohol polymer (PVA), a well-known refractory pollutant, is abundant in wastewater effluents since it is heavily used in industry as paper coating and polarization layer in liquid crystal displays (LCDs). These polymers are non-biodegradable and contaminant to water resources. Alternatively, they can be effectively removed by advanced oxidation processes (AOPs). This study investigates the photo-oxidative degradation of aqueous PVA solution in UV/H2O2 photoreactors and the effect of hydrogen peroxide feeding strategies on the photoreactor performance. The research covers thoroughly the impact of operating conditions on the polymer number average molecular weight (Mn), TOC content, and H2O2 residual under batch, fed-batch and continuous modes of operation. The experimental results show that the performance of the fed-batch photoreactor was higher than the batch system for similar experimental conditions revealing that the way H2O2 is fed into the system has a considerable effect on the PVA degradation. The experimental result of batch system was used as a guide to develop a photochemical kinetic model of the PVA degradation in UV/H2O2 batch process that describes the disintegration of the polymer chains in which the statistical moment approach was considered. The model predictions are in good agreement with data. Realizing the limitations of batch and fed-batch UV/H2O2 processes, an innovative continuous treatment technique was devised to enhance the process performance and to minimize UV dosage. Response surface methodology (RSM), based on Box-Behnken method, was adopted for design set of experiments required to determine the impact of operating variables and their interaction on the process performance. Finally, the results show that Mn was reduced from 130 kg/mol to 24.9, 20.3, and 2.2 kg/mol, corresponding to percent TOC removal of 41.5, 64.2 and 94.4 and H202 residual of 17, 3 and 1% were achieved in batch, fed-batch (120-min), and continuous (30-min) UV/H2O2 photoreactors, respectively. In addition, the overall power consumption of the process was assessed to determine the economic incentive for continuous feeding strategy and ensure the possibility of the process scale-up.

scholarly journals FACTORS AFFECTING CHINESE HAMSTER OVARY CELL PROLIFERATION AND VIABILITY

2019 ◽  
Vol 1 ◽  
pp. 245
Author(s):  
Alina Rekena ◽  
Dora Livkisa ◽  
Dagnija Loca
Keyword(s):  
Cell Proliferation ◽  
Cell Line ◽  
Cell Density ◽  
Chinese Hamster Ovary ◽  
Chinese Hamster ◽  
Viable Cell ◽  
Viable Cell Density ◽  
Fed Batch ◽  
Cho Cell ◽  
Decline Phase

Advantageous cultivation procedures for the Chinese hamster ovary (CHO) cells are necessary for the productive commercial production of biopharmaceuticals. A main challenge that needs to be addressed during the process development is the differences in each cell line requirements concerning the nutrients and feed strategies in order to achieve the desired growth characteristics. Therefore, within the current research, a naïve high cell density serum free suspension adapted CHO cell line was tested with glucose and glutamine rich feeds in fed-batch Erlenmeyer shake flask cultures. Glucose consumption rate was adjusted to develop the optimal feed strategies. Obtained results indicated that high glucose and l-glutamine feeding did not improve maximum viable cell density compared to the control samples. During the exponential phase, cell proliferation and viability of all feeds showed no statistically significant difference. Instead, the fed-batch processes tested led to statistically significant differences in viable cell density and cell viability during the decline phase, compared to control (batch) culture. The difference between glucose and glutamine feeding was indistinguishable, most probably due to the concentration imbalance with the rest of the nutrients in feed. The overall study presented a method to slow down the decrease in CHO cell proliferation and viability during the decline phase, instead of increasing the maximum cell density at the plateau phase. 

Effects of feeding strategies on the performance of an anaerobic discontinuous reactor containing immobilized biomass with circulation system for liquid-phase mixing

2004 ◽  
Vol 49 (11-12) ◽  
pp. 303-310 ◽  
Author(s):  
A.A. Orra ◽  
S.M. Ratusznei ◽  
J.A.D. Rodrigues ◽  
E. Foresti ◽  
M. Zaiat
Keyword(s):  
Liquid Phase ◽  
High Efficiency ◽  
Feeding Strategy ◽  
Current System ◽  
Operating Conditions ◽  
Circulation System ◽  
Feeding Strategies ◽  
Order Kinetic ◽  
Fed Batch ◽  
Batch Mode

Data on the influence of feeding strategy on the performance of a fed-batch anaerobic sequencing reactor containing biomass immobilized on polyurethane foam and subjected to liquid phase circulation are presented and discussed. Six-hour cycles, temperature of 30°C and circulation flow rate of 6 L/h were used. During each cycle 890 mL of synthetic domestic wastewater, with organic matter concentration of 500 mgCOD/L were fed to the reactor. The feeding strategies were implemented using fill times of 6 min (batch mode), 60, 120, 240 (fed-batch/batch mode) and 360 min (fed-batch mode). The system attained high efficiency and stability for all the operating conditions, and the substrate removal efficiency based on filtered samples presented a slight decrease from 85% to 81% when fill time was increased from 6 min to 360 min. A model considering a first-order kinetic equation was fitted to the experimental data. The apparent kinetic parameters for both batch and fed-batch phases were estimated, thus permitting evaluation of the influence of the feeding strategy on the reactor performance. The current system may be considered flexible in terms of the operating conditions it is subjected to.

scholarly journals Production of L (+) Lactic Acid by Lactobacillus casei Ke11: Fed Batch Fermentation Strategies

Fermentation ◽  
2021 ◽  
Vol 7 (3) ◽  
pp. 151
Author(s):  
Paola Monteiro de Oliveira ◽  
Larissa Provasi Santos ◽  
Luciana Fontes Coelho ◽  
Paulo Marcelo Avila Neto ◽  
Daiane Cristina Sass ◽  
...  
Keyword(s):  
Lactic Acid ◽  
Batch Fermentation ◽  
Lactobacillus Casei ◽  
Culture Media ◽  
Feeding Strategy ◽  
High Yield ◽  
Feeding Strategies ◽  
Efficient Production ◽  
Fed Batch ◽  
Fed Batch Fermentation

Lactic acid and its derivatives are widely used in pharmaceutical, leather, textile and food industries. However, until now there have been few systematic reports on fed-batch fermentation for efficient production and high concentration of l-lactic acid by lactic acid bacteria. This study describes the obtainment of L (+) lactic acid from sucrose using the Lactobacillus casei Ke11 strain through different feeding strategies using an accessible pH neutralizer such as CaCO3. The exponential feeding strategy can increase lactic acid production and productivity (175.84 g/L and 3.74 g/L/h, respectively) with a 95% yield, avoiding inhibition by high initial substrate concentration and, combined with the selected agent controller, avoids the cellular stress that could be caused by the high osmotic pressure of the culture media. The purification of the acid using charcoal and celite, followed by the use of a cation exchange column proved to be highly efficient, allowing a high yield of lactic acid, high removal of sugars and proteins. The described process shows great potential for the production of lactic acid, as well as the simple, efficient and low-cost purification method. This way, this work is useful to the large-scale fermentation of L. casei Ke11 for production of l-lactic acid.

scholarly journals Experimental investigation of polyvinyl alcohol degradation in UV/H202 photochemical reactors using different hydrogen peroxide feeding strategies

2021 ◽  
Author(s):  
Dina Hamad
Keyword(s):  
Hydrogen Peroxide ◽  
Polyvinyl Alcohol ◽  
Operating Conditions ◽  
Continuous Treatment ◽  
Experimental Result ◽  
Feeding Strategies ◽  
Process Performance ◽  
Fed Batch ◽  
Batch System ◽  
The Impact

Synthetic water-soluble polymers are popular in industry and they are produced in large scale owing to their wide spectrum of applications. In particular, the polyvinyl alcohol polymer (PVA), a well-known refractory pollutant, is abundant in wastewater effluents since it is heavily used in industry as paper coating and polarization layer in liquid crystal displays (LCDs). These polymers are non-biodegradable and contaminant to water resources. Alternatively, they can be effectively removed by advanced oxidation processes (AOPs). This study investigates the photo-oxidative degradation of aqueous PVA solution in UV/H2O2 photoreactors and the effect of hydrogen peroxide feeding strategies on the photoreactor performance. The research covers thoroughly the impact of operating conditions on the polymer number average molecular weight (Mn), TOC content, and H2O2 residual under batch, fed-batch and continuous modes of operation. The experimental results show that the performance of the fed-batch photoreactor was higher than the batch system for similar experimental conditions revealing that the way H2O2 is fed into the system has a considerable effect on the PVA degradation. The experimental result of batch system was used as a guide to develop a photochemical kinetic model of the PVA degradation in UV/H2O2 batch process that describes the disintegration of the polymer chains in which the statistical moment approach was considered. The model predictions are in good agreement with data. Realizing the limitations of batch and fed-batch UV/H2O2 processes, an innovative continuous treatment technique was devised to enhance the process performance and to minimize UV dosage. Response surface methodology (RSM), based on Box-Behnken method, was adopted for design set of experiments required to determine the impact of operating variables and their interaction on the process performance. Finally, the results show that Mn was reduced from 130 kg/mol to 24.9, 20.3, and 2.2 kg/mol, corresponding to percent TOC removal of 41.5, 64.2 and 94.4 and H202 residual of 17, 3 and 1% were achieved in batch, fed-batch (120-min), and continuous (30-min) UV/H2O2 photoreactors, respectively. In addition, the overall power consumption of the process was assessed to determine the economic incentive for continuous feeding strategy and ensure the possibility of the process scale-up.

scholarly journals Alpha-Ketoglutaric Acid Production from a Mixture of Glycerol and Rapeseed Oil by Yarrowia lipolytica Using Different Substrate Feeding Strategies

2020 ◽  
Vol 12 (15) ◽  
pp. 6109 ◽  
Author(s):  
Anita Rywińska ◽  
Ludwika Tomaszewska-Hetman ◽  
Magdalena Rakicka-Pustułka ◽  
Piotr Juszczyk ◽  
Waldemar Rymowicz
Keyword(s):  
Yarrowia Lipolytica ◽  
Batch Culture ◽  
Rapeseed Oil ◽  
Feeding Strategy ◽  
Wild Strain ◽  
Control Culture ◽  
Feeding Strategies ◽  
Fed Batch ◽  
Repeated Batch ◽  
Substrate Feeding

The microbiological biosynthesis of α-ketoglutaric acid (KGA) has recently captured the attention of many scientists as an alternative to its common chemical synthesis. The present study aimed to evaluate the effect of the feeding strategy of substrates, i.e., glycerol (G = 20 g·dm−3) and rapeseed oil (O = 20 g·dm−3), on yeast growth and the parameters of KGA biosynthesis by a wild strain Yarrowia lipolytica A-8 in fed-batch and repeated-batch cultures. The effectiveness of KGA biosynthesis was demonstrated to depend on thiamine concentration and the substrate feeding method. In the fed-batch culture incubated with 3 µg·dm−3 of thiamine and a substrate feeding variant 2G(_OGO), KGA was produced in the amount of 62.1 g·dm−3 at the volumetric production rate of 0.37 g·dm−3·h−1. These values of KGA production parameters were higher than these obtained in the control culture (with rapeseed oil only). During 10 cycles of the 1788-h repeated-batch culture carried out acc. to the feeding strategy 2G(_OGO), in the last 5 cycles the yeast produced from 55.6 to 58.2 g·dm−3 of KGA and maximally 2.9 g·dm−3 of the pyruvic acid as a by-product.

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