scholarly journals Control of Specific Growth Rate in Fed-Batch Bioprocesses: Novel Controller Design for Improved Noise Management

Processes ◽  
2020 ◽  
Vol 8 (6) ◽  
pp. 679 ◽  
Author(s):  
Yann Brignoli ◽  
Brian Freeland ◽  
David Cunningham ◽  
Michal Dabros
Keyword(s):  
Growth Rate ◽  
Specific Growth Rate ◽  
Real Time ◽  
Specific Growth ◽  
Controller Design ◽  
Control Variable ◽  
Biomass Concentration ◽  
Growth Dynamics ◽  
Fed Batch ◽  
Batch Cultures

Accurate control of the specific growth rate (µ) of microorganisms is dependent on the ability to quantify the evolution of biomass reliably in real time. Biomass concentration can be monitored online using various tools and methods, but the obtained signal is often very noisy and unstable, leading to inaccuracies in the estimation of μ. Furthermore, controlling the growth rate is challenging as the process evolves nonlinearly and is subject to unpredictable disturbances originating from the culture’s metabolism. In this work, a novel feedforward-feedback controller logic is presented to counter the problem of noise and oscillations in the control variable and to address the exponential growth dynamics more effectively. The controller was tested on fed-batch cultures of Kluyveromyces marxianus, during which μ was estimated in real time from online biomass concentration measurements obtained with dielectric spectroscopy. It is shown that the specific growth rate can be maintained at different setpoint values with an average root mean square control error of 23 ± 6%.

Influence of specific growth rate over the secretory expression of recombinant potato carboxypeptidase inhibitor in fed-batch cultures of Escherichia coli

2010 ◽  
Vol 45 (8) ◽  
pp. 1334-1341 ◽  
Author(s):  
Juan-Miguel Puertas ◽  
Jordi Ruiz ◽  
Mónica Rodríguez de la Vega ◽  
Julia Lorenzo ◽  
Glòria Caminal ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Growth Rate ◽  
Specific Growth Rate ◽  
Specific Growth ◽  
Fed Batch ◽  
Secretory Expression ◽  
Batch Cultures ◽  
Carboxypeptidase Inhibitor

scholarly journals Real-time metabolic heat-based specific growth rate soft sensor for monitoring and control of high molecular weight HA production by Streptococcus zooepidemicus.

2020 ◽  
Author(s):  
Naresh Mohan ◽  
Satya Sai Pavan ◽  
Anjali Jayakumar ◽  
Sivakumar Rathinavelu ◽  
Senthilkumar Sivaprakasam
Keyword(s):  
Molecular Weight ◽  
Growth Rate ◽  
Specific Growth Rate ◽  
Real Time ◽  
High Molecular Weight ◽  
Specific Growth ◽  
Fed Batch ◽  
Molecular Weight Range ◽  
Weight Range ◽  
Metabolic Heat

Abstract Background: Hyaluronic acid (HA) is an important mucopolysaccharide of higher molecular weight range and holds sheer economic interest. Its applications are widely acknowledged in rheumatoid arthritis treatment, tissue engineering, and cosmetics industries. This present investigation aims for the fed-batch production of high molecular weight range HA by application of real-time metabolic heat measurements. Results: Fed-batch strategies based on Feedforward (FF) and Feedback (FB) control was devised to improve the Molecular Weight (MW) of HA production by S. zooepidemicus . Metabolic heat measurements (Fermentation calorimetry) were modeled to decipher real-time specific growth rate, [[EQUATION]] was looped to the PID circuit, envisaged to control [[EQUATION]] to their desired setpoint values 0.05 [[EQUATION]] , 0.1 [[EQUATION]] and 0.15 [[EQUATION]] respectively. The developed FB strategy established a robust control on maintaining the specific growth rate (µ) close to the [[EQUATION]] value with a minimal tracking error. Exponential feed rate carried out with a lowest [[EQUATION]] of 0.05 [[EQUATION]] improved the MW of HA significantly to 2.98 MDa and 2.94 MDa for the FF and FB based control strategies respectively. An optimal HA titer of 4.73 g/L was achieved in a FF control strategy at [[EQUATION]] . Biomass and Lactic acid (LA) concentrations were found to be concomitant with the increase in [[EQUATION]] from 0.05 [[EQUATION]] to 0.15 [[EQUATION]] . Superior control of µ at low [[EQUATION]] value was observed to influence positively the HA polymerization attributing to improved MW and desired Polydispersity Index (PDI) of HA. Conclusions: This present investigation attempts to address the metabolic bottleneck in synthesis of high MW HA by S. zooepidemicus and illustrates the application of calorimetric fed-batch control of µ at a narrower range. PID control offers advantage over conventional fed-batch method to synthesize HA at an improved MW. Calorimetric signal based µ control by PID negates adverse effects due to the secretion of other metabolites albeit maintaining homeostasis.

scholarly journals Preventing Overflow Metabolism in Crabtree-Positive Microorganisms through On-Line Monitoring and Control of Fed-Batch Fermentations

Fermentation ◽  
2018 ◽  
Vol 4 (3) ◽  
pp. 79 ◽  
Author(s):  
Loïc Habegger ◽  
Kelly Rodrigues Crespo ◽  
Michal Dabros
Keyword(s):  
Growth Rate ◽  
Specific Growth Rate ◽  
Specific Growth ◽  
Biomass Concentration ◽  
Critical Value ◽  
Overflow Metabolism ◽  
Monitoring And Control ◽  
Fed Batch ◽  
Batch Mode ◽  
On Line

At specific growth rates above a particular critical value, Crabtree-positive microorganisms exceed their respiratory capacity and enter diauxic growth metabolism. Excess substrate is converted reductively to an overflow metabolite, resulting in decreased biomass yield and productivity. To prevent this scenario, the cells can be cultivated in a fed-batch mode at a growth rate maintained below the critical value, µcrit. This approach entails two major challenges: accurately estimating the current specific growth rate and controlling it successfully over the course of the fermentation. In this work, the specific growth rate of S. cerevisiae and E. coli was estimated from enhanced on-line biomass concentration measurements obtained with dielectric spectroscopy and turbidity. A feedforward-feedback control scheme was implemented to maintain the specific growth rate at a setpoint below µcrit, while on-line FTIR measurements provided the early detection of the overflow metabolites. The proposed approach is in line with the principles of Bioprocess Analytical Technology (BioPAT), and provides a means to increase the productivity of Crabtree-positive microorganisms.

scholarly journals Real-time metabolic heat-based specific growth rate soft sensor for monitoring and control of high molecular weight HA production by Streptococcus zooepidemicus.

2020 ◽  
Author(s):  
Naresh Mohan ◽  
Satya Sai Pavan ◽  
Anjali Jayakumar ◽  
Sivakumar Rathinavelu ◽  
Senthilkumar Sivaprakasam
Keyword(s):  
Molecular Weight ◽  
Growth Rate ◽  
Specific Growth Rate ◽  
Real Time ◽  
High Molecular Weight ◽  
Specific Growth ◽  
Fed Batch ◽  
Molecular Weight Range ◽  
Weight Range ◽  
Metabolic Heat

Abstract Background: Hyaluronic acid (HA) is an important mucopolysaccharide of higher molecular weight range and holds sheer economic interest. Its applications are widely acknowledged in rheumatoid arthritis treatment, tissue engineering, and cosmetics industries. This present investigation aims for the fed-batch production of high molecular weight range HA by application of real-time metabolic heat measurements.Results: Fed-batch strategies based on Feedforward (FF) and Feedback (FB) control was devised to improve the Molecular Weight (MW) of HA production by S. zooepidemicus. Metabolic heat measurements (Fermentation calorimetry) were modeled to decipher real-time specific growth rate, µest was looped to the PID circuit, envisaged to control µSP to their desired setpoint values 0.05 h-1, 0.1 h-1 and 0.15 h-1 respectively. The developed FB strategy established a robust control on maintaining the specific growth rate (µ) close to the µSP value with a minimal tracking error. Exponential feed rate carried out with a lowest µSP of 0.05 h-1 improved the MW of HA significantly to 2.98 MDa and 2.94 MDa for the FF and FB based control strategies respectively. An optimal HA titer of 4.73 g/L was achieved in a FF control strategy at µSP = 0.15 h-1. Biomass and Lactic acid (LA) concentrations were found to be concomitant with the increase in µSP from 0.05 h-1 to 0.15 h-1. Superior control of µ at low µSP value was observed to influence positively the HA polymerization attributing to improved MW and desired Polydispersity Index (PDI) of HA.Conclusions: This present investigation attempts to address the metabolic bottleneck in synthesis of high MW HA by S. zooepidemicus and illustrates the application of calorimetric fed-batch control of µ at a narrower range. PID control offers advantage over conventional fed-batch method to synthesize HA at an improved MW. Calorimetric signal based µ control by PID negates adverse effects due to the secretion of other metabolites albeit maintaining homeostasis.

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