Purification of alginate and feasible production of monoclonal antibodies by the alginate-immobilized hybridoma cells

Selimoglu, S. Mert; Ayyildiz-Tamis, Duygu; Gürhan, İsmet Deliloğlu; Elibol, Murat

doi:10.1016/j.jbiosc.2011.09.020

Cited by 10 publications

(8 citation statements)

References 27 publications

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“…A typical BR or FBR reactor is equipped with temperature, pressure (mechanical agitation, air sparger, pH, and dissolved oxygen (DO) control systems; see a simplified scheme in Figure 1). In the present study, the BR studied by LG17 (that is [44]) www.videleaf.com was adapted to investigate a semi-continuous fed-batch bioreactor (FBR) operation mode, allowing for the addition of the substrate solution (with a variable feed flow rate), and of viable biomass (immobilized inside alginate porous beads [50][51][52]) during the batch according to optimal policies to be determined. This in-silico (model-based) analysis will allow comparing the FBR vs. BR performances under various operating alternatives.…”

Section: Sbr Culture and Bioprocess Dynamicsmentioning

confidence: 99%

“…The higher biomass fed concentration is used, the more vigorous aeration is employed (pure oxygen, if necessary). (iii) The used immobilized biomass is best suitable alternative for a variable (optimal) feeding of the FBR with biomass, because it is easy to dose [50][51][52]. www.videleaf.com Table 2: Key-species mass balances in the fed-batch bioreactor FBR model, including the bioprocess kinetic model LGM of LG17, together with the associated rate constants.…”

Section: Sbr Culture and Bioprocess Dynamicsmentioning

confidence: 99%

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Model-Based Optimization of a Fed-Batch Bioreactor for mAb Production Using a Hybridoma Cell Culture

Maria¹

2021

Prime Archives in Molecular Sciences

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Production of monoclonal antibodies (mAbs) is a well-known method used to synthesize a large number of identical antibodies, which are molecules of huge importance in medicine. Due to such reasons, intense efforts have been invested to maximize the mAbs production in bioreactors with hybridoma cell cultures. However, the optimal control of such sensitive bioreactors is an engineering problem difficult to solve due to the large number of state-variables with highly nonlinear dynamics, which often translates into a non-convex optimization problem that involves a significant number of decision (control) variables. Based on an adequate kinetic model adopted from the literature, this paper focuses on developing an in-silico (model-based, offline) numerical analysis of a fed-batch bioreactor (FBR) with an immobilized hybridoma culture to determine its optimal feeding policy by considering a small number of control variables, thus ensuring maximization of mAbs production. The obtained time stepwise optimal feeding policies of FBR were proven to obtain better performances than those of simple batch operation (BR) for all the verified alternatives in terms of raw material consumption and mAbs productivity. Several elements of novelty (i-iv) are pointed out in the -conclusions‖ section (e.g., considering the continuously added biomass as a control variable during FBR).

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Section: Sbr Culture and Bioprocess Dynamicsmentioning

confidence: 99%

Section: Sbr Culture and Bioprocess Dynamicsmentioning

confidence: 99%

Model-Based Optimization of a Fed-Batch Bioreactor for mAb Production Using a Hybridoma Cell Culture

Maria¹

2021

Prime Archives in Molecular Sciences

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“…(2) form. Such variables could include [9,36]: the biomass X n quality, immobilization type, etc [9,26,27,39].…”

Section: Bioprocess / Bioreactor Dynamic Model Bioprocess Kinetic Modelmentioning

confidence: 99%

“…By adopting an adequate kinetic model (experimentally checked) from literature [24], this paper is aiming at insilico investigating the influence of various operating variables (that is, the initial glucose GLC, glutamine GLN, and viable biomass X v ) on the performances of a TPMAB with immobilized hybridoma culture on porous alginate beads [26,27]. As an element of novelty, an increased attention is given to the major role played by the initial load, and the net evolution of the viable biomass (growth, and decay) during the batch in the optimal operating setpoint location.…”

mentioning

confidence: 99%

In-silico Optimization of a Batch Bioreactor for mAbs Production in Relationship to the Net Evolution of the Hybridoma Cell Culture

Maria¹,

Gîjiu²,

Cebanu³

et al. 2019

Rev. Chim.

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Bioreactor optimization is a common engineering problem difficult to be solved due to the large number of influential variables of high variability. Production of monoclonal antibody is a well-known method to synthesize a large number of identical antibodies (that is of uniform characteristics, also called monoclonal antibodies, mAb). Due to such reasons intense efforts have been invested to maximize the production of mAb by using hybridoma cell culture. Based on an adequate kinetic model from literature (experimentally checked) this paper focus on pointing-out the major role of the net evolution of the viable biomass (growth, and decay) in the location of the optimal operating setpoint (SP) of a three-phase mechanically agitated batch bioreactor (TPMAB) with immobilized hybridoma culture. This in-silico analysis opens the possibility I) to optimize the bioreactor performances by placing the SP in the most favourable location, by adjusting the substrate and biomass initial load in the bioreactor according to the preliminary determined characteristics of a modified / improved biomass; ii) to optimize the batch-to-batch operation mode (not approached here) according to the time-varying characteristics of the biomass culture, or iii) to determine the optimal operation of the bioreactor in a fed-batch operating mode (not approached here).

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“…Cell confinement makes hybridomas grow, forming biofilms and conglomerates. This different environment interacts with cell development, altering morphology and membrane permeability, as well as surface tension and osmotic pressure 31,35,39 . Maximum specific rates found in this work were slightly higher than lactate and ammonium specific production rates and glucose specific consumption rate reported by Ozturk and Palsson 40 (0.13, 0.002, and 0.14 h -1 , respectively).…”

Section: -Evolution Of Antibody Concentration (Samples Taken From Thementioning

confidence: 99%

Diffusion and Inhibition Processes in a Hollow-fiber Membrane Bioreactor for Hybridoma Culture. Development of a Mathematical Model

Legazpi

Laca

Collado

et al. 2016

Chem.Biochem.Eng.Q.

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The performance of a hollow-fiber membrane bioreactor (HFBR) (molecular weight cut-off 30 kD, fiber surface area 2050 cm 2 ) containing a culture of hybridoma cells has been investigated. Experimental data were used as basis to develop a model of general application. Concentrations of fundamental nutrients (glucose and glutamine), inhibitory products (ammonium and lactate), and monoclonal antibodies (MAb) against bovine lactoferrin (IgG 1 ) were monitored over time. Exchange of nutrients and products occurred across the capillary surface, whereas cells and MAb remained in the extra-capillary space (ECS). A protein-free culture medium (Hybrimax) with and without antibiotics was used. In both cases, the final MAb concentration was the same; however, antibiotic presence slowed down the time to achieve this concentration. Diffusion assays have been carried out in order to support the development of a mathematical model that describes the performance of the HFBR, including mass transfer and reaction terms. Inhibition by ammonium and lactate has been considered in the kinetics, providing model results consistent with experimental data. Further research with other cell lines and/or culture media will allow to broaden the field of application of this model for general use in HFBR systems.

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Purification of alginate and feasible production of monoclonal antibodies by the alginate-immobilized hybridoma cells

Cited by 10 publications

References 27 publications

Model-Based Optimization of a Fed-Batch Bioreactor for mAb Production Using a Hybridoma Cell Culture

Model-Based Optimization of a Fed-Batch Bioreactor for mAb Production Using a Hybridoma Cell Culture

In-silico Optimization of a Batch Bioreactor for mAbs Production in Relationship to the Net Evolution of the Hybridoma Cell Culture

Diffusion and Inhibition Processes in a Hollow-fiber Membrane Bioreactor for Hybridoma Culture. Development of a Mathematical Model

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