课程文献中心 更多>>

摘要： The progressive acceleration of continuous bioprocessing method has become the focal point of advanced research and study for the biotech companies in recent years. Implementation of this method is a tedious and lengthy process but has been proven beneficial down the line. Advancement of this methodology is initiated by the U. S. Food and Drug Administration (FDA) through introduction of Quality by Design (QbD) approach. In parallel, sophisticated bioreactors are now available in the market with various applications to support the continuous upstream process. In motion, monoclonal antibodies (mAb’s) are produced by studying the behavior of CHO cell culture, affected by different media and controlled variables. Focus of this thesis is to demonstrate a systematic approach towards developing a control strategy for the critical process parameters (CPPs) of the bioreactor. Based on the study of bioreactor, control relevant process models have been developed using experimental data. Feedback control architecture has been developed in silico using proportional integral derivative (PID) controller. Further, on using advanced model predictive control (MPC) algorithm, the performance of these feedback-control loops has been investigated and compared with the performance of the PID controller. Framework for the integration of bioreactor with the control platform has been explained. As the industry is shifting towards the development of continuous process, it becomes important to make sure that these continuous processes never run short on the material. For the success of such processes, timely refilling of the required material to the feeding system becomes necessary. To illustrate this idea, refill strategy for the feed tank has been developed by mathematical modelling approach. Case studies have been conducted to investigate the impact of ambient temperature on fluid inside the feed tank during refill period.

关键词： Glycolysis   Tryptophan synthesis   Modified E   coli   Fed-batch bioreactor   Cell structured kinetic model   Hybrid modular model  

摘要： This paper presents a novel methodology to develop complex structured bi-level (hybrid) kinetic models of some important cell bioprocesses. The approached case study refers to the tryptophan (TRP) synthe-sis in E. coli cells. The required experimental data were collected from a fed-batch bioreactor (FBR). The developed structured kinetic model includes several inter-connected reaction pathway (modules) able to simulate the kinetics of glycolysis, TRP-operon expression, ATP-recovery system, all belonging to the cen-tral carbon metabolism (CCM). Experiments were carried out by using an E. coli strain modified to replace the PTS-system with a more efficient one to uptake the glucose (GLC) from the environment. By linking the FBR macroscopic state variables with the nano-scale variables describing the cell metabolic processes of interest, the resulted structured hybrid dynamic model presents a large number of advantages, such as: allows further in-silico (model-based) more accurate engineering developments;it can be used for bioinformatics purposes. (c) 2021 Elsevier Ltd. All rights reserved.

关键词： denitrifying bioreactor   biochar   nitrate   phosphate   tile drainage  

摘要： Biochar has received increased attention in environmental applications in recent years. Therefore, three pilot-scale denitrifying bioreactors, one filled with woodchips only and the other two enriched with 10% and 20% by volume of biochar from deciduous wood, were tested under field conditions for the removal of nitrate (NO3-N) and phosphate (PO4-P) from tile drainage water in Lithuania over a 3-year period. The experiment showed the possibility to improve NO3-N removal by incorporating 20% biochar into woodchips. Compared to the woodchips only and woodchips amended with 10% biochar, the NO3-N removal effect was particularly higher at temperatures below 10.0 degrees C. The results also revealed that woodchips alone can be a suitable medium for PO4-P removal, while the amendment of biochar to woodchips (regardless of 10% or 20%) can lead to large releases of PO4-P and other elements. Due to the potential adverse effects, the use of biochar in woodchip bioreactors has proven to be very limited and complicated. The experiment highlighted the need to determine the retention capacity of biochar for relevant substances depending on the feedstock and its physical and chemical properties before using it in denitrifying bioreactors.

关键词： In-situ bio-methanation   Membrane bioreactor   Biogas up-grading   Power-to-gas  

摘要： A bioreactor using membrane technologies was used to demonstrate the feasibility of in-situ bio-methanation coupled to industrial wastewater treatment for biogas upgrading. High biogas productivity (1.7 Nm3Biogas/ m3Bioreactor/day) with high CH4 content (97.9%) was reached. In-situ bio-methanation did not affect the COD removal efficiency of anerobic digestion (>94%). Process resilience has been tested for both substrate overload and H2 intermittence injection. Recovery of high CH4 content after 7 days without H2 injection occurred within few hours. Influence of microbial community has been studied showing that both hydrogenotrophic and homoacetogenic-acetoclastic pathways were involved.

关键词： Anammox bacteria   Electro-bioreactor   Membrane bioreactor   Nitrogen removal at low carbon   Simultaneous nitrification denitrification   Submerged membrane electro-bioreactor  

摘要： The objective of this research was to explore the feasibility of removing ammonium and nitrate in a single electro-bioreactor at low carbon concentration. For that purpose a submerged membrane electro-bioreactor was operated at three influent carbon/nitrogen ratios (3:1, 2:1 and 1:1). For each carbon/nitrogen ratio, a submerged membrane electro-bioreactor and a membrane bioreactor were operated at the same conditions for 60 days. Results showed that the submerged membrane electro-bioreactor successfully removed ammonium and nitrate at all carbon/nitrogen ratios over membrane bioreactor. At carbon/nitrogen ratio of 1:1, the submerged membrane electro-bioreactor exhibited 9%, 55% and 25% higher removal efficiency over membrane bioreactor for ammonium, nitrate and total nitrogen, respectively. At carbon/nitrogen ratio of 3:1, the submerged membrane electro-bioreactor exhibited 0.0%, 89% and 14% higher removal efficiency over membrane bioreactor for ammonium, nitrate and total nitrogen, respectively. Submerged membrane electro-bioreactor system showed its capacity to remove ammonium, nitrate and total nitrogen regardless of carbon/nitrogen ratio. Submerged membrane electro-bioreactor capacity to remove nitrogen components is feasible because the system can be electrically controlled to operate at alternative aerobic/anaerobic conditions. The efficiency of the submerged membrane electro-bioreactor to remove nitrogen components was found to enhance over time, even though carbon is at low concentration, as higher concentrations of anammox bacteria are built up in the system. Beside nitrogen removal, submerged membrane electro-bioreactor showed on average more than 90% removal of orthophosphate.

关键词： Methanotrophic bacteria   Storage response   Biopolymer production   Poly-hydroxybutyrate   Methane usage]   Methane usage  

摘要： Methanotrophic biotechnologies for methane mitigation and nitrogen removal are becoming more apparent. How-ever, the sludge produced during these processes is often underutilized and instead can be applied for resources re-covery. Fortunately, methanotrophic bacteria can utilize methane while also producing poly-hydroxy-butyrate (PHB), bioplastics, under nutrients deficient conditions. Bioplastics are increasing in popularity and can be produced from unexploited resources, such as methane and carbon dioxide, within wastewater facilities. This research demonstrates that methanotrophic sludge generated during a methanotrophic-based nitrogen removal process, which has been recently suggested, can be directly utilized for PHB production. It was found that the PHB storage response of the methanotrophic driven mixed culture was greatest when methane and oxygen were supplied in equal volume to volume ratios. In addition, the PHB response due to imposing feast-like conditions along with nitrogen or phosphorus depri-vation were assessed. The highest PHB storage achieved was 21 +/- 1.31% after one cycle under methane sufficient and nitrogen limited conditions. Whereas, only applying feast-like conditions demonstrated a PHB storage of 15 +/- 0.67% while simultaneously removing nitrate. Finally, further optimization and continued feast-and famine-like cycles can lead to a greater PHB storage response by the culture. (c) 2021, The Society for Biotechnology, Japan. All rights reserved.

关键词： Microbial fuel cell   Membrane fouling   Membrane bioreactor   Phenol degradation   Micro-electric field  

摘要： This study evaluated the feasibility of phenol degradation in microbial fuel cell (MFC) and membrane bioreactor (MBR) coupling system, and explored the mechanism of MBR membrane fouling. Four aspects were researched in open and closed circuit conditions: the degradation capacity of the coupling system, the increase of transmembrane pressure (TMP), and the adhesion of phenol degradation products and microorganisms on the membrane. The results showed that the degradation of phenol and COD in the closed circuit coupling system was higher than that in the open circuit. The micro-electric field can inhibit the growth of TMP and keep dodecamethylcyclohexasiloxane away from the membrane, meanwhile can also reduce the abundance and species diversity of microorganisms. Nevertheless, the micro-electric field could not completely eliminate the membrane fouling due to the fact that the phenol degradation product of ethanethiol, microorganisms of Proteobacteria and Actinobacteria were more favorable on the membrane.

关键词： Photodynamic therapy   Chemodynamic therapy   Glutathione-depleting   Magnetic resonance imaging   Starvation therapy  

摘要： The combination of photodynamic therapy (PDT) and chemodynamic therapy (CDT) have attracted a great deal of interest, but tumor hypoxia and glutathione (GSH) overproduction still limit their further applications. Herein, an intelligent reactive oxygen species (ROS) nanogenerator Ce6/GOx@ZIF-8/PDA@MnO2 (denoted as CGZPM;Ce6, GOx, ZIF-8, PDA, MnO2 are chlorin e6, glucose oxidase, zeolitic imidazolate framework-8, polydopamine and manganese dioxide respectively) with O-2-generating and GSH-/glucose-depleting abilities was constructed by a facile and green one-pot method. After intake by tumor cells, the outer MnO2 was rapidly degraded by the acidic pH, and the overexpression of hydrogen peroxide (H2O2) and GSH with abundant Mn2+ and O-2 produced would eventually achieve multifunctionality. The Mn2+ acted as an ideal Fenton-like agent and magnetic resonance (MR) imaging contrast agent, while the O-2 promoted the PDT via hypoxia relief and facilitated the intratumoral glucose oxidation by GOx for starvation therapy (ST). Benefiting from the GOx-based glycolysis process, sufficient H2O2 was generated to improve the CDT efficacy through Mn2+-mediated Fenton-like reaction. Notably, MnO2 and PDA could decrease the tumor antioxidant activity by consuming GSH, resulting in remarkably enhanced PDT/CDT. Such a novel cascade bioreactor with tumor microenvironment (TME)-modulating capability opens new opportunities for ROS-based and combinational treatment paradigms. (C) 2021 Elsevier Inc. All rights reserved.

关键词： Advanced therapy medicinal products   hMSC spheroids   Hydrodynamics   Microcarriers   Shear stress  

摘要： Human mesenchymal stem cells (hMSCs) are manufactured as cell therapy products. This requires a tightly controlled and fully understood production process, usually taking place in a stirred-tank bioreactor. In this review, the impact of bioreactor geometry as well as equipment-related parameters is discussed. We provide a theoretical background for the engineering of hMSC spheroids with a defined size and evaluate the process parameters needed for the microcarrier-based expansion of hMSCs. Finally, and based on experimental data, ideal bioreactor setups for each type of process are recommended.

关键词： Accelerostat   Residual glucose   cAMP   Dimorphic transition   Microfluidic bioreactor   Yarrowia lipolytica  

摘要： Yarrowia lipolytica, with a diverse array of biotechnological applications, is able to grow as ovoid yeasts or filamentous hyphae depending on environmental conditions. This study has explored the relationship between residual glucose levels and dimorphism in Y. lipolytica. Under pH stress conditions, the morphological and physiological characteristics of the yeast were examined during well-controlled accelerostat cultures using both a 1 L-laboratory scale and a 1 mL-microfluidic bioreactor. The accelerostat mode, via a smooth increase of dilution rate (D), enabled the cell growth rate to increase gradually up to the cell wash-out (D >mu max of the strain), which was accompanied by a progressive increase in residual glucose concentration. The results showed that Y. lipolytica maintained an ovoid morphology when residual glucose concentration was below a threshold value of around 0.35-0.37 mg L-1. Transitions towards more elongated forms were triggered at this threshold and progressively intensified with the increase in residual glucose levels. The effect of cAMP on the dimorphic transition was assessed by the exogenous addition of cAMP and the quantification of its intracellular levels during the accelerostat. cAMP has been reported to be an important mediator of environmental stimuli that inhibit filamentous growth in Y. lipolytica by activating the cAMP-PKA regulatory pathway. It was confirmed that the exogenous addition of cAMP inhibited the mycelial morphology of Y. lipolytica, even with glucose concentrations exceeding the threshold level. The results suggest that dimorphic responses in Y. lipolytica are regulated by sugar signaling pathways, most likely via the cAMP-PKA dependent pathway.