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关键词： bioreactor   CFD   mass transfer   scaling  

摘要： The timely delivery of the most up-to-date medicines and drug products is essential for patients throughout the world. Successful scaling of the bioreactors used within the biopharmaceutical industry plays a large part in the quality and time to market of these products. Scale and topology differences between vessels add a large degree of complication and uncertainty within the scaling process. Currently, this approach is primarily achieved through extensive experimentation and facile empirical correlations, which can be costly and time consuming while providing limited information. The work undertaken in the current study demonstrates a more robust and complete approach using computational fluid dynamics (CFD) to provide potent multiparameter scalability, which only requires geometric and material properties before a comprehensive and detailed solution can be generated. The CFD model output parameters that can be applied in the scale-up include mass transfer rates, mixing times, shear rates, gas hold-up values, and bubble residence times. The authors examined three bioreactors with variable geometries and were able to validate them based on single-phase and multiphase experiments. Furthermore, leveraging the resulting CFD output information enabled the authors to successfully scale-up from a known 2kL to a novel and disparate 5kL single-use bioreactor in the first attempted cell culture. This multiparameter scaling approach promises to ultimately lead to a reduction in the time to market providing patients with earlier access to the most groundbreaking medicines.

关键词： Dark H-2 fermentation   Dynamic membrane bioreactor   Biofilm   Homoacetogenesis   PICRUSt  

摘要： In this study, a laboratory-scale acidogenic dynamic membrane bioreactor (DMBR) was operated with or without alginate immobilization under various hydraulic retention times. The interactions between biofilm formation, metabolic flux and predicted functional genes were investigated in the DMBR. Regardless of the alginate immobilization, hydrogen yield was increased after biofilm was formed on a supporting material. Metabolic flux shifts from homoacetogenic to hydrogenic pathways along with biofilm formation was confirmed by flux balance analysis for metabolites. KEGG ortholog count prediction of functional genes from microbial consortia using bioinformatics package (PICRUSt). Predicted enzymes showed similar levels of functional gene expression regardless of the immobilization status. PICRUSt result showed strong evidence of the functional relationship among hydrogen production, biofilm formation, and metabolic pathway. Taken together, this study provides to estimate characteristics of biofilm formation changes and to better understand the microbial metabolism of DMBR.

关键词： Nitrogen removal   Solid carbon source   Dosing methods   Distribution characteristics   Functional genes   Microbial community  

摘要： To explore an effective approach of simultaneous nitrification and denitrification in wastewater with low C/N ratios, integrated packed bed bioreactors based on poly(3-hydroxybutyrate-hydroxyvalerate) (PHBV) with different dosing methods were designed. The removal efficiency of NH4+-N in bioreactor with aeration was 88.62%, and higher NO3--N removal efficiency was observed in bioreactor filled with grainy PHBV (95.21%) than bioreactor filled with strip PHBV (93.34%). Microbial study indicated that microbes harboring amoA and nirS genes preferred to attach on the surface of ceramsite, and significant differences in microbial community compositions at phylum and genus levels were observed. To summarize, it is feasible to utilize grainy PHBV for simultaneous and efficient removal of NH4+-N and NO3--N from wastewater with low C/N ratios.

关键词： In-situ product recovery   Immersed membrane bioreactor   High organic loading rate   Volatile fatty acids   Microbial dynamics  

摘要： The organic loading rate (OLR) is an essential parameter that controls the anaerobic digestion process. This work investigated the performance of immersed membrane bioreactors operated at high OLRs of 4, 6, 8 and 10 g volatile solids (VS)/L/d regarding the fermentation behavior, product recovery and microbial dynamics during the acidogenic fermentation of food waste to volatile fatty acids (VFAs) and hydrogen. The highest yield of 0.52 g VFA/gVS(added) was attained at 6 g VS/L/d, while an optimal hydrogen yield of 14.7 NmL/gVS(added) was obtained at 8 g VS/L/d. The bacterial populations, analyzed using 16S rRNA gene amplicon sequencing, consisted mainly of Firmicutes and Actinobacteria at OLRs 4 and 8 g VS/L/d while Firmicutes, Actinobacteria and Proteobacteria phyla dominated at 6 and 10 g VS/L/d. Moreover, the presence of Clostridium and Lactobacillus genera correlated with the acetate, butyrate, caproate and lactate production. (c) 2020 Elsevier Ltd. All rights reserved.

关键词： Membrane bioreactor   Vegetable oil refinery wastewater   Organic loading rate   Membrane fouling   Mixed liquor physicochemical properties  

摘要： The present study aims to shed more light on the use of membrane bioreactors (MBRs) for the treatment of vegetable oil refinery wastewaters (VORWs). A MBR was operated for 157 days in which it was fed with real VORW of varying composition at a range of organic loading rates (0.20 +/- 0.05-3.79 +/- 0.29 kg COD m(-3) day(-1)). The hitherto unconsidered fate of VORW constituents through the biological process was followed using gas chromatography/mass spectrometry analysis. This analysis revealed that only 19% of the identified feed constituents remained in the MBR effluent whereas ten new compounds were formed. Linear correlation analysis attributed the effluent residual COD to soluble microbial products (SMP) and non-readily biodegradable recalcitrant oily compounds. Trend of change of MLSS, mixed liquor viscosity and SMP with increasing OLR suggested that when MBR is operated under industrial conditions for the VORW treatment, the mixed liquor fouling propensity potentially increases with increasing OLR in the range studied.

关键词： X-ray microtomography   Perfusion bioreactor   Tissue engineering   Channeling effect   Tissue morphology  

摘要： Background: Perfusion bioreactors for tissue engineering hold great promises. Indeed, the perfusion of culture medium enhances species transport and mechanically stimulates the cells, thereby increasing cell proliferation and tissue formation. Nonetheless, their development is still hampered by a lack of understanding of the relationship between mechanical cues and tissue growth. Methods: Combining tissue engineering, three-dimensional visualization and numerical simulations, we analyze the morphological evolution of neo-tissue in a model bioreactor with respect to the local flow pattern. NIH-3T3 cells were grown under perfusion for one, two and three weeks on a stack of 2 mm polyacetal beads. The model bioreactor was then imaged by X-ray micro-tomography and local tissue morphology was analyzed. To relate experimental observations and mechanical stimulii, a computational fluid dynamics model of flow around spheres in a canal was developed and solved using the finite element method. Results: We observe a preferential tissue formation at the bioreactor periphery, and relate it to a channeling effect leading to regions of higher flow intensity. Additionally, we find that circular crater-like tissue patterns form in narrow channel regions at early culture times. Using computational fluid dynamic simulations, we show that the location and morphology of these patterns match those of shear stress maxima. Finally, the morphology of the tissue is qualitatively described as the tissue grows and reorganizes itself. Conclusion: Altogether, our study points out the key role of local flow conditions on the tissue morphology developed on a stack of beads in perfusion bioreactors and provides new insights for effective design of hydrodynamic bioreactors for tissue engineering using bead packings.

关键词： mechanotransduction   ovarian cancer   bioreactor   compression   three dimensional   hydrostatic pressure   ovarian tumors   hydrogels   compressive stress   high grade serous  

摘要： This report investigates the role of compressive stress on ovarian cancer in a 3D custom built bioreactor. Cells within the ovarian tumor microenvironment experience a range of compressive stimuli that contribute to mechanotransduction. As the ovarian tumor expands, cells are exposed to chronic load from hydrostatic pressure, displacement of surrounding cells, and growth induced stress. External dynamic stimuli have been correlated with an increase in metastasis, cancer stem cell marker expression, chemoresistance, and proliferation in a variety of cancers. However, how these compressive stimuli contribute to ovarian cancer progression is not fully understood. In this report, high grade serous ovarian cancer cell lines were encapsulated within an ECM mimicking hydrogel comprising of agarose and collagen type I, and stimulated with confined cyclic or static compressive stresses for 24 and 72 h. Compression stimulation resulted in a significant increase in proliferation, invasive morphology, and chemoresistance. Additionally, CDC42 was upregulated in compression stimulated conditions, and was necessary to drive increased proliferation and chemoresistance. Inhibition of CDC42 lead to significant decrease in proliferation, survival, and increased chemosensitivity. In summary, the dynamic in vitro 3D platform developed in this report, is ideal for understanding the influence of compressive stimuli, and can be widely applicable to any epithelial cancers. This work reinforces the critical need to consider compressive stimulation in basic cancer biology and therapeutic developments.

关键词： Mixotrophic denitrification   Ni(II) removal   TPSA composite material   Immobilized bioreactor   Community diversity  

摘要： This study presents the novel composite material TMCC/PAA/SA@Fe(TPSA), a bacteria immobilized carrier for use in bioreactor systems to enhance the simultaneous removal efficiency of nitrate, Ni(II) and phosphorus. The influence of various operational factors were evaluated on the performance of nitrate, phosphorus and Ni(II) removal. Results demonstrate that under optimum conditions of an hydraulic retention time (HRT) of 8 h and pH 7.0, nitrate and phosphorus removal reached nearly 100% and 61.7%, respectively. When the initial Ni(II) concentration was 1 mg/L, approximately 100% Ni(II) removal efficiency was achieved. Furthermore, the morphology and components of the TPSA immobilized bacterial pellets were analyzed to investigate the mechanism of simultaneous nitrate, Ni(II) and phosphorus removal. Microbial metabolism was more active in the experimental reactor compared with control, although high concentrations of Ni(II) could inhibit bacterial activity.

关键词： Aerobic membrane bioreactor   Activated sludge process   Municipal wastewater   Water recycle and reuse  

摘要： This paper explored the positive attributes of aerobic membrane bioreactor for recycling and reuse of domestic wastewater for irrigation. For this purpose, performances of two different full-scale treatment plants, one designed as aerobic membrane bioreactor (AMBR) equipped with a hollow fiber membrane with a nominal pore size of 0.03 mu m, and the other, as a conventional nitrogen removal activated sludge plant with pre-denitrification (A(2)O) were evaluated and compared. The effluent of the A(2)O system included an average of 109 mg L-1 chemical oxygen demand (COD), 32 mg L-1 total suspended solids (TSS) and 17 mg L-1 of total nitrogen. The AMBR system was able to reduce the effluent COD level to 24 mg L-1, obviously with lower TSS and turbidity. The effluent quality of the AMBR was in compliance with irrigation water standards;its nitrogen content should be evaluated as an added nutritional value for most plants. Considering the additional profit of the recovered water, the investment and operational costs of A(2)O and AMBR processes were compatible. The results underlined the merit of AMBR process, especially in low populated areas also requiring resources for irrigation.

关键词： Antimicrobial peptides   Plant expression   Minimum inhibitory concentration   Nicotiana benthamiana   Elastin-like polypeptide  

摘要： As antibiotic-resistant bacterial pathogens become an ever-increasing concern, antimicrobial peptides (AMPs) have grown increasingly attractive as alternatives. Potentially, plants could be used as cost-effective AMP bioreactors;however, reported heterologous AMP expression is much lower in plants than in E. coll. expression systems and often results in plant cytotoxicity, even for AMPs fused to carrier proteins. This suggests that there may be a physical characteristic of the previously described heterologous AMPs which impedes efficient expression in plants. Using a meta-analysis of protein databases, this study has determined that native plant AMPs were significantly less cationic than AMPs native to other taxa. To apply this finding to plant expression, the transient expression of 10 different heterologous AMPs, ranging in charge from + 7 to -5, was tested in the tobacco, Nicotiana benthamiana. Elastin-like polypeptide (ELP) was used as the carrier protein for AMP expression. ELP fusion allowed for a simple, cost-effective temperature shift purification. Using this system, all five anionic AMPs expressed well, with two at unusually high levels (375 and 563 mu g/gfw). Furthermore, antimicrobial activity against Staphylococcus epidermidis was an order of magnitude greater (average minimum inhibitory concentration MIC of 0.26 mu M) than that typically seen for AMPs expressed in E. coll. systems and was associated with the uncleaved fusion peptide. In summary, this study describes a means of expressing AMP fusions in plants in high yield, purified by a simple temperature-shift protocol, resulting in a fusion peptide with high antimicrobial activity and without the need for a peptide cleavage step.