We developed a scale-up model of a previously reported alternative diesel fuel production plant and evaluated the characteristics of the fuel produced. For this plant, two reactors with internal ...diameters (I.D.s) of 8mm and 14mm, were constructed and evaluated. Our research showed that the 8mm I.D. reactor offered better performance in terms of reaction velocity than the 14mm I.D. reactor, and that the composition of the fuel produced in the 8mm I.D. reactor was nearly identical to that produced by our first small-scale test plant. We then evaluated fuel production at several reaction temperatures. The results of these evaluations showed that the reaction rate of thermal cracking increased at higher reaction temperatures, consequently improving the kinetic viscosity, pour point, iodine value and other physical characteristics of the fuel. However, it was also found that the overall fuel quality was affected by the quality of the material oils used in our plant and, as a result, it is essential to employ a suitable reaction temperature when using low-quality waste edible oils.
Advanced oxidation processes (AOPs) are promising technologies for partial or complete mineralization of contaminants of emerging concern by highly reactive hydroxyl, hydroperoxyl, superoxide, and ...sulphate radicals. Detailed investigations and reviews have been reported for conventional AOP systems that have been installed in full-scale wastewater treatment plants. However, recent efforts have focused on the peroxymonosulphate, persulphate, catalytic ozonation, ultrasonication and hydrodynamic cavitation, gamma radiation, electrochemical oxidation, modified Fenton, and plasma-assisted AOPs. This critical review presents the detailed mechanisms of emerging AOP technologies, their performance for treatment of contaminants of emerging concern, the relative advantages and disadvantages of each technology, and the remaining challenges to scale-up and implementation. Among the evaluated technologies, the modified electrochemical oxidation, gamma radiation, and plasma-assisted systems demonstrated the greatest potential for successful and sustainable implementation in wastewater treatment due to their environmental safety, compatibility, and efficient transformation of contaminants of emerging concern by a variety of reactive species. The other emerging AOP systems were also promising, but additional scale-up trials and a deeper understanding of their reaction kinetics in complex wastewater matrices are necessary to determine the technical and economic feasibility of full-scale processes.
•Recent updates in the field of advanced oxidation processes are summarized.•Advantages, and disadvantages of emerging advanced oxidations are elucidated.•Real-scale commercialization status of emerging advanced oxidations are discussed.•Bottlenecks and prospects related to advanced oxidations are discussed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Rapid advances in intensifying upstream processes for biologics production have left downstream processing as a bottleneck in the manufacturing scheme. Biomanufacturers are pursuing continuous ...downstream process development to increase efficiency and flexibility, reduce footprint and cost of goods, and improve product consistency and quality. Even after successful laboratory trials, the implementation of a continuous process at manufacturing scale is not easy to achieve. This paper reviews specific challenges in converting each downstream unit operation to a continuous mode. Key elements of developing practical strategies for overcoming these challenges are detailed. These include equipment valve complexity, favorable column aspect ratio, protein‐A resin selection, quantitative assessment of chromatogram peak size and shape, holistic process characterization approach, and a customized process economic evaluation. Overall, this study provides a comprehensive review of current trends and the path forward for implementing continuous downstream processing at the manufacturing scale.
Rapid advances in intensifying upstream processes for biologics production have left downstream processing as a bottleneck in the manufacturing scheme. Biomanufacturers are pursuing continuous downstream process development to increase efficiency and flexibility, reduce footprint and cost of goods, and improve product consistency and quality. Even after successful laboratory trials, the implementation of a continuous process at manufacturing scale is not easy to achieve.
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Aqueous two‐phase systems (ATPS) have proved to be an efficient and integrative operation to enhance recovery of industrially relevant bioproducts. After ATPS discovery, a variety of works have been ...published regarding their scaling from 10 to 1000 L. Although ATPS have achieved high recovery and purity yields, there is still a gap between their bench‐scale use and potential industrial applications. In this context, this review paper critically analyzes ATPS scale‐up strategies to enhance the potential industrial adoption. In particular, large‐scale operation considerations, different phase separation procedures, the available optimization techniques (univariate, response surface methodology, and genetic algorithms) to maximize recovery and purity and economic modeling to predict large‐scale costs, are discussed. ATPS intensification to increase the amount of sample to process at each system, developing recycling strategies and creating highly efficient predictive models, are still areas of great significance that can be further exploited with the use of high‐throughput techniques. Moreover, the development of novel ATPS can maximize their specificity increasing the possibilities for the future industry adoption of ATPS. This review work attempts to present the areas of opportunity to increase ATPS attractiveness at industrial levels.
There is a lack of inclusion of aqueous two‐phase systems (ATPS) into industrial‐scale bioprocesses, although there is a large amount of research at laboratory or pilot‐scale. To changes, the present review discusses large‐scale considerations of ATPS operation and different strategies to maximize their attractiveness, such as high‐throughput screening and optimization techniques, different phase separation strategies, novel bioprocess modeling on ATPS‐based processes and economic analyses, research the removal of ATPS components after separation and recycling of phase forming chemicals and the application of novel ATPS types.
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Plant molecular farming (PMF) has been promoted as a fast, efficient and cost-effective alternative to bacteria and animal cells for the production of biopharmaceutical proteins. Numerous plant ...species have been tested to produce a wide range of drug candidates. However, PMF generally lacks a systematic, streamlined and seamless workflow to continuously fill the product pipeline. Therefore, it is currently unable to compete with established platforms in terms of routine, throughput and horizontal integration (the rapid translation of product candidates to preclinical and clinical development). Individual management decisions, limited funding and a lack of qualified production capacity can hinder the execution of such projects, but we also lack suitable technologies for sample handling and data management. This perspectives article will highlight current bottlenecks in PMF and offer potential solutions that combine PMF with existing technologies to build an integrated facility of the future for product development, testing, manufacturing and clinical translation. Ten major bottlenecks have been identified and are discussed in turn: automated cloning and simplified transformation options, reproducibility of bacterial cultivation, bioreactor integration with automated cell handling, options for rapid mid-scale candidate and product manufacturing, interconnection with (group-specific or personalized) clinical trials, diversity of (post-)infiltration conditions, development of downstream processing platforms, continuous process operation, compliance of manufacturing conditions with biosafety regulations, scaling requirements for cascading biomass.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To harness the full potential of human pluripotent stem cells (hPSCs) we combined instrumented stirred tank bioreactor (STBR) technology with the power of in silico process modeling to overcome ...substantial, hPSC‐specific hurdles toward their mass production. Perfused suspension culture (3D) of matrix‐free hPSC aggregates in STBRs was applied to identify and control process‐limiting parameters including pH, dissolved oxygen, glucose and lactate levels, and the obviation of osmolality peaks provoked by high density culture. Media supplements promoted single cell‐based process inoculation and hydrodynamic aggregate size control. Wet lab‐derived process characteristics enabled predictive in silico modeling as a new rational for hPSC cultivation. Consequently, hPSC line‐independent maintenance of exponential cell proliferation was achieved. The strategy yielded 70‐fold cell expansion in 7 days achieving an unmatched density of 35 × 106 cells/mL equivalent to 5.25 billion hPSC in 150 mL scale while pluripotency, differentiation potential, and karyotype stability was maintained. In parallel, media requirements were reduced by 75% demonstrating the outstanding increase in efficiency. Minimal input to our in silico model accurately predicts all main process parameters; combined with calculation‐controlled hPSC aggregation kinetics, linear process upscaling is also enabled and demonstrated for up to 500 mL scale in an independent bioreactor system. Thus, by merging applied stem cell research with recent knowhow from industrial cell fermentation, a new level of hPSC bioprocessing is revealed fueling their automated production for industrial and therapeutic applications.
Wet lab‐derived process characteristics enabled predictive in silico modeling as a rational for suspension‐based human pluripotent stem cells (hPSC) cultivation in stirred bioreactors. Consequently, this hPSC line‐independent strategy yielded 70‐fold cell expansion in 7 days achieving a density of 35 × 106 cells/mL equivalent to 5.25 billion hPSC in 150 mL scale while maintaining a pluripotent phenotype and simultaneously reducing media requirements by 75%.
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Summary
This work presents a scale‐up and feasibility study for the establishment of supercritical CO
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extraction plants to produce grape seeds oil. The scale‐up factors are determined using ...experimental and modelling results based on seeds from six grape cultivars over 2 harvest years. The purchased cost of the production plant is estimated using ‘the six‐tenth rule’ from the cost of a pilot scale unit. The results indicate that, at the current minimum retail selling price of extra virgin grape seeds oil, the proposed project is technically viable and economically feasible with a breakeven point of US$ 7.46 per kg‐oil and rate of return on investment of 28%.
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The demand for rounded graphite for lithium-ion batteries will increase rapidly in the next years, mainly driven by the growing number of electric vehicles. Due to the different particle morphology, ...synthetic and natural graphite materials have different processing requirements to produce battery-grade materials. However, similar rounding processes with batch-wise operating classifier mills or continuously running classifier mill cascades are used today. For natural graphite in particular, these processes are not very efficient due to their low yield and high energy demand. In this paper, we present a newly developed rounding process for natural graphite, with lower specific energy consumption and higher yield compared to the existing processes. These advantages make the proposed process more economical especially in periods of time with high energy prices. The quality of the material produced by the new process was investigated and compared with the material produced by the existing process, by showing similar graphite properties. Furthermore, the scalability of the new spheroidization process is demonstrated in this paper. Finally, the good cycling performance of the rounded natural graphite material produced by the new process is demonstrated in stacked pouch cells assembled with double side coated anodes. The tested pouch cells still had a capacity retention of over 88% after more than 1000 charge and discharge cycles.
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L‐tryptophan is an essential amino acid widely used in food and pharmaceutical industries. However, its production via Escherichia coli fermentation suffers severely from both low glucose conversion ...efficiency and acetic acid inhibition, and to date effective process control methods have rarely been explored to facilitate its industrial scale production. To resolve these challenges, in the current research an engineered strain of E. coli was used to overproduce L‐tryptophan. To achieve this, a novel dynamic control strategy which incorporates an optimized anthranilic acid feeding into a dissolved oxygen‐stat (DO‐stat) glucose feeding framework was proposed for the first time. Three original contributions were observed. Firstly, compared to previous DO control methods, the current strategy was able to inhibit completely the production of acetic acid, and its glucose to L‐tryptophan yield reached 0.211 g/g, 62.3% higher than the previously reported. Secondly, a rigorous kinetic model was constructed to simulate the underlying biochemical process and identify the effect of anthranilic acid on both glucose conversion and L‐tryptophan synthesis. Finally, a thorough investigation was conducted to testify the capability of both the kinetic model and the novel control strategy for process scale‐up. It was found that the model possesses great predictive power, and the presented strategy achieved the highest glucose to L‐tryptophan yield (0.224 g/g) ever reported in large scale processes, which approaches the theoretical maximum yield of 0.227 g/g. This research, therefore, paves the way to significantly enhance the profitability of the investigated bioprocess.
A novel dynamic control strategy incorporating an optimized anthranilic acid feeding into a dissolved oxygen‐stat glucose feeding framework was proposed for the first time to overproduce L‐tryptophan from an engineered Escherichia coli strain. Furthermore, a rigorous kinetic model was particularly constructed to investigate the underlying biochemical mechanisms. Based on this strategy, the current study resulted in the highest glucose to L‐tryptophan yield (0.224 g/g) ever reported in both laboratory‐scale and large‐scale processes, approaching the theoretical maximum yield of 0.227 g/g.
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