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Two scale-down tools for the optimization of perfusion bioreactors for the manufacture of biopharmaceuticals 用于优化生物制药灌流生物反应器的两种缩放工具
Pub Date : 2024-06-07 DOI: 10.1002/amp2.10180
Ciara Lucas, Martin Blackman, Andrea Rayat, David Mainwaring, Martina Micheletti

As the occurrences of cancer rise and the requirement for biotherapeutics increases, there is a growing demand for cost-efficient methods to manufacture mammalian cell-based biopharmaceuticals. Currently, the most cost-efficient manufacturing solution is the cultivation of cells in perfusion mode. Perfusion allows for high cell densities of up to 200 million viable cells per mL (MVC mL−1) to be achieved, resulting in an increase in yield and volumetric productivity, which is the production of product per unit volume and time. However, culturing in perfusion mode requires large volumes of media, which is a significant expense in process development. Therefore, methods that allow rapid optimization of perfusion media are desirable to decrease operating costs and increase productivity. In this work, a quasi-perfusion methodology using microwell plates (MWP) is used for media optimization to culture CHO-S cells producing IgG1 monoclonal antibodies (mAb) known as trastuzumab, which have clinical applications treating HER2+ breast cancer. Results show blending glucose-rich supplements and sodium butyrate with perfusion-specific base media can lead to an 8-fold increase in monoclonal antibody titre compared with traditional fed-batch media. The original and optimized media were then scaled-up to a custom made, mini bioreactor (MBR) running in perfusion mode. Two-fold higher cell density is achieved in the MBR compared with the MWP, however, when normalizing for cell density, mAb productivity is comparable between the two methodologies. The combined MWP and 250 mL MBR methodology is an optimization tool that enables process development cost savings due to reduced volume of media utilization.

随着癌症发病率的上升和对生物治疗药物需求的增加,人们越来越需要具有成本效益的方法来生产基于哺乳动物细胞的生物制药。目前,最具成本效益的生产解决方案是采用灌流模式培养细胞。灌流可实现高达每毫升 2 亿个活细胞(MVC mL-1)的高细胞密度,从而提高产量和体积生产率,即单位体积和时间内的产品产量。然而,灌流模式培养需要大量培养基,这在工艺开发中是一笔不小的开支。因此,最好能采用快速优化灌注培养基的方法,以降低运营成本,提高生产率。在这项工作中,使用微孔板(MWP)的准灌注方法对培养基进行了优化,以培养 CHO-S 细胞生产 IgG1 单克隆抗体(mAb),即曲妥珠单抗(trastuzumab),曲妥珠单抗具有治疗 HER2+ 乳腺癌的临床应用价值。结果表明,将富含葡萄糖的补充剂和丁酸钠与灌注专用基础培养基混合,可使单克隆抗体滴度比传统的喂养式培养基提高 8 倍。然后,将原始和优化培养基放大到以灌流模式运行的定制微型生物反应器(MBR)中。与 MWP 相比,MBR 中的细胞密度高出两倍,然而,当细胞密度归一化时,两种方法的 mAb 生产率相当。MWP 和 250 mL MBR 组合方法是一种优化工具,可通过减少培养基使用量来节约工艺开发成本。
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引用次数: 0
CFD modeling and numerical simulation of an industrial adsorption process 工业吸附过程的 CFD 建模和数值模拟
Pub Date : 2024-06-07 DOI: 10.1002/amp2.10178
Flora Esposito, Cristian Cardenas, Abderrazak M. Latifi, Stéphanie Marsteau

This paper investigates the model performance of an industrial box used to remove ammonia from the air using a doped activated carbon. To this end, process models are developed and experimental measurements are carried out. The models are based on momentum and mass balance equations along with thermodynamic, hydrodynamic and adsorption kinetic relations. The measurements consist of pressure drops in the air purification box and breakthrough curves of ammonia on activated carbon. The models are implemented and solved using COMSOL Multiphysics®. Adsorption is investigated by means of a Fickian multi-scale model, which demonstrated to efficiently predict the experimental data. The optimal values of the most estimable unknown parameters involved in each model, as well as their confidence intervals are determined from experimental measurements. The performance of the industrial air purification model is rigorously assessed using statistical criteria, including mean-square error (RMSE = 0.0013) and Pearson correlation coefficient (r = 0.999).

本文研究了使用掺杂活性炭去除空气中氨气的工业箱的模型性能。为此,开发了工艺模型并进行了实验测量。模型基于动量和质量平衡方程以及热力学、流体力学和吸附动力学关系。测量包括空气净化箱中的压降和氨在活性炭上的突破曲线。模型使用 COMSOL Multiphysics® 实现并求解。通过 Fickian 多尺度模型对吸附进行了研究,结果表明该模型可以有效预测实验数据。根据实验测量结果,确定了每个模型中最可估算的未知参数的最佳值及其置信区间。工业空气净化模型的性能使用统计标准进行了严格评估,包括均方误差(RMSE = 0.0013)和皮尔逊相关系数(r = 0.999)。
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引用次数: 0
Enhancing decanter centrifuge process design with data-driven material parameters in multi-compartment modeling 在多隔室建模中利用数据驱动的材料参数改进卧螺离心机工艺设计
Pub Date : 2024-06-03 DOI: 10.1002/amp2.10179
Ouwen Zhai, Niklas Ehret, Frank Rhein, Marco Gleiss

Predicting the separation performance of decanter centrifuges is challenging due to dynamic events within the apparatus. Current methods for designing decanter centrifuges rely on simplified models, often leading to inaccuracies. Consequently, manufacturers must perform time-intensive pilot scale experiments to derive their own correction factors. Growing computing power sparks interest in alternative modeling strategies. Grey box models (GBM) combine mechanistic white box models (WBM) and data-driven black box models (BBM), with the optimal structure (parallel or serial) varying by application. For modeling decanter centrifuges, we propose a serial GBM that comprises an artificial neural network that outputs unknown material parameters into a first-principle multi-compartment model. Comparing this approach to alternative data-driven modeling strategies (pure BBM, parallel GBM), we conclude that the serial GBM excels in terms of extrapolation, prediction ability, and transparency while also enabling a better comprehension of the separation process.

由于设备内存在动态事件,预测卧螺离心机的分离性能具有挑战性。目前设计卧螺离心机的方法依赖于简化模型,这往往会导致误差。因此,制造商必须进行时间密集的中试实验,以得出自己的修正系数。计算能力的不断提高激发了人们对其他建模策略的兴趣。灰盒模型(GBM)结合了机理白盒模型(WBM)和数据驱动黑盒模型(BBM),最佳结构(并行或串行)因应用而异。针对卧螺离心机建模,我们提出了一种串行 GBM,它由一个人工神经网络组成,可将未知材料参数输出到第一原理多隔室模型中。通过将这种方法与其他数据驱动建模策略(纯 BBM、并行 GBM)进行比较,我们得出结论:串行 GBM 在外推法、预测能力和透明度方面表现出色,同时还能更好地理解分离过程。
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引用次数: 0
Discovering [C4C1im][BF4] as draw solution in forward osmosis 发现[C4C1im][BF4]可作为正向渗透的牵引溶液
Pub Date : 2024-03-07 DOI: 10.1002/amp2.10177
Mohd Amirul Mukmin Abdullah, Mazrul Nizam Abu Seman, Syamsul B. Abdullah

Promising forward osmosis (FO) membrane desalination is a potentially viable energy-efficient performance technology compared to other techniques. Searching for the ideal draw solute that creates high osmotic pressure difference and ease of regeneration is critical for water desalination using the FO system. However, many fundamental aspects still need to be adapted, such as needing more screening potential anions and cations based on the predictive method. The Group Contribution Method (GCM) was used in this study to predict the value of the van't Hoff factor denoted by (i). In the end, 1-butyl-3-methylimidazolium tetrafluoroborate ([C4C1im][BF4]) was selected as a draw solution for later experimental work.

与其他技术相比,前景广阔的正渗透(FO)膜海水淡化技术是一种可行的节能技术。寻找能产生高渗透压差且易于再生的理想汲取溶质,对于使用 FO 系统进行海水淡化至关重要。然而,许多基本方面仍需调整,例如需要根据预测方法筛选出更多潜在的阴离子和阳离子。本研究采用了分组贡献法 (GCM) 来预测用 (i) 表示的范特霍夫因子值。最终,1-丁基-3-甲基咪唑鎓四氟硼酸盐([C4C1im][BF4])被选为以后实验工作的抽样溶液。
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引用次数: 0
Numerical and experimental investigation of the unexpected thickening effect during PolyActive™ coating of TFC membranes 对聚碳酸酯膜涂覆 PolyActive™ 过程中意外增厚效应的数值和实验研究
Pub Date : 2024-02-20 DOI: 10.1002/amp2.10175
Florian Brennecke, Juliana Clodt, Torsten Brinkmann, Volker Abetz

In this work, we used a previously described computational fluid dynamics (CFD) model of a roll-to-roll coating process for the fabrication of thin-film composite membranes to predict the final coating thickness for PolyActive™, a commercially available multiblock copolymer utilized for CO2 removal membranes. We found a strong thickening effect that could not be explained by our previous model. We investigated the process experimentally. In addition, we conducted a variety of simulations with extensions of the initial CFD model. Based on our findings, we conclude that the Marangoni effect, that is, gradients of surface tension that induce secondary flow patterns in the meniscus region, is the most likely source of the observed thickening. We explain the simulation results in order to understand the physical mechanisms at play and to show how especially surface tension gradients that arise from the particular flow structure in the meniscus may explain the additional transfer of polymer solution to the membrane. Finally, we draw some conclusions on future research and give ideas on future improvements of the process. To our knowledge, Marangoni effects for the coating of PolyActive™ were not described so far in the literature, even though it is a well-known polymer for gas separation membranes targeted at CO2 removal. Roll-to-roll coating is a well-established coating method and often believed to be suitable for the scale-up of membrane production, therefore we think that this work will help membrane researchers who are using similar coating devices to be cautious about possible complications in the process.

在这项工作中,我们使用了之前描述的用于制造薄膜复合膜的辊对辊涂层工艺的计算流体动力学(CFD)模型来预测 PolyActive™ 的最终涂层厚度,PolyActive™ 是一种用于二氧化碳去除膜的市售多嵌段共聚物。我们发现之前的模型无法解释强烈的增厚效应。我们对这一过程进行了实验研究。此外,我们还对最初的 CFD 模型进行了各种模拟。根据我们的研究结果,我们得出结论:马兰戈尼效应,即表面张力梯度在半月板区域诱发二次流动模式,是观察到的增厚现象最可能的来源。我们对模拟结果进行了解释,以了解其中的物理机制,并说明由半月板中特殊流动结构产生的表面张力梯度如何解释聚合物溶液向膜的额外转移。最后,我们就未来的研究得出了一些结论,并提出了未来改进工艺的想法。据我们所知,尽管 PolyActive™ 是一种众所周知的用于去除二氧化碳的气体分离膜的聚合物,但迄今为止,文献中还没有关于 PolyActive™ 涂层的马兰戈尼效应的描述。辊对辊涂覆是一种成熟的涂覆方法,通常被认为适用于膜生产规模的扩大,因此我们认为这项工作将有助于使用类似涂覆设备的膜研究人员谨慎对待过程中可能出现的复杂情况。
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引用次数: 0
Liquid organic hydrogen carriers: Process design and economic analysis for manufacturing N-ethylcarbazole 液态有机氢载体:制造 N-乙基咔唑的工艺设计和经济分析
Pub Date : 2024-02-12 DOI: 10.1002/amp2.10173
E. M. T. Uijthof, B. S. Chavan, M. J. Sluijer, V. C. Komath, A. G. J. van der Ham, H. van den Berg, J.-P. Lange, A. Higler, S. Wijnans

This paper revisits the economics of manufacturing N-ethylcarbazole (NEC), a strong candidate for large-scale liquid organic hydrogen carrier (LOHC) supply chains, because of its high H2 storage capacity (6 wt%), selective hydrogenation and dehydrogenation reactions, and favorable reaction enthalpy and reaction temperatures compared to other LOHC systems. Two different process routes for producing NEC from industrial chemicals are selected out of 10 possible options: one using aniline and the other using cyclohexanone and nitrobenzene as feedstock. The required capital and operational costs are estimated to determine a NEC break-even cost for a capacity of 225 ktpa. NEC break-even costs of $3.0 and $2.6 per kg LOHC are found for the routes. This is significantly less than the $40/kg cost that has generally been reported in literature for NEC, thus improving the economic viability of using NEC as LOHC. The total fixed capital costs are estimated to be $200 MM and $250 MM. Furthermore, the prices of the feedstock show the largest influence (76% and 72%) on the final NEC break-even costs. The overall LOHC price contribution to the levelized H2 cost is estimated to be $0.77–$0.90 per kg H2 for a 60-day roundtrip and $0.09–$0.10 per kg H2 for a 7-day roundtrip. It is important to note that both routes rely heavily on laboratory scale data and the corresponding assumptions that stem from this limitation. Therefore, this research can serve as a guide to future experimental studies into validating the key assumptions made for this analysis.

本文重新探讨了制造 N-乙基咔唑(NEC)的经济性,NEC 是大规模液态有机氢载体(LOHC)供应链的有力候选者,因为与其他 LOHC 系统相比,NEC 具有高 H2 储存能力(6 wt%)、选择性氢化和脱氢反应以及有利的反应热焓和反应温度。从 10 种可能的方案中选出了两种从工业化学品生产 NEC 的不同工艺路线:一种使用苯胺,另一种使用环己酮和硝基苯作为原料。对所需的资本和运营成本进行了估算,以确定年产 225 ktpa 的 NEC 盈亏平衡成本。结果发现,这些路线的 NEC 盈亏平衡成本分别为每公斤 LOHC 3.0 美元和 2.6 美元。这大大低于文献中普遍报道的每公斤 40 美元的 NEC 成本,从而提高了使用 NEC 作为 LOHC 的经济可行性。据估计,固定资本总成本分别为 2 亿美元和 2.5 亿美元。此外,原料价格对最终 NEC 盈亏平衡成本的影响最大(分别为 76% 和 72%)。据估计,60 天往返的 LOHC 价格对平准化 H2 成本的总体影响为每公斤 H2 0.77 美元至 0.90 美元,7 天往返的 LOHC 价格对平准化 H2 成本的总体影响为每公斤 H2 0.09 美元至 0.10 美元。值得注意的是,这两条路线都严重依赖实验室规模的数据以及由此产生的相应假设。因此,本研究可作为未来实验研究的指南,以验证本分析的关键假设。
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引用次数: 0
Conceptual range estimation for total cost of ownership of modular process‐intensified chemical plants 模块化流程强化化工厂总拥有成本的概念范围估算
Pub Date : 2024-02-12 DOI: 10.1002/amp2.10176
Khaled I. Alhamouri, James T. O'Connor, Karl R. Haapala, Brian K. Paul
Chemical companies have used modularization to reduce capital costs and project timelines, putting capital to work faster and lowering the risk of entering new markets. Nevertheless, the impacts of using modularization along with advanced technologies, such as process intensification, have not yet been fully realized, often due to the uncertain business risks associated with their implementation. Therefore, new methods are needed for quantifying the impact of modular chemical process intensification (MCPI) on the capital and operating costs of chemical plants to help build a business case for this novel approach. This article presents a new conceptual range estimation technique for total cost of ownership that addresses the deficiencies of existing methods for quantifying MCPI impacts. The incorporation of percentage range estimates was employed to allow for adaptability across various cost and size scales. This work also begins to elucidate how chemical engineering and construction firms can benefit from MCPI and identifies barriers that inhibit MCPI applications in the chemical industry.
化工企业利用模块化降低了资本成本,缩短了项目时间,使资本更快地发挥作用,降低了进入新市场的风险。然而,模块化技术与工艺集约化等先进技术一起使用所产生的影响尚未得到充分认识,这通常是由于实施这些技术所带来的不确定商业风险。因此,需要新的方法来量化模块化化学工艺强化(MCPI)对化工厂资本和运营成本的影响,以帮助为这种新方法建立商业案例。本文针对总拥有成本提出了一种新的概念范围估算技术,以解决现有方法在量化 MCPI 影响方面的不足。文章采用了百分比范围估算,以适应不同的成本和规模。这项工作还开始阐明化学工程和建筑公司如何从 MCPI 中获益,并确定了阻碍 MCPI 在化工行业应用的障碍。
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引用次数: 0
Liquid organic hydrogen carriers: Process design and economic analysis for manufacturing N‐ethylcarbazole 液态有机氢载体:制造 N-乙基咔唑的工艺设计和经济分析
Pub Date : 2024-02-12 DOI: 10.1002/amp2.10173
E. M. T. Uijthof, B. S. Chavan, M. J. Sluijer, V. C. Komath, A. G. J. van der Ham, H. van den Berg, J.‐P. Lange, A. Higler, S. Wijnans
This paper revisits the economics of manufacturing N‐ethylcarbazole (NEC), a strong candidate for large‐scale liquid organic hydrogen carrier (LOHC) supply chains, because of its high H2 storage capacity (6 wt%), selective hydrogenation and dehydrogenation reactions, and favorable reaction enthalpy and reaction temperatures compared to other LOHC systems. Two different process routes for producing NEC from industrial chemicals are selected out of 10 possible options: one using aniline and the other using cyclohexanone and nitrobenzene as feedstock. The required capital and operational costs are estimated to determine a NEC break‐even cost for a capacity of 225 ktpa. NEC break‐even costs of $3.0 and $2.6 per kg LOHC are found for the routes. This is significantly less than the $40/kg cost that has generally been reported in literature for NEC, thus improving the economic viability of using NEC as LOHC. The total fixed capital costs are estimated to be $200 MM and $250 MM. Furthermore, the prices of the feedstock show the largest influence (76% and 72%) on the final NEC break‐even costs. The overall LOHC price contribution to the levelized H2 cost is estimated to be $0.77–$0.90 per kg H2 for a 60‐day roundtrip and $0.09–$0.10 per kg H2 for a 7‐day roundtrip. It is important to note that both routes rely heavily on laboratory scale data and the corresponding assumptions that stem from this limitation. Therefore, this research can serve as a guide to future experimental studies into validating the key assumptions made for this analysis.
本文重新探讨了制造 N-乙基咔唑(NEC)的经济性,NEC 是大规模液态有机氢载体(LOHC)供应链的有力候选者,因为与其他 LOHC 系统相比,NEC 具有高 H2 储存能力(6 wt%)、选择性氢化和脱氢反应以及有利的反应热焓和反应温度。从 10 种可能的方案中选出了两种从工业化学品生产 NEC 的不同工艺路线:一种使用苯胺,另一种使用环己酮和硝基苯作为原料。对所需的资本和运营成本进行了估算,以确定年产 225 ktpa 的 NEC 盈亏平衡成本。结果发现,这些路线的 NEC 盈亏平衡成本分别为每公斤 LOHC 3.0 美元和 2.6 美元。这大大低于文献中普遍报道的每公斤 40 美元的 NEC 成本,从而提高了使用 NEC 作为 LOHC 的经济可行性。据估计,固定资本总成本分别为 2 亿美元和 2.5 亿美元。此外,原料价格对最终 NEC 盈亏平衡成本的影响最大(分别为 76% 和 72%)。据估计,60 天往返的 LOHC 价格对平准化 H2 成本的总体影响为每公斤 H2 0.77 美元至 0.90 美元,7 天往返的 LOHC 价格对平准化 H2 成本的总体影响为每公斤 H2 0.09 美元至 0.10 美元。值得注意的是,这两条路线都严重依赖实验室规模的数据以及由此产生的相应假设。因此,本研究可作为未来实验研究的指南,以验证本分析的关键假设。
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引用次数: 0
Conceptual range estimation for total cost of ownership of modular process-intensified chemical plants 模块化流程强化化工厂总拥有成本的概念范围估算
Pub Date : 2024-02-12 DOI: 10.1002/amp2.10176
Khaled I. Alhamouri, James T. O'Connor, Karl R. Haapala, Brian K. Paul

Chemical companies have used modularization to reduce capital costs and project timelines, putting capital to work faster and lowering the risk of entering new markets. Nevertheless, the impacts of using modularization along with advanced technologies, such as process intensification, have not yet been fully realized, often due to the uncertain business risks associated with their implementation. Therefore, new methods are needed for quantifying the impact of modular chemical process intensification (MCPI) on the capital and operating costs of chemical plants to help build a business case for this novel approach. This article presents a new conceptual range estimation technique for total cost of ownership that addresses the deficiencies of existing methods for quantifying MCPI impacts. The incorporation of percentage range estimates was employed to allow for adaptability across various cost and size scales. This work also begins to elucidate how chemical engineering and construction firms can benefit from MCPI and identifies barriers that inhibit MCPI applications in the chemical industry.

化工企业利用模块化降低了资本成本,缩短了项目时间,使资本更快地发挥作用,降低了进入新市场的风险。然而,模块化技术与工艺集约化等先进技术一起使用所产生的影响尚未得到充分认识,这通常是由于实施这些技术所带来的不确定商业风险。因此,需要新的方法来量化模块化化学工艺强化(MCPI)对化工厂资本和运营成本的影响,以帮助为这种新方法建立商业案例。本文针对总拥有成本提出了一种新的概念范围估算技术,以解决现有方法在量化 MCPI 影响方面的不足。文章采用了百分比范围估算,以适应不同的成本和规模。这项工作还开始阐明化学工程和建筑公司如何从 MCPI 中获益,并确定了阻碍 MCPI 在化工行业应用的障碍。
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引用次数: 0
From circular to elliptical: A useful reformulation of the closed loop economy? 从循环到椭圆:闭环经济的有效重构?
Pub Date : 2024-01-21 DOI: 10.1002/amp2.10174
Matthew J. Realff, Mehdi Tajvidi

In this commentary, we discuss the concept of an elliptical economy as opposed to a circular economy. The change of shape emphasizes that the duration of the different phases of the lifecycle is often different and so the implications for the lifecycle may be important.

在这篇评论中,我们讨论了与循环经济相对的椭圆经济概念。形状的变化强调了生命周期不同阶段的持续时间往往不同,因此对生命周期的影响可能很重要。
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引用次数: 0
期刊
Journal of advanced manufacturing and processing
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