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Deep neural network for prediction and control of permeability decline in single pass tangential flow ultrafiltration in continuous processing of monoclonal antibodies 基于深度神经网络的单克隆抗体连续加工中单道切向流超滤渗透率下降预测与控制
Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2023-07-20 DOI: 10.3389/fceng.2023.1182817
Naveen G. Jesubalan, Garima Thakur, A. Rathore
Single-pass tangential flow filtration (SPTFF) is a crucial technology enabling the continuous manufacturing of monoclonal antibodies (mAbs). By significantly increasing the membrane area utilized in the process, SPTFF allows the mAb process stream to be concentrated up to the desired final target in a single pass across the membrane surface without the need for recirculation. However, a key challenge in SPTFF is compensating for flux decline across the membrane due to concentration polarization and surface fouling phenomena. In continuous downstream processing, flux decline immediately impacts the continuous process flowrates. It reduces the concentration factor achievable in a single pass, thereby reducing the final concentration attained at the outlet of the SPTFF module. In this work, we develop a deep neural network model to predict the NWP in real-time without the need to conduct actual NWP measurements. The developed model incorporates process parameters such as pressure and feed concentrations through inline sensors and a spectroscopy-coupled data model (NIR-PLS model). The model determines the optimal timing for membrane cleaning steps when the normalized water permeability (NWP) falls below 60%. Using SCADA and PLC, a distributed control system was developed to integrate the monitoring sensors and control elements, such as the NIRS sensor for concentration monitoring, the DNN model for NWP prediction, weighing balances, pressure sensors, pumps, and valves. The model was tested in real-time, and the NWP was predicted within <5% error in three independent test cases, successfully enabling control of the SPTFF step in line with the Quality by Design paradigm.
单道切向流过滤(SPTFF)是实现单克隆抗体(mab)连续生产的关键技术。通过显著增加工艺中使用的膜面积,SPTFF允许单抗工艺流通过膜表面一次集中到所需的最终目标,而无需再循环。然而,SPTFF的一个关键挑战是补偿由于浓度极化和表面污染现象而导致的膜通量下降。在连续的下游加工中,通量的下降直接影响到连续的工艺流量。它降低了单次通过可达到的浓度系数,从而降低了SPTFF模块出口达到的最终浓度。在这项工作中,我们开发了一个深度神经网络模型来实时预测NWP,而无需进行实际的NWP测量。开发的模型通过内联传感器和光谱耦合数据模型(NIR-PLS模型)结合了工艺参数,如压力和进料浓度。该模型确定了归一化水渗透性(NWP)低于60%时膜清洗步骤的最佳时机。利用SCADA和PLC,开发了一个分布式控制系统,以集成监测传感器和控制元件,如用于浓度监测的NIRS传感器、用于NWP预测的DNN模型、称重秤、压力传感器、泵和阀门。该模型进行了实时测试,在三个独立的测试用例中,NWP的预测误差小于5%,成功地使SPTFF步骤的控制符合设计质量范式。
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引用次数: 0
Editorial: Advances in the sustainable production of biofuels and bioderivatives 社论:生物燃料和生物杀菌剂的可持续生产进展
Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2023-07-14 DOI: 10.3389/fceng.2023.1237945
Muhammad Sajid, J.H.P. Américo-Pinheiro, Abdur Raheem, M. M. Azim
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引用次数: 0
Review of synergy between machine learning and first principles models for asset integrity management 资产完整性管理中机器学习与第一性原理模型的协同作用综述
Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2023-07-12 DOI: 10.3389/fceng.2023.1138283
Tianxing Cai, Jian Fang, Sharath Daida, H. Lou
The chemical process industry (CPI) accumulated a rich data asset through industrial 4.0. There is a strong drive to develop and utilize effective approaches for process performance prediction and improvement, process control, sensor development, asset management, etc. The synergy between machine learning and first principles models can bring new insights and add tremendous value to the CPI. This paper reviews various applications of the synergies towards asset integrity management. An overview of some related commercial software packages are also provided.
化工过程工业(CPI)通过工业4.0积累了丰富的数据资产。开发和利用过程性能预测和改进、过程控制、传感器开发、资产管理等有效方法的动力很大。机器学习和第一性原理模型之间的协同作用可以带来新的见解,并为CPI增加巨大价值。本文综述了协同效应在资产完整性管理中的各种应用。还提供了一些相关商业软件包的概述。
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引用次数: 0
Potential and prospects of biomass as a source of renewable energy in Pakistan 巴基斯坦生物质作为可再生能源的潜力和前景
Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2023-07-11 DOI: 10.3389/fceng.2023.1193806
Asad Ali, Khurram Shahzad Ayub, Muhammad Tahseen Sadiq, M. Tanveer, Hamza Naseer, Zoha Nadeem, Hafiz Muhammad Aamir
In an agricultural country like Pakistan, producing affordable and clean energy can be a challenging task. However, Pakistan has the potential to utilize various biomass feedstocks to generate renewable energy and tackle climate change while promoting sustainable development. Wheat, rice, sugarcane, and corn are the four main crops that yield a significant amount of residue, totaling 112.1 million tons per year. These residues have the potential to produce 3,050 kWh/ton of energy, which can meet 14% of the energy demand in Pakistan, equivalent to 9.85TW, starting in 2022. Gasification technology is a versatile option that efficiently converts biomass into energy while reducing negative environmental impacts. The current research explores the feasibility of generating clean energy from crop residues with low emissions, addressing the country’s energy needs, and supporting policymakers in promoting the use of biomass for energy production. According to this study, rice husk, corn cobs, wheat straw, and sugar bagasse all produce hydrogen at rates of 6.9 wt.%, 6.4 wt.%, 5.69 wt.%, and 5.35 wt.%, respectively. Therefore, our study demonstrates that corn cobs have a significant potential for energy production.
在巴基斯坦这样的农业国家,生产负担得起的清洁能源可能是一项具有挑战性的任务。然而,巴基斯坦有潜力利用各种生物质原料生产可再生能源,并在促进可持续发展的同时应对气候变化。小麦、水稻、甘蔗和玉米是产生大量残留物的四种主要作物,每年总共产生1.121亿吨残留物。从2022年开始,这些残留物有可能产生3050千瓦时/吨的能源,可以满足巴基斯坦14%的能源需求,相当于9.85太瓦。气化技术是一种多功能的选择,可以有效地将生物质转化为能源,同时减少对环境的负面影响。目前的研究探索了利用低排放的作物秸秆生产清洁能源的可行性,解决了该国的能源需求,并支持政策制定者促进将生物质能用于能源生产。根据这项研究,稻壳、玉米芯、麦秆和甘蔗渣的产氢率分别为6.9%、6.4%、5.69和5.35 wt.%。因此,我们的研究表明,玉米芯具有巨大的能源生产潜力。
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引用次数: 0
Analysis of protein-protein interaction and weighted co-expression networks revealed key modules and genes in multiple organs of Agave sisalana 蛋白质相互作用和加权共表达网络分析揭示了龙舌兰多器官的关键模块和基因
Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2023-05-26 DOI: 10.3389/fceng.2023.1175235
L. M. Carvalho, N. V. Silva, L. G. D. de Abreu, Marina Pupke Marone, Alexandra Russolo Cardelli, Fábio Trigo Raya, Guido Araujo, M. Carazzolle, G. G. Guimarães Pereira
Agave plants are well-known for their drought resilience and commercial applications. Among them, Agave sisalana (sisal) is the species most used to produce hard fibers, and it is of great importance for semiarid regions. Agaves also show potential as bioenergy feedstocks, as they can accumulate large amounts of biomass and fermentable sugar. This study aimed to reconstruct the A. sisalana interactome, and identify key genes and modules involved in multiple plant tissues (root, stem, and leaf) through RNA-Seq analysis. We integrated A. sisalana transcriptome sequences and gene expression generated from stem, leaf, and root tissues to build global and conditional co-expression networks across the entire transcriptome. By combining the co-expression network, module classification, and function enrichment tools, we identified 20 functional modules related to at least one A. sisalana tissue, covering functions such as photosynthesis, leaf formation, auxin-activated signaling pathway, floral organ abscission, response to farnesol, brassinosteroid mediated signaling pathway, and light-harvesting. The final interactome of A. sisalana contains 2,582 nodes and 15,083 edges. In the reconstructed interactome, we identified submodules related to plant processes to validate the reconstruction. In addition, we identified 6 hub genes that were searched for in the co-expression modules. The intersection of hub genes identified by both the protein-protein interaction networks (PPI networks) and co-expression analyses using gene significance and module membership revealed six potential candidate genes for key genes. In conclusion, we identified six potential key genes for specific studies in Agave transcriptome atlas studies, biological processes related to plant survival in unfavorable environments and provide strategies for breeding programs.
龙舌兰植物以其抗旱能力和商业应用而闻名。其中,剑麻(Agave sisalana)是生产硬纤维最常用的物种,在半干旱地区具有重要的应用价值。龙舌兰也显示出作为生物能源原料的潜力,因为它们可以积累大量的生物质和可发酵糖。本研究旨在通过RNA-Seq分析,重建剑麻相互作用组,并鉴定参与植物多组织(根、茎、叶)的关键基因和模块。我们整合了剑麻转录组序列和茎、叶和根组织产生的基因表达,构建了覆盖整个转录组的全局和条件共表达网络。通过结合共表达网络、模块分类和功能富集工具,我们确定了与至少一种剑麻组织相关的20个功能模块,包括光合作用、叶片形成、生长素激活的信号通路、花器官脱落、法尼醇响应、油菜素类固醇介导的信号通路和光收获等功能。剑麻的最终交互组包含2582个节点和15083条边。在重建的交互组中,我们确定了与植物过程相关的子模块来验证重建。此外,我们还在共表达模块中发现了6个中心基因。通过蛋白-蛋白相互作用网络(PPI网络)和利用基因显著性和模块隶属度进行的共表达分析发现了6个潜在的关键基因候选基因。总之,我们确定了6个潜在的关键基因,用于龙舌兰转录组图谱研究、植物在不利环境中生存的生物学过程和育种计划的具体研究。
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引用次数: 0
Improvement of Saccharomyces propagation performance through oxygen-enriched air and aeration parameter variation 富氧空气及曝气参数变化对酵母菌繁殖性能的影响
Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2023-05-18 DOI: 10.3389/fceng.2023.1193230
A. Beugholt, D. Geier, T. Becker
A variety of yeast applications in the food and beverage industry require individual and reproducible yeast propagation at high yields and consistent quality. One quality-determining parameter for yeast propagation is effective aeration to avoid oxygen depletion. Therefore, this work investigated three important aeration parameters: airflow, pulse time, and oxygen concentration, for their influence on yeast propagation. The aeration of a propagator involves phase transitions which are gradient-driven processes and can be accelerated with higher gradients between the liquid medium and the gas bubbles. In this study, oxygen-enriched air generated with membrane filters was used to aerate the system in an easy and cost-efficient way without the need for expensive technical gas usage. Propagation experiments were carried out in a pilot-scale reactor equipped with a membrane filter system for enhanced oxygen concentrations in ingas and online sensors for representative monitoring of the process. The membrane filter system is based on the separation of nitrogen in compressed air, leading to oxygen enrichment. Using oxygen-enriched air for propagation aeration showed higher oxygen transfer into the medium and the anaerobic process time caused by oxygen depletion due to high cell numbers was reduced by an average of 7.4% for pulsed aeration. Additionally, we conducted experiments with controlled measures of dissolved oxygen using different oxygen concentrations for aeration. The main objective of this study is to present a new and affordable optimization of propagation aeration using membrane filtration to enrich process air. The results showed increased cell counts for higher ingas oxygen concentrations and no negative impact on cell vitality was observed. Hence, our investigations showed that using oxygen-enriched air reduced the frequency of pulsed aeration, thus hindering foam formation, a limiting factor of the yeast propagation process.
食品和饮料行业中的各种酵母应用需要以高产率和一致的质量进行单独和可重复的酵母繁殖。酵母繁殖的一个质量决定参数是有效曝气以避免氧气耗尽。因此,本工作研究了三个重要的曝气参数:气流、脉冲时间和氧气浓度,以了解它们对酵母繁殖的影响。传播子的充气涉及相变,相变是梯度驱动的过程,并且可以在液体介质和气泡之间以更高的梯度加速。在这项研究中,使用膜过滤器产生的富氧空气以一种简单且经济高效的方式为系统充气,而不需要昂贵的技术气体使用。在中试规模的反应器中进行了传播实验,该反应器配备了用于提高ingas中氧气浓度的膜过滤系统和用于代表性监测该过程的在线传感器。膜过滤系统是基于压缩空气中氮气的分离,从而实现富氧。使用富氧空气进行繁殖曝气显示出更高的氧气转移到培养基中,并且对于脉冲曝气,由高细胞数引起的氧气消耗引起的厌氧过程时间平均减少7.4%。此外,我们使用不同的氧气浓度进行曝气,对溶解氧进行控制测量。本研究的主要目的是提出一种新的、价格合理的繁殖曝气优化方法,使用膜过滤来富集工艺空气。结果表明,ingas氧浓度越高,细胞计数越高,对细胞活力没有负面影响。因此,我们的研究表明,使用富氧空气降低了脉冲曝气的频率,从而阻碍了泡沫的形成,这是酵母繁殖过程的一个限制因素。
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引用次数: 0
Graphene nanoplatelets promoted CoO-based catalyst for low temperature CO2 methanation reaction 石墨烯纳米片促进低温CO2甲烷化反应的CoO基催化剂
Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2023-05-15 DOI: 10.3389/fceng.2023.1160254
Liping Zhong, Thi Ha Giang Pham, Youngdon Ko, A. Züttel
Methanation of CO2 is an important reaction for reducing CO2 emissions in a power-to-gas system. Compared to cobalt supported on gamma-Al2O3, cobalt supported on graphene nanoplatelets (GNPs) showed significantly better performance for CO2 methanation. Cobalt supported on GNPs was capable of 15% conversion of CO2 to CH4 at temperatures below 250°C, compared to 5% for cobalt supported on Al2O3. In situ thermogravimetric analysis (TGA) demonstrated that the Co/GNP catalyst was stable to 400°C. The maximum catalyst mass-specific CH4 yield was obtained at a Co loading of 5wt% on GNPs; however, high Co loading on GNPs deactivated the reactivity of the Co/GNP catalyst. Transmission electron microscopy (TEM) demonstrated that 5wt% Co/GNPs had the smallest and most dispersed cobalt nanoparticles. Excessive loading of cobalt tended to form isolated large Co nanoparticles. X-ray photoelectron spectroscopy (XPS) and Raman spectrometry revealed that more CoO phases were maintained on the surface of 5wt% Co/GNPs, indicating that the interaction between the Co and the GNPs had more of an impact on cobalt’s redox capacity than did particle size, which ultimately affected cobalt’s active phase during the CO2 reduction process. Furthermore, Raman spectrometry demonstrated that Co loading led to an increase in graphene defects. Higher Co loading on GNPs resulted in fewer interfaces between Co and GNPs due to the agglomeration of Co nanoparticles.
二氧化碳的甲烷化是减少电力-天然气系统中二氧化碳排放的重要反应。与负载在γ-Al2O3上的钴相比,负载在石墨烯纳米片(GNP)上的钴在CO2甲烷化方面表现出明显更好的性能。在低于250°C的温度下,负载在GNP上的钴能够将15%的CO2转化为CH4,而负载在Al2O3上的钴的转化率为5%。原位热重分析(TGA)表明,Co/GNP催化剂在400°C下是稳定的。在GNP上的Co负载量为5wt%时获得了最大催化剂质量比CH4产率;然而,GNP上的高Co负载使Co/GNP催化剂的反应性失活。透射电子显微镜(TEM)表明,5wt%的Co/GNP具有最小和最分散的钴纳米颗粒。过量的钴负载倾向于形成分离的大的钴纳米颗粒。X射线光电子能谱(XPS)和拉曼光谱显示,在5wt%Co/GNP的表面上保留了更多的CoO相,这表明Co和GNP之间的相互作用对钴的氧化还原能力的影响比颗粒尺寸的影响更大,颗粒尺寸最终影响了CO2还原过程中钴的活性相。此外,拉曼光谱分析表明,Co负载导致石墨烯缺陷的增加。由于Co纳米颗粒的团聚,GNP上较高的Co负载量导致Co和GNP之间的界面较少。
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引用次数: 0
Hybrid modeling for biopharmaceutical processes: advantages, opportunities, and implementation 生物制药过程的混合建模:优势、机会和实现
Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2023-05-15 DOI: 10.3389/fceng.2023.1157889
H. Narayanan, M. von Stosch, F. Feidl, M. Sokolov, M. Morbidelli, A. Butté
Process models are mathematical formulations (essentially a set of equations) that try to represent the real system/process in a digital or virtual form. These are derived either based on fundamental physical laws often combined with empirical assumptions or learned based on data. The former has been existing for several decades in chemical and process engineering while the latter has recently received a lot of attention with the emergence of several artificial intelligence/machine learning techniques. Hybrid modeling is an emerging modeling paradigm that explores the synergy between existing these two paradigms, taking advantage of the existing process knowledge (or engineering know-how) and information disseminated by the collected data. Such an approach is especially suitable for systems and industries where data generation is significantly resource intensive while at the same time fundamentally not completely deciphered such as the processes involved in the biopharmaceutical pipeline. This technology could, in fact, be the enabler to meeting the demands and goals of several initiatives such as Quality by design, Process Analytical tools, and Pharma 4.0. In addition, it can aid in different process applications throughout process development and Chemistry, Manufacturing, and Control (CMC) to make it more strategic and efficient. This article focuses on providing a step-by-step guide to the different considerations to be made to develop a reliable and applicable hybrid model. In addition, the article aims at highlighting the need for such tools in the biopharmaceutical industry and summarizes the works that advocate its implications. Subsequently, the key qualities of hybrid modeling that make it a key enabler in the biopharmaceutical industry are elaborated with reference to the literature demonstrating such qualities.
过程模型是试图以数字或虚拟形式表示真实系统/过程的数学公式(本质上是一组方程)。它们要么是基于基本的物理定律(通常与经验假设相结合),要么是根据数据得出的。前者在化学和过程工程中已经存在了几十年,而后者最近随着几种人工智能/机器学习技术的出现而受到广泛关注。混合建模是一种新兴的建模范式,它探索现有这两种范式之间的协同作用,利用现有的过程知识(或工程技术诀窍)和通过收集的数据传播的信息。这种方法特别适用于数据生成非常资源密集型的系统和行业,同时基本上不能完全破译,例如生物制药管道中涉及的过程。事实上,这项技术可以成为满足一些计划的需求和目标的推动者,例如质量设计、过程分析工具和制药4.0。此外,它还可以在整个过程开发和化学、制造和控制(CMC)的不同过程应用中提供帮助,使其更具战略性和效率。本文重点介绍了开发可靠且适用的混合模型时需要考虑的不同事项。此外,本文旨在强调生物制药行业对此类工具的需求,并总结了倡导其含义的作品。随后,参考文献阐述了混合建模的关键品质,使其成为生物制药行业的关键推动者。
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引用次数: 3
Non-invasive rust detection of steel plates determined through interfacial modulus 用界面模量测定钢板的无损锈蚀检测
Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2023-05-11 DOI: 10.3389/fceng.2023.1150776
Dipen K. Patel, Y. Bhimavarapu, A. Jena, R. Tadmor, Tianxing Cai
Initial methods to detect rust in pipelines have been conducted through invasive probes and sectioning off parts of the facility as the plant is running. These methods greatly increase the costs overall. The need for a feasible solution to this issue lies in the detection of rust formation through a non-invasive method. This study’s objective is to measure rust formation through droplet motion on the outer layer of pipelines. Multiple experiments are conducted using carbon steel sheets whose bottom layer has been exposed to acid for different durations of time. As rust formation in the metal is a voltaic phenomenon, it would mean that the acid corrosion of the bottom layer would adversely affect the top layer of the substrate. Consequentially, droplet motion and the droplet’s contour would change in different corrosive scenarios which we could then detect with novel parameters in our lab. One such parameter is the Interfacial Modulus (GS), which describes the initial resistance of the solid’s outer layer towards the liquid. We can understand this parameter with the aid of the novel device, known as the Centrifugal Adhesion Balance (CAB). As we cause the drop to slide across the substrate at constant normal force condition, we observe the difference in the contour of the drop as it slides across the substrate. The real-time change in contact angles at each edge of the drop, along with its change in external lateral force, causes a change in the GS values, which varies in different corrosive scenarios.
检测管道锈蚀的初步方法是通过侵入式探头进行的,并在工厂运行时切断设施的部分。这些方法大大增加了总体成本。对这个问题的可行解决方案的需要在于通过非侵入性方法检测铁锈的形成。本研究的目的是通过液滴在管道外层的运动来测量铁锈的形成。使用底层已暴露于酸中不同持续时间的碳钢薄板进行了多项实验。由于金属中的铁锈形成是一种电压现象,这意味着底层的酸腐蚀将对基底的顶层产生不利影响。因此,液滴运动和液滴轮廓会在不同的腐蚀情况下发生变化,然后我们可以在实验室中用新的参数来检测。其中一个参数是界面模量(GS),它描述了固体外层对液体的初始阻力。我们可以借助于被称为离心附着力天平(CAB)的新型装置来了解这个参数。当我们使液滴在恒定法向力条件下滑过基底时,我们观察到液滴在滑过基底时的轮廓差异。液滴每个边缘接触角的实时变化,以及外部侧向力的变化,会导致GS值的变化,而GS值在不同的腐蚀情况下会发生变化。
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引用次数: 0
Review of innovative uses of biochar in environmental applications for nitrobenzene removal in aqueous and soil phases 生物炭在水相和土壤中去除硝基苯的环境应用中的创新用途综述
Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2023-05-11 DOI: 10.3389/fceng.2023.1186878
Avinashkumar V. Karre, Tianxing Cai
Biochar has been found to be an effective material for the removal of nitrobenzene from both aqueous and soil phases. Some innovative uses of biochar in environmental applications for nitrobenzene removal include: 1) Biochar amendments for soil remediation. 2) Biochar for water treatment. 3) Biochar-based adsorbents. 4) Biochar-based membranes. Therefore, biochar is a promising material for the removal of nitrobenzene from both aqueous and soil phases, and its innovative uses in environmental applications continue to be explored. This paper presents the toxicity of nitrobenzene and potential hazards, with a discussion on the motivation and recent resolutions for nitrobenzene removal in aqueous and soil phases. Methodological cornerstones of innovative uses of biochar in environmental applications for nitrobenzene removal in aqueous and soil phases are introduced and reviewed. Overview and perspectives for the corresponding application are also provided. The innovative uses of biochar in environmental applications for nitrobenzene removal in aqueous and soil phases can bring new insights and add tremendous value to environmental chemical engineering.
生物炭已被发现是去除水中和土壤中硝基苯的有效材料。生物炭在环境中去除硝基苯的一些创新用途包括:1)生物炭改性用于土壤修复。2)生物炭用于水处理。3)生物炭基吸附剂。4)生物炭基膜。因此,生物炭是一种很有前途的去除水中和土壤中硝基苯的材料,其在环境应用中的创新用途仍在继续探索。本文介绍了硝基苯的毒性和潜在危害,讨论了在水相和土壤相中去除硝基苯的动机和最近的解决方案。介绍和回顾了生物炭在水相和土壤相去除硝基苯的环境应用中的创新用途的方法学基础。还提供了相应应用程序的概述和透视图。生物炭在水相和土壤中去除硝基苯的创新应用为环境化学工程带来了新的见解和巨大的价值。
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引用次数: 0
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