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Introduction : Anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) is a subtype of glutamate receptor that mediates most of the fast excitatory neurotransmission in the brain. Anti-AMPAR encephalitis is an autoimmune-mediated neurological disorder, frequently accompanied by the presence of neoplasms, comprising a spectrum of paraneoplastic syndrome. Patient concerns: A 56-year-old man was admitted for deterioration in memory and aberrant psychological behaviors, which lasted for at least 20 days Diagnosis: The patient was diagnosed as anti-AMPAR encephalitis and 4 months later, he was diagnosed with small cell lung cancer. Interventions: Once diagnosis for anti-AMPAR encephalitis was confirmed, methylprednisolone was prescribed with initial dose 500 mg/d for 14 days until the patient returned to pre-illness state. Then he was discharged with oral treatment with corticosteroids. Following the diagnosis of small cell lung cancer, he received 5 rounds of chemotherapy, including carboplatin and etoposide. Outcomes: After taken the prescription of Methylprednisolone for anti-AMPAR encephalitis, he returned to pre-illness state and was discharged. In April 21, 2017, after symptoms of respiratory system showed up, he was diagnosed with small cell lung cancer and he eventually died of respiratory failure. Conclusion: Though progress has been made in recent years in diagnosis and treatment for autoimmune encephalitis, it is challenging to diagnose due to the similarity in clinical findings with other autoimmune or infectious encephalitis. In addition, it is necessary for these patients to regularly have tumor screening, considering AMPAR antibody encephalitis is closely associated with neoplasm, and the incidence of paraneoplastic syndrome is 63% to 70%.

In this chapter, major green metrics are described as they have been applied to microflow continuous processes (e.g., mass intensity (MI)/process mass intensity (PMI), E‐factor, atom economy, etc.). Thereafter, life cycle assessment (LCA) and life cycle costing (LCC) analysis are reviewed in the framework of their application to evaluate microflow continuous processes. Green metrics, LCA, and LCC allow an objective quantitative measurement and decision support tool to evaluate the ecological, environmental as well as the economic impact of a chemical synthesis and process. Within the approach of green chemistry, continuous microflow processing has become a major method to achieve process intensification and engineering support. Accordingly, the specific sustainability characteristics of microflow continuous processes will be described. A comparison of microscale continuous processes and conventional macroscale processes accompanied by green metrics and LCA will be conducted. This is done in a hierarchical manner, starting from single microflow reaction optimization (both with single and bundled innovation drivers) toward combined microflow reaction separation and microflow multistep reactions. The production volume under consideration is both small (pharma) and large (fine/bulk chemical). This scenario analysis allows one to draw some generic conclusions about the environmental opportunities of continuous microflow technology and, vice versa, on the suitability of these green assessment tools. Each case scenario is for a typical, mostly experimentally validated microreactor application and illustrates the pros and cons of microflow continuous processes in the fine chemical and pharmaceutical industry. The environmental analysis is completed by a snapshot of LCC analysis for these microreactor case scenarios.

Nitrogen is the most basic element responsible for the growth of living creatures on earth. Chemical nitrogen fixation process is one of the most important chemical processes, which sustains the growing global population. Wherein the life changing Haber-Bosch process comes into the picture, which produces more than 130 million tons of ammonia per year by consuming ∼1–2% of the world's total energy consumption and sustains ∼40% of the world's population. Several efforts have been invested to develop an energy efficient alternative to this not-so-environmentally-friendly process. Nitric oxide and ammonia synthesis, with plasma as an alternative energy form, have been investigated extensively over the last 100 years. This review covers the important findings in the field of plasma nitrogen fixation and critically analyzes the studies reported from 1900 to 2014.

Catalytic processes are of paramount importance in the chemical industry. Homogeneous catalysts are of great interest for synthesizing fine-chemical/specialty chemical/pharmaceutical products for their advantages of high activity and selectivity. However, their separation from the product remains a challenge. Transition metals and especially platinum group metals are used extensively as catalysts. They are expensive and there are strict regulations on the permitted levels of these metals in pharmaceutical products. Therefore, their effective separation is required. Moreover, we are running short of these and many other valuable metals. This puts more emphasis on the need to separate these homogeneous metal catalysts in their active form and recycle them back to the reactor. This review aims to provide the reader with an overview of the current literature on the separation/recycling methods of homogeneous transition metal catalysts in continuous flow. These include heterogenization, scavenging, using biphasic systems and organic solvent nanofiltration. There are numerous successful demonstrations on the laboratory scale and recently also on the industrial scale.

The environmental profile of plasma assisted methane reforming for the production of synthesis gas was researched. A miniaturized gliding arc discharge reactor was applied for the partial oxidation of methane in this study. The best operational condition regarding to the lowest CO2-eq emission was screened out. Studied were the global warming potential, the acidification potential, the eutrophication potential, the human toxicity, the NOx photochemical oxidant creation potential, and the ozone depletion potential. The electricity consumption was the main contribution to the four of these six impacts. A sensitivity research of different energy resources of electricity and electricity mix of different countries was carried out in order to decrease the emission caused by the electricity consumption. Then, the conventional steam reforming was benchmarked to the plasma reforming process, which shows that the global warming potential of the plasma reforming is comparably on the same level as the conventional reforming only in the case when the electricity is generated from renewable or clean energy. So, the environmental impact research of the plasma assisted methane reforming in lab scale shed light on its industrial application from the viewpoint of the environmental profile. In order to decrease the emissions from electricity production, it’s recommended that such plasma plant should be built close to power plants from the renewable or clean energy. The compactness of plasma plants due to their expected process intensification would facilitate such distributed approach, while conventional reforming plants are very large and need Verbund-type integration into ChemParks. Finally, another option to make the plasma reforming process more energy efficient and green is proposed which is to combine the plasma reforming unit with Solid Oxide Fuel Cells.

EDGE denotes “Explain, Demonstrate, Guide, Enable” and comes from a concept for youth leadership development training. Biotechnical and enzymatic micro-flow reactors are a young discipline. Here the enthusiasm level mirrors its technological growth and vice versa. Rather than being a linear function, enthusiasm first goes down after sudden realization of all bottlenecks and technological shortcomings which are to overcome in a Hercules task action. However, with increasing provision of technology and security in its performance, the enthusiasm level rises again. This “valley of death” needs to be crossed to bridge to a market. The enzymatic micro-flow reactors mirror the above depicted development of their counterparts – the chemical microreactors – which is already about 20 years old. This “Déjà vu” forms a feature story which encompasses a review about enzymatic microreactors and their synthetic applications which are shown in all their facets. This compilation is structured in chapters about reactor and enzyme support technology, transport intensification, chemical intensification, process-design intensification, and finally first steps into the bio-based economy.

This mini-review discusses some of the recent work on novel process windows by the Micro Flow Chemistry and Process Technology group at the Eindhoven University of Technology, and their associates. Novel process windows consist of unconventional approaches to boost chemical production, often requiring harsh reaction conditions at short to very short time-scales. These approaches are divided into six routes: the use of high temperatures, high pressures, and high concentrations (or solvent-free), new chemical transformations, explosive conditions, and process simplification and integration. Microstructured reactors, due to their inherent safety, short time-scales, and the high degree of process control, are the means that make such extreme chemistry possible.

Together with transport and chemical intensification, process-design intensification is situated under the umbrella of Novel Process Windows and heads for integrated and simplified smart-scaled (micro/meso) flow process design in a holistic picture. As a demonstration example, the direct oxidation of cyclohexene with hydrogen peroxide for adipic acid synthesis is considered. It provides an innovative alternative to the two-step industrial process currently used. It is aimed to design an energy efficient process for this novel route. For systematically and holistically analyzing the process and, in particular, its heat integration, pinch analysis is employed. With the use of the software Aspen Energy Analyzer, the available energy recovery potential is determined, and a heat exchanger network is designed that gives a minimum total annual cost. Compared with the initial heat exchanger network where energy requirements are supplied with utility streams, the improved heat exchanger network designed enables 70% saving in operating cost which enables to pay back the extra capital cost requirement in 8 months. The heat exchanger selection is also a very important design consideration. The utilization of compact heat exchangers (including microchannel-based), which have proven advantages in thermal effectiveness, safety, and reduced size, can enable further benefits in terms of total plant cost and plant complexity. The opportunity to have lower operable temperature approach gives the possibility to lower the utility requirement by 20%. For the case of temperature cross, the additional capital cost requirement can be halved. As a consequence, for operation of flow processes using micro/meso-reactors at large scale, the utility/energy support and heat exchanger selection should be taken into consideration. Such holistic thinking has not been detailed and justified so far for micro- or similar smart-scale flow reactors, to our best knowledge.

The importance of nitrogen fixation is evident in every aspect of a human being’s life -from the synthesis of vital for all organisms nutrients and, in turn, the ecosystem conservation to the production of fertilizers, plastics and many other daily usage products. However, increasing concerns about the environmental sustainability of contemporary chemical industry seem to impose, nowadays, great challenges to the industrial nitrogen fixation which is linked to immense energy consumption and burdened emissions profile. Upon these considerations, it becomes imperative to adopt a holistic approach towards the development of novel “green” process technologies for the synthesis of fixed nitrogen. A considerable effort to that direction has been made by means of plasma technology mainly at laboratory scale. Although research studies have shown promising results, little attention has been placed on conceptualizing plasma-assisted nitrogen fixation at an industrial scale and evaluating its environmental footprint. This issue is practically addressed in the present research work which focuses on the ex-ante process design of plasma-assisted nitric acid synthesis for a modular plant and the respective Life Cycle Assessment (LCA) incorporating renewable energy sources. In order to facilitate the analysis of the LCA study, a sensitivity analysis has been considered on the reaction yield, the plasma power consumption, the recycle of unreacted gas stream and the energy recovery in the plasma reactor. LCA results exhibit for the plasma-assisted nitric acid, incorporating the recycle of the tail gas and solar energy, an improvement in the Global Warming Potential of 20% as compared to the conventional production pathway.

Konti-Prozesse mit mikrostrukturierten Reaktoren ermoglichen Paradigmenwechsel in der Prozessentwicklung und damit auch kurzere Entwicklungszeiten bis hin zur Produktionsanlage. Der Schlussel liegt hier in analogen Prozesszustanden in der Entwicklungskette (Numbering-up), Standardisierung (Modularitat) und Intensivierung. Das Resultat ist letztendlich eine reduzierte Apparateanzahl und -grose und eine hohere Voraussagekraft im Scale-out der Anlagen. Dies wird bislang meistens uber die Transport-Intensivierung in mikrostrukturierten Reaktoren bewirkt. Ein neuer, mehr und mehr genutzter Ansatz ist die Chemie-Intensivierung durch Einsatz harscher Chemie bei ungewohnlichen Reaktionsparametern und masgeschneiderter Reaktionsumgebung. Eine ganz neuer Ansatz besteht zudem in der Prozessdesign-Intensivierung – zum einen brauchen selektivitatsoptimierte Durchflussprozesse weniger Reinigungsaufwand, zum anderen haben mikrostrukturierte Reaktoren aufgrund ihrer kleinen Baugrose und der Moglichkeit zur internen Funktionalisierung groses Potenzial fur die Systemintegration. Beide Masnahmen verandern und vereinfachen das gesamte Prozessschema grundlegend. Der modulare Aufbau der kleinen Konti-Einheiten erlaubt eine einfache Implementation in moderne modulare Anlagenumgebungen, in denen alle Testzyklen (Labor, Pilot, Produktion) in einer Anlagenumgebung durchgefuhrt werden sollen, wie z. B. Container-Anlagen. Flow processes with microstructured reactors allow paradigm chances in process development and thus can enable a faster development time to the final production plant. They do this by exploiting similarity effects along the development chain (modularity) and intensification. The final result can be a reduction of the number and size of apparatus in the plant, and a higher predictability in the scale-out of the apparatus. So far, this was mainly achieved via transport intensification given in microstructured reactors. A new idea is chemical intensification through deliberate use of harsh chemistry at unusual reaction parameters and tailor-made reaction environment. A very new idea is the process design intensification – the reaction-maximized flow processes need less separation expenditure and the small unit size together with the high degree in functionality gives large potential for system integration. The modular nature of the small flow units allow an easy implementation to modern modular plant environments, that enable to perform all the testing cycles (lab, pilot, production) in one plant environment, e.g. container plants.

Life cycle assessment (LCA) and life cycle cost analysis are two prime tools that have been used to evaluate the sustainability of novel EU projects, which investigated new strategies to improve product yields and reduce costs, while ensuring a good ecological footprint and cost efficiency. These include EU projects focussed on developing modular, compact production platforms with intensified reactors–such as the F3 Factory, COPIRIDE (combining process intensification-driven manufacture of microstructured reactors and process design regarding to industrial dimensions and environment), POLYCAT (modern polymer-based catalysts and microflow conditions as key elements of innovations in fine chemical synthesis) and SYNFLOW (Innovative Synthesis in Continuous-flow Processes for Sustainable Chemical Production). New projects such as the MAPSYN (Microwave, Acoustic and Plasma assisted SYNtheses) and BIOGO (Catalytic Partial Oxidation of Bio Gas and Reforming of Pyrolysis Oil (Bio Oil) for an Autothermal Synthesis Gas Production and Conversion into Fuels) continue this, but by using alternative energy and a biomass-based, heat-integrated process, respectively. Thus, this paper is a review of EU projects that have carried out LCA and cost analyses and used the results to aid decision-making in the context of process intensification, flow chemistry and modular plants. Copyright © 2015 Curtin University of Technology and John Wiley & Sons, Ltd.

Review: recent work on novel unconventional approaches to boost chemical production including use of high temperatures, high pressure and high concentrations; 80 refs.

A check on environmental sustainability of microreaction technology is given based on a new process idea as a study case, which is the direct synthesis of adipic acid (ADA) in a continuous flow process using a milli-packed bed reactor with micro-sized fluid interstices. Main aim is to determine impactful process parameters and to have a holistic idea of the environmental profile for this new process by means of life cycle assessment. Second main aim is to benchmark the flow process against conventional technology to produce ADA which takes place in two steps. Whereas the conventional process for ADA synthesis occurs in two steps from oxidation of cyclohexane by air followed by nitration oxidation, the direct route is from cyclohexene and uses hydrogen peroxide as oxidant. This results in higher ADA yield and simplified process with one step less. Drawbacks of the direct synthesis are long reaction time and increased safety issues, which can be overcome by using microreactors. The reaction rate is increased by the largely improved mass transfer and the use of higher temperature. Life cycle assessment (LCA) shows that for a number of impact categories the direct process is greener; yet there are also categories for which the conventional route is more environmentally sustainable. The results, analyzed from cradle to factory gate, shed some light on the truth and comprehensiveness of the statement frequently found in the literature, that H2O2 is a green oxidant because of atom economy and non-toxicity of water produced (Noyori et al., 2003; Grigoropoulo et al., 2003; Usui and Sato, 2003; Podgorsek et al., 2009; Edwards et al., 2005; Tse et al., 2005) [1] , [2] , [3] , [4] , [5] , [6] . Further, cooling energy plays also an important role for the environmental profile. In this way, fast decisions and recommendations for process variants in the newly designed route can be given and lead to a more focused research plan which is exemplified at the end of the paper.

The MAPSYN project of the European Union (standing for Microwave, Acoustic and Plasma SYNtheses) aims at the utilization of plasma technology for nitrogen fixation reactions on an industrial scale and with industrial plasma reactor technology, developed and utilised commercially [1]. Key motif is enhanced energy efficiency to make an industrial plasma process viable for chemical industry. The corresponding enabling technologies – plasma catalysis, smart reactors (microreactors) and more – go beyond prior approaches. Continuing a first more project-based literature compilation, this overview focus on the two first enabling functions, plasma catalysis and smart reactor technology, which are reviewed for industrial and near-industrial plasma-based applications. It is thereby evident that notable promise is given for the nitrogen fixation as well and indeed this has been demonstrated also for nitrogen fixation; yet, initially and without the holistic system engineering dimension.

Novel Process Windows make use of process conditions that are far from conventional practices. This involves the use of high temperatures, high pressures, high concentrations (solvent-free), new chemical transformations, explosive conditions, and process simplification and integration to boost synthetic chemistry on both the laboratory and production scale. Such harsh reaction conditions can be safely reached in microstructured reactors due to their excellent transport intensification properties. This Review discusses the different routes towards Novel Process Windows and provides several examples for each route grouped into different classes of chemical and process-design intensification.

Recently, much focus has been given to a new type of chemical production plant, with the aim of a much faster time-to-market (“50% idea”) and better cash-flow revenue. The main enabling technology is to have the plants pre-manufactured and assembled by a modular construction and to use innovative, smart-scale processing and apparatus technology, in order to achieve a compact overall plant footprint. Focal points in such technology are on the one hand, flow processing, with micro process technology as a cutting-edge cornerstone, and on the other hand, the container framework. Yet, other process-intensified technologies are suitable as well such as milli-flow or upgraded batch technologies. Finally, process robustness and short-time applicability make the decision. In this paper, for the first time, a CAPEX and OPEX analysis of the new plant technology is done, at the example of the Evotrainer production platform. This platform is pre-manufactured in serial and provides all the utilities needed around the reactor and e.g., separator to be tailored and inserted. The unit-operational modularization, with respective definition of interfaces, was developed further to a so-called functional modularization, where different cabinets with pre-defined functions and equipment are proposed. Three virtual microreactor applications were used and stand as model-based scenarios for market applications in bulk chemistry, fine chemistry and pharmacy. It is shown, in many facets, that the Evotrainer infrastructure based plants indeed have a faster payback and higher earnings as compared to conventional technology, particularly when serving high-priced markets such as pharmaceutical applications. Further, the combination with novel chemical routes or novel processing (Novel Process Windows) is advantageous. Micro process technology is one of the key enablers and was taken here, since the dataset of such technology was readily available to the authors due to past research efforts and there is some general belief in the combination to the so-called “Future Factories”. Yet, it stands also for any other process intensification technology which can achieve the same performance level and which is able to satisfy the needs of a producing industry.

Flow processes with microstructured reactors allow paradigm changes in process development and thus can enable a faster development time to the final production plant. They do this by exploiting similarity effects along the development chain (modularity) and intensification. The final result can be a (significantly) reduced number of apparatus in the plant, a (significantly) reduced apparatus size, and a higher predictability in the scale-out of the apparatus. So far, this was mainly achieved via transport intensification given in microstructured reactors – improved mixing and heat transfer which increase productivity and possibly improve selectivity. A more new idea is chemical intensification through deliberate use of harsh chemistries at unusual (high) pressure, temperature, concentration, and reaction environment which again increases productivity. A very new idea is the process design intensification – the reaction-maximized flow processes need less separation expenditure and the small unit size together with the high degree in functionality gives large potential for system integration. Both means change and simplify the process scheme totally which can lead to a reduced number of apparatus and has impact on predictability. The modular nature of the small flow units allow an easy implementation to modern modular plant environments (Future Factories) which enables to perform all the testing cycles (lab, pilot, production) in one plant environment; an example are here container plants. All these measures have large potential for (much) decreased overall development time.