Cost-competitive Process Research Articles

Process Development for the Manufacture of the Antimalarial Amodiaquine Dihydrochloride Dihydrate.

A robust process for the manufacture of the active pharmaceutical ingredient (API) amodiaquine dihydrochloride dihydrate (ADQ, 3), an important antimalarial, is reported. The process consists of a three-step synthetic route that involves a Mannich reaction, substitution with 4,7-dichloroquinoline (4,7-DCQ, 5), and rehydration. Additionally, a cost-competitive process for the production of 4,7-DCQ (5) is also reported wherein 4,7-DCQ (5) was prepared in four steps from meta-chloroaniline (7). 4-Acetamido-2-(diethylaminomethyl)phenol (14), 4,7-DCQ (5), and ADQ (3) were obtained in yields of 92, 89, and 90%, respectively. Costing and process mass intensities of 4,7-DCQ and ADQ are also reported.

Understanding the structure and composition of recalcitrant oligosaccharides in hydrolysate using high-throughput biotin-based glycome profiling and mass spectrometry

Novel Immunological and Mass Spectrometry Methods for Comprehensive Analysis of Recalcitrant Oligosaccharides in AFEX Pretreated Corn Stover. Lignocellulosic biomass is a sustainable alternative to fossil fuel and is extensively used for developing bio-based technologies to produce products such as food, feed, fuel, and chemicals. The key to these technologies is to develop cost competitive processes to convert complex carbohydrates present in plant cell wall to simple sugars such as glucose, xylose, and arabinose. Since lignocellulosic biomass is highly recalcitrant, it must undergo a combination of thermochemical treatment such as Ammonia Fiber Expansion (AFEX), dilute acid (DA), Ionic Liquid (IL) and biological treatment such as enzyme hydrolysis and microbial fermentation to produce desired products. However, when using commercial fungal enzymes during hydrolysis, only 75–85% of the soluble sugars generated are monomeric sugars, while the remaining 15–25% are soluble recalcitrant oligosaccharides that cannot be easily utilized by microorganisms. Previously, we successfully separated and purified the soluble recalcitrant oligosaccharides using a combination of charcoal and celite-based separation followed by size exclusion chromatography and studies their inhibitory properties on enzymes. We discovered that the oligosaccharides with higher degree of polymerization (DP) containing methylated uronic acid substitutions were more recalcitrant towards commercial enzyme mixtures than lower DP and neutral oligosaccharides. Here, we report the use of several complementary techniques that include glycome profiling using plant biomass glycan specific monoclonal antibodies (mAbs) to characterize sugar linkages in plant cell walls and enzymatic hydrolysate, matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) using structurally-informative diagnostic peaks offered by negative ion post-secondary decay spectra, gas chromatography followed by mass spectrometry (GC–MS) to characterize oligosaccharide sugar linkages with and without derivatization. Since oligosaccharides (DP 4–20) are small, it is challenging to mobilize these molecules for mAbs binding and characterization. To overcome this problem, we have applied a new biotin-coupling based oligosaccharide immobilization method that successfully tagged most of the low DP soluble oligosaccharides on to a micro-plate surface followed by specific linkage analysis using mAbs in a high-throughput system. This new approach will help develop more advanced versions of future high throughput glycome profiling methods that can be used to separate and characterize oligosaccharides present in biomarkers for diagnostic applications.

Asymmetric Organocatalysis and Continuous Chemistry for an Efficient and Cost-Competitive Process to Pregabalin

Herein, we present the scale up development of an innovative synthetic process to pregabalin. The process is underpinned by two enabling technologies critical to its success; continuous chemistry allowed a safe and clean production of nitroalkene, and asymmetric organocatalysis gave access to the chiral intermediate in an enantioenriched form. Crucial to the success of the process was the careful development of a continuous process to nitroalkene and optimization of the organocatalyst and of the reaction conditions to attain remarkably high turn-over frequency in the catalytic asymmetric reaction. Successful recycle of the organocatalysts was also developed in order to achieve a cost-competitive process.

Fused filament fabrication for anode supported SOFC development: Towards advanced, scalable and cost-competitive energetic systems

Solid Oxide Fuel Cells (SOFC) are electrochemical devices that efficiently convert hydrogen or other fuels into energy and heat and are considered a promising and environmentally friendly alternative to mitigate the effects of climate change. The difficulties found for the SOFC devices implementation into the market have triggered an enhanced need of research on the manufacturing strategy, since the cells and stack fabrication remain a complicated procedure. In this work, the capabilities of an additive manufacturing (AM) process, as it is Fused Filament Fabrication (FFF), applied to anode supported SOFC were explored for the first time, due to the strengths this technology offers in terms of materials versatility and cost-competitive process. Moreover, the ability of tuning the support porosity during the printing process was demonstrated, minimizing the pore former concentration required and avoiding reformulation of the feedstock to achieve higher porosity in the anode. In the cell fabrication, low-cost techniques for thin film deposition were employed. The preliminary geometry investigated represents a novel SOFC device that shows an electrochemical performance comparable to that found in the conventional SOFC fabrication and it opens the possibility of potential single-cell and stack designs in which the use of ceramic sealing could be avoided and the system durability increased.

A critical review on the progress and challenges to a more sustainable, cost competitive synthesis of adipic acid

A review of recent developments and remaining challenges to the development of greener, cost competitive processes for adipic acid manufacture. Chemical and biotechnological processes from both petroleum based and renewable feedstocks are reviewed.

Enhancing the decolorization activity of Bacillus pumilus W3 CotA-laccase to Reactive Black 5 by site-saturation mutagenesis.

Reactive Black 5 (RB5) is a typical refractory azo dye. Widespread utilization of RB5 has caused a variety of environmental and health problems. The enzymatic degradation of RB5 can be a promising solution due to its superiority as an eco-friendly and cost-competitive process. Bacterial CotA-laccase shows great application prospect to eliminate hazardous dyes from wastewater. However, efficient decolorization of RB5 CotA-laccase generally requires the participation of costly, toxic mediators. In the present study, we modified the amino acids Thr415 and Thr418 near the type 1 copper site and the amino acid Gln442 at the entrance of the substrate-binding pocket of Bacillus pumilus W3 CotA-laccase to boost its RB5 decolorization activity based on molecular docking analysis and site-saturation mutagenesis. Through the strategies, two double site mutants T415D/Q442A and T418K/Q442A obtained demonstrated 43.94 and 52.64% RB5 decolorization rates in the absence of a mediator at pH10.0, respectively, which were about 3.70- and 4.43-fold higher compared with the wild-type CotA-laccase. Unexpectedly, the catalytic efficiency of the T418K/Q442A to ABTS was enhanced by 5.33-fold compared with the wild-type CotA-laccase. The mechanisms of conferring enhanced activity to the mutants were proposed by structural analysis. In summary, the mutants T415D/Q442A and T418K/Q442A have good application potentials for the biodegradation of RB5. KEY POINTS: • Three amino acids of CotA-laccase were manipulated by site-saturation mutagenesis. • Decolorization rate of two mutants to RB5 was enhanced 3.70- and 4.43-fold, respectively. • The mechanisms of awarding enhanced activity to the mutants were supposed.

An economic analysis of twenty light olefin production pathways

Abstract A comprehensive economic analysis of twenty light olefin production pathways has been performed, covering current and promising processes from fossil (petroleum, coal and natural gas) and renewable resources (biomass and CO2). Taking steam cracking of naphtha as the benchmark, this study gives an economic perspective and points out the bottleneck in different olefin production pathways. The assessment indicates that nearly all renewable pathways are economically unattractive currently and the raw material cost accounts for dominant contribution in most pathways, especially in the oil-, natural gas- and CO2-derived pathways. For the ways of methanol-to-olefins and methanol-to-propylene, fossil pathways are cost-competitive according to the date of current Chinese market prices. However, the price of feedstock hydrogen needs to be lowered by 55% to fill the cost gap between CO2-derived pathways and the benchmark. For the ways of oxidative coupling of methane and Fischer-Tropsch synthesis to olefins, fossil pathways enable cost-competitive processes by feedstock price fall, but further process improvement is required to approach benchmark in renewable pathways. Conditionally, a decrease in ethanol price by 45% can make ethanol dehydration pathway profitable. In addition, costs can reduce by 4%–23% in different pathways as the production scales expand from 100 to 1000 kt/a, resulting in a change from high cost to economic profit for some of the pathways. The results quantify the need for improvements on feedstock price, scale size and process improvement to achieve competitive production costs.

Synthesis of Carboxylic Acids by Palladium-Catalyzed Hydroxycarbonylation.

The synthesis of carboxylic acids is of fundamental importance in the chemical industry and the corresponding products find numerous applications for polymers, cosmetics, pharmaceuticals, agrochemicals, and other manufactured chemicals. Although hydroxycarbonylations of olefins have been known for more than 60 years, currently known catalyst systems for this transformation do not fulfill industrial requirements, for example, stability. Presented herein for the first time is an aqueous-phase protocol that allows conversion of various olefins, including sterically hindered and demanding tetra-, tri-, and 1,1-disubstituted systems, as well as terminal alkenes, into the corresponding carboxylic acids in excellent yields. The outstanding stability of the catalyst system (26 recycling runs in 32 days without measurable loss of activity), is showcased in the preparation of an industrially relevant fatty acid. Key-to-success is the use of a built-in-base ligand under acidic aqueous conditions. This catalytic system is expected to provide a basis for new cost-competitive processes for the industrial production of carboxylic acids.

Preparation of petroleum-based mesophase pitch toward cost-competitive high-performance carbon fibers

Spinnable mesophase pitch precursor containing more than 98% mesophase content was successfully prepared from FCC-DO (fluid catalytic cracking-decant oil) without hydrogenation or catalytic reaction. The preparation method involved thermal condensation, vacuum treatment, and annealing treatment. Petroleum mesophase pitch-based carbon fibers are produced by melt spinning of pitch precursors, followed by stabilization and carbonization. The resulting carbon fiber exhibited good mechanical performances up to tensile strength of 2.1 GPa and tensile modulus of 212 GPa, with strain-to-failure higher than 1.0%. These properties ensuring that the automotive grade carbon fibers can be successfully prepared from FCC-DO derived petroleum mesophase pitches through the cost-competitive processes.

The effect of temperature during culture enrichment on methanotrophic polyhydroxyalkanoate production

Climate change and plastic pollution are likely the most relevant environmental problems of the 21st Century. Thus, one of the most promising solutions to remedy both environmental problems simultaneously is the bioconversion of greenhouse gases, such as methane (CH4), into bioplastics (PHAs). However, the optimization of this bioconversion platform is still required to turn CH4 biotransformation into a cost-effective and cost-competitive process. In this context, the research presented here aimed at elucidating the best temperature culture conditions to enhance both PHA accumulation and methane degradation. Six different enrichments were carried out at 25, 30 and 37 °C using different inocula and methane as the only energy and carbon source. CH4 biodegradation rates, specific growth rates, PHA accumulations and the community structure were characterized. Higher temperatures (30 and 37 °C) increased the PHAs accumulation up to 30% regardless of the inoculum. Moreover, Methylocystis became the dominant genus (∼30% of the total population) regardless of the temperature and inoculum used. This research demonstrated for the first time the fundamental role of temperature in increasing both the accumulation of PHAs and methane abatement during the enrichment of PHA cell-factories from methane, thus enhancing the cost-effectiveness of the process.

Advances and opportunities in biomass conversion technologies and biorefineries for the development of a bio-based economy

The desire to have a more sustainable future, with lower emissions of carbon and sulfur to the atmosphere, a more appropriate reuse and valorization of wastes, and less dependency on oil has motivated the society to develop processes where renewable biomass is used as a feedstock for the production of fuels, chemicals, energy and materials. In addition, a bio-based economy has also potential to generate new jobs and new opportunities for entrepreneurship, with further benefits to the society. In view of this, great efforts have been done in order to develop efficient, sustainable and cost competitive bio-based processes able to be implemented in industrial scale. Although important advances were achieved and some processes are already available in a large scale, improvements are still needed to have a final product at a more competitive market price. In this sense, the strategy of integrating biorefineries to produce a variety of products from biomass has been considered as an important alternative to improve the financial performance. This paper highlights the most recent advances and opportunities in biomass conversion technologies and biorefineries for the development of a bio-based economy. Technological aspects including the hemicellulose integration and use of sugars for different products, lignin valorization, development of efficient and low-cost pretreatment technologies and development of highly efficient fermentation processes are also presented and discussed.

Optimization of lipase production by Aspergillus ibericus from oil cakes and its application in esterification reactions

Due to the actual emphasis in revalorization of agro-industrial wastes and cost reduction of enzymes production, this work aimed the optimization of lipase production from different oil cakes (OCs) produced in Brazil, by solid-state fermentation using Aspergillus ibericus MUM 03.49 and the application of the produced lipase in hydrolysis and esterification reactions. Higher lipase production was obtained using palm kernel oil cake (PKOC), yielding 127±17U/g ​of lipase (per mass of dry substrate). Through SSF optimization, using PKOC mixed with sesame oil cake (SOC) in a ratio of 0.45g of PKOC per g total substrate at 57% moisture content (MC), a production of 460±38U/g of lipase was obtained after 6days of fermentation. The obtained lipase was used in hydrolysis reactions, where it was observed higher production in short-chain triacylglycerols (TAGs) substrates. Also, it was applied in esterification reactions, where the formation of butyl decanoate using 5% (w/v) of biocatalyst was the most efficient. SSF of PKOC and SOC is a low cost competitive process to obtain A. ibericus lipase that can be used in aroma esters production, with application in the food industry.

Economic feasibility of high-temperature reactors for industrial cogeneration: an investor's perspective

ABSTRACTThis paper studies the economic potential of using high-temperature nuclear reactors (HTRs) for cogeneration of industrial process heat and electricity. A reference case HTR is found to deliver cost-competitive process heat with temperatures of ≥200 °C, rendering the chemical and pulp and paper industries potential candidates. The reference case investment yields a positive net present value of €304 million. Real options analysis is employed to account for the uncertain environment and the resulting managerial flexibilities of the project. A real option model for optimal investment timing is adapted to HTRs for industrial cogeneration. The value of the option to invest in an HTR is determined at €667 million and the electricity price threshold for an optimal investment at 79 €/MWh. Though the option to invest in an HTR represents a significant value for a utility, the investment should be delayed until the electricity price has reached the threshold value. We also propose a model to calculate the option value of switching between two different operating modes (cogeneration vs. electricity only). For the reference case, this option value turns out to be €85 million.

A purification process for heparin and precursor polysaccharides using the pH responsive behavior of chitosan.

The contamination crisis of 2008 has brought to light several risks associated with use of animal tissue derived heparin. Because the total chemical synthesis of heparin is not feasible, a bioengineered approach has been proposed, relying on recombinant enzymes derived from the heparin/HS biosynthetic pathway and Escherichia coli K5 capsular polysaccharide. Intensive process engineering efforts are required to achieve a cost-competitive process for bioengineered heparin compared to commercially available porcine heparins. Towards this goal, we have used 96-well plate based screening for development of a chitosan-based purification process for heparin and precursor polysaccharides. The unique pH responsive behavior of chitosan enables simplified capture of target heparin or related polysaccharides, under low pH and complex solution conditions, followed by elution under mildly basic conditions. The use of mild, basic recovery conditions are compatible with the chemical N-deacetylation/N-sulfonation step used in the bioengineered heparin process. Selective precipitation of glycosaminoglycans (GAGs) leads to significant removal of process related impurities such as proteins, DNA and endotoxins. Use of highly sensitive liquid chromatography-mass spectrometry and nuclear magnetic resonance analytical techniques reveal a minimum impact of chitosan-based purification on heparin product composition.

Tubular thermal crosslinked-PEBA/ceramic membrane for aromatic/aliphatic pervaporation

Pervaporation could be a cost-competitive process for separating aromatic/aliphatic hydrocarbon mixtures in the chemical industry. In this study, commercial poly(ether-block-amide) (PEBA) and ceramic tubular substrates were used to prepare pervaporation membrane for separating aromatic/aliphatic mixtures through a facile thermal crosslinking method. The adsorption and diffusion properties of toluene and n-heptane in PEBA were determined by swelling experiment and inverse gas chromatography technique. FTIR and XRD were used to investigate the hydrogen bonding and crystallinity of PEBA molecule through thermal crosslinking. The morphology and structure of PEBA/ceramic composite membrane were characterized by SEM and EDX. The separation performance of the composite membrane can be adjusted by controlling PEBA concentration, thermal crosslinking temperature and time. Ceramic tubular substrate could suppress the excessive swelling and thereby enhance the stability of the membrane. Furthermore, different types of fillers were incorporated into PEBA matrix to improve the separation performance. The results demonstrate that PEBA/graphite hybrid membrane has the highest separation factor for separating 50wt% toluene/n-heptane mixtures. This study is expected to extend the membrane material and simplify the membrane preparation procedures in aromatic/aliphatic pervaporation fields.

Economics of High-Temperature Nuclear Reactors for Industrial Cogeneration

The EU Emissions Trading Scheme challenges the cost-competitiveness of energy-intensive industries in Europe, and induces them to search for low-carbon alternatives for their process heat requirements, such as cogeneration or the employment of nuclear power plants. The high-temperature nuclear reactor (HTR) is a technology option that combines these two aspects. In this paper, the economic potential of using HTRs for cogeneration of industrial process heat and electricity is studied. We show that a reference case HTR can deliver cost-competitive process heat at temperatures of 200°C and above, rendering the chemical and pulp & paper industry as potential candidates. The economic evaluation of the reference case yields a positive net present value of € 304 million and an internal rate of return of 12.3%, which is above the cost of capital. Real options analysis is employed to account for the uncertain environment and the resulting managerial flexibilities of the project. A real option model for optimal investment timing (Pindyck, 1991) is adapted to HTRs for industrial cogeneration. The value of the option to invest in a HTR is determined at € 667 million and the electricity price threshold for an optimal investment at 78.97 €/MWh. Hence, the option to invest in a HTR represents a significant value for a utility. Yet, the investment should be delayed until the electricity price reaches the threshold value. We also propose a model to calculate the option to switch between two different modes of operation that is based on Kulatilaka and Trigeorgis (1994) but builds on a time-continuous price path instead of a binomial lattice. For the reference case, the option to switch the power plant’s output from cogeneration to electricity only is found to be worth € 85 million.

Enabling technologies to advance microbial isoprenoid production.

Microbial production of isoprenoids provides an attractive alternative to biomass extraction and chemical synthesis. Although widespread research aims for isoprenoid biosynthesis, it is still in its infancy in terms of delivering commercial products. Large barriers remain in realizing a cost-competitive process, for example, developing an optimal microbial cell factory. Here, we summarize the many tools and methods that have been developed in the metabolic engineering of isoprenoid production, with the advent of systems biology and synthetic biology, and discuss how these technologies advance to accelerate the design-build-test engineering cycle to obtain optimum microbial systems. It is anticipated that innovative combinations of new and existing technologies will continue to emerge, which will enable further development of microbial cell factories for commercial isoprenoid production.

Design and techno-economic evaluation of microbial oil production as a renewable resource for biodiesel and oleochemical production

Experimental results from the open literature have been employed for the design and techno-economic evaluation of four process flowsheets for the production of microbial oil or biodiesel. The fermentation of glucose-based media using the yeast strain Rhodosporidium toruloides has been considered. Biodiesel production was based on the exploitation of either direct transesterification (without extraction of lipids from microbial biomass) or indirect transesterifaction of extracted microbial oil. When glucose-based renewable resources are used as carbon source for an annual production capacity of 10,000t microbial oil and zero cost of glucose (assuming development of integrated biorefineries in existing industries utilising waste or by-product streams) the estimated unitary cost of purified microbial oil is $3.4/kg. Biodiesel production via indirect transesterification of extracted microbial oil proved more cost-competitive process compared to the direct conversion of dried yeast cells. For a price of glucose of $400/t oil production cost and biodiesel production cost are estimated to be $5.5/kg oil and $5.9/kg biodiesel, correspondingly. Industrial implementation of microbial oil production from oleaginous yeast is strongly dependent on the feedstock used and on the fermentation stage where significantly higher productivities and final microbial oil concentrations should be achieved.

55.2: Ink‐Jet Printed AMOLED Displays Based on High Mobility IGZO TFTs: Cost Does Matter!

AbstractAMOLED displays based on metal oxide film as active channel layer are fabricated. To achieve cost‐competitive process in OLED manufacturing, solution‐processed HIL, HTL and pixilated EML (RGB) layers followed by evaporation process for other layers are demonstrated in this work. Meanwhile, the AMOLED backplanes possessing low power consumption and high frequency were fabricated on metal oxide TFTs with high mobility (23.13 cm2/Vs) technology. A 14” qHD AMOLED in 79 ppi‐resolution was realized with IGZO based active matrix panel.

Thermophilic, lignocellulolytic bacteria for ethanol production: current state and perspectives

Lignocellulosic biomass contains a variety of carbohydrates, and their conversion into ethanol by fermentation requires an efficient microbial platform to achieve high yield, productivity, and final titer of ethanol. In recent years, growing attention has been devoted to the development of cellulolytic and saccharolytic thermophilic bacteria for lignocellulosic ethanol production because of their unique properties. First of all, thermophilic bacteria possess unique cellulolytic and hemicellulolytic systems and are considered as potential sources of highly active and thermostable enzymes for efficient biomass hydrolysis. Secondly, thermophilic bacteria ferment a broad range of carbohydrates into ethanol, and some of them display potential for ethanologenic fermentation at high yield. Thirdly, the establishment of the genetic tools for thermophilic bacteria has allowed metabolic engineering, in particular with emphasis on improving ethanol yield, and this facilitates their employment for ethanol production. Finally, different processes for second-generation ethanol production based on thermophilic bacteria have been proposed with the aim to achieve cost-competitive processes. However, thermophilic bacteria exhibit an inherent low tolerance to ethanol and inhibitors in the pretreated biomass, and this is at present the greatest barrier to their industrial application. Further improvement of the properties of thermophilic bacteria, together with the optimization production processes, is equally important for achieving a realistic industrial ethanol production.