Laboratory Scale Production Research Articles

ChemInform Abstract: New Synthesis of Alkane‐ and Arylsulfonyl Chlorides by Oxidation of Thiols and Disulfides with Chlorine Dioxide.

Sulfonyl chlorides are extensively used in the production of detergents, ion-exchange resins, elastomers, pharmaceuticals, dyes, herbicides, as semiproducts in the synthesis of sulfonic acids esters. Industrial and laboratory scale production of sulfonyl chlorides is based on reactions of aliphatic hydrocarbons with sulfuryl halides or with a mixture of sulfur dioxide and chlorine, on the oxidative chlorination of thiols, sulfi des, disulfi des; on the oxidation of sulfenyl chlorides; on the reaction of sulfonic acids and their derivatives with PCl5, COCl2, thionyl chloride, chlorine, and chlorosulfonic acid. Sulfonyl halides form also in reactions of organomagnesium compounds with sulfuryl halide or of diazonium salts with sulfur dioxide and CuCl 2 [1]. However all these methods have certain disadvantages due to the severe reaction conditions and side processes. The method of synthesis of sulfonyl chlorides we developed is convenient and simple for application, provides a high yield of the reaction product (45–82%), and does not require any special conditions for the process (heating or cooling, or high pressure). This new reaction of sulfonyl chlorides preparation previously was not described in the literature. It consists in the reaction of alkanethiols or arylthiols and disulfi des with chlorine dioxide. Chlorine dioxide is one among effi cient and available oxidants produced on the industrial scale applied to the bleaching of cellulose and disinfection of drinking water. It s well soluble in water and organic solvents, therefore it can be used in various media and allows variation in charging reagents. We formerly demonstrated that chlorine dioxide selectively oxidized sulfi des to sulfoxides [2–5] and tiols to disulfi des [6]. We used as initial compounds hexanethiol (Ia), hexadecanethiol (IIa), phenylmethanethiol (IIIa), 4-methylbenzenethiol (IVa), dibutyl disulfide (Va), diphenyl disulfi de (VIa).

Mechanochemical Approaches to Ceramic Ink Formulation for Digital Fabrication of Solid Oxide Fuel Cells

Four different ink processing protocols were investigated to control the particle size distribution of lab scale batches of inkjet inks used for printing Solid Oxide Fuel Cell (SOFC) anodes. The inks were composed of a mixture of commercial Nickel Oxide (NiO) and Yttria-stabilized Zirconia (YSZ) powders dispersed in organic solvents. Protocols incorporating high energy wet and dry milling using a SPEX 8000 mixer mill were compared to traditional low energy milling/dispersion methods. Brunauer-Emmett-Teller (B.E.T.) surface area measurements were used in conjunction with scanning electron microscopy (S.E.M.) to determine the effects of the milling protocols on the dry powder particle sizes and morphologies. Dynamic light scattering (D.L.S.) was used to measure the particle size distributions of the inks. Low energy dispersion of the NiO and YSZ powders produced an ink with a number weighted particle size distribution peaked ∼ 300 nm and a significant tail of particles as large as 1 μm. Adding high energy dry milling or high energy slurry dispersion to the process removed most of the large particle size tail, but the particle size distribution remained peaked at 250 – 300 nm. By combining high energy dry powder milling with high energy slurry dispersion, the main peak in the particle size distribution shifted to 180 nm with minimal particles above 600 nm. These results indicate that the combination of high energy milling and dispersion enable lab scale production of nanoscale NiO/YSZ inks from commercial powders. The protocols developed in this work provide a first step towards the goal of controlling the microstructure of inkjet printed solid oxide fuel cell (SOFC) anodes through control of the ink particle size distribution.

Lab-scale production of biogenic sulphide for metal precipitation in remote areas

Batch cultures with wheat straw, biomass of Paja Brava ( Festuca orthophylla ), filter paper, newspaper and beech leaves ( Fagus sylvatica ) were established to produce sulphide. Sulphide production, sulphate reduction, concentration of Volatile Fatty Acids (VFAs), enzyme activities and Fluorescence in situ hybridisation were determined. Approximately 5 mM of sulphide was produced during anaerobic digestion of wheat straw, while the production with newspaper as carbon source was the lowest (ca.1 mM). The sulphide production (2–5 mM) in the semi-continuous culture of the consortium A10, using wheat straw supported Cu(II), Pb (II) and Zn (II) removal up to 90%.

From highly ramified, large scale dendrite patterns of drying “alginate/Au NPs” solutions to capillary fabrication of lab-scale composite hydrogel microfibers

The processes of complexation, aggregation and self-assembly involving natural polymers are not only ubiquitous in biological systems (proteins), but they are also crucial for environmental and technological applications (humic acids, polysaccharide-based hydrogels). In this paper, we address these issues through a model study of the drying structures of bi-component solutions of oppositely charged alginate polysaccharide and gold nanoparticles. Unlike single component alginate and nanoparticle solutions, we show that the sessile drops of the bicomponent mixtures lead, upon drying, to fibrillar dendrite patterns of rather unusual size and ramification density. We discuss the key parameters and the mechanisms which drive the formation of these highly ramified dendrite structures. These involve, on the one hand the composition (residual salt content), the drying mode and nanoparticle size, and on the other hand, the shear-drainage and concentration, the counterion condensation, and the co-assembly and co-crystallization of the polymer, the nanoparticles and the residual salts. Finally, inspired by these fibril-like drying patterns and the gel forming property of alginate, we have developed a microfabrication process of composite hydrogel microfibers, which we showed to be an effective and flexible tool for a lab-scale production, characterization and functional optimization of such nanomaterials, before large production.

Occurrence and growth of lactic acid bacteria species during the fermentation of shalgam (salgam), a traditional Turkish fermented beverage

Shalgam (salgam) is a traditional lactic acid beverage produced from the lactic acid fermentation of black carrot, turnip, rock-salt, sourdough, bulgur flour and drinkable water. The aim of this study was to examine quantitatively the occurrence and growth of lactic acid bacteria during the course of fermentation using the traditional production method consisting of two stages: First fermentation and second fermentation. Isolated strains from experiments made at university laboratory, and large and small scale production plants in industry were identified by morphological, physiological and biochemical characterisations and using the commercially available system API 50 CH for the characterisation of carbohydrate fermentation patterns. The number of LAB increased during the fermentations. The most dominant LAB during the first and second fermentations was Lactobacillus plantarum. Next to L. plantarum, Lactobacillus paracasei subsp. paracasei was quantitatively the most important LAB recovered from all fermentations. Lactobacillus brevis and Lactobacillus fermentum were also subsequently determined in some fermentations. Low populations of Leuconostoc mesenteroides subsp. mesenteroides, Pediococcus pentosaceaceus, and Lactobacillus delbrueckii subsp. delbrueckii were present at the beginning but died off during the fermentation.

Nevirapine nanosuspension: comparative investigation of production methods

Increasing number of antiretroviral drugs coming from high throughput screening besides their high dose has poor solubility profile. Formulation development of these drugs is a major obstacle to their clinical application. To overcome extremely low water solubility and associated poor bioavailability they can be formulated as nanosuspensions. This paper is not only focuses on production of parenteral nevirapine nanosuspensions but also on scaling up of formulations for clinical use. Lab scale (APV LAB 40, 40 mL) and medium scale (Avestin C50, 2 kg) production was performed using piston gap high pressure homogenization (HPH), while the feasibility for pilot scale up was checked using a bead milling technique in continuous mode (PM, Bühler PML-2). Nanosuspension was characterized for particle sizes, zeta potential, crystallanity and stability. The mean particle sizes for lab scale, medium scale and pilot scale production obtained were 481 nm, 429 nm and 211 nm, respectively. Independent of the production method (lab and pilot scale) all processed formulations showed more or less similar zeta potential (~15 mV) in conductivity adjusted water. Long term stability over 1 year showed significant increase in particle size at all storage conditions for lab scale and medium scale production (high energy size reduction) whereas they remained physically stable (with negligible increase) for the milled product (low energy size reduction). As the technology has been scaled up successfully for nevirapine nanosuspension, the product can be considered for commercial exploitation. The prepared nevirapine nanosuspensions can be administered for parenteral or oral use.

Laboratory-Scale Production of 13C-Labeled Lycopene and Phytoene by Bioengineered Escherichia coli

Consumption of tomato products has been associated with decreased risks of chronic diseases such as cardiovascular disease and cancer, and therefore the biological functions of tomato carotenoids such as lycopene, phytoene, and phytofluene are being investigated. To study the absorption, distribution, metabolism, and excretion of these carotenoids, a bioengineered Escherichia coli model was evaluated for laboratory-scale production of stable isotope-labeled carotenoids. Carotenoid biosynthetic genes from Enterobacter agglomerans were introduced into the BL21Star(DE3) strain to yield lycopene. Over 96% of accumulated lycopene was in the all-trans form, and the molecules were highly enriched with 13C by 13C-glucose dosing. In addition, error-prone PCR was used to disrupt phytoene desaturase (crtI) function and create a phytoene-accumulating strain, which was also found to maintain the transcription of phytoene synthase (crtB). Phytoene molecules were also highly enriched with 13C when the 13C-glucose was the only carbon source. The development of this production model will provide carotenoid researchers a source of labeled tracer materials to further investigate the metabolism and biological functions of these carotenoids.

New synthesis of alkane- and arylsulfonyl chlorides by oxidation of thiols and disulfides with chlorine dioxide

Sulfonyl chlorides are extensively used in the production of detergents, ion-exchange resins, elastomers, pharmaceuticals, dyes, herbicides, as semiproducts in the synthesis of sulfonic acids esters. Industrial and laboratory scale production of sulfonyl chlorides is based on reactions of aliphatic hydrocarbons with sulfuryl halides or with a mixture of sulfur dioxide and chlorine, on the oxidative chlorination of thiols, sulfi des, disulfi des; on the oxidation of sulfenyl chlorides; on the reaction of sulfonic acids and their derivatives with PCl5, COCl2, thionyl chloride, chlorine, and chlorosulfonic acid. Sulfonyl halides form also in reactions of organomagnesium compounds with sulfuryl halide or of diazonium salts with sulfur dioxide and CuCl 2 [1]. However all these methods have certain disadvantages due to the severe reaction conditions and side processes. The method of synthesis of sulfonyl chlorides we developed is convenient and simple for application, provides a high yield of the reaction product (45–82%), and does not require any special conditions for the process (heating or cooling, or high pressure). This new reaction of sulfonyl chlorides preparation previously was not described in the literature. It consists in the reaction of alkanethiols or arylthiols and disulfi des with chlorine dioxide. Chlorine dioxide is one among effi cient and available oxidants produced on the industrial scale applied to the bleaching of cellulose and disinfection of drinking water. It s well soluble in water and organic solvents, therefore it can be used in various media and allows variation in charging reagents. We formerly demonstrated that chlorine dioxide selectively oxidized sulfi des to sulfoxides [2–5] and tiols to disulfi des [6]. We used as initial compounds hexanethiol (Ia), hexadecanethiol (IIa), phenylmethanethiol (IIIa), 4-methylbenzenethiol (IVa), dibutyl disulfide (Va), diphenyl disulfi de (VIa).

Where process development begins: A multiple case study of front end activities in process firms

The front end phase of the new product development has been examined extensively, yet few if any studies have examined the front end phase of new process development. By means of a multiple case study of process firms, this article aims to bridge this knowledge gap. Our results show that substantial differences in front end activities exist between the product development and process development domains. We conceptualize the front end in process development to be an iterative trial-and-error process, dominated by activities such as idea generation and refinement, literature reviews, anticipation of end-product changes, and various forms of experiments in bench scale, lab scale, and full-scale production. In addition, we highlight key problems in the front end and managerial remedies for how to mitigate them. While these findings provide theoretical implications for research into product development, process development and production management, the findings are particularly relevant to process development managers, plant managers, and development engineers interested in increasing the efficiency of production processes.

Manufacturing and characterization of carbon fibre/epoxy composite prepregs containing carbon nanotubes

Prepregs of carbon fibre-reinforced polymer (CFRP) composites containing carbon nanotubes (CNTs) have been successfully produced based on a solventless prepregging process. This work provides one of the most comprehensive evaluation to date of the processing and cure parameters affected by the incorporation of CNTs in CFRP prepreg manufacturing. The results confirmed that high-speed shear mixing and functionalisation of CNT are effective in lowering the viscosity of the CNT-epoxy nanocomposites. Based on the findings obtained from the rheological studies, suitable processing parameters are chosen for lab-scale production of CFRP composite prepregs. The effects of surfactant-treated CNTs on cure behaviour of epoxy and CFRP prepreg are evaluated. The catalytic activity of CNTs is negligible for a 0.5 wt% filler content whereas it becomes prominent when the CNT content is increased to 1.0 wt%. The degree of cure is lower for the prepregs containing 0.5–1.0 wt% CNTs than those without or containing a lower CNT content.

Improved arc discharge setup for synthesis of single and multi walled carbon nanotubes

This paper presents development of a laboratory scale setup for production of CNTs by arc discharge process in an argon gas environment. The main problem with existing lab scale production is the cleaning of the chamber which is resolved in presented work by placing a circular metal sheet inside the chamber which is removed after the synthesis, thus allowing easy cleaning and recovery of the CNTs. The most noteworthy feature of the presented setup is its low cost, offering for the first time the synthesis of economical CNTs on small scale. In addition to offering better control over operating conditions, another unique feature of the developed setup is its capability to synthesize SWCNTs and MWCNTs with versatile range of diameters.

A toolbox for the upscaling of ethanolic human serum albumin (HSA) desolvation

Nanoparticles consisting of human serum albumin (HSA) play an emerging role in the development of new drug delivery systems. Many of these protein-based colloidal carriers are prepared by the well-known desolvation technique, which has shown to be a robust and reproducible method for the laboratory-scale production of HSA nanoparticles. The aim of the present study was to upscale the ethanolic desolvation process utilizing the paddle stirring systems Nanopaddle I and II in combination with a HPLC pump in order to find the optimal conditions for the controlled desolvation of up to 2000 mg of the protein. For characterization of the HSA nanoparticles particle size, zeta potential as a function of the pH, polydispersity index and particle content were investigated. The particle content was determined by microgravimetry and by a turbidimetry to allow optimized in-process control for the novel desolvation technique. Furthermore the sedimentation coefficient was measured by analytical ultracentrifugation (AUC) to gain deeper insight into the size distribution of the nanoparticles. The formed nanocarriers were freeze dryed to achieve a solid preparation for long-term storage and further processing. Particles ranging in size between 251.2 ± 27.0 and 234.1 ± 1.5 nm and with a polydispersity index below 0.2 were achieved.

Automated lab‐scale production of PVA/PEG‐enzyme immobilisates

Entrapment of biocatalysts by cryogelation is a gentle method to extend the scope of biocatalysis. To foster the use of this versatile method we devised an automated injector for the production of PVA/PEG beads. The device consists of a thermostated reservoir connected to a programmable injector nozzle and an agitated receiving bath for the droplets. This lab-scale production unit yields up to 1500 beads with immobilized enzyme per minute with a narrow size distribution and good roundness.

Laboratory scale production of 13C labeled chitosan by fungi Absidia coerulea and Gongronella butleri grown in solid substrate and submerged fermentation

Nowadays, chitin and chitosan are applied in many medical and pharmaceutical products. However little is known about the metabolism of chitin and chitosan in vivo. In the human body, lysozyme will degrade chitin and chitosan into chito-oligosaccharides. 13C labeled chitosan is an essential prerequisite for the further study of the fate of chito-oligosaccharides in vivo. To fulfill this requirement, chitosans were extracted from mycelia of fungi, Absidia coerulea ATCC 14076 and Gongronella butleri USDB 0201 and ATCC 42618 grown in solid substrate fermentation (SSF) and submerged fermentation (SMF) to select the best fungus and fermentation method for the production of 13C labeled chitosan. Based on the production yield of chitosan, the SSF method is the best method for the production of fungal chitosan when compared with SMF methods (i.e., fed-batch fermentation and batch fermentation). However synthesis of 13C labeled chitosan in cell wall of G. butleri grown in SSF medium coated with 1- 13C-glucose was not observed. Alternatively, fungus A. coerulea was grown in SMF medium containing 2- 13C-glucose. The successful synthesis of 13C labeled glucosamine from 2- 13C-glucose was observed in mycelia of A. coerulea grown in SMF medium containing 2- 13C-glucose in a yield of about 13 g/100 g mycelia.

Preparation of pure hydrogen peroxide and anhydrous peroxide solutions from crystalline serine perhydrate

Hydrogen peroxide is one of the most versatile oxidation reagents, still it has not fully been exploited by synthetic chemists since anhydrous (let alone pure) hydrogen peroxide requires hazardous preparation protocols. We have recently reported on the crystallization of serine and other amino acid perhydrates, thus paving the way for a new method for laboratory-scale production of anhydrous hydrogen peroxide solutions. Serine is insoluble in most organic solvents (e.g., methanol, ethyl acetate, and methyl acetate) that readily dissolve hydrogen peroxide. Moreover, since the adduct of hydrogen peroxide and serine is unstable in these organic solvents, crystalline serine perhydrate readily decomposes to give anhydrous solutions of hydrogen peroxide and crystalline precipitate of the amino acid. This procedure can then yield an anhydrous hydrogen peroxide solution in a single step. Moreover, filtration of the amino acid, and room temperature evaporation of the volatile solvent (e.g., methyl acetate), yields over 99% hydrogen peroxide.

Lab-Scale production of Bacillus atrophaeus' spores by solid state fermentation in fifferent types of bioreactors

Studies were conducted to evaluate Bacillus atrophaeus spores' production by solid-state fermentation (SSF) using sugarcane bagasse as support and soybean molasses as substrate at lab-scale in column bioreactors (forced aeration), plastic bags and Erlenmeyer flasks (aeration by diffusion). Different moisture contents (84%, 86% and 88%; 89%, 91% and 93%) and aeration rates (30mL/min, 45mL/min, 60mL/min and 90mL/min) were studied. The best condition for spore production (3.3x10(10) CFU.g-¹dry matter) in column bioreactor was 80% of initial humidity and no aeration. In Erlenmeyer flasks and plastic bags the best sporulation production reached 1.7 up to 4.7x10(10) CFU.g-1dry matter with 88-93% of initial moisture. The aeration rate had no significant effect on the spore yield. The initial moisture had a significant effect depending on the bioreactor type. Sporulation kinetic's assay was carried out and it showed the possibility to reduce the time of spore formation in two days.

A Novel Method for Synthesis of Titania Nanotube Powders using Rapid Breakdown Anodization

The present paper describes a new method utilizing rapid anodization to quickly synthesize high-quality, high aspect ratio, robust titanium dioxide nanotube powders. TiO2 nanotube powders, with a typical nanotube outer diameter of approximately 40 nm, wall thickness of approximately 8−15 nm, and length of about 10−35 μm, were synthesized by potentiostatic rapid breakdown anodization of titanium foils in aqueous electrolytes of 0.3 M NaCl or 0.1 M HClO4 under an applied potential of 20 V. High reactivity and ultrahigh reaction rate are cornerstones responsible for periodic release of TiO2 nanotubes into solution and formation of a white precipitate of TiO2 nanotubes. The reaction yield is approximately 4−6 g in less than 3 h, and the approximate cost of the material is $3.50/g, based on the laboratory-scale production. Various characterization techniques, including FESEM, HRTEM, EDX, XRD, XPS, FT-IR, UV−visible diffuse-reflectance, and N2 adsorption, have been used to probe morphology, microstructure, crys...

Solid state fermentation of lipopeptide antibiotic iturin A by using a novel solid state fermentation reactor system

A new solid state fermentation reactor (SSFR) for solid substrate was used for the production of lipopeptide antibiotic iturin A using Bacillus subtilis RB14-CS. Solid state fermentation (SSF) is the technique of cultivation of microorganisms on solid and moist substrates in the absence of free water. SSF has shown much promise in the development of several bioprocesses and products because of their several advantages like absence of free water that allows simplified downstream processing and low cost. SSFR allows agitation of the SSF culture with improved temperature control and air supply. Interestingly, when okara, the widely available waste product from the tofu industries, was used as the solid substrate for the SSFR, no iturin A production was observed. However, without agitation, production of iturin A was observed in the SSFR but the production level remained low. The low production of iturin A was found to be due to the heat generation and excess temperature rise inside the reactor system during the fermentation process. Maintaining the temperature within a range of 25–30°C, production of iturin A was significantly improved in the SSFR. This was comparable to the laboratory scale production, and signifies the potential application of the SSFR for SSF.

Laboratory-scale production of biofuel pellets from electron beam treated Scots pine ( Pinus silvestris L.) sawdust

The effect of electron beam (EB) treatment on pine sawdust used as raw material for fuel pellets was studied. Dry sawdust was EB treated at different dosage levels up to 100 kGy. The effect of EB treatment on fatty and resin acid composition was studied for different dosage levels and compared to untreated sawdust. Pellets were pressed in a laboratory single pellet press unit according to a D-optimal, response surface modeling (RSM) experimental design, where sawdust moisture content and die temperature were varied independently for EB treatment dosages of 0, 18.2 and 48.9 kGy. The responses of the designed experiment were density and strength for the produced pellets. The results showed that the free fatty and resin acid content in the sawdust initially decreased with increasing EB doses but at the highest EB doses it increased. The total content of extractives however initially increased and then decreased with increasing EB dose. Pellets made of EB treated sawdust had a significantly (at 95% confidence level) higher density and compressive strength than pellets made from untreated sawdust. EB treated sawdust behaved similarly to stored (mature) sawdust as a pellet raw material. Thus, EB treatment opens the possibility for controlled ageing (maturation) of pellet raw materials.

Comparison of Alcohol Free GSH Production by Ultrasonic and Homogenizing Method

Homogenizer and ultrasonicator that we call as mechanical methods were used in the lab scale production of alcohol free reduced glutathione (alcohol free GSH) from baker's yeast. The study was done to determine the effects of specific parameters of the methods and the pH of the medium on the production of the GSH. The cell disruptions were run at a wide range of those parameters at the suitable common parameters of the methods. The disrupted cells suspension was then centrifuged at 12,000 rpm for 20 min and the GSH content in the supernatant was analyzed by taking the absorbance (A) value of the solution by spectrophotometer at 412 nm. The results obtained showed that the production of GSH was affected by the adjusted specific parameters of each method and the yield of production by the homogenizing and ultrasonic method was found 3.3 and 4.1 times, respectively, better than the yield of production by the unadjusted parameters. Ultrasonic method which produced 23.2 mg/L product was found 1.3 times better than the homogenizing method (18.5 mg/L) in producing the GSH. The result obtained from the lab scale study of the above mentioned mechanical methods showed that the implementation of them in the large scale production of the alcohol free GSH is possible.