Identify Process Parameters Research Articles

Genetically encoded sensors enable real-time observation of metabolite production

Engineering cells to produce valuable metabolic products is hindered by the slow and laborious methods available for evaluating product concentration. Consequently, many designs go unevaluated, and the dynamics of product formation over time go unobserved. In this work, we develop a framework for observing product formation in real time without the need for sample preparation or laborious analytical methods. We use genetically encoded biosensors derived from small-molecule responsive transcription factors to provide a fluorescent readout that is proportional to the intracellular concentration of a target metabolite. Combining an appropriate biosensor with cells designed to produce a metabolic product allows us to track product formation by observing fluorescence. With individual cells exhibiting fluorescent intensities proportional to the amount of metabolite they produce, high-throughput methods can be used to rank the quality of genetic variants or production conditions. We observe production of several renewable plastic precursors with fluorescent readouts and demonstrate that higher fluorescence is indeed an indicator of higher product titer. Using fluorescence as a guide, we identify process parameters that produce 3-hydroxypropionate at 4.2 g/L, 23-fold higher than previously reported. We also report, to our knowledge, the first engineered route from glucose to acrylate, a plastic precursor with global sales of $14 billion. Finally, we monitor the production of glucarate, a replacement for environmentally damaging detergents, and muconate, a renewable precursor to polyethylene terephthalate and nylon with combined markets of $51 billion, in real time, demonstrating that our method is applicable to a wide range of molecules.

The effect of welding parameters on surface quality of AA6351 aluminium alloy

In the present work, the effects of gas metal arc welding-cold metal transfer (GMAW-CMT) parameters on surface roughness are experimentally assessed. The purpose of this study is to develop a better understanding of the effects of welding speed, material thickness and contact tip to work distance on the surface roughness. Experiments are conducted using single pass gas metal arc welding-cold metal transfer (GMAW-CMT) welding technique to join the material. The material used in this experiment was AA6351 aluminum alloy with the thickness of 5mm and 6mm. A Mahr Marsuft XR 20 machine was used to measure the average roughness (Ra) of AA6351 joints. The main and interaction effect analysis was carried out to identify process parameters that affect the surface roughness. The results show that all the input process parameters affect the surface roughness of AA6351 joints. Additionally, the average roughness (Ra) results also show a decreasing trend with increased of welding speed. It is proven that gas metal arc welding-cold metal transfer (GMAW-CMT)welding process has been successful in term of providing weld joint of good surface quality for AA6351 based on the low value surface roughness condition obtained in this setup. The outcome of this experimental shall be valuable for future fabrication process in order to obtained high good quality weld.

3D Printing of Inorganic Sand Moulds for Casting Applications

The paper at hand introduces a 3D printing (3DP) process for additive manufacturing of inorganically bound sand moulds. The fundamental differences to 3DP with organic binders (which is state of the art) are explained and the quality relevant process parameters of the inorganic process are introduced. Since the inorganic binder system is thermally activated during the printing process the main focus lies on the heating procedure. The properties of printed specimens are measured by the quality features fluid migration and strength for which novel methods of moulding sand testing are used. Results show that the identified process parameters have a significant influence on specimen properties. The interaction of the attributes fluid migration and strength are also shown. By understanding the relationship between process parameters and quality features the properties of printed inorganic sand moulds can be tailored to fit casting specific requirements.

Spray forming of high density sheets

Porosity is one of the most important quality criteria of spray‐formed materials in the as‐sprayed condition. Typically, spray‐formed sheets have a porous rim close to the substrate and depending on the spray conditions cold or hot porosity may also be present in the core of the deposit. This porosity has to be removed or minimized to make further processing steps such as rolling, forging or extrusion possible.In this paper, the influence of both substrate temperature and deposit surface temperature on porosity in spray‐formed sheets is studied.For this purpose spray forming experiments (sheet size 1000 mm × 250 mm) were carried out using three different materials: aluminium‐bronze, tin‐bronze and a nitriding steel. For the copper‐base alloys preheated steel‐substrates with different temperatures were moved through a scanning spray cone. In the case of steel a ceramic substrate at room temperature was used. In addition to the variation of the substrate temperature, the gas to metal mass flow ratio (GMR) was varied to achieve different deposit surface temperatures. During the run the surface temperature in the deposition zone was measured using a scanning, multi‐wavelength pyrometer. Samples of the deposits were polished and rasterized by light microscopy. The local porosity was characterized by digital image analysis.The influence of the substrate temperature and the GMR on the porosity in the vicinity of the substrate is evaluated and discussed in detail. The impact of the deposit surface temperature on the porosity was analyzed and is discussed as well. It was found that the deposit surface temperature has a strong impact on porosity for spray‐formed sheets.Finally, experimental results were used to develop a new approach to predict the porosity in spray‐formed sheets. The results clearly show the dependence on material properties. This approach can be used to identify process parameters to generate high density sheets in the future.

The application of a pinless tool in friction stir spot welding: an experimental and numerical study

A pinless friction stir spot welding tool with a scrolled convex shoulder is used to create spot welds on aluminum alloy plates. The effects that the rotation rate, the dwell time, the plunge depth, and the plunge rate have on the spot welding process are investigated. A strong correlation was found to exist between the joint strength versus the tool rotation rate and the joint strength versus the dwell time. Low rotation rates and short dwell times resulted in significantly stronger welds and, conversely, higher rotation rates and longer dwell times resulted in spot welds with hooking defects and lower joint strengths. Using shear tests and macrosection analysis on the spot welds, the dependences of the joint strength, the spindle torque, the temperature and the axial force on the identified process parameters are discussed. A computational fluid dynamics model is created to simulate the effect that the tool rotation rate has on the heat generated and the material flow during spot welding.

Corrective finishing of extreme ultraviolet photomask blanks by precessed bonnet polisher.

The progressive transition from Excimer to extreme ultraviolet (EUV) lithography is driving a need for flatter and smoother photomask blanks. It is, however, proving difficult to meet the next-generation specification with the conventional chemical mechanical polishing technology commonly used for finishing photomask blanks. This paper reports on the application of subaperture computer numerical control precessed bonnet polishing technology to the corrective finishing of photomask substrates for EUV lithography. Full-factorial analysis was used to identify process parameters capable of delivering microroughness below 0.5nm rms while retaining relatively high removal rates. Experimental results show that masks prepolished to 300-600nm peak-to-valley (P-V) flatness by chemical/mechanical polishing can then be improved down to 50-100nm P-V flatness using the automated technology described in this paper. A series of edge polishing experiments also hints at the possibility of increasing the quality area beyond the 142mm square defined in the official EUV photomask specification.

Effect of Synthesis Conditions on Formation Pathways of Metal Organic Framework (MOF-5) Crystals

Metal Organic Frameworks (MOFs) represent a class of nanoporous crystalline materials with far reaching potential in gas storage, catalysis, and medical devices. We investigated the effects of synthesis process parameters on production of MOF-5 from terephthalic acid and zinc nitrate in diethylformamide. Under favorable synthesis conditions, we systematically mapped a solid formation diagram in terms of time and temperature for both stirred and unstirred conditions. The synthesis of MOF-5 has been previously reported as a straightforward reaction progressing from precursor compounds in solution directly to the final MOF-5 solid phase product. However, we show that the solid phase formation process is far more complex, invariably transferring through metastable intermediate crystalline phases before the final MOF-5 phase is reached, providing new insights into the formation pathways of MOFs. We also identify process parameters suitable for scale-up and continuous manufacturing of high purity MOF-5.

Optimisation of shock absorber process parameters using failure mode and effect analysis and genetic algorithm

The various process parameters affecting the quality characteristics of the shock absorber during the process were identified using the Ishikawa diagram and by failure mode and effect analysis. The identified process parameters are welding process parameters (squeeze, heat control, wheel speed, and air pressure), damper sealing process parameters (load, hydraulic pressure, air pressure, and fixture height), washing process parameters (total alkalinity, temperature, pH value of rinsing water, and timing), and painting process parameters (flowability, coating thickness, pointage, and temperature). In this paper, the process parameters, namely, painting and washing process parameters, are optimized by Taguchi method. Though the defects are reasonably minimized by Taguchi method, in order to achieve zero defects during the processes, genetic algorithm technique is applied on the optimized parameters obtained by Taguchi method.

Optimization of a refolding step for a therapeutic fusion protein in the quality by design (QbD) paradigm

Production of biotech therapeutics in Escherichia coli involves protein expression as insoluble inclusion bodies that need to be denatured and the resulting protein refolded into the native structure. In this paper, we apply a Quality by Design approach using Design of Experiments for optimization of the refolding process for a recombinant biotech therapeutic, granulocyte colony stimulating factor. First, risk analysis was performed to identify process parameters that require experimental examination. Next, the chosen parameters were examined using a fractional factorial screening design. Based on the results of this study, parameters that have significant effect on refold yield and product quality were identified and examined using a full factorial Design of Experiments for their interactions. The final model was statistically significant and delivered a refolding yield of 77%. Further, kinetics of refolding was evaluated under optimal conditions and was found to be of first order with a rate constant of 0.132/min. Design space was established for the three parameters for a given permissible range of yield, protein concentration, and purity. The primary objective of this paper is to provide a roadmap for implementing Quality by Design for development of a protein refolding step.

Microcosm study on the decomposability of hydrochars in a Cambisol

The process of hydrothermal carbonization (HTC) converts biomass into a carbonaceous product named hydrochar. It is hypothesized that due to a high recalcitrance against microbial decomposition in soil, hydrochar may contribute to carbon (C) sequestration, thereby sustaining its function as a soil conditioner. The objective of this microcosm study was to identify process parameters of hydrochar production affecting the stability of hydrochar-C against decomposition, and thus its C sequestration potential.A variety of hydrochars differing in processing temperature (180–250 °C) and time (4–12 h), and feedstock material (sugarbeet pulp, draff) as well as reference materials (wheat straw (WS), mature compost (MC), white peat (WP), sugarbeet pulp biochar (SB)) were applied to soil in a concentration equivalent to 30 t ha−1 incorporated into 15 cm soil depth. After 248 days of incubation, C mineralized from the hydrochars ranged from 12 to 32%; it decreased considerably with increasing processing temperature from 200 to 250 °C, and less pronounced with increasing processing time from 4 to 12 h, whereas feedstock had no distinct effect. Higher processing temperature reduced oxygen content in hydrochar thus decreasing its reactivity, which resulted in both a higher amount and mean residence time of the stable hydrochar-C fraction. The mean residence times of tested organic materials followed the order: WS << hydrochars < WP <<< SB, MC. Thus, the application of hydrochar as a soil conditioner under field conditions may offer a moderate potential for C sequestration. A comprehensive evaluation of the complete HTC process chain including C and energy balances is prospectively required.

Application of Quality by Design to the characterization of the cell culture process of an Fc-Fusion protein

The production bioreactor step of an Fc-Fusion protein manufacturing cell culture process was characterized following Quality by Design principles. Using scientific knowledge derived from the literature and process knowledge gathered during development studies and manufacturing to support clinical trials, potential critical and key process parameters with a possible impact on product quality and process performance, respectively, were determined during a risk assessment exercise. The identified process parameters were evaluated using a design of experiment approach. The regression models generated from the data allowed characterizing the impact of the identified process parameters on quality attributes. The main parameters having an impact on product titer were pH and dissolved oxygen, while those having the highest impact on process- and product-related impurities and variants were pH and culture duration. The models derived from characterization studies were used to define the cell culture process design space. The design space limits were set in such a way as to ensure that the drug substance material would consistently have the desired quality.

Determination of robustness and optimal work conditions for a purification process of a therapeutic recombinant protein using response surface methodology

A typical chromatographic purification step has numerous operating parameters that can impact its performance. As it is not feasible to evaluate the influence of each one, the current practice in biopharmaceutical industry is to apply risk analysis approach to identify process parameters that should be examined during process characterization. Once these parameters are identified, a response surface study can be run to help understand the relationship between critical inputs and outputs. We performed a study comprising optimization and robustness determination for a Blue-Sepharose purification step of rhEPO, a well-known therapeutic glycoprotein. Initially, risk analysis was fulfilled to identify key parameters. A small-scale model was created and qualified before its use in experimental studies, given by a Box-Behnken design with three factors. This method proved to be a very useful tool in bioprocess validation studies in which many input variables can affect product quality and safety.

In situ methods to explore microstructure evolution in chemically derived oxide thin films

In situ residual gas analyzer techniques were used to identify process-property relationships that regulate microstructure evolution in chemical solution-deposited BaTiO3films. In situ analysis of furnace exhaust gasses enabled quantitative exploration of thermolysis and crystallization reactions and an ability to identify processing parameters that influence the temperature ranges over which they occur. The atmospheric analysis was instrumental in identifying heat treatments that produced optimally consolidated precursor gels that crystallized into BaTiO3layers with optimized structure and properties. Slow ramp rates resulted in higher porosity, larger grain size, and a dramatic drop in the capacitor yield. Fast ramp rates produced similar trends; however, the mechanisms were distinct. The effects of oxygen partial pressure were also explored. BaTiO3grain size increased with increasing pO2, whereas there was no appreciable influence on density and capacitor yield. Optimal firing parameters, i.e., 20 °C/min ramp rate at a pO2of 10−13atm, were identified as those that produced an overlap in the temperature ranges of thermolysis and crystallization reactions and thus a precursor gel with a density and compliance that supports crystallization and densification while tolerating the associated volume contraction. This in situ approach to analyze downstream furnace gas is shown to be a generically applicable means to understand synthesis methods that are complicated by simultaneous mechanisms of precursor decomposition, extraction of volatile components, and crystallization.

The Development of Direct Metallic Rapid Tooling System

In recent years, rapid tooling (RT) has become increasingly important because of the requirement of rapid manufacturing. RT can be used to produce temporary molds as well as permanent molds in mass production. RT provides more benefits from the design stage to mass production. The objective of this research is to develop the direct metallic RT system and identify process parameters of laser cladding. A 2.5-kW Nd-AG laser system, a metallic powder feeder system, a lateral powder nozzle system, a PC-based motion controller, and a shielding gas-supply system are incorporated for the hardware architecture in the proposed RT system. The critical process parameters influencing the dimensional accuracy were analyzed with Taguchi's experimental design. From the analysis of variance computational results, the factors Scanning speed and Tool path offset are the influential factors affecting the layer thickness of RT parts. From the experimental results, the dimensional accuracy of the dual nozzle RT system is better than the single-nozzle RT system. Finally, the proposed RT system could fabricate the mold inserts. After finishing the mold inserts and assembling the plenary injection mold, the injection molding machine can generate acrylonitrile butadiene styrene plastic parts with excellent quality. Note to Practitioners-Rapid prototyping (RP) technologies have provided a new way of making models or producing visualization prototype in a fast fashion. However, there is an urgent demand from the industry for much faster ways to make physical prototypes, with the desired material using the appropriate production method. RP technologies have introduced a new generation of RT processes. Producing tooling directly from computer-aided-design (CAD) models is regarded as an important process of reducing the cost and time to market for new products. In this paper, a direct metallic rapid tooling (RT) system is developed to fabricate the metallic parts and molds directly from 3-D CAD models. The experimental investigations are implemented to study the proposed RT system. Using Taguchi's method, the critical performance process parameters have been analyzed. The analysis of variance method is used to decide the important process parameters. The developed RT system can produce the mold inserts directly. After assembling the plenary injection mold, the Acrylonitrile butadiene styrene ABS plastic parts have been generated from this RT mold to demonstrate the success of the process. In the future, it is possible to develop a grading alloy RT system, which can control the ratio of the alloy grading layers. Because the grading alloy rapid mold can use varied metallic powders with varied ratio, the cooling time and the residual stress can be reduced. Furthermore, the RT system can also adopt the coaxial nozzle which can be integrated with the optical system. The advantage of the coaxial nozzle is the independence of the powder supply direction in which the workpiece moves

Effects of design and operating variables on process characteristicsin a methane discharge: a numerical study

A self-consistent two-dimensional radio frequency capacitivelycoupled glow discharge model has been developed in cylindrical coordinates fora methane discharge using a fluid model. The objective of the study is toidentify the effects of design and operating variables of the reactor on theprocess characteristics such as the deposition rate, uniformity and thequality of the diamond-like-carbon film. The simulations provide insights tocharged species dynamics and investigate their effects on the plasma processfor a depositing methane discharge. The model includes continuity equationsfor electrons and positive and negative ions, and energy equation forelectrons. Swarm data as a function of electron energy are provided as inputto the model. The model predicts the electron density, ion density, and theirfluxes and energies to the cathode. The roles of electrons, dominating ionsand radicals in a capacitively coupled discharge are investigated. The radicaland neutral densities in the discharge are calculated using a gas phasechemistry model. The diamond-like-carbon thin-film deposition rate ispredicted using surface chemistry model. The gas phase chemistry modelconsiders diffusion of radicals and neutrals along with creation and lossterms. The surface deposition/etching process involves adsorption-desorption,adsorption layer reaction, ion stitching, direct ion incorporation, etchingand carbon sputtering. A systematic parametric study of plasma processing hasbeen performed to identify process parameters to obtain better filmdeposition/etching on a wafer. The present work shows how plasma equipmentsimulation can be used for the practical investigation and optimization of aplasma-assisted chemical vapour deposition process. The simultaneous treatmentof plasma dynamics and surface processes enables a very precise prediction ofthe process characteristics in terms of the film deposition rate, uniformityand the quality as functions of discharge control parameters and the reactorgeometry.

Identifying useful real-time control parameters in ozonation process

Industrial wastewaters that contain phenolic compounds are resistant to biodegradation and need preoxidation to improve their biodegradabilities. Preoxidation of these wastewaters by using ozone as the chemical oxidant has been found previously to be quite effective in promoting their biodegradability. In combined ozonation and biological processes, if we want to stop ozonation at the optimum condition (i.e. the maximum biodegradability), a biodegradation test is required. Since biodegradation tests such as BOD/TOC and oxygen uptake would take a long time, we could not know the time to stop ozonation immediately. This study was undertaken to identify process parameters (pH, ORP, ozone concentration in water, ozone gas concentration at the reactor outlet) that could be useful for monitoring and real-time control purposes in ozonation processes. We want to correlate these parameters with biodegradability and intermediates formed in ozonation processes. Results showed that the rapid increase of dissolved ozone and the first plateau termination of off-gas ozone concentrations are good indicators for the depletion of p-nitrophenol, the maximum of biodegradability and the elimination of toxicity. From the mean oxidation state curve, ozonation of p-nitrophenol could be divided into three stages, and a similar pattern could also be observed in ORP profiles. From the results of this research, the application of ozone concentration and ORP profiles as real-time control parameters seems promising.

Quantification of re-evaporated mass from loaded fibre-mist eliminators.

Airborne lubricant emissions are a serious health hazard for employees in the metal working industry. The basic components of lubricants are oils and additives for adapting the properties to achieve the process demands. The oils used in lubricants are either mineral, synthetic or of biological origin. The lubricants are used as water-emulsions and also as straight oils. Extreme process conditions cause considerable amounts of aerosol and vapour emissions of lubricants into the working environment. Fibre filters are used in industrial demisters for pollution control and also for sampling purposes. Re-evaporation of separated lubricants from loaded fibre filters causes increased vapour emissions. Quantification of lubricant vapour emission was the subject of this research. An apparatus and an appropriate procedure for measuring the dynamic behaviour of evaporative losses from fibre filters were developed. The test piece of a loaded fibre filter was fixed in a sampling probe according to VDI 2066. The vapour concentration of organic compounds in downstream air was measured in real-time by using a photo-ionisation detector (PID). The PID was checked by sampling the vapour on an oleophilic adsorbent resin, solvent extraction and quantitative IR analysis and also gravimetrically. The two basic processes of filtering volatile aerosols are, on the one hand, collecting droplets on the fibres and, on the other hand, the evaporation of collected liquid. These two processes had to be separated in order to measure the increase of the vapour concentration caused by the tested fibre filter. The experiments were carried out using pure dodecane and hexadecane in order to avoid difficulties due to the unknown chemical composition of lubricant vapour. The variation of the air flow and the initial liquid mass on the filter covered the relevant range for industrial fibre demisters and for sampling methods based on collecting aerosols on fibre filters. It was found that the downstream air was saturated with lubricant vapour for a wide range of filter loads and filtration velocities. From the results obtained it can be concluded that loaded industrial filter systems emit air with saturation vapour concentration throughout their operation. Hence, vapour emissions can be estimated easily if the saturation vapour pressure and the mean relative molecular mass are known. Moreover, results obtained from measurements of filters with low loads confirm that the phase transition from liquid to vapour is influenced by the identified process parameters. This is relevant for measurement methods using fibre filters for sampling volatile aerosols. A semi-empirical model to estimate the evaporative losses for low loadings is proposed. However, further research is necessary to determine the full range of parameters that are relevant for evaporative losses from filters loaded with low masses of aerosols.

Sequencing Batch Reactor System for Nutrient Removal: ORP and pH Profiles

The sequencing batch reactor (SBR) process is known for its flexibility to meet a wide range of treatment needs, including nutrient removal. However, information related to the operational stability of SBR nutrient removal systems and control parameters to adjust the cyclic duration is sparse. Consequently, this study was undertaken to identify process parameters (pH and oxidation reduction potential) that could be useful for monitoring and real-time control purposes. In general, the system achieved removal efficiencies of 91, 98 and 98%, respectively, for Chemical Oxygen Demand, total nitrogen and phosphate at the solids retention time of 10 days, with a cyclic duration of 6 h. Shock loadings of nitrogen (20 mg dm -3 of NH 4 + -N, four cycles) exhibited little impact on effluent quality, except for a higher nitrate content. Activated sludge settled well throughout the entire study period. Several significant points associated with different reactions within SBR cycle, e.g. end of nitrification, end of phosphate release and completion of phosphate uptake, were identified in pH profiles. Slope changes in pH profiles (dpH/dt, or d 2 pH/dt 2 ) were found to better represent the corresponding biological reactions. The application of these significant points in pH profiles as real time control parameters appears promising.

Modelling of pulsed current weld microstructures

Microstructural modification caused by pulsed arc welding was investigated. An analytical temperature distribution model was used to identify process parameters for two series of experiments. Mild ...

Nonlinear Systems Identification using the Lyapunov Method

The purpose of this paper is to present a technique of parameter identification for nonlinear stationary systems. The unknown coefficients of plants are determined via Lyapunov’s method using the model reference concept. The identified process parameters are calculated as a solution of nonlinear differential equations. The aim of this paper is to show how to solve a problem of determining parameter values and prove convergence of the proposed scheme. The use of the Lyapunov method makes the solution of the identification problem for nonlinear stationary systems straightforward.