Facilitate Process Design Research Articles

CO2 Physisorption over an Industrial Molecular Sieve Zeolite: An Experimental and Theoretical Approach.

The present work studies the adsorption of CO2 using a zeolitic industrial molecular sieve (IMS) with a high surface area. The effect of the CO2 feed concentration and the adsorption temperature in conjunction with multiple adsorption-desorption cycles was experimentally investigated. To assess the validity of the experimental results, theoretical calculations based on well-established equations were employed and the values of equilibrium, kinetic, and thermodynamic parameters are presented. Three additional column kinetic models were applied to the data obtained experimentally, in order to predict the breakthrough curves and thus facilitate process design. Results showed a negative correlation between temperature and adsorption capacity, indicating that physical adsorption takes place. Theoretical calculations revealed that the Langmuir isotherm, the Bangham kinetic model (i.e., pore diffusion is the rate-determining step), and the Thomas and Yoon-Nelson models were suitable to describe the CO2 adsorption process by the IMS. The IMS adsorbent material maintained its high CO2 adsorption capacity (>200 mg g-1) after multiple adsorption-desorption cycles, showing excellent regenerability and requiring only a mild desorption treatment (200 °C for 15 min) for regeneration.

Targeted hydrolysis of native potato protein: A novel workflow for obtaining hydrolysates with improved interfacial properties

Peptides and protein hydrolysates are promising alternatives to substitute chemical additives as functional food ingredients. In this study, we present a novel workflow for producing a potato protein hydrolysate with improved emulsifying and foaming properties using quantitative proteomics and bioinformatic prediction to facilitate targeted hydrolysis design. Based on previous studies, we selected 15 potent emulsifier peptides derived from abundant potato proteins as targets. Through in silico analysis, we determined that from a range of industrial proteases (Neutrase (Neut), Alcalase (Alc), Flavourzyme (Flav) and Trypsin (Tryp)), Tryp was found more likely to release peptides resembling the targets. After applying all proteases individually, hydrolysates were assayed for in vitro emulsifying and foaming properties. No direct correlation between degree of hydrolysis and interfacial properties was found. Tryp (E/S = 3%) produced a hydrolysate (DH = 5.4%) with high aqueous solubility and the highest (P < 0.05) emulsifying and foaming abilities, validating the hypothesis. Using LC-MS/MS, we identified >10,000 peptides in each hydrolysate. Peptide mapping revealed that random overlapping with known peptide emulsifiers is not sufficient to quantitatively describe hydrolysate functionality. However, validated release of targeted peptides by 3% Tryp appears to increase surface activity of the hydrolysate. Our data also suggest that terminal hydrophobic anchor domains may be important for high interfacial partitioning and activity. While modest yields and residual unhydrolyzed protein indicate room for process improvement, this work shows that bioinformatics-guided and data-driven targeted hydrolysis is a promising, interdisciplinary approach to facilitate process design for production of functional hydrolysates from alternative protein sources.

Preliminary project design for insect production: part 5 – models and simulation of insect production – organism development

The issue dealt with here is the rearing of an organism from egg to larva to pupa as is commonly done with various mealworms and black soldier flies, while organism development is the principal subject of interest. In order to obtain a uniform product at harvest time, the population should be synchronised as much as possible and this means that variability in development in the population must be reduced to the greatest possible extent. Four main sources of variability in development were identified, two of them operational and two biological in nature. These are: (1) distribution of the initial ages of the eggs; (2) distribution of incubation temperatures of the organisms; (3) inherent variability in the development rate of individual organisms; and (4) distribution in temperature sensitivity of the organisms. The combined effects of the various sources of variability on production and productivity were examined by means of simulation. This kind of exercise is useful in a number of contexts: (a) during the very early stage of project planning, as part of preliminary project design, before any formal design work is started and well before any major financial commitments are made; (b) during trouble-shooting of a low-performing process in order to upgrade its product quality; (c) to develop specifications for egg age distribution, design specifications for incubation equipment, etc.; (d) to better understand what data are required about the organism of interest so as to facilitate process design; and (e) to set objectives for organism breeding efforts. Examples are presented of how variabilities in the various factors can combine to yield organism development distributions at harvest time and how understanding the interactions between factors can help in designing a better production process.

A perspective on gas-phase synthesis of nanomaterials: Process design, impact and outlook

For over a century, gas-phase (aerosol) technology has enabled manufacture of nanostructured commodities (i.e. carbon black, fumed oxides and metals) at high temperatures. As such this technology impacts consumer products like tires, paints, optical fibers, photocatalysts, pharmaceutics and microelectronics. Even though its early development was largely Edisonian, today is on a firm scientific basis through multiscale process design and sophisticated diagnostics. As a result, it’s attractive for its undisputable scale-up to tons/h and, most importantly, for its capacity to form novel materials with closely controlled size, morphology and composition that are inaccessible by solid state or wet chemistry processes. Coagulation, sintering and surface reactions largely determine material characteristics through the high temperature particle residence time, in sync with classical reaction engineering. The inevitable high particle concentrations during manufacturing lead to rapid attainment of asymptotic particle size distributions (self-preserving) and structures (fractal-like) following power laws for agglomerate, aggregate and primary particle sizes. As a result, particle dynamics are described by particle number, area and mass (volume) balances that can be readily interfaced with fluid mechanics without always involving cumbersome population balances. These facilitate process design and inspire research for the development of flexible processes (i.e. flame spray pyrolysis) for synthesis of unique particle compositions and morphologies that exhibit superior performance in catalysis, gas sensing and a spectrum of biomedical applications. Such advances motivate the development of new products that lead to creation of spinoffs blossoming in niche markets.

Thermochemical analysis of smelting of ferruginous manganese ore for silicomanganese production

Ferruginous manganese ores contain high concentrations of iron and having low Mn/Fe ratio and are not suitable to produce standard grade of silicomanganese. Thermochemical calculations based on available thermodynamics databases were used to understand the smelting behavior of the ore mix consisting of ferruginous manganese ore and slag from high carbon ferromanganese. A basicity map was constructed in terms of input burden material basicity B (= (CaO wt%+MgO wt%)/SiO2 wt%) and input R (= (CaO wt%+ MgO wt%)/Al2O3 wt%) value for estimating the optimum operating basicity window for low manganese and silicon partition ratio or high alloy recovery. Various experiments were conducted to check the maximum grade and recovery of the alloy based on the thermochemical equilibrium simulation study. The present study reveals usefulness of preliminary thermochemical calculations to facilitate process design and development of silicomanganese smelting using ore mix consisting of ferruginous manganese ore and slag from high carbon ferromanganese.

Material tracking in a continuous direct capsule-filling process via residence time distribution measurements

Continuous production of pharmaceuticals requires traceability from the raw material to the final dosage form. With that regard, understanding the residence time distribution (RTD) of the whole process and its unit operations is crucial. This work describes a structured approach to characterizing and modelling of RTDs in a continuous blender and a tamping pin capsule filling machine, including insights into data processing. The parametrized RTD models were interconnected to model a continuous direct capsule-filling process, showing the batch transition as well as the propagation of a 2 min feed disturbance throughout the process. Various control strategies were investigated in-silico, aiding in the selection of optimal material diversion point to minimize the material waste. Additionally, the RTD models can facilitate process design and optimization. In this work, adaptions to the capsule filling machine were made and their influence on the RTD was examined to achieve an optimal machine setup.

Mechanisms of inactivation of Candida humilis and Saccharomyces cerevisiae by pulsed electric fields

AimsThis study aimed to determine how electric field strength, pulse width and shape, and specific energy input relate to the effect of pulsed electric fields (PEF) on viability and membrane permeabilization in Candida humilis and Saccharomyces cerevisiae suspended in potassium phosphate buffer. Methods and resultsCells were treated with a micro-scale system with parallel plate electrodes. Propidium iodide was added before or after treatments to differentiate between reversible and irreversible membrane permeabilization. Treatments of C. humilis with 71kV/cm and 48kJ/kg reduced cell counts by 3.9±0.6 log (cfu/mL). Pulse shape or width had only a small influence on the treatment lethality. Variation of electric field strength (17–71kV/cm), pulse width (0.086–4μs), and specific energy input (8–46kJ/kg) demonstrated that specific energy input correlated to the membrane permeabilization (r2=0.84), while other parameters were uncorrelated. A minimum energy input of 3 and 12kJ/kg was required to achieve reversible membrane permeabilization and a reduction of cell counts, respectively, of C. humilis. ConclusionsEnergy input was the parameter that best described the inactivation efficiency of PEF. Significance and impact of studyThis study is an important step to identify key process parameters and to facilitate process design for improved cost-effectiveness of commercial PEF treatment.

A modeling framework for manufacturing services in Service-oriented Holonic Manufacturing Systems

Holonic and Service-Oriented Architectures have been proposed as solutions for the conception of flexible and reactive systems. The combination of both architectures has been recognized as an attractive solution for the conception of more flexible and reactive systems. Services, originally conceived for web applications, need new models that better adapt to the needs of manufacturing systems namely, the specification and planning of processes. This paper proposes a methodology for designing customizable product-process specifications based on manufacturing-services that are suitable for product driven applications. A framework is proposed for modeling manufacturing-services designed for its application in Holonic Manufacturing Systems, preserving the fractal character found in products and processes. Three types of manufacturing processes are identified based on the relations among its composing operations and a model is proposed for each type. Application service-ontologies are created to describe operations and resource capabilities rather than complex semantic descriptions to facilitate process design and reduce the computational load of service discovery for planning. The framework leverages service reusability among process families in the same way as physical features are reused among product families. An illustrative example describes the design of a product's process specification based on the manufacturing service framework in a Holonic Manufacturing System, giving rise to Service-oriented Holonic Manufacturing Systems.

Surface Energetics of Protein Adsorption on to Chromatographic Supports

Protein separation behavior during adsorption chromatography is governed by system thermodynamics and kinetic factors. Hydrophobic interaction chromatography (HIC) is widely utilized since many important biological products present a quite hydrophobic character. In this work, the interaction between a set of model proteins (n = 9) and a commercial adsorbent (Phenyl Sepharose FF, high substitution, GE Healthcare) was studied via extended DLVO (XDLVO) calculations. Psychochemical properties of both separand and adsorbent were gathered by contact angle determination and zeta potential measurements. Proteins were subjected to the mentioned measurements in the hydrated and the dehydrated state, so as to simulate protein properties in a low vs. high salt concentration milieu, respectively. In HIC, protein adsorption usually take place at high concentrations of ammonium sulphate (up to 1.7M) and protein desorption occurs by decreasing salt concentration in the mobile phase. The mentioned XDLVO approach allowed the calculation of the free energy of interaction vs. distance profiles between the interacting surfaces, in the aqueous environment provided by the operating mobile phase. XDLVO calculations were correlated with the actual chromatography behavior of the studied model proteins. This correlation revealed that these proteins can be segregated in two main groups, according to surface energy calculations and elution position during chromatography: i) strong binding showing a deeper secondary minimum energy >|0.20| kT ii) and weak binding having a small secondary minimum energy <|0.12| kT, thus calculations were able to predict early or late elution from a gradient chromatography experiment; the more the calculated interaction energy, the stronger will be protein binding and the later will be the elution time. The knowledge generated from these studies will generate a better understanding of real downstream bioprocess behavior which could, in turn, facilitate process design and optimization.

Adsorption of amino acids on MFI-type zeolite: DFT calculations and experimental results

Adsorption is a common unit operation in separation and purification of biotechnological products where chromatography steps can make up more than half the amount of the total purification costs [1]. The molecular mechanisms of adsorption are still not understood in detail. Further understanding of interactions between adsorbent surfaces and adsorptives could help to facilitate process design in a more cost efficient manner. In this work the interaction of MFI-type zeolite MFI-27 (Al/Si=13) with Alanine and Phenylalanine is investigated by quantum chemical (QM) calculations which are compared to experimental adsorption data. For the QM calculations T3-clusters are used as MFI-27 surface models which were shown to be successful e.g. in the case of protolytic cracking of alkanes [2,3]. In order to model different pH-values Alanine and Phenylalanine are applied in their protonated, zwitterionic and deprotonated state. Geometry optimisations and frequency analysis of all molecular structures are performed with Density Functional Theory (DFT) using the B3LYP functional with different basis sets. Calculated complex energies are corrected for BSSE and ZPE. Adsorption isotherms are derived from corresponding experiments. Regarding the adsorption isotherms it is shown that a high adsorption of Alanine and Phenylalanine on MFI-27 takes place at low pH values (near the pKa of the amino acids). Less adsorption occurs with an increased pH equalling the amino acids’ isoelectric points. At the pH of the amico acids’ pKb values adsorption is no longer observed. These trends can be correlated with the corresponding QM calculations. High binding energies are calculated for the protonated amino acids. Zwitterionic states lead to lower binding energies. The deprotonated amino acids do not show any binding affinity to MFI-27. These first results indicate the reliability of the applied methods for our model system.

Sterilizing Filtration of Liposome and Related Lipid-Containing Solutions: Enhancing Successful Filter Qualification

Bacterial penetration of integral sterilizing-grade 0.2 μm rated filters, although rare, is not a new phenomenon in the biopharmaceutical industry. It is recognized by both the Parenteral Drug Association and the Food and Drug Administration via recommended bacterial retention qualification (also commonly called filter validation) performed in relevant product fluids or suitable surrogates when necessary (1-3). As noted in recent work, formulations such as some adjuvanted vaccines, liposome-based drug delivery solutions, and similar surfactant or emulsion-based product fluids increase the likelihood of such penetration events (4). Here we demonstrate that some 0.2 μm rated sterilizing-grade filters from different filter manufacturers may perform less effectively than expected when their membranes are challenged with one of these bacterial penetration risk-related solutions. Some filters provided very little sterility assurance (titer reductions < 6 logs) and others provided substantial sterility assurance (titer reduction > 8 log). From this, it is clear that the product formulation most likely to lead to filter penetration must be identified early in the design process to facilitate process design and minimize qualification costs. In this way, the solution can be matched with the appropriate sterilizing-grade filter and the appropriate process conditions. Bacterial penetration of intact sterilizing-grade filters during filter qualification, although rare, is not a new phenomenon in the biopharmaceutical industry. Because these incidences are identified in the filter validation process, there is no risk to the drug product end-user, but these failures do incur additional expense to the pharmaceutical manufacturer and could prevent the manufacture of very important drug formulations. Formulations such as some adjuvanted vaccines, liposome-based drug delivery solutions, and similar surfactant or emulsion-based product fluids have been documented to lead to an increased risk of penetration events. Here we demonstrate that some sterilizing-grade filters may perform differently from expected when their membranes are challenged with one of these solutions related to bacterial penetration risk. Some filters provided very little sterility assurance and others provided substantial sterility assurance. From this, it is clear that the pharmaceutical products and product formulation most likely to lead to filter penetration must be identified early in the design process to facilitate process design and minimize qualification costs. Moreover, that solution should be matched with the appropriate sterilizing-grade filter and process conditions to ensure expected sterility.

Flocculation of wall-deficient cells of Chlamydomonas reinhardtii mutant cw15 by calcium and methanol

Abstract Flocculation is a common and inexpensive method for harvesting algae from solution. After nitrogen starvation, it was shown that 83 ± 3% of the wall-deficient cells of the cw 15 mutant of Chlamydomonas reinhardtii flocculated from 12 mL samples within 15 min after the addition of 15 mM calcium chloride at pH 8.4. Only 24 ± 2% of the wildtype strain flocculated under these conditions, thus demonstrating how a simple mutation might facilitate process design. The data suggested that algae grown in waters with similar calcium concentrations (e.g. certain wastewaters) might be harvested through simple pH adjustment. It was also discovered that the addition of small amounts ( cw15 cells flocculated. Methanol is fully recoverable by distillation, and its use might enable flocculation without further water salinization when media calcium concentrations fall short of 15 mM. It was further shown that substrates for and/or products of cellular growth affected flocculation adversely. Nearly 81% of cells flocculated from fresh medium compared to only 54% in spent medium.

Developmental Engineering: A New Paradigm for the Design and Manufacturing of Cell-Based Products. Part II. From Genes to Networks: Tissue Engineering from the Viewpoint of Systems Biology and Network Science

The field of tissue engineering is moving toward a new concept of "in vitro biomimetics of in vivo tissue development." In Part I of this series, we proposed a theoretical framework integrating the concepts of developmental biology with those of process design to provide the rules for the design of biomimetic processes. We named this methodology "developmental engineering" to emphasize that it is not the tissue but the process of in vitro tissue development that has to be engineered. To formulate the process design rules in a rigorous way that will allow a computational design, we should refer to mathematical methods to model the biological process taking place in vitro. Tissue functions cannot be attributed to individual molecules but rather to complex interactions between the numerous components of a cell and interactions between cells in a tissue that form a network. For tissue engineering to advance to the level of a technologically driven discipline amenable to well-established principles of process engineering, a scientifically rigorous formulation is needed of the general design rules so that the behavior of networks of genes, proteins, or cells that govern the unfolding of developmental processes could be related to the design parameters. Now that sufficient experimental data exist to construct plausible mathematical models of many biological control circuits, explicit hypotheses can be evaluated using computational approaches to facilitate process design. Recent progress in systems biology has shown that the empirical concepts of developmental biology that we used in Part I to extract the rules of biomimetic process design can be expressed in rigorous mathematical terms. This allows the accurate characterization of manufacturing processes in tissue engineering as well as the properties of the artificial tissues themselves. In addition, network science has recently shown that the behavior of biological networks strongly depends on their topology and has developed the necessary concepts and methods to describe it, allowing therefore a deeper understanding of the behavior of networks during biomimetic processes. These advances thus open the door to a transition for tissue engineering from a substantially empirical endeavor to a technology-based discipline comparable to other branches of engineering.

Thermophilic ethanologenesis: future prospects for second-generation bioethanol production

Strategies for improving fermentative ethanol production have focused almost exclusively on the development of processes based on the utilization of the carbohydrate fraction of lignocellulosic material. These so-called 'second-generation' technologies require metabolically engineered production strains that possess a high degree of catabolic versatility and are homoethanologenic. It has been suggested that the production of ethanol at higher temperatures would facilitate process design, and as a result the engineered progeny of Geobacillus thermoglucosidasius, Thermoanerobacterium saccharolyticum and Thermoanerobacter mathranii now form the platform technology of several new biotechnology companies. This review highlights the milestones in the development of these production strains, with particular focus on the development of reliable methods for cell competency, gene deletion or upregulation.

Multiscale modelling of hydrothermal biomass pretreatment for chip size optimization

The objective of this work is to develop a relationship between biomass chip size and the energy requirement of hydrothermal pretreatment processes using a multiscale modelling approach. The severity factor or modified severity factor is currently used to characterize some hydrothermal pretreatment methods. Although these factors enable an easy comparison of experimental results to facilitate process design and operation, they are not representative of all the factors affecting the efficiency of pretreatment, because processes with the same temperature, residence time, and pH will not have same effect on biomass chips of different size. In our study, a model based on the diffusion of liquid or steam in the biomass that takes into account the interrelationship between chip size and time is developed. With the aid of our developed model, a method to find the optimum chip size that minimizes the energy requirement of grinding and pretreatment processes is proposed. We show that with the proposed optimization method, an average saving equivalent to a 5% improvement in the yield of biomass to ethanol conversion process can be achieved.

Process Modeling and Integration of The Salicide Process Module for Sub-Half Micron Technology.

AbstractMetal silicides have been used extensively in CMOS technology for reducing electrical resistance. As wafer-scale features have shrunk to the sub-half micron domain, obtaining a self-aligned silicide - or salicide - process that satisfies all requirements has become a significant challenge. One part of this challenge lies in developing the necessary scientific insights and technological innovations for the actual salicide process, while the other part lies in building a complete salicide process module which meets requirements of performance, reliability, ease of integration, control, etc. at the least possible cost and cycle-time for technology development. This second part is seldom addressed by researchers, and yet, is fundamentally important for successful application of any salicide technology to actual integrated circuit products. This paper presents a complete picture of the salicide module in the context of all the aforesaid components; and describes the use of abstraction and hierarchical models to capture process information and to facilitate process design. Prototype compact models for key wafer-state and performance outputs such as TiSi2 thickness and resistance are presented to demonstrate implementation of this process module.

Equilibrium pressure of CO2 over aqueous alkanolamine solutions: A practical view

Abstract A practical view of the equilibrium partial pressure of CO 2 over aqueous alkanolamine is presented here to facilitate process design. The entire equilibrium is divided into two parts, namely first equilibrium and final equilibrium. The non-ideality of the amine solutions used in industrial practice could be accounted for by using final equilibrium data available or generated. The same factor can be used to predict the equilibrium partial pressure of CO 2 for a real situation using the ‘first equilibrium concept’. The expressions developed are very simple and can be handled easily on a programmable calculator. The method is illustrated with the help of published data.