Integration Of Unit Operations Research Articles

Small-Scale Solids Production Plant with Cooling Crystallization, Washing, and Drying in a Modular, Continuous Plant

Small-scale continuous apparatuses for solid product manufacturing are receiving increasing interest due to the demand for the fast market availability of specialty chemical products manufactured in integrated and modular processing plants. Relevant unit operations span from crystallization over solid–liquid separation and filter cake washing to drying. For this purpose, the quasi-continuous filter belt crystallizer (QCFBC) was developed and is presented here. The newly integrated unit operations with positive pressure filtration (Δpmax = 0.8 bar), filter cake washing (V˙wash = 55 mL·min−1), and convection drying (Tdry = 60 °C) have been individually characterized and integrated into the filter apparatus that has been modified for continuous operation. They were synchronized with the flexible cooling crystallization, enabling for a seamless production process. Sucrose in water was used as model substance system. Long-term operations of up to 14 h were successfully performed with dry product filter cakes (22.64 g ± 1.64 g·h−1) of constant quality attributes (x50,3 = 216.095 ± 14.766, span = 0.347 ± 0.109, Yrel. = 69.9% ± 5%, XRM = 1.64 mg·g−1 ± 1.38 mg·g−1).

Continuous electrocoagulation-membrane distillation unit for treating hydraulic fracturing produced water

Hydraulic fracturing oil and gas produced water is frequently highly impaired. While it is often deep well injected, there is great interest in treating this water for beneficial uses. Given the complexity of these produced waters, multiple unit operations are necessary. Electrocoagulation has been considered as a promising pretreatment technology. Here electrocoagulation is considered as a pretreatment prior to membrane distillation. The focus of this work is on understanding the electrocoagulation process in order to design an integrated unit operation. Electrocoagulation is used to remove organic compounds that will foul the membrane leading to membrane failure during membrane distillation. Using aluminum or iron electrodes, half-cell reactions in the electrocoagulation cell and electrode potentials have been calculated. Electrocoagulation was conducted using a continuous electrocoagulation reactor with actual produced water using aluminum, iron or mixed aluminum and iron electrodes. The results obtained here indicate that electrocoagulation can obtain good removal efficiency of total organic carbon (TOC) by using different reaction conditions. Removal of organic compounds is essential to minimize fouling during membrane distillation. Further the performance of the electrocoagulation process depends strongly on the quality of the feed water. Insoluble species were more effectively coagulated than dissolved organic species. Continuous electrocoagulation shows great potential as a scalable unit operation for pretreating hydraulic fracturing produced water.

Extraction techniques in food industry: Insights into process parameters and their optimization

This review presents critical evaluation of the key parameters that affect the extraction of targeted components, giving due consideration to safety and environmental aspects. The crucial aspects of the extraction technologies along with protocols and process parameters for designing unit operations have been emphasized. The parameters like solvent usage, substrate type, concentration, particle size, temperature, quality and storage of extract as well as stability of extraction have been elaborately discussed. The process optimization using mathematical and computational modeling highlighting information and communication technologies have been given importance aiming for a green and sustainable industry level scaleup. The findings indicate that the extraction processes vary significantly depending on the category of food and its structure. There is no single extraction method or universal set of process conditions identified for extracting all value-added products from respective sources. A comprehensive understanding of process parameters and their optimization as well as synergistic combination of multiple extraction processes can aid in enhancement of the overall extraction efficiency. Future efforts must be directed toward the design of integrated unit operations that cause minimal harm to the environment along with investigations on economic feasibility to ensure sustainable extraction systems.

Complete Cocrystal Formation during Resonant Acoustic Wet Granulation: Effect of Granulation Liquids.

The manufacturing of solid pharmaceutical dosage forms composed of cocrystals requires numerous processes during which there is risk of dissociation into parent molecules. Resonant acoustic wet granulation (RAG) was devised in an effort to complete theophylline–citric acid (THPCIT) cocrystal formation during the granulation process, thereby reducing the number of operations. In addition, the influence of granulation liquid was investigated. A mixture of anhydrous THP (drug), anhydrous CIT (coformer), and hydroxypropyl cellulose (granulating agent) was processed by RAG with water or ethanol as a granulation liquid. The purposes were to (i) form granules using RAG as a breakthrough method; (ii) accomplish the cocrystallization during the integrated unit operation; and (iii) characterize the final solid product (i.e., tablet). The RAG procedure achieved complete cocrystal formation (>99%) and adequately sized granules (d50: >250 μm). The granulation using water (GW) facilitated formation of cocrystal hydrate which were then transformed into anhydrous cocrystal after drying, while the granulation using ethanol (GE) resulted in the formation of anhydrous cocrystal before and after drying. The dissolution of the highly dense GW tablet, which was compressed from granules including fine powder due to the dehydration, was slower than that of the GE tablet.

Genetic Cell-Surface Modification for Optimized Foam Fractionation.

Rhamnolipids are among the glycolipids that have been investigated intensively in the last decades, mostly produced by the facultative pathogen Pseudomonas aeruginosa using plant oils as carbon source and antifoam agent. Simplification of downstream processing is envisaged using hydrophilic carbon sources, such as glucose, employing recombinant non-pathogenic Pseudomonas putida KT2440 for rhamnolipid or 3-(3-hydroxyalkanoyloxy)alkanoic acid (HAA, i.e., rhamnolipid precursors) production. However, during scale-up of the cultivation from shake flask to bioreactor, excessive foam formation hinders the use of standard fermentation protocols. In this study, the foam was guided from the reactor to a foam fractionation column to separate biosurfactants from medium and bacterial cells. Applying this integrated unit operation, the space-time yield (STY) for rhamnolipid synthesis could be increased by a factor of 2.8 (STY = 0.17 gRL/L·h) compared to the production in shake flasks. The accumulation of bacteria at the gas-liquid interface of the foam resulted in removal of whole-cell biocatalyst from the reactor with the strong consequence of reduced rhamnolipid production. To diminish the accumulation of bacteria at the gas-liquid interface, we deleted genes encoding cell-surface structures, focusing on hydrophobic proteins present on P. putida KT2440. Strains lacking, e.g., the flagellum, fimbriae, exopolysaccharides, and specific surface proteins, were tested for cell surface hydrophobicity and foam adsorption. Without flagellum or the large adhesion protein F (LapF), foam enrichment of these modified P. putida KT2440 was reduced by 23 and 51%, respectively. In a bioreactor cultivation of the non-motile strain with integrated rhamnolipid production genes, biomass enrichment in the foam was reduced by 46% compared to the reference strain. The intensification of rhamnolipid production from hydrophilic carbon sources presented here is an example for integrated strain and process engineering. This approach will become routine in the development of whole-cell catalysts for the envisaged bioeconomy. The results are discussed in the context of the importance of interacting strain and process engineering early in the development of bioprocesses.

Techniques of lipid extraction from microalgae for biofuel production: a review

Microalgae are feedstocks for production of carbon-neutral biofuels. Efforts have been performed to market microalgae biofuels, yet the production of microalgae biofuel remains a challenge due to the high production cost and low product yield. In particular, lipid extraction is a critical step to be optimized. Here, we review lipid extraction technologies and cell lysis strategies. Extraction techniques involve solvents such as organic solvents, supercritical fluids, ionic liquids, deep eutectic solvents and switchable solvents. Advantages and shortcomings of solvents are discussed. Besides, strategies have been designed to reduce power costs by integration of unit operations in downstream processing. We present single-step processes for simultaneous cell lysis and lipid extraction, such as ultrasound-, microwave-, bead-beating-, surfactant- and pulsed electric field-assisted extractions. The lipid extraction yield is enhanced by incorporating cell disruption into the lipid extraction process.

Process intensification of Three Phase Partition for extraction of custard apple seed oil using Microwave Pretreatment

The application of microwave was observed to be an emerging intensification tool in the field of extraction. A recent study in extraction revels the rising prospectus of the microwave as an integrated unit operation with Three Phase Partitioning (TPP). This work aims to determine the best mode of microwave application for TPP assisted extraction of oil from custard apple seeds, which has significant industrial potential as a biopesticide. A maximum oil extraction yield of 33.23 (w/w) % was obtained by opting microwave pre-treatment assisted Three Pase partitioning (MPTPP) with 120 W applied power for 60 s as optimized parameters. Parameters affecting TPP, such as salt concentration, aqueous to t-butanol ratio, and slurry to t-butanol ratio, were also optimized as 45% (w/v), 1:2 (v/v) and 1:10 respectively. Also, MPTPP was observed to extract 18.46 (w/w) % of protein along with the maximum oil extraction. In MPTPP, the yield of oil was improved by 1.13-fold than the conventional method, and the process time was reduced by 2.5 times than TPP.

Design of condition-based maintenance framework for process operations management in pharmaceutical continuous manufacturing.

Continuous manufacturing, an emerging technology in the pharmaceutical industry, has the potential to increase the efficiency, and agility of pharmaceutical manufacturing processes. To realize these potential benefits of continuous operations, effectively managing materials, equipment, analyzers, and data is vital. Developments for continuous pharmaceutical manufacturing have led to novel technologies and methods for processing material, designing and configuring individual equipment and process analyzers, as well as implementing strategies for active process control. However, limited work has been reported on managing abnormal conditions during operations to prevent unplanned deviations and downtime and sustain system capabilities. Moreover, although the sourcing, analysis, and management of real-time data have received growing attention, limited discussion exists on the continued verification of the infrastructure for ensuring reliable operations. Hence, this work introduces condition-based maintenance (CBM) as a general strategy for continually verifying and sustaining advanced pharmaceutical manufacturing systems, with a focus on the continuous manufacture of oral solid drug products (OSD-CM). Frameworks, such as CBM, benefit unified efforts towards continued verification and operational excellence by leveraging process knowledge and the availability of real-time data. A vital implementation consideration for manufacturing operations management applications, such as CBM, is a systems architecture and an enabling infrastructure. This work outlines the systems architecture design for CBM in OSD-CM and highlights sample fault scenarios involving equipment and process analyzers. For illustrative purposes, this work also describes the infrastructure implemented on an OSD-CM testbed, which uses commercially available automation systems and leverages enterprise architecture standards. With the increasing digitalization of manufacturing operations in the pharmaceutical industry, proactively using process data towards modernizing maintenance practices is relevant to a single unit operation as well as to a series of physically integrated unit operations.

Self-sustainable azolla-biorefinery platform for valorization of biobased products with circular-cascading design

As the circular bioeconomy is gaining momentum around the globe, biorefinery will play a key role in the framework of sustainability as integral component. A self-sustainable biorefinery model using azolla cultivation was designed at the focal point of a circular loop. This model is aimed to enable a cascading valorization of bio-based products through a series of sequentially integrated biological/thermal unit operations. Azolla pinnata with an inherent ability to sequester CO2 along with simultaneous nitrogen fixation capability will serves as a potential and renewable carbon resource (feedstock) for the integrated unit operations viz., acidogenesis, photosynthesis, hydrolysis, and pyrolysis. The cascading loop is initiated by acidogenesis of spent wash (distillery wastewater-DSW) in a semi pilot scale bioreactor for the production of biohydrogen and volatile fatty acids (VFA). Treated spent wash after acidogenesis (TSW) was used as feed for Azolla pinnata cultivation, which eventually depicted good COD and nitrates removal efficiency. Harvested A. pinnata biomass (AB) showed presence of good amount of carbohydrates (237 mg/g) and proteins (160 mg/g) along with 11% of lipids (composed of 22% omega fatty acids) thus making it a good nutritional feed for livestock. AB after lipid extraction was subjected to mild acid-hydrolysis and the hydrolysate was used as substrate for acidogenesis to facilitate circular/closed loop operation. The techno-economics of biorefinery process evaluated using SuperPro Designer software depicted the feasibility of the integrated strategy. This study extends the scope of biobased platform with self-sustainability as core objective.

Upgrading of Postconsumer Absorbent Hygiene Products for Bioethanol Production

Postconsumer absorbent hygiene products (AHPs), one of the most intractable municipal solid waste (MSW) streams, are generally subjected to landfills, causing urban waste management difficulties and environmental pollution. This study investigated the viability of recycling the cellulose component from postconsumer AHPs, demonstrated the fermentability of obtained cellulosic sugars for bioethanol production, and evaluated the technical feasibility of the process through scale-up. A set of integrated unit operations was developed to effectively upcycle the recovered AHPs into bioproducts. The processes were further optimized and scaled up 50-fold. Up to 83.5% glucose and 46.0% xylose yields were achieved during enzymatic saccharification. The sugars were readily fermentable through separate hydrolysis and fermentation (SHF) as well as simultaneous saccharification and fermentation (SSF) with maximum 89.9% ethanol theoretical yield.

Design and control of integrated chromatography column sequences.

To increase the productivity in biopharmaceutical production, a natural step is to introduce integrated continuous biomanufacturing which leads to fewer buffer and storage tanks, smaller sizes of integrated unit operations, and full automation of the operation. The main contribution of this work is to illustrate a methodology for design and control of a downstream process based on integrated column sequences. For small scale production, for example, pre-clinical studies, integrated column sequences can be implemented on a single chromatography system. This makes for a very efficient drug development platform. The proposed methodology is composed of four steps and is governed by a set of tools, that is presented, that makes the transition from batch separations to a complete integrated separation sequence as easy as possible. This methodology, its associated tools and the physical implementation is presented and illustrated on a case study where the target protein is separated from impurities through an integrated four column sequence. This article shows that the design and control of an integrated column sequence was successfully implemented for a tertiary protein separation problem. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:923-930, 2017.

Progress in thermochemical hydrogen production with the copper–chlorine cycle

Recent advances are reported by an international team on research and development of the copper chlorine (Cu–Cl) cycle for thermochemical hydrogen production. New experimental and numerical results are given for several processes of the cycle. Experimental results for CuCl/HCl electrolysis and integration of unit operations in the Cu–Cl cycle are presented. A new solubility model for the CuCl–CuCl2–HCl–H2O quaternary system is presented, which optimizes the cupric chloride selective precipitation prior to the hydrolysis reactor. Also, recent progress on photo-electrochemical cell development for enhancement of the electrolysis process is reported along with its integration with a concentrated solar radiation system.

Sequential/parallel production of potential Malaria vaccines – A direct way from single batch to quasi-continuous integrated production

An intensification of pharmaceutical protein production processes can be achieved by the integration of unit operations and application of recurring sequences of all biochemical process steps. Within optimization procedures each individual step as well as the overall process has to be in the focus of scientific interest. This paper includes a description of the development of a fully automated production plant, starting with a two step upstream followed by a four step downstream line, including cell clarification, broth cleaning with microfiltration, product concentration with ultrafiltration and purification with column chromatography. Recursive production strategies are developed where a cell breeding, the protein production and the whole downstream is operated in series but also in parallel, each main operation shifted by one day. The quality and reproducibility of the recursive protein expression is monitored on-line by Golden Batch and this is controlled by Model Predictive Multivariate Control (MPMC). As a demonstration process the production of potential Malaria vaccines with Pichia pastoris is under investigation.

A Hybrid MPC-PID Control System Design for the Continuous Purification and Processing of Active Pharmaceutical Ingredients

In this work, a hybrid MPC (model predictive control)-PID (proportional-integral-derivative) control system has been designed for the continuous purification and processing framework of active pharmaceutical ingredients (APIs). The specific unit operations associated with the purification and processing of API have been developed from first-principles and connected in a continuous framework in the form of a flowsheet model. These integrated unit operations are highly interactive along with the presence of process delays. Therefore, a hybrid MPC-PID is a promising alternative to achieve the desired control loop performance as mandated by the regulatory authorities. The integrated flowsheet model has been simulated in gPROMSTM (Process System Enterprise, London, UK). This flowsheet model has been linearized in order to design the control scheme. The ability to track the set point and reject disturbances has been evaluated. A comparative study between the performance of the hybrid MPC-PID and a PID-only control scheme has been presented. The results show that an enhanced control loop performance can be obtained under the hybrid control scheme and demonstrate that such a scheme has high potential in improving the efficiency of pharmaceutical manufacturing operations.

A water–water preheater and a steam–water heater network: Temperature dynamics

The dynamic simulation of an integrated, double pipe heat exchanger network was validated through experimentation. A steam–water, concentric tube, heat exchanger was coupled to a water–water preheater. When the preheater was configured for cocurrent flow with equal fluid velocities in its annulus and core, Lagrangian-based derivations yielded analytical solutions that accurately predicted observed temperature dynamics. When the preheater was configured for countercurrent flow with distinct fluid velocities in its annulus and core, analytical solutions for the heater and connecting tubing were coupled with Eulerian based numerical solutions for the preheater. Programming used Mathcad. Nonlinear regression analysis of steady state data was used to determine system parameters. The significance of time delays through the integration of unit operations is illustrated.

Cereal‐based biorefinery development: Integrated enzyme production for cereal flour hydrolysis

Restructuring the traditional fermentation industry into viable biorefineries for the production of fuels, chemicals and plastics is essential in order to replace (petro)chemical processing. This work presents engineering aspects of Aspergillus awamori submerged fermentation for on-site production of an enzymatic consortium that contains glucoamylase, protease and phosphatase. The crude broth filtrate was used for the production of wheat flour hydrolysates. Improvements on traditional starch hydrolysis carried out in two stages (liquefaction and saccharification) were attempted through integration of unit operations and reduction of processing temperature and reaction duration. An initial increase of temperature to 68 degrees C and a subsequent decrease to 60 degrees C for the rest of the enzymatic hydrolysis resulted in a starch to glucose conversion yield of 94 and 92% when a wheat flour concentration and commercial starch concentration of 225 g L(-1) was used, respectively. The use of crude broth filtrates resulted in the simultaneous hydrolysis of wheat protein and phytic acid, as was indicated by the increase in free amino nitrogen and phosphorus concentration, respectively.

Model predictive control of integrated unit operations: Control of a divided wall column

The integration of several unit operations into one common apparatus (process intensification) has the potential to substantially improve the economics of chemical processes if applied to adequate problems. On the other hand, the integration typically causes strong interactions of different process quantities and a loss in degrees of freedom. This may require a more elaborate automatic control scheme. In this study, the control of a divided wall column has been investigated in comparison to the control with a single loop PI controller concept. Although the PI controller concept can be implemented successfully, the model predictive controller shows a considerably improved control behaviour in respect to maximum deviations of the controlled variables and the time to reach steady state.

Purification of plasmid DNA by an integrated operation comprising tangential flow filtration and nitrocellulose adsorption.

There is an increasing interest in the development of scaleable and reproducible plasmid DNA purification protocols for vaccine and gene therapy. The use of an integrated unit operation, comprising tangential flow microfiltration coupled with the adsorption of contaminants onto nitrocellulose membranes as a single processing step was examined in this work. Experiments were performed using a custom-built tangential flow microfiltration rig (membrane area=12.5 cm(2)). Tangential flow filtration-adsorption of E. coli lysates containing a plasmid product removed most solids (>75%) and decreased chromosomal DNA contamination by 75% w/w. Total plasmid DNA concentration and supercoiled content of the permeate were virtually identical to those of the feed, indicating a recovery yield of 100% (transmission equal to 1). Results were similar for E. coli lysates containing either a 6.9 kb or a 20 kb plasmid. Significant reductions in RNA, endotoxin, and protein levels were also observed. The reproducibility and potential for scale up of this integrated filtration-adsorption operation makes it at attractive option for intermediate- to large-scale pharmaceutical-grade plasmid processing.

Optimal operation processes of discrete-continuous biochemical processes

Biohemical processes and so-called hybrid biochemical processes, carried out in integrated unit operations such as membrane bioreactors, have found numerous applications in food and pharmaceutical process industries. However, such processes have hardly been investigated comprehensively. Dynamic modeling and especially dynamic optimization attempts were restricted because these unit operations combine continuous and discrete dynamic behavior and contain time and state events. In this paper we present a robust model of a process of high industrial significance, namely critic acid production in a membrane bioreactor, as well as a successful application of control parameterization numerical optimal control techniques to the fed-batch bioreactor, and a membrane bioreactor. In order to evaluate the advantages and disadvantages of the design alternatives, the incremental objective function between batch and fed-batch, batch and different operations in a membrane bioreactor was formulated in terms of profit maximization. The determination of the optimal performance for the fed-batch fermentor and membrane bioreactor requires the solution of multiple optimal control problems, namely determining optimal feed and inlet concentration profiles, initial conditions and a production time. We show how the systematic combination of rigorous mathematical modeling, the integration of design and operational decisions and innovative discrete-continuous dynamic optimization techniques allow the generation of optimal designs and operating policies for hybrid biochemical processes that increase the profit of important production processes such as citric acid production.

Combination and/or Integration of Unit Operations in Dry Municipal Waste Processes

Combination and/or Integration of Unit Operations in Dry Municipal Waste Processes