Cross-linked starch nanocapsules (NCs) were synthesized by interfacial polymerization carried out using the inverse mini-emulsion technique. 2,4-toluene diisocyanate (TDI) was used as the cross-linker. The influence of TDI concentrations on the polymeric shell, particle size, and encapsulation efficiency of a hydrophilic dye, sulforhodamine 101 (SR 101), was investigated by Fourier transform infrared (FT-IR) spectroscopy, dynamic light scattering (DLS), and fluorescence measurements, respectively. The final NC morphology was confirmed by scanning electron microscopy. The leakage of SR 101 through the shell of NCs was monitored at 37 °C for seven days, and afterwards the NCs were redispersed in water. Depending on cross-linker content, permeable and impermeable NCs shell could be designed. Enzyme-triggered release of SR 101 through impermeable NC shells was investigated using UV spectroscopy with different α-amylase concentrations. Impermeable NCs shell were able to release their cargo... [more]

Water-soluble polymers with high molecular weights are known to decrease the frictional drag in turbulent flow very effectively at concentrations of tens or hundreds of ppm. This drag reduction efficiency of water-soluble polymers is well known to be closely associated with the flow conditions and rheological, physical, and/or chemical characteristics of the polymers added. Among the many promising polymers introduced in the past several decades, this review focuses on recent progress in the drag reduction capability of various water-soluble macromolecules in turbulent flow including both synthetic and natural polymers such as poly(ethylene oxide), poly(acrylic acid), polyacrylamide, poly(N-vinyl formamide), gums, and DNA. The polymeric species, experimental parameters, and numerical analysis of these water-soluble polymers in turbulent drag reduction are highlighted, along with several existing and potential applications. The proposed drag reduction mechanisms are also discussed based... [more]

Water-soluble, carboxylic acid monomers are known to exhibit peculiar kinetics when polymerized in aqueous solution. Namely, their free-radical polymerization rate is affected by several parameters such as monomer concentration, ionic strength, and pH. Focusing on methacrylic acid (MAA), even though this monomer has been largely addressed, a systematic investigation of the effects of the above-mentioned parameters on its polymerization rate is missing, in particular in the fully ionized case. In this work, the kinetics of non-ionized and fully ionized MAA are characterized by in-situ nuclear magnetic resonance (NMR). Such accurate monitoring of the reaction rate enables the identification of relevant but substantially different effects of the monomer and electrolyte concentration on polymerization rate in the two ionization cases. For non-ionized MAA, the development of a kinetic model based on literature rate coefficients allows us to nicely simulate the experimental data of conversio... [more]

A discrete element model (DEM) has been developed for an industrial batch bin blender in which three different types of materials are mixed. The mixing dynamics have been evaluated from a model-based study with respect to the blend critical quality attributes (CQAs) which are relative standard deviation (RSD) and segregation intensity. In the actual industrial setup, a sensor mounted on the blender lid is used to determine the blend composition in this region. A model-based analysis has been used to understand the mixing efficiency in the other zones inside the blender and to determine if the data obtained near the blender-lid region are able to provide a good representation of the overall blend quality. Sub-optimal mixing zones have been identified and other potential sampling locations have been investigated in order to obtain a good approximation of the blend variability. The model has been used to study how the mixing efficiency can be improved by varying the key processing paramet... [more]

Hydrogels based on poly(2-hydroxyethyl methacrylate) (PHEMA) are a very important class of biomaterials with several applications mainly in tissue engineering and contacts lenses. Although the polymerization kinetics of HEMA have been investigated in the literature, the development of a model, accounting for both the chemical reaction mechanism and diffusion-controlled phenomena and valid over the whole conversion range, has not appeared so far. Moreover, research on the synthesis of nanocomposite materials based on a polymer matrix has grown rapidly recently because of the improved mechanical, thermal and physical properties provided by the polymer. In this framework, the objective of this research is two-fold: to provide a kinetic model for the polymerization of HEMA with accurate estimations of the kinetic and diffusional parameters employed and to investigate the effect of adding various types and amounts of nano-additives to the polymerization rate. In the first part, experimental... [more]

An in situ nuclear magnetic resonance spectroscopy (NMR) technique is used to monitor the aqueous-phase copolymerization kinetics of methacrylic acid (MAA) and poly(ethylene glycol) methyl ether methacrylate (PEGMA) macromonomers. In particular, the study analyses the effect of the number of ethylene glycol (EG) groups along the lateral chains of PEGMA and is carried out under fully ionized conditions of MAA at different initial monomer ratios and initial overall monomer concentrations (5⁻20 wt % in aqueous solution). The composition drift with conversion indicates that PEGMA macromonomer is more reactive than MAA. Individual monomer consumption rates show that the rates of consumption of both monomers are not first order with respect to overall concentration of the monomer. The reactivity ratios estimated from the copolymerization kinetics reveal, that for the short PEGMA, the reactivity ratios rMAA and rPEGMA increase with the solids content (SC). A totally different trend is obtaine... [more]

While many perceive mammalian cell culture-based manufacturing for biopharmaceuticals an established technology, numerous open questions remain to be solved. Genetic diversity and mutation rates in CHO cells have been underestimated since progeny of a clonal CHO cell become genetically diverse with each cell division. This is an important issue since products are made in bioreactors containing up to 1014 cells that have divided for weeks. Regulatory interest in “Proof of Clonality” is a misguided and misunderstood concern in this context. We revisit decades of research on scope and rate of genetic changes in CHO cells and suggest approaches to minimize trends for genomic instability when establishing reliable manufacturing processes. A concept is proposed for transfection-derived cell populations containing relatively stable (The term “stable” will always be used in a context of relative stability—considering time frames of weeks to months at best.) “CHO master sequence” genomes (conta... [more]

A series of PDLLA-PEG1k-PDLLA tri-block co-polymers with various compositions, i.e., containing 2⁻10 lactoyl units, were prepared via ring opening polymerisation of d,l-lactide in the presence of poly (ethylene glycol) (PEG) (Mn = 1000 g·mol−1) as the initiator and stannous 2-ethylhexanoate as the catalyst at different feed ratios. PDLLA-PEG1k-PDLLA co-polymers were then functionalised with acrylate groups using acryloyl chloride under various reaction conditions. The diacrylated PDLLA-PEG1k-PDLLA (diacryl-PDLLA-PEG1k-PDLLA) were further polymerised to synthesize soluble hyperbranched polymers by either homo-polymerisation or co-polymerisation with poly(ethylene glycol) methyl ether methylacrylate (PEGMEMA) via free radical polymerisation. The polymer samples obtained were characterised by ¹H NMR (proton Nuclear Magnetic Resonance), FTIR (Fourier Transform Infra-red spectroscopy), and GPC (Gel Permeation Chromatography). Moreover, the diacryl-PDLLA-PEG1k-PDLLA macromers were used for t... [more]

A new Automatic Continuous Online Monitoring of Polymerization reactions (ACOMP) system has been developed with multiple light scattering and viscosity detection stages in serial flow, where solution conditions are different at each stage. Solution conditions can include ionic strength (IS), pH, surfactants, concentration, and other factors. This allows behavior of a polymer under simultaneous, varying solution conditions to be monitored at each instant of its synthesis. The system can potentially be used for realtime formulation, where a solution formulation is built up additively in successive stages. It can also monitor the effect of solution conditions on stimuli responsive polymers, as their responsiveness changes during synthesis. In this first work, the new ACOMP system monitored light scattering and reduced viscosity properties of copolymeric polyelectrolytes under various IS during synthesis. Aqueous copolymerization of acrylamide (Am) and styrene sulfonate (SS) was used. Poly... [more]

The realization of physiologically-relevant advanced in vitro models is not just related to the reproduction of a three-dimensional multicellular architecture, but also to the maintenance of a cell culture environment in which parameters, such as temperature, pH, and hydrostatic pressure are finely controlled. Tunable and reproducible culture conditions are crucial for the study of environment-sensitive cells, and can also be used for mimicking pathophysiological conditions related with alterations of temperature, pressure and pH. Here, we present the SUITE (Supervising Unit for In Vitro Testing) system, a platform able to monitor and adjust local environmental variables in dynamic cell culture experiments. The physical core of the control system is a mixing chamber, which can be connected to different bioreactors and acts as a media reservoir equipped with a pH meter and pressure sensors. The chamber is heated by external resistive elements and the temperature is controlled using a th... [more]

Background: Magnetic fields can interact with liquid matter in a homogeneous and instantaneous way, without physical contact, independently of its temperature, pressure, and agitation degree, and without modifying recipes nor heat and mass transfer conditions. In addition, magnetic fields may affect the mechanisms of generation and termination of free radicals. This paper is devoted to the elucidation of the appropriate conditions needed to develop magnetic field effects for controlling the kinetics of polymerization of water soluble monomers. Methods: Thermal- and photochemically-initiated polymerizations were investigated at different initiator and monomer concentrations, temperatures, viscosities, and magnetic field intensities. Results: Significant magnetic field impact on the polymerization kinetics was only observed in photochemically-initiated polymerizations carried out in viscous media and performed at relatively low magnetic field intensity. Magnetic field effects were absent... [more]

Electrical stimulation is ubiquitous as a method for activating neuronal tissue, but there is still significant room for advancement in the ability of these electrical devices to implement smart stimulus waveform design to more selectively target populations of neurons. The capability of a device to encode more complicated and precise messages to a neuronal network greatly increases if the stimulus input space is broadened to include variable shaped waveforms and multiple stimulating electrodes. The relationship between a stimulating electrode and the activated population is unknown; a priori. For that reason, the population of excitable neurons must be characterized in real-time and for every combination of stimulating electrodes and neuronal populations. Our automated experimental system allows investigation into the stimulus-evoked neuronal response to a current pulse using dissociated neuronal cultures grown atop microelectrode arrays (MEAs). The studies presented here demonstrate... [more]

The gut microbiome is a highly complex microbial community that strongly impacts human health and disease. The two dominant phyla in healthy humans are Bacteroidetes and Firmicutes, with minor phyla such as Proteobacteria having elevated abundances in various disease states. While the gut microbiome has been widely studied, relatively little is known about the role of interspecies interactions in promoting microbiome stability and function. We developed a biofilm metabolic model of a very simple gut microbiome community consisting of a representative bacteroidete (Bacteroides thetaiotaomicron), firmicute (Faecalibacterium prausnitzii) and proteobacterium (Escherichia coli) to investigate the putative role of metabolic byproduct cross feeding between species on community stability, robustness and flexibility. The model predicted coexistence of the three species only if four essential cross-feeding relationships were present. We found that cross feeding allowed coexistence to be robustly... [more]

As the demand for textile products and synthetic dyes increases with the growing global population, textile dye wastewater is becoming one of the most significant water pollution contributors. Azo dyes represent 70% of dyes used worldwide, and are hence a significant contributor to textile waste. In this work, the removal of a reactive azo dye (Reactive Orange 16) from water by adsorption with chitosan grafted poly(poly(ethylene glycol) methyl ether methacrylate) (CTS-GMA-g-PPEGMA) was investigated. The chitosan (CTS) was first functionalized with glycidyl methacrylate and then grafted with poly(poly(ethylene glycol) methyl ether methacrylate) using a nitroxide-mediated polymerization grafting to approach. Equilibrium adsorption experiments were carried out at different initial dye concentrations and were successfully fitted to the Langmuir and Freundlich adsorption isotherm models. Adsorption isotherms showed maximum adsorption capacities of CTS-g-GMA-PPEGMA and chitosan of 200 mg/g a... [more]

The process of oxygenic photosynthesis is robust and ubiquitous, relying centrally on input of light, carbon dioxide, and water, which in many environments are all abundantly available, and from which are produced, principally, oxygen and reduced organic carbon. However, photosynthetic machinery can be conflicted by the simultaneous presence of carbon dioxide and oxygen through a process sometimes called photorespiration. We present here a model of phototrophy, including competition for RuBisCO binding sites between oxygen and carbon dioxide, in a chemostat-based microbial population. The model connects to the idea of metabolic pathways to track carbon and degree of reduction through the system. We find decomposition of kinetics into elementary flux modes a mathematically natural way to study synchronization of mismatched rates of photon input and chemostat turnover. In the single species case, though total biomass is reduced by photorespiration, protection from excess light exposures... [more]

Nonlinear model predictive control has been established as a powerful methodology to provide feedback for dynamic processes over the last decades. In practice it is usually combined with parameter and state estimation techniques, which allows to cope with uncertainty on many levels. To reduce the uncertainty it has also been suggested to include optimal experimental design into the sequential process of estimation and control calculation. Most of the focus so far was on dual control approaches, i.e., on using the controls to simultaneously excite the system dynamics (learning) as well as minimizing a given objective (performing). We propose a new algorithm, which sequentially solves robust optimal control, optimal experimental design, state and parameter estimation problems. Thus, we decouple the control and the experimental design problems. This has the advantages that we can analyze the impact of measurement timing (sampling) independently, and is practically relevant for application... [more]

We present a sensitivity-based predictor-corrector path-following algorithm for fast nonlinear model predictive control (NMPC) and demonstrate it on a large case study with an economic cost function. The path-following method is applied within the advanced-step NMPC framework to obtain fast and accurate approximate solutions of the NMPC problem. In our approach, we solve a sequence of quadratic programs to trace the optimal NMPC solution along a parameter change. A distinguishing feature of the path-following algorithm in this paper is that the strongly-active inequality constraints are included as equality constraints in the quadratic programs, while the weakly-active constraints are left as inequalities. This leads to close tracking of the optimal solution. The approach is applied to an economic NMPC case study consisting of a process with a reactor, a distillation column and a recycler. We compare the path-following NMPC solution with an ideal NMPC solution, which is obtained by sol... [more]

The complete error-in-variables-model (EVM) framework, consisting of both design of experiments and parameter estimation stages, is applied to the terpolymerization of 2-acrylamido-2-methylpropane sulfonic acid (AMPS, M₁), acrylamide (AAm, M₂) and acrylic acid (AAc, M₃). This water-soluble terpolymer has potential for applications in enhanced oil recovery, but the associated terpolymerization kinetic characteristics are largely unstudied. In the current paper, EVM is used to design optimal experiments (for the first time in the literature), and reactivity ratios are subsequently estimated based on both low and medium-high conversion data. The results from the medium-high conversion data are more precise than those from the low conversion data, and are therefore used next to predict the terpolymer composition trajectory over the full course of conversion. Good agreement is seen between experimental data and model predictions, which confirms the accuracy of the newly determined ternary r... [more]

Nitroxide-mediated polymerization using the succinimidyl ester functional unimolecular alkoxyamine initiator (NHS-BlocBuilder) was used to first copolymerize tert-butyl methacrylate/2-vinylpyridine (tBMA/2VP) with low dispersity (Đ = 1.30⁻1.41) and controlled growth (linear number average molecular Mn versus conversion, Mn = 3.8⁻10.4 kg·mol−1) across a wide composition of ranges (initial mol fraction 2VP, f2VP,0 = 0.10⁻0.90). The resulting statistical copolymers were first de-protected to give statistical polyampholytic copolymers comprised of methacrylic acid/2VP (MAA/2VP) units. These copolymers exhibited tunable water-solubility due to the different pKas of the acidic MAA and basic 2VP units; being soluble at very low pH < 3 and high pH > 8. One of the tBMA/2VP copolymers was used as a macroinitiator for a 4-acryloylmorpholine/4-acryloylpiperidine (4AM/4AP) mixture, to provide a second block with thermo-responsive behavior with tunable cloud point temperature (CPT), depending on the... [more]

In this study, the effect of ultra-high-pressure homogenization (UHPH: 100 or 200 MPa at 25 °C), in comparison to colloid mill (CM: 5000 rpm at 20 °C) and conventional homogenization (CH: 15 MPa at 60 °C), on the stability of oil-in-water emulsions with different oil concentrations (10, 30 or 50 g/100 g) emulsified by whey protein isolate (4 g/100 g) was investigated. Emulsions were characterized for their microstructure, rheological properties, surface protein concentration (SPC), stability to creaming and oxidative stability under light (2000 lux/m²). UHPH produced emulsions containing lipid droplets in the sub-micron range (100⁻200 nm) and with low protein concentrations on droplet surfaces. Droplet size (d3.2, µm) was increased in CH and UHPH emulsions by increasing the oil concentration. CM emulsions exhibited Newtonian flow behaviour at all oil concentrations studied; however, the rheological behaviour of CH and UHPH emulsions varied from Newtonian flow (n ≈ 1) to shear-thinning... [more]

Biofilms are spatially-structured communities of different microbes, which have a huge impact on both ecosystems and human life. Mathematical models are powerful tools for understanding the function and evolution of biofilms as diverse communities. In this article, we give a review of some recently-developed models focusing on the interactions of different species within a biofilm, the evolution of biofilm due to genetic and environmental causes and factors that affect the structure of a biofilm.

The editors of Processes would like to express their sincere gratitude to the following reviewers for assessing manuscripts in 2016.[...]

This paper discusses the problems associated with the implementation of Real Time Optimization/Model Predictive Control (RTO/MPC) systems, taking as reference the hydrogen distribution network of an oil refinery involving eighteen plants. This paper addresses the main problems related to the operation of the network, combining data reconciliation and a RTO system, designed for the optimal generation and redistribution of hydrogen, with a predictive controller for the on-line implementation of the optimal policies. This paper describes the architecture of the implementation, showing how RTO and MPC can be integrated, as well as the benefits obtained in terms of improved information about the process, increased hydrocarbon load to the treatment plants and reduction of the hydrogen required for performing the operations.

We address in the paper the problem of designing an economic model predictive control (EMPC) algorithm that asymptotically achieves the optimal performance despite the presence of plant-model mismatch. To motivate the problem, we present an example of a continuous stirred tank reactor in which available EMPC and tracking model predictive control (MPC) algorithms do not reach the optimal steady state operation. We propose to use an offset-free disturbance model and to modify the target optimization problem with a correction term that is iteratively computed to enforce the necessary conditions of optimality in the presence of plant-model mismatch. Then, we show how the proposed formulation behaves on the motivating example, highlighting the role of the stage cost function used in the finite horizon MPC problem.

The modifier approach has been extensively explored and offers a theoretically-sound and practically-useful method to deploy real-time optimization. The recent directional-modifier adaptation algorithm offers a heuristic to tackle the modifier approach. The directional-modifier adaptation algorithm, supported by strong theoretical properties and the ease of deployment in practice, proposes a meaningful compromise between process optimality and quickly improving the quality of the estimation of the gradient of the process cost function. This paper proposes a novel view of the directional-modifier adaptation algorithm, as an approximation of the optimal trade-off between the underlying experimental design problem and the process optimization problem. It moreover suggests a minor modification in the tuning of the algorithm, so as to make it a more genuine approximation.