Synthesis of an eco-inspired anticorrosive composite for mild steel applications.

We synthesised a polyaniline/mica (Mica-PANI) nanocomposite using naturally occurring muscovite mica by a top-down approach. The developed coating materials were characterised using a different technique to investigate their chemical and structural properties using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and thermogravimetric analysis (TGA). Furthermore, the electrochemical properties of the coating materials were investigated by linear sweep voltammetry (LSV). SEM images elucidate the composite's average particle diameter of the prepared nano-mica, approximately 80 nm. The existence of relevant functional groups and bonding in the prepared Mica-PANI composite material was confirmed by means of XPS and FTIR techniques. Moreover, the synthesised composite with 5% w/w shows high anticorrosion protection, i.e. 84 µm per year, compared to competing materials, including commercial paint and individual raw materials (0.35 mm per year). The anti-corrosive effect occurs mainly due to two opposing effects: the formation of an Fe(OH)3 passive layer on the steel surface by oxidation of surface iron atoms by the PANI and the barrier effect of mica NPs through inhibition of corrosive agents. Therefore, the eco-inspired composite could be an ideal cost-effective coating material to prevent the corrosion of mild steel surfaces.

Recommended Best Practices in Freeze Dryer Equipment Performance Qualification: 2022.

Best practices for performing freeze dryer equipment qualification are recommended, focusing on identifying methods to quantify shelf thermal uniformity (also known as "shelf surface uniformity"), equipment capability, and performance metrics of the freeze dryer essential to the pharmaceutical Quality by Design paradigm. Specific guidelines for performing shelf temperature mapping, freeze dryer equipment limit testing (the capability curve), and condenser performance metrics have been provided. Concerning shelf temperature mapping and equipment capability measurements, the importance of paying attention to the test setup and the use of appropriate testing tools are stressed. In all the guidelines provided, much attention has been paid to identifying the balance between obtaining useful process knowledge, logistical challenges associated with testing in the production environment vs that at laboratory scale, and the frequency of the testing necessary to obtain such useful information. Furthermore, merits and demerits of thermal conditions maintained on the cooled surfaces of the freeze dryer condenser have been discussed identifying the specific influence of the condenser surface temperature on the process conditions using experimental data to support the guidelines. Finally, guidelines for systematic leak rate testing criteria for a freeze dryer are presented. These specific procedural recommendations are based on calculations, measurements, and experience to provide useful process and equipment knowledge.

Combining Azimuthal and Polar Angle Resolved Shadow Mask Deposition and Nanosphere Lithography to Uncover Unique Nano-Crystals.

In this article, we present a systematic investigation on a multistep nanosphere lithography technique to uncover its potential in fabricating a wide range of two- and three-dimensional nanostructures. A tilted (polar angle) electron beam shower on a nanosphere mask results in an angled shadow mask deposition. The shape of the shadow also depends on the azimuthal angle of the mask sitting on top of the substrate. We performed angled shadow mask depositions with systematic variation of these two angular parameters, giving rise to complex nanostructures (down to 50 nm), repeated over a large area without defect. In this article, nanosphere lithography with two- and four-fold azimuthal symmetry was studied at constant tilt angles followed by variations in tilt without azimuthal rotation of the substrate. Finally, both angular parameters were simultaneously varied. The structure of shadow crystals was explained using Matlab simulation. This work stretches the horizons of nanosphere lithography, opening up new scopes in plasmonic and magnonic research.

Direct imaging of an inhomogeneous electric current distribution using the trajectory of magnetic half-skyrmions.

The direct imaging of current density vector distributions in thin films has remained a daring challenge. Here, we report that an inhomogeneous current distribution can be mapped directly by the trajectories of magnetic half-skyrmions driven by an electrical current in Pt/Co/Ta trilayer, using polar magneto-optical Kerr microscopy. The half-skyrmion carries a topological charge of 0.5 due to the presence of Dzyaloshinskii-Moriya interaction, which leads to the half-skyrmion Hall effect. The Hall angle of half-skyrmions is independent of current density and can be reduced to as small as 4° by tuning the thickness of the Co layer. The Hall angle is so small that the elongation path of half-skyrmion approximately delineates the invisible current flow as demonstrated in both a continuous film and a curved track. Our work provides a practical technique to directly map inhomogeneous current distribution even in complex geometries for both fundamental research and industrial applications.

Mass spectrometry in freeze-drying: Motivations for using a bespoke PAT for laboratory and production environment.

Mass Spectrometry has commonly been used in the semi-conductor industry where maintaining a clean environment with minimum contaminants under high vacuum is crucial for successful manufacturing. Since the technology's early usage for pharmaceutical manufacturing in the 1980 s, particularly in the freeze-drying environment, much has changed. The focus of the current work is aimed at asking some key questions regarding the maturity of the technology, its challenges and importance of having an application-specific instrument for quantitative process analyses applied to freeze-drying. Furthermore, we compare the use of mass spectrometers in early installations from the '80s with recent experiences of the technology in the production and laboratory environments comparing data from different MS technologies. In addition, the manuscript covers broad application of the technology towards detection of and sensitivity for analytes including silicone oil and Helium. It also explores the option of using MS in detecting water vapor and nitrogen concentration not just in primary drying, but also in secondary drying. The technology, when purpose built, has the potential for use as a robust, multi-purpose PAT tool in the freeze-drying laboratory and production environments.

Recommended Best Practices for Process Monitoring Instrumentation in Pharmaceutical Freeze Drying-2017.

Recommended best practices in monitoring of product status during pharmaceutical freeze drying are presented, focusing on methods that apply to both laboratory and production scale. With respect to product temperature measurement, sources of uncertainty associated with any type of measurement probe are discussed, as well as important differences between the two most common types of temperature-measuring instruments-thermocouples and resistance temperature detectors (RTD). Two types of pressure transducers are discussed-thermal conductivity-type gauges and capacitance manometers, with the Pirani gauge being the thermal conductivity-type gauge of choice. It is recommended that both types of pressure gauge be used on both the product chamber and the condenser for freeze dryers with an external condenser, and the reasoning for this recommendation is discussed. Developing technology for process monitoring worthy of further investigation is also briefly reviewed, including wireless product temperature monitoring, tunable diode laser absorption spectroscopy at manufacturing scale, heat flux measurement, and mass spectrometry as process monitoring tools.

Spatial Variation of Pressure in the Lyophilization Product Chamber Part 2: Experimental Measurements and Implications for Scale-up and Batch Uniformity.

Product temperature during the primary drying step of freeze-drying is controlled by a set point chamber pressure and shelf temperature. However, recent computational modeling suggests a possible variation in local chamber pressure. The current work presents an experimental verification of the local chamber pressure gradients in a lab-scale freeze-dryer. Pressure differences between the center and the edges of a lab-scale freeze-dryer shelf were measured as a function of sublimation flux and clearance between the sublimation front and the shelf above. A modest 3-mTorr difference in pressure was observed as the sublimation flux was doubled from 0.5 to 1.0 kg·h-1·m-2 at a clearance of 2.6 cm. Further, at a constant sublimation flux of 1.0 kg·h-1·m-2, an 8-fold increase in the pressure drop was observed across the shelf as the clearance was decreased from 4 to 1.6 cm. Scale-up of the pressure variation from lab- to a manufacturing-scale freeze-dryer predicted an increased uniformity in drying rates across the batch for two frequently used pharmaceutical excipients (mannitol and sucrose at 5% w/w). However, at an atypical condition of shelf temperature of +10°C and chamber pressure of 50 mTorr, the product temperature in the center vials was calculated to be a degree higher than the edge vial for a low resistance product, thus reversing the typical edge and center vial behavior. Thus, the effect of local pressure variation is more significant at the manufacturing-scale than at a lab-scale and accounting for the contribution of variations in the local chamber pressures can improve success in scale-up.

Spatial Variation of Pressure in the Lyophilization Product Chamber Part 1: Computational Modeling.

The flow physics in the product chamber of a freeze dryer involves coupled heat and mass transfer at different length and time scales. The low-pressure environment and the relatively small flow velocities make it difficult to quantify the flow structure experimentally. The current work presents the three-dimensional computational fluid dynamics (CFD) modeling for vapor flow in a laboratory scale freeze dryer validated with experimental data and theory. The model accounts for the presence of a non-condensable gas such as nitrogen or air using a continuum multi-species model. The flow structure at different sublimation rates, chamber pressures, and shelf-gaps are systematically investigated. Emphasis has been placed on accurately predicting the pressure variation across the subliming front. At a chamber set pressure of 115 mtorr and a sublimation rate of 1.3 kg/h/m2, the pressure variation reaches about 9 mtorr. The pressure variation increased linearly with sublimation rate in the range of 0.5 to 1.3 kg/h/m2. The dependence of pressure variation on the shelf-gap was also studied both computationally and experimentally. The CFD modeling results are found to agree within 10% with the experimental measurements. The computational model was also compared to analytical solution valid for small shelf-gaps. Thus, the current work presents validation study motivating broader use of CFD in optimizing freeze-drying process and equipment design.

Tunable Magnetization Dynamics in Interfacially Modified Ni81Fe19/Pt Bilayer Thin Film Microstructures.

Interface modification for control of ultrafast magnetic properties using low-dose focused ion beam irradiation is demonstrated for bilayers of two technologically important materials: Ni81Fe19 and Pt. Magnetization dynamics were studied using an all-optical time-resolved magneto-optical Kerr microscopy method. Magnetization relaxation, precession, damping and the spatial coherence of magnetization dynamics were studied. Magnetization precession was fitted with a single-mode damped sinusoid to extract the Gilbert damping parameter. A systematic study of the damping parameter and frequency as a function of irradiation dose varying from 0 to 3.3 pC/µm(2) shows a complex dependence upon ion beam dose. This is interpreted in terms of both intrinsic effects and extrinsic two-magnon scattering effects resulting from the expansion of the interfacial region and the creation of a compositionally graded alloy. The results suggest a new direction for the control of precessional magnetization dynamics, and open the opportunity to optimize high-speed magnetic devices.

Markov chain aggregation and its applications to combinatorial reaction networks.

We consider a continuous-time Markov chain (CTMC) whose state space is partitioned into aggregates, and each aggregate is assigned a probability measure. A sufficient condition for defining a CTMC over the aggregates is presented as a variant of weak lumpability, which also characterizes that the measure over the original process can be recovered from that of the aggregated one. We show how the applicability of de-aggregation depends on the initial distribution. The application section is devoted to illustrate how the developed theory aids in reducing CTMC models of biochemical systems particularly in connection to protein-protein interactions. We assume that the model is written by a biologist in form of site-graph-rewrite rules. Site-graph-rewrite rules compactly express that, often, only a local context of a protein (instead of a full molecular species) needs to be in a certain configuration in order to trigger a reaction event. This observation leads to suitable aggregate Markov chains with smaller state spaces, thereby providing sufficient reduction in computational complexity. This is further exemplified in two case studies: simple unbounded polymerization and early EGFR/insulin crosstalk.

Polarizing effect of aligned nanoparticles in terahertz frequency region.

We report the polarizing behavior of aligned Ni nanoparticles (NPs) having average diameter of 165±15 nm in ~210 µm thick polyvinyl alcohol (PVA) matrix in the frequency range of 0.2-1.6 THz. The NPs have been prepared via a wet chemical route and then aligned in PVA film by using an external magnetic field. When the polarization of THz electric field is parallel to the NPs alignment direction, a strong THz absorption is observed whereas a minimum THz absorption is noticed for the corresponding perpendicular configuration. Degree of polarization is calculated to be 0.9±0.08. Considering the good polarizing performance, ease of preparation, durability, and low maintenance, this aligned NP system is a perfect candidate to emerge as a potential THz polarizer.

Freeze-drying simulation framework coupling product attributes and equipment capability: toward accelerating process by equipment modifications.

A physics-based model for the sublimation-transport-condensation processes occurring in pharmaceutical freeze-drying by coupling product attributes and equipment capabilities into a unified simulation framework is presented. The system-level model is used to determine the effect of operating conditions such as shelf temperature, chamber pressure, and the load size on occurrence of choking for a production-scale dryer. Several data sets corresponding to production-scale runs with a load from 120 to 485 L have been compared with simulations. A subset of data is used for calibration, whereas another data set corresponding to a load of 150 L is used for model validation. The model predictions for both the onset and extent of choking as well as for the measured product temperature agree well with the production-scale measurements. Additionally, we study the effect of resistance to vapor transport presented by the duct with a valve and a baffle in the production-scale freeze-dryer. Computation Fluid Dynamics (CFD) techniques augmented with a system-level unsteady heat and mass transfer model allow to predict dynamic process conditions taking into consideration specific dryer design. CFD modeling of flow structure in the duct presented here for a production-scale freeze-dryer quantifies the benefit of reducing the obstruction to the flow through several design modifications. It is found that the use of a combined valve-baffle system can increase vapor flow rate by a factor of 2.2. Moreover, minor design changes such as moving the baffle downstream by about 10 cm can increase the flow rate by 54%. The proposed design changes can increase drying rates, improve efficiency, and reduce cycle times due to fewer obstructions in the vapor flow path. The comprehensive simulation framework combining the system-level model and the detailed CFD computations can provide a process analytical tool for more efficient and robust freeze-drying of bio-pharmaceuticals.

Experimental determination of the key heat transfer mechanisms in pharmaceutical freeze-drying.

The study is aimed at quantifying the relative contribution of key heat transfer modes in lyophilization. Measurements of vial heat transfer rates in a laboratory-scale freeze-dryer were performed using pure water, which was partially sublimed under various conditions. The separation distance between the shelf and the vial was systematically varied, and sublimation rates were determined gravimetrically. The heat transfer rates were observed to be independent of separation distance between the vial and the shelf and linearly dependent on pressure in the free molecular flow limit, realized at low pressures (<50 mTorr). However, under higher pressures (>120 mTorr), heat transfer rates were independent of pressure and inversely proportional to separation distance. Previous heat transfer studies in conventional freeze-drying cycles have attributed a dominant portion of the total heat transfer to radiation, the rest to conduction, whereas convection has been found to be insignificant. Although the measurements reported here confirm the significance of the radiative and gas conduction components, the convective component has been found to be comparable to the gas conduction contribution at pressures greater than 100 mTorr. The current investigation supports the conclusion that the convective component of the heat transfer cannot be ignored in typical laboratory-scale freeze-drying conditions.

Hybrid spatial Gillespie and particle tracking simulation.

MOTIVATION: Cellular signal transduction involves spatial-temporal dynamics and often stochastic effects due to the low particle abundance of some molecular species. Others can, however, be of high abundances. Such a system can be simulated either with the spatial Gillespie/Stochastic Simulation Algorithm (SSA) or Brownian/Smoluchowski dynamics if space and stochasticity are important. To combine the accuracy of particle-based methods with the superior performance of the SSA, we suggest a hybrid simulation. RESULTS: The proposed simulation allows an interactive or automated switching for regions or species of interest in the cell. Especially we see an application if for instance receptor clustering at the membrane is modeled in detail and the transport through the cytoplasm is included as well. The results show the increase in performance of the overall simulation, and the limits of the approach if crowding is included. Future work will include the development of a GUI to improve control of the simulation. AVAILABILITY OF IMPLEMENTATION: www.bison.ethz.ch/research/spatial_simulations. CONTACT: mklann@ee.ethz.ch or koeppl@ethz.ch Supplementary/Information: Supplementary data are available at Bioinformatics online.

Computational analysis of fluid dynamics in pharmaceutical freeze-drying.

Analysis of water vapor flows encountered in pharmaceutical freeze-drying systems, laboratory-scale and industrial, is presented based on the computational fluid dynamics (CFD) techniques. The flows under continuum gas conditions are analyzed using the solution of the Navier-Stokes equations whereas the rarefied flow solutions are obtained by the direct simulation Monte Carlo (DSMC) method for the Boltzmann equation. Examples of application of CFD techniques to laboratory-scale and industrial scale freeze-drying processes are discussed with an emphasis on the utility of CFD for improvement of design and experimental characterization of pharmaceutical freeze-drying hardware and processes. The current article presents a two-dimensional simulation of a laboratory scale dryer with an emphasis on the importance of drying conditions and hardware design on process control and a three-dimensional simulation of an industrial dryer containing a comparison of the obtained results with analytical viscous flow solutions. It was found that the presence of clean in place (CIP)/sterilize in place (SIP) piping in the duct lead to significant changes in the flow field characteristics. The simulation results for vapor flow rates in an industrial freeze-dryer have been compared to tunable diode laser absorption spectroscopy (TDLAS) and gravimetric measurements.