Capsule Fabrication Research Articles

Modeling of Release Mechanism of Sage (Salvia fruticosa Miller) Phenolics Encapsulated in Alginate Capsule: Physicochemical Properties

Alginate capsules are promising delivery systems for encapsulation and release of phenolics since they can be fabricated from food‐grade biopolymers using mild processes. On the other hand, knowing the release kinetic of the phenolic in the capsules is critical for capsule fabrication and product quality improvement This study is aimed at mathematically modeling the transfer of encapsulated sage (Salvia fruticosa Miller) phenolics in alginate particles to water and to determine some physicochemical properties of capsules containing different concentrations of phenolics. The water activity values (aw) of the capsule varied between 0.9976 and 0.9990. Sphericity factors of 1 (37.5 ppm), 2 (75 ppm), 3 (150 ppm), 4 (300 ppm), and control (0 ppm) samples were determined as 0.042, 0.044, 0.043, 0.273, and 0.039, respectively. The yellowness (+b ∗) value of the samples increased significantly as the added sage extract concentration increased. While the phenolic content of the samples was determined between 0.174 and 1.1831 mg/kg GAE, the antioxidant activity values were determined between 0.9602 and 6.6930. To understand the mechanism of phenolic release from the capsules, six different mathematical models were used (First Order, Higuchi, Korsmeyer-Peppas, Hixson and Crowell, The Peppas-Sahlin, and Gompertz). The highest R2 (0.9952‐0.9979) and the lowest RMSE (1.0171‐1.7032) values were calculated in The Peppas‐Sahlin among the six models. The Peppas‐Sahlin model kinetic parameters indicated the dominance of Fickian diffusion and the minor effect of relaxation process in the mechanism of phenolic release.

A standard capsule design for structural material testing in the Advanced Test Reactor

Nuclear materials testing is commonly completed in various material test and research reactors throughout the world, including the Advanced Test Reactor (ATR), but the current capsule design, analysis, and fabrication process can take years to complete. To decrease the costs and time associated with materials testing, a standard capsule has been designed which houses various specimen geometries and allows irradiation in virtually any ATR test position. The standard capsule features locking end caps which connect and lock together to form the capsule stack, eliminating the need for a basket and maximizing the quantity of specimens which are contained within the capsule. A customizable internal gas gap provides thermal resistance between the specimens and reactor coolant, making specimen temperatures from approximately 370 to 1000 K achievable. The flexibility of the capsule design allows experimenters to choose irradiation positions based off desired neutron flux, with typical fluences per cycle ranging from 8.8x1019 to 2.3x1021 n/cm2, depending on experiment position. This paper presents and discusses the standard capsule design and analysis.

Investigating boosted decision trees as a guide for inertial confinement fusion design

Inertial confined fusion experiments at the National Ignition Facility have recently entered a new regime approaching ignition. Improved modeling and exploration of the experimental parameter space were essential to deepening our understanding of the mechanisms that degrade and amplify the neutron yield. The growing prevalence of machine learning in fusion studies opens a new avenue for investigation. In this paper, we have applied the Gradient-Boosted Decision Tree machine-learning architecture to further explore the parameter space and find correlations with the neutron yield, a key performance indicator. We find reasonable agreement between the measured and predicted yield, with a mean absolute percentage error on a randomly assigned test set of 35.5%. This model finds the characteristics of the laser pulse to be the most influential in prediction, as well as the hohlraum laser entrance hole diameter and an enhanced capsule fabrication technique. We used the trained model to scan over the design space of experiments from three different campaigns to evaluate the potential of this technique to provide design changes that could improve the resulting neutron yield. While these data-driven model cannot predict ignition without examples of ignited shots in the training set, it can be used to indicate that an unseen shot design will at least be in the upper range of previously observed neutron yields.

Cu2+-assisted sensing of fungicide Thiram in food, soil, and plant samples and the ratiometric detection of Hg2+ in living cells by a low cytotoxic and red emissive fluorescent sensor

Metal ions and pesticides are extensively used in many industries and agriculture. However, they cause significant environmental pollution and various adverse health effects. Therefore, the development of sensitive and selective techniques to detect them is necessary for human health and the ecosystem. In this paper, we report a novel red-emitting fluorescence probe with a large Stokes shift (∼220 nm) based on rhodamine and isophorone units. The probe shows a ratiometric fluorescence response toward Hg2+ ions; however, Cu2+ ions quench the red fluorescence signal. The decomposition of the probe-Cu2+ complex allows detection of Thiram followed by recovery of the red fluorescence signal of the probe. In addition, the probe shows a good linear response to Hg2+, Cu2+, and Thiram, with detection limits of 122.0 nM, 29.0 nM, and 72.0 nM, respectively. The practical applicability of the probe has been successfully tested in real samples. Moreover, smartphone detection and light-responsive capsule fabrication have been established, for easy and quick detection. The probe possesses very low cytotoxicity and allows visualization of Hg2+ and Cu2+ ions in HeLa cells. Therefore, the present probe is expected to be an effective tool assisting in easy, quick, and reliable detection of Thiram, Hg2+, and Cu2+ ions.

Printed asymmetric microcapsules: Facile loading and multiple stimuli-responsiveness.

Engineering of colloidal particles and capsules despite substantial progress is still facing a number of unsolved issues including low loading capacity, non-uniform size and shape of carriers, tailoring different functionalities and versatility to encapsulated cargo. In this work, we propose a method for defined-shaped functionally asymmetric polymer capsule fabrication based on a soft lithography approach. The developed capsules consist of two classes of polymers - the main part "cup" is made out of polyelectrolyte multilayers (PAH-PSS) and "lid" is made of biodegradable polyether (PLGA). Asymmetric capsules combine advantages from both traditional layer-by-layer capsules and recently developed printed "pelmeni" capsules. This combination provides stimuli-responsiveness due to polyelectrolyte multilayer properties differing from PLGA. The inner volume of capsules can be loaded with a variety of active compounds and the capsule's geometry is defined due to the soft-lithography method. Capsules have a core-shell structure and monodisperse size distribution. Three methods to trigger cargo release have been demonstrated, namely temperature treatment, ultrasonication and pH shift. Steroidal drug dexamethasone was used to illustrate the applicability of the systems for triggered drug release. The application of proposed asymmetric capsules includes but is not limited to pharmacology, diagnostics, sensors, micro- and nanoreactors and chemical actuators.

Direct-drive implosion experiment of diamond capsules fabricated with hot filament chemical vapor deposition technique

Diamond is a promising alternative capsule material for direct-drive inertial confinement fusion. Previous investigations suggest that the stiffness and higher density of diamond can mitigate laser imprinting, which is an initial perturbation on the ablation surface caused by non-uniform laser irradiation. We conduct diamond capsule fabrication using the hot filament chemical vapor deposition (HF-CVD) technique. This technique is the most suitable diamond deposition method in terms of mass production, since the deposition area can be easily extended just by increasing the number of hot filaments. This paper presents the first direct-drive implosion experiment concerning diamond capsules fabricated using the HF-CVD technique. The compression of thin diamond capsules, with an inner capsule diameter of 482 μm and a shell thickness of 1.6 μm, is successfully achieved, and the implosion trajectory of diamond capsules, with the same diameter and thickness, is consistent with 1D radiation hydrodynamic simulation calculations. However, for diamond capsules with an inner diameter of 482 μm and a shell thickness of 2.4 μm, asymmetry of the implosion trajectory and unexpected x-ray emission are observed. This is attributed to the remaining silicon (Si) mold inside the capsule left over from the fabrication process, revealing that the etching method of Si in diamond capsules should be improved.

Application of VERDI detectors for neutron fluence measurements during the JET 2019 Deuterium-Deuterium campaign

The Novel Neutron Detector for Fusion (VERDI) project aims to develop a passive detector which will provide a robust approach for neutron detection in current and future fusion devices. The detector comprises a low activation capsule, capable to withstand the harsh fusion conditions, containing defined added metallic elements, the activation of which provides neutron fluence and energy spectrum information. In the present work, VERDI detectors were employed for the first time to determine neutron fluence and energy spectra at the Joint European Torus (JET) Long Term Irradiation Station (LTIS) during the 2019 Deuterium-Deuterium (DD) campaign. Two materials, graphite and carbon fibre reinforced silicon carbide composite, were used for the capsule fabrication containing disc-shaped activation foils (Ag, Mn, Nb, Ni, Rh, Ti, Y). Post-irradiation gamma-spectrometry measurements were performed in order to identify the product isotopes and derive the incident neutron fluence. The results were fed into the MAXED code to reconstruct the neutron spectrum. The derived spectrum was in very good agreement with the calculated one using the MCNP code. A difference of 8% was found between the derived and the experimentally determined total integrated neutron flux. This work demonstrates the feasibility of employing VERDI detectors for neutron measurements in real fusion environments.

Monodisperse Selectively Permeable Hydrogel Capsules Made from Single Emulsion Drops.

Capsules are often used to protect chemical and biological entities from the environment, to control the timing and location of their release, or to facilitate the collection of waste. Their performance depends on the thickness and composition of their shells, which can be closely controlled if capsules are made from double emulsion drops that are produced with microfluidics. However, the fabrication of such double emulsions is delicate, limiting throughput and increasing costs. Here, a fast, scalable method to produce monodisperse microcapsules possessing mechanically robust, thin, semipermeable hydrogel shells from single emulsion drops is introduced. This is achieved by selectively polymerizing reagents in close proximity to the drop surface to form a biocompatible 1.6 μm-thick hydrogel shell that encompasses a liquid core. The size-selective permeability of the shell enables the growth of living yeast and bacteria in their cores. Moreover, if capsules are loaded with adsorbents, they can repetitively remove waste products from water. The simplicity and robustness of the capsule fabrication makes the process scalable and cost effective. It has thus the potential to extend the use of calibrated capsules possessing well-defined dimensions to cost sensitive fields, including food, waste water treatment, or oil recovery.

Focused ultrasound-mediated fluorescence of composite microcapsules loaded with magnetite nanoparticles: In vitro and in vivo study

High intensity focused ultrasound (HIFU) is widely used in medical practice, including cancer therapy. Also this approach is promising for remote release of encapsulated drugs in various other biomedical applications where local treatment is needed. Our approach underpins the minimization of HIFU impact on possible degradation of biological tissues and expand the use of HIFU in the controlled release of encapsulated drugs. We demonstrated the efficient ultrasound-induced release of labeled protein (Cy7-BSA) from elaborated nanocomposite microcapsules in vitro an in vivo. The capsule fabrication was done using combination of recently developed freezing-induced loading (FIL) technique and Layer-by-Layer assembly (LbL) used for the preparation of complex multilayer BSA/tannic acid nanocomposite capsules sensitive to HIFU. These capsules contain NIR fluorescent Cy7-labeled BSA in the shell for tracking in vivo and the high concentration of labels inside the capsules resulted in self-quenching provides the real-time detection of the protein once it is released from the capsule. Ultrasound-induced release in vivo of Cy7-labeled BSA initially quenched by magnetite nanoparticles was confirmed by fluorescent tomography. The significant decrease of Cy7 fluorescence under HIFU treatment in vitro was found to be due to a generation of reactive oxygen species and fast dye oxidation. Our results demonstrate that adapted HIFU setup can be used for the directed release of encapsulated substances in vivo under tissue compatible NIR monitoring by fluorescent tomography.

Multilayer Capsules Inside Biological Systems: State-of-the-Art and Open Challenges.

There are many reports about the interaction of multilayer capsules with biological systems in the literature. A majority of them are devoted to the in vitro study with two-dimensional cell cultures. Multilayer capsule fabrication had been under intensive investigation from 1990s and 2000s by Prof. Helmuth Möhwald, and many of his followers further developed their own research directions, focusing on capsule implementation in various fields of biology and medicine. The aim of this future article is to consistently consider the most recent advances in cell-capsule interactions for different biomedical applications, including functionalization of clinically relevant cells, nonviral gene delivery, magnetization of cells to control their movement, and in vivo drug delivery. Finally, the description and discussion of the new trends and perspectives for improved functionalities of capsules in design and functionalization of cell-assisted drug vehicles are the major topics of this work.

Microcapsule-Containing Self-Reporting Polymers.

Self-reporting polymers, which can indicate damage or exposure to excessive stress with a clearly perceptible optical signal, are potentially useful for several technological applications, including stress-sensitive sensors that enable in situ monitoring of mechanical events and structural health monitoring systems. A versatile and simple concept to realize this function is the exploitation of microcapsules that are filled with solutions of dyes that are released and chemically or physically activated when the protective shell is damaged. Such microcapsules can readily be incorporated into polymers and the composites thus made can be processed into films, coatings, or other objects. Mechanochromic effects can be realized with different types of dyes and activation schemes. In this concept article, a selection of recent key studies is presented to provide an overview of the state of the field. Different architectures and operating principles and their advantages and drawbacks are reviewed. The parameters that influence the design of microcapsule-based mechanochromic systems are considered and unexplored chromophore systems that might be useful to design future self-reporting polymers are discussed. Finally, specific aspects of capsule design, fabrication, and integration into polymers are presented. Throughout the article, challenges and opportunities of the concept are highlighted and possible future directions are discussed.

Design considerations for indirectly driven double shell capsules

Double shell capsules are predicted to ignite and burn at relatively low temperature (∼3 keV) via volume ignition and are a potential low-convergence path to substantial α-heating and possibly ignition at the National Ignition Facility. Double shells consist of a dense, high-Z pusher, which first shock heats and then performs work due to changes in pressure and volume (PdV work) on deuterium-tritium gas, bringing the entire fuel volume to high pressure thermonuclear conditions near implosion stagnation. The high-Z pusher is accelerated via a shock and subsequent compression of an intervening foam cushion by an ablatively driven low-Z outer shell. A broad capsule design parameter space exists due to the inherent flexibility of potential materials for the outer and inner shells and foam cushion. This is narrowed down by design physics choices and the ability to fabricate and assemble the separate pieces forming a double shell capsule. We describe the key physics for good double shell performance, the trade-offs in various design choices, and the challenges for capsule fabrication. Both 1D and 2D calculations from radiation-hydrodynamic simulations are presented.

Preliminary experiments on hohlraum-driven double-shell implosion at the ShenGuang-III laser facility

Double-shell implosion is proposed as a non-cryogenic target design for ignition, offering a robust implosion platform for inertial confinement fusion research. Hohlraum-driven double-shell implosions have been performed at the ShenGuang-III laser facility; a vacuum hohlraum with a high CCR value was employed. With 96kJ laser energy in a squared temporal profile, the implosion neutron yield was close to 1010, and the YOC1D was about 27%. A fuel areal density of 14 mg cm−2 was inferred from the measured yield ratio of secondary and primary neutrons. The implosion trajectory was diagnosed via the 4.75 keV x-ray backlight. The measured implosion velocity and hot-spot x-ray emission history indicate a predictable hydrodynamic process in the double-shell implosion. Two crucial factors which might detrimentally affect implosion performance are the implosion symmetry and pusher–gas mix. The loss of four driven laser beams in the backlight shot caused the YOC1D to decrease to 5% and fuel areal density to decrease to 4 mg cm−2. In future, optimization of the implosion symmetry and the capsule fabrication will be implemented to improve the double-shell implosion performance.

An F82H steel pressurized tube creep capsule for irradiation in HFIR

A novel capsule design has been developed for measurement of irradiation creep in pressurized tubes and is being used to irradiate reduced activation ferritic/martensitic F82H steel creep test specimens. These tests are being conducted in the flux trap of the High Flux Isotope Reactor at the Oak Ridge National Laboratory. The capsule design uses a tight-fitting corrugated aluminum foil placed in the center of a vanadium alloy holder to conduct heat from the centrally located test specimen. The foil acts as a compressible thermal interface between the pressurized tube and holder, maintaining a constant thermal resistance (and thus a constant tube temperature gradient) during irradiation, regardless of differential thermal expansion, creep, and swelling in the test specimen. Mechanical interference with creep deformation of the specimen tube is minimized by using a thin (0.05 mm) foil with sufficient room to crush. Finite element analysis of the contact pressure between the specimen and foil, combined with thermal creep in the foil, showed little interference with specimen stress conditions. Specimens were designed to experience hoop stresses of 380, 300, 150, and 0 MPa at a temperature of 300 °C while being irradiated to a dose of 3.7 dpa. Passive SiC thermometry is located within the pressurized tube and the holder material for confirmation of experiment irradiation target temperatures. This work discusses aspects of the capsule's fabrication and design, including thermal models of the capsule during irradiation.

Macro-encapsulation and characterization of chloride based inorganic Phase change materials for high temperature thermal energy storage systems

A novel approach involving the use of ceramic materials was investigated for encapsulating chloride based PCMs with melting points higher than 650 °C. Low-cost ceramics with excellent thermal and chemical stability under molten-salt conditions were identified as the encapsulants. The processing procedure for these materials was discerned by systematic porosity distribution and materials compatibility studies. The influence of sintering temperature on the reactivity of feldspar, ball clay, kaolin and the mixture thereof with molten sodium chloride was investigated by IR spectroscopy. The porosity of the sintered ceramic samples was analyzed through water and dye absorption tests, as well as SEM analysis. The results were used for developing an optimum ceramic capsule fabrication procedure, which involved the use of a green ceramic body followed by sintering at 1190 °C. Sodium chloride and its eutectic with potassium chloride were used as the PCMs. The selected PCM was poured into and filled the fabricated ceramic capsule through a hole which was sealed at a temperature close to or higher than the melting temperature of the PCM. The fabricated capsules have been tested and have survived more than 150 thermal cycles without showing degradation in their thermo-physical properties.

Recent progress in ICF target fabrication at RCLF

Target is one of the essential parts in inertial confinement fusion (ICF) experiments. To ensure the symmetry and hydrodynamic stability in the implosion, there are stringent specifications for the target. Driven by the need to fabricate the target required by ICF experiments, a series of target fabrication techniques, including capsule fabrication techniques and the techniques of target characterization and assembly, are developed by the Research Center of Laser Fusion (RCLF), China Academy of Engineering Physics (CAEP). The capsule fabrication techniques for preparing polymer shells, glow discharge polymer (GDP) shells and hollow glass micro-sphere (HGM) are studied, and the techniques of target characterization and assembly are also investigated in this paper. Fundamental research about the target fabrication is also done to improve the quality of the target. Based on the development of target fabrication techniques, some kinds of target have been prepared and applied in the ICF experiments.

A facile and efficient strategy to encapsulate the model basic protein lysozyme into porous CaCO3.

Basic proteins play important roles in biological activities and disease treatment, but their high sensitivity to the body environment and short life time have limited their applications. Encapsulating the proteins into carriers has been demonstrated to be an effective way to prolong the protein half life time and to control the release temporally and spatially. However, fabricating protein carriers with high protein loading efficacy under mild conditions is still a big challenge. The capsules generated by the combination of the layer by layer (LBL) technique and sacrificial templates have been extensively investigated for the encapsulation of proteins. Porous CaCO3 is an effective sacrificial template with the ability to load various drugs efficiently under mild conditions, but it shows very poor ability in loading basic proteins. Here, we developed a highly efficient but very simple method to encapsulate lysozyme into porous CaCO3. An efficiency of 99.5% and capacity of 91.6 mg g-1 under very gentle conditions were obtained by doping heparin into porous CaCO3. Most importantly, the activity of the encapsulated lysozyme was almost 100% retained. Furthermore, we evaluated the encapsulation efficiency of the loaded lysozyme during the LBL wrapping process and demonstrated that the loss of the loaded lysozyme was controllable by choosing suitable polyelectrolyte pairs. Considering the multi-interaction mode of heparin with various proteins and the ability to retain the function of the loaded protein demonstrated in our study, we believe that the developed approach has great potential for encapsulating various functional proteins with a wide range of applications in catalysis, disease treatment, and tissue engineering.

Polyelectrolyte capsules preloaded with interconnected alginate matrix: An effective capsule system for encapsulation and release of macromolecules

In recent years, the design of stimuli-responsive hollow polymeric capsules is of tremendous interest for the scientific community because of the broad application of these capsules in the biomedical field. The use of weak polyelectrolytes as layer components for capsule fabrication is especially interesting as it results in hollow capsules that show unique release characteristics under physiological conditions. In this work, a methodology to prepare sub-micron sized alginate doped calcium carbonate (CaCO3) particles through controlled precipitation in the presence of alginate is reported. Hollow capsules obtained by Layer-by-Layer (LbL) assembly of poly(allylamine hydrochloride) (PAH) and poly(methacrylic acid) (PMA) are showing an interconnected alginate matrix in the interior of the capsules. Investigations showed that the presence of alginate matrix enhances the encapsulation of cationic molecules (e.g. doxorubicin hydrochloride) manifold by charge controlled attraction mechanism. Capsule permeability investigated by confocal laser scanning microscopy revealed that the transformation from an open state to closed state is accompanied by an intermediate state where capsules are neither open nor closed. Furthermore, time dependent study indicated that the encapsulation process is linear as a function of time. The cell viability experiments demonstrated excellent biocompatibility of hollow capsules with mouse embryonic fibroblast cells. Anticancer investigations showed that DOX loaded capsules have significant anti-proliferative characteristics against HeLa cells. Such capsules have high potential for use as drug carrier for cationic drugs in cancer therapy.

Fabrication of Double-Layered Alginate Capsules Using Coaxial Nozzle

Multilayered encapsulation has been of great interest for various pharmaceutical, chemical, and food industries. Fabrication of well-defined capsules with more than one shell layer still poses a significant fabrication challenge. This study aims to investigate the feasibility of using a coaxial nozzle to fabricate double-layered (core–shell–shell) capsules during vibration-assisted dripping. A three-layered coaxial nozzle has been designed, manufactured, and tested for double-layered capsule fabrication when using sodium alginate solutions as the model liquid material for inner and outer shell layers and calcium chloride solution as the core fluid. To facilitate the droplet formation process, a vibrator has been integrated into the fabrication system to provide necessary perturbation for effective breakup of the fluid flow. It is demonstrated that double-layered alginate capsules can be successfully fabricated using the proposed three-layered coaxial nozzle fabrication system. During fabrication, increasing the core flow rate leads to an increase in capsule and core diameters while the inner and outer shell layer thicknesses decrease. Increasing annular flow rate results in an increase in capsule diameter and inner shell layer thickness while the outer shell layer thickness decreases. An increase in the sheath flow rate leads to an increase in capsule diameter and outer shell layer thickness but has no significant effect on the core diameter and inner shell layer thickness.

Glass encapsulated phase change materials for high temperature thermal energy storage

A new encapsulation method for high temperature phase change materials (PCM) is developed. Nitrate salts and metals are used as the PCM core with melting temperatures in the 300-400 °C range. Borosilicate is used as encapsulating material based on its high thermal resistance, non-reactivity and optical properties. Its transparency combined with the transparency of some PCM in the molten state allows the analysis of the melting process through visual observation. The volume expansion of the PCM is managed through a void space inside the capsules. The capsule design, fabrication, and testing is described in detail. The PCM melting and solidification process is identified using a combination of visual and infrared images. The experimental observations are complemented by a finite difference method to solve the energy equations simulating the transient melting/freezing process inside a spherical PCM. The model analyzes the effect of the convective heat transfer coefficient on the PCM capsule melting and freezing starting times and the duration of the PCM melting process. Boundary conditions are set to match those in the experimental rig developed. Results show that the main system parameters can be qualitatively assessed and adequately determined to describe the experimental observations.