Small Microcapsules Research Articles

Simulation of Microcapsule Transport in Fractured Media Using Coupled CFD‐DEM

AbstractGeothermal energy is sustainable and gaining momentum as a solution to energy crises and environmental issues. However, challenges like production temperature and thermal breakthrough can impact geothermal project efficiency. One innovative solution to alleviate the thermal breakthrough is to inject polymer‐based materials that are encapsulated in microcapsules into fractures to modify fracture permeability and prevent preferential flow. In our study, we utilized a coupled computational fluid dynamics and discrete element method to simulate the transport of microcapsules under various scenarios controlled by microcapsule size, microcapsule concentration, and fracture roughness. For a smooth fracture, the results indicate that small microcapsules can travel through a smooth fracture regardless of their concentrations. Large microcapsules can transport through a smooth fracture when present in lower concentrations. However, medium and mixed‐size microcapsules tend to cause the sealing of a smooth fracture, irrespective of their concentrations. For a rough fracture, the transport of microcapsules is complicated by their interactions with the rough fracture walls. The presence of two sealing positions in a rough fracture adds further complexity to this transport phenomenon. The size and concentration of microcapsules control one sealing location, while the rough fracture walls determine the other sealing location. The rough walls substantially affect microcapsule transport, rendering the role of microcapsule size and concentration less significant. The simulation results suggest that complex fracture surfaces significantly elevate the occurrence of sealing behavior. To mitigate sealing behavior within more complex fractures, it would be beneficial to use smaller and lower concentrations of microcapsules.

Modular assembly of microswimmers with liquid compartments.

Artificial microswimmers, i.e. colloidal scale objects capable of self-propulsion, have garnered significant attention due to their central role as models for out of equilibrium systems. Moreover, their potential applications in diverse fields such as biomedicine, environmental remediation, and materials science have long been hypothesized, often in conjunction with their ability to deliver cargoes to overcome mass transport limitations. A very efficient way to load molecular cargoes is to disperse them in a liquid compartment, however, fabricating microswimmers with multiple liquid compartments remains a significant challenge. To address this challenge, we present a modular fabrication platform that combines microfluidic synthesis and sequential capillarity-assisted particle assembly (sCAPA) for microswimmers with various liquid compartments. We demonstrate the synthesis of monodisperse, small polymer-based microcapsules (Ø = 3-6μm) with different liquid cargoes using a flow-focusing microfluidic device. By employing the sCAPA technique, we assemble multiple microcapsules into microswimmers with high precision, resulting in versatile microswimmers with multiple liquid compartments and programmable functionalities. Our work provides a flexible approach for the fabrication of modular microswimmers, which could potentially actively transport cargoes and release them on demand in the future.

Self-Assembly of DNA Homopolymers by Pathway Dependence to Evade Metastable States.

A pathway-dependent strategy is proposed to assist single-stranded DNA polyadenine (poly(dA)) in evading metastable states and to achieve morphological regulation from microcapsules to microbowls by fractional n-butanol addition and emulsification (shaking) in a soft emulsion template (water-in-n-butanol). The first stage is the formation of small microcapsules by a fourth solvent addition and shaking. The second stage is the expansion of the small microcapsules initiated by the fifth solvent addition and shaking, drawing them to a new pathway to evade metastable states. Osmotic re-equilibrium and shaking are two indispensable conditions for overcoming the energy barriers. The third stage is the buckling of the expanded microcapsules and the evolution into microbowls after the evaporation of n-butanol to reach a global free energy minimum stable state. Conversely, the conventional one-time solvent addition and shaking pathway do not obtain microbowls. This kinetics pathway-dependent strategy evades metastability and shapes DNA oligonucleotides into desired structures via self-assembly.

Optimization of the Electrospraying Parameters for Formulation of Biopolymeric Microcapsules

There has been a surge in applying alginate microcapsules in diverse fields due to the numerous advantages of their non-toxicity, simple synthesis, and mechanical and chemical stability. Electrospraying is a simple and excellent technique for producing small microcapsules. This study aimed to analyse the trends in the operational parameters of the electrospraying technique, observed extreme conditions of the electrospraying, and selected the best performing parameters for producing small and spherical microcapsules. Alginate concentration was found to produce smaller microcapsules when kept at a minimum. However, the Implosion of microcapsules formed with less than 2%w/v alginate concentration was observed. Voltage increment produced smaller capsules, and fibre formation began at 21kV. Lower feed rates favoured both smaller microcapsules and better sphericity. Reduction in the needle orifice also favoured the formation of smaller microcapsules with less sphericity. Overall, a needle gauge of 27G, a voltage of 21kV, a flowrate of 0.5ml/h, and 2% w/v calcium chloride concentration were the best parameter combinations for producing small and spherical microcapsules.

Novel slow release ammonium persulfate capsules for in situ remediation of high arsenic groundwater

Slow-release materials (SRMs) are a promising oxidant delivery technology for in situ chemical oxidation (ISCO) to remove arsenic (As) from groundwater on site. Microcapsules capable of slowly releasing ammonium persulfate (APS) have been developed and applied to aquifer Fe-coating technology. APS microcapsules and dissolved Fe(II) can be injected into an As-contaminated aquifer to boost the formation of hydrous ferric oxide or hydroxide, thus immobilizing aqueous arsenic via adsorption. This study reports on the use of microcapsules with extended release time to control the redox environment in the in situ remediation of As-contaminated groundwater and prevent the reductive dissolution of hydrous ferric oxide or hydroxide. The experimental results demonstrate that microcapsules capable of slowly releasing the APS oxidant were successfully prepared. The core–shell structure of the microcapsules in which APS was enclosed with poly(methyl methacrylate) (PMMA) was confirmed with X-ray diffraction (XRD) and X-ray photo-electron spectroscopic (XPS) analyses, and the uniform morphology of the 1-µm microcapsules was revealed by scanning electron microscopy (SEM). The life span of the APS microcapsules was estimated to be 9 days. Zero-order release kinetics could qualitatively explain the experimental curve and predict the release mechanism. The small microcapsules had satisfactory transport performance in porous media and could represent a more efficient, long-term strategy for in situ remediation of high arsenic groundwater.

Oxidation and RGD Modification Affect the Early Neural Differentiation of Murine Embryonic Stem Cells Cultured in Core-Shell Alginate Hydrogel Microcapsules

Directed neural differentiation of embryonic stem cells (ESCs) has been studied extensively to improve the treatment of neurodegenerative disorders. This can be done through stromal-cell derived inducing activity (SDIA), by culturing ESCs directly on top of a layer of feeder stromal cells. However, the stem cells usually become mixed with the feeder cells during the differentiation process, making it difficult to obtain a pure population of the differentiated cells for further use. To address this issue, a non-planar microfluidic device is used here to encapsulate murine ESCs (mESCs) in the 3D liquid core of microcapsules with an alginate hydrogel shell of different sizes for early neural differentiation through SDIA, by culturing mESC-laden microcapsules over a feeder layer of PA6 cells. Furthermore, the alginate hydrogel shell of the microcapsules is modified via oxidation or RGD peptide conjugation to examine the mechanical and chemical effects on neural differentiation of the encapsulated mESC aggregates. A higher expression of Nestin is observed in the aggregates encapsulated in small (∼300 μm) microcapsules and cultured over the PA6 cell feeder layer. Furthermore, the modification of the alginate with RGD facilitates early neurite extension within the microcapsules. This study demonstrates that the presence of the RGD peptide, the SDIA effect of the PA6 cells, and the absence of leukemia inhibition factor from the medium can lead to the early differentiation of mESCs with extensive neurites within the 3D microenvironment of the small microcapsules. This is the first study to investigate the effects of cell adhesion and degradation of the encapsulation materials for directed neural differentiation of mESCs. The simple modifications (i.e., oxidation and RGD incorporation) of the miniaturized 3D environment for improved early neural differentiation of mESCs may potentially enhance further downstream differentiation of the mESCs into more specialized neurons for therapeutic use and drug screening.

Antibacterial finishing of cotton fabric with clove oil microcapsules

The present study was conducted to develop a microencapsulated antibacterial finish using clove essential oil for cotton fabric. Microcapsules of clove essential oil (Syzygium fragranceticum) were developed with phase separation - complex coacervation technique using five concentrations of essential oil for application on cotton fabric. The finished cotton fabric was tested for SEM analysis and anti-bacterial finish using standard test methods. Findings of SEM analysis revealed that small spherical shape microcapsules in the treated samples were located at interstices between the fibres and on the fibre surface. The zone of inhibition was found maximum at concentration 5 of MCCL treated cotton fabric before wash with 12.5 mm ± 1.5 and 12.33 mm ± 0.57 (Mean and SD) against S. aureus and E. coli. MCCL oil treated cotton fabric showed the good wash durability against S. aureus as compared to E.coli. The antimicrobial property decreased with increasing number of wash cycles.

Liquid Crystals under Confinement in Submicrometer Capsules.

Liquid crystal (LC) ordering and phase transition behavior under confined conditions have attracted extensive attention and enabled many applications. However, the ordering and phase transition behavior of LCs in submicrometer capsules have seldom been studied, primarily due to the lack of proper capsulizing and visualization approaches to such small LC microcapsules. Herein, we achieve submicrometer LC capsules with the sizes down to 100 nm by using emulsion-based interfacial sol-gel reaction. The behavior of LCs under the submicrometer confinement conditions is investigated while the sizes and chemical composition of the microcapsule shell surface are tuned in a controllable way. The phase transition temperatures of LCs in the submicrometer capsules shift from those of bulk LCs due to the surface-induced ordering of LCs under the strong confinement conditions, which causes formation of topological defects and alters the order parameter. Using nonlinear optical imaging technology, we explore the structures of director field of LCs that arise as a result of the competition between the surface boundary conditions and LC elasticity. The results show that the nanoscale encapsulation can significantly influence the structural configurations of the director and phase transitions of LCs under various confinement conditions.

Surface modified alginate multicore microcapsules and their application in self-healing epoxy coatings for metallic protection

Conventionally, self-healing microcapsules are synthesized from synthetic polymers associated with complicated fabrication process. It appears in the range of (10–400 μm) to suit different applications. Here, we report green self-healing microcapsules synthesized from alginate biopolymer. The synthesis process is straightforward, require no pH and temperature change. Using simple methods (electrospraying and air atomization), alginate/epoxy microcapsules of two size range (∼350 μm and ∼150 μm) are fabricated. However, the smaller air atomized microcapsules collapsed after drying. Chitosan coating successfully provides structural support to small air atomized microcapsules and improves the elastic modulus of both microcapsules. Peak force quantitative nanomechanical mapping (PFQNM) under atomic force microscopy (AFM) is used to acquire the capsules elastic modulus. Chitosan coating slightly improved the elastic modulus of electrosprayed microcapsules from 3.43 ± 0.80 GPa to 4.45 ± 0.80 GPa. Although HNTs are unable to enhance the structural integrity of small microcapsules, it improves the elastic modulus of big microcapsules up to 6.04 ± 0.20 GPa. To evaluate the self-healing ability, these microcapsules and Scandium (III) triflate catalyst are incorporated into epoxy coating and applied on a metallic substrate. The capsule-catalyst self-healing coatings showed good self-healing performance in closing the gaps on the scratch.

Thermochromic microcapsules with highly transparent shells obtained through in-situ polymerization of urea formaldehyde around thermochromic cores for smart wood coatings

In this paper, thermochromic microcapsules were synthesized in situ polymerization with urea formaldehyde as shell material and thermochromic compounds as core material. The effects of emulsifying agent and conditions on surface morphology and particle size of microcapsules were studied. It was found that the size and surface morphology of microcapsules were strongly depending on stirring rate and the ratio of core to shell. The stable and small size spherical microcapsules with excellent transparency can be obtained at an emulsifying agent to core to shell ratio as 1:5:7.5 under mechanical stirring at 12 krpm for 15 min. Finally, the thermochromic property was discussed by loading microcapsules in wood and wood coatings. Results indicate that microcapsules can realize the thermochromic property while incorporated with wood and coatings, and could have high potential in smart material fabrication.

Glucose-stimulated insulin release: Parallel perifusion studies of free and hydrogel encapsulated human pancreatic islets.

To explore the effects immune-isolating encapsulation has on the insulin secretion of pancreatic islets and to improve our ability to quantitatively describe the glucose-stimulated insulin release (GSIR) of pancreatic islets, we conducted dynamic perifusion experiments with isolated human islets. Free (unencapsulated) and hydrogel encapsulated islets were perifused, in parallel, using an automated multi-channel system that allows sample collection with high temporal resolution. Results indicated that free human islets secrete less insulin per unit mass or islet equivalent (IEQ) than murine islets and with a less pronounced first-phase peak. While small microcapsules (d = 700 µm) caused only a slightly delayed and blunted first-phase insulin response compared to unencapsulated islets, larger capsules (d = 1,800 µm) completely blunted the first-phase peak and decreased the total amount of insulin released. Experimentally obtained insulin time-profiles were fitted with our complex insulin secretion computational model. This allowed further fine-tuning of the hormone-release parameters of this model, which was implemented in COMSOL Multiphysics to couple hormone secretion and nutrient consumption kinetics with diffusive and convective transport. The results of these GSIR experiments, which were also supported by computational modeling, indicate that larger capsules unavoidably lead to dampening of the first-phase insulin response and to a sustained-release type insulin secretion that can only slowly respond to changes in glucose concentration. Bioartificial pancreas type devices can provide long-term and physiologically desirable solutions only if immunoisolation and biocompatibility considerations are integrated with optimized nutrient diffusion and insulin release characteristics by design.

Polyvinyl Alcohol-salt Hydrate Mixtures as Passive Thermal Energy Storage Systems

Inorganic salt hydrates are promising candidates as latent heat storage materials entailing, for example, a high thermal energy storage density and cheap price [1,2] in spite that they have many handicaps. For almost all applications, Phase change materials (PCMs) have to be encapsulated, that is, they have to be hermetically sealed within barrier containments, preferably within small microcapsules. Encapsulation improves heat transfer, cycling stability, and material compatibility with the environment. However, no attempt has been completely successful to microencapsulate salt hydrates so far due to the high surface polarities of these substances, edge alignment effects, their tendency to alter their water content [3]. This work is aimed to encapsulate some commonly used salt hydrates; sodium sulphate decahydrate (Na2SO4.10H2O) and calcium chloride hexahydrate (CaCl2.6H2O) in a hydrophilic polymer; polyvinyl alcohol (PVA) stably for passive thermal energy storage systems. So that an economically beneficial application mean will be validated.

Nozzleless Fabrication of Oil-Core Biopolymeric Microcapsules by the Interfacial Gelation of Pickering Emulsion Templates.

Ionotropic gelation has been an attractive method for the fabrication of biopolymeric oil-core microcapsules due to its safe and mild processing conditions. However, the mandatory use of a nozzle system to form the microcapsules restricts the process scalability and the production of small microcapsules (<100 μm). We report, for the first time, a nozzleless and surfactant-free approach to fabricate oil-core biopolymeric microcapsules through ionotropic gelation at the interface of an O/W Pickering emulsion. This approach involves the self-assembly of calcium carbonate (CaCO3) nanoparticles at the interface of O/W emulsion droplets followed by the addition of a polyanionic biopolymer into the aqueous phase. Subsequently, CaCO3 nanoparticles are dissolved by pH reduction, thus liberating Ca(2+) ions to cross-link the surrounding polyanionic biopolymer to form a shell that encapsulates the oil droplet. We demonstrate the versatility of this method by fabricating microcapsules from different types of polyanionic biopolymers (i.e., alginate, pectin, and gellan gum) and water-immiscible liquid cores (i.e., palm olein, cyclohexane, dichloromethane, and toluene). In addition, small microcapsules with a mean size smaller than 100 μm can be produced by selecting the appropriate conventional emulsification methods available to prepare the Pickering emulsion. The simplicity and versatility of this method allows biopolymeric microcapsules to be fabricated with ease by ionotropic gelation for numerous applications.

Microencapsulated tumor assay: Evaluation of the nude mouse model of pancreatic cancer

To establish a more stable and accurate nude mouse model of pancreatic cancer using cancer cell microencapsulation. The assay is based on microencapsulation technology, wherein human tumor cells are encapsulated in small microcapsules (approximately 420 μm in diameter) constructed of semipermeable membranes. We implemented two kinds of subcutaneous implantation models in nude mice using the injection of single tumor cells and encapsulated pancreatic tumor cells. The size of subcutaneously implanted tumors was observed on a weekly basis using two methods, and growth curves were generated from these data. The growth and metastasis of orthotopically injected single tumor cells and encapsulated pancreatic tumor cells were evaluated at four and eight weeks postimplantation by positron emission tomography-computed tomography scan and necropsy. The pancreatic tumor samples obtained from each method were then sent for pathological examination. We evaluated differences in the rates of tumor incidence and the presence of metastasis and variations in tumor volume and tumor weight in the cancer microcapsules vs single-cell suspensions. Sequential in vitro observations of the microcapsules showed that the cancer cells in microcapsules proliferated well and formed spheroids at days 4 to 6. Further in vitro culture resulted in bursting of the membrane of the microcapsules and cells deviated outward and continued to grow in flasks. The optimum injection time was found to be 5 d after tumor encapsulation. In the subcutaneous implantation model, there were no significant differences in terms of tumor volume between the encapsulated pancreatic tumor cells and cells alone and rate of tumor incidence. There was a significant difference in the rate of successful implantation between the cancer cell microencapsulation group and the single tumor-cell suspension group (100% vs 71.43%, respectively, P = 0.0489) in the orthotropic implantation model. The former method displayed an obvious advantage in tumor mass (4th wk: 0.0461 ± 0.0399 vs 0.0313 ± 0.021, t = -0.81, P = 0.4379; 8th wk: 0.1284 ± 0.0284 vs 0.0943 ± 0.0571, t = -2.28, respectively, P = 0.0457) compared with the latter in the orthotopic implantation model. Encapsulation of pancreatic tumor cells is a reliable method for establishing a pancreatic tumor animal model.

Erratum to: Small microcapsules of crystal proteins and spores of Bacillus thuringiensis by an emulsification/internal gelation method

Erratum to: Small microcapsules of crystal proteins and spores of Bacillus thuringiensis by an emulsification/internal gelation method

A laboratory-scale device for the straightforward production of uniform, small sized cell microcapsules with long-term cell viability

Microencapsulated and genetically engineered cells may be used for prolonged delivery of therapeutically active proteins. The objective of this study was to develop a simple, inexpensive and flexible laboratory-scale device for the production of cell microcapsules, especially capsules of small diameter (<300 μm). Many microencapsulation devices are expensive, difficult to assemble and to use, and often more suitable for large-scale experiments. However, the simplicity and low price of the encapsulation system should not limit the quality of capsules and reproducibility of the process: for successful in vitro and in vivo experiments it is important to be able to produce uniform, spherical microcapsules without deformities with high reproducibility. In addition, an advantage of the present procedure compared to other similar, co-axial laminar gas flow systems is the possibility to produce also small microcapsules, less than 200 μm in diameter, with narrow size distribution. First, design, optimization and reproducibility testing of this custom-built device were carried out. Second, microencapsulated retinal pigment epithelial cells (ARPE-19) capable of secreting soluble vascular endothelial growth factor receptor 1 (sVEGFR1) were engineered. The cells remained viable in alginate-poly-L-lysine-alginate microcapsules and secreted sVEGFR1 for prolonged periods.

Small microcapsules of crystal proteins and spores of Bacillus thuringiensis by an emulsification/internal gelation method

This paper describes a microencapsulation process of a spore crystal aggregate produced by Bacillus thuringiensis var. kurstaki HD-1. The methodology is based on the emulsification/internal gelation method, and was implemented to produce microcapsules of small diameter (< 10 μm) with the capacity to protect the spore crystal aggregate from extreme ultraviolet radiation. The diameter of microcapsules was in the range of 3.1 ± 0.2-6.8 ± 0.4 μm, which is considered adequate for biological control purposes. The protective effect of the alginate coat was verified by the remaining 60 ± 2% and 40 ± 1% of spore viability and protein activity, respectively, after UV-B radiation of 236 J, and with bioassays with Spodoptera frugiperda. It is expected that the protective effect of the alginate coat will improve the effectiveness of the Bt-HD1 formulated as small diameter microcapsules, and their yield, once they are released into the environment, will also be improved.

Preferential vitrification of water in small alginate microcapsules significantly augments cell cryopreservation by vitrification

The morphological changes of small (approximately 100 microm) alginate microcapsules and the biophysical alterations of water in the microcapsules during cryopreservation were studied using cryomicroscopy and scanning calorimetry. It was found that water in the small microcapsules can be preferentially vitrified over water in the bulk solution in the presence of 10% (v/v) or more dimethylsulfoxide (DMSO, a cryoprotectant), which resulted in an intact morphology of the microcapsules post cryopreservation with a cooling rate of 100 degrees Celsius/min. A small amount of Ca(2+) (up to 0.15 M) was also found to help maintain the microcapsule integrity during cryopreservation, which is attributed to the enhancement of the alginate matrix strength by Ca(2+) rather than promoting vitrification of water in the microcapsules. The preferential vitrification of water in small microcapsules was further found to significantly augment cell cryopreservation by vitrification at a low concentration of cryoprotectants (i.e., 10% (v/v)) using a small quartz microcapillary (400 microm in diameter). Therefore, the small alginate microcapsule could be a great system for protecting living cells that are highly sensitive to stresses due to freezing (i.e., ice formation) and high concentration of cryoprotectants from injury during cryopreservation.

Small Agarose Microcapsules with Cell-Enclosing Hollow Core for Cell Therapy: Transplantation of Ifosfamide-Activating Cells to the Mice with Preestablished Subcutaneous Tumor

Cell transplantation after enclosing in microcapsules has been studied as an alternative approach for treatment of wide variety of diseases. In the present study, we examined the feasibility of using agarose microcapsules, having a cell-enclosing hollow core of 100-150 microm in diameter and agarose gel membrane of about 20 microm in thickness, as a device for the methodology. We enclosed cells that had been genetically engineered to express cytochrome P450 2B1, an enzyme that activates the anticancer prodrug ifosfamide. The enclosed cells were shown to express the enzymatic function in the microcapsules in that they suppressed the growth of tumor cells in medium containing ifosfamide. In addition, a more significant regression of preformed tumors was observed in the nude mice implanted with the cell-enclosing microcapsules compared with those implanted with empty capsules after administration of ifosfamide. Preformed tumors shrank by less than 40% in volume in 6 of the 10 recipients implanted with cell-enclosing microcapsules. In contrast, only 1 in 10 of the preformed tumors in the recipient implanted with empty microcapsules shrank by this amount. These results suggest that agarose microcapsules containing cytochrome P450 2B1 enzyme-expressing cells are feasible devices for improving the chemotherapy of tumors. Thus, agarose microcapsule having hollow cores are generally a good candidate as vehicles for cell-encapsulation approaches to cell therapy.

Encapsulation of Living Cells in Small (∼100 μm) Alginate Microcapsules by Electrostatic Spraying: A Parametric Study

A parametric study was performed to understand the effect of preparation parameters on size, morphology, and encapsulation efficiency (i.e., cells/microcapsule) of alginate microcapsules prepared using the electrostatic spray method. The preparation parameters studied include sodium alginate concentration, spray voltage, flow rate, and cell density. It was found that both the flow rate and spray voltage have a significant impact on microcapsule size while the microcapsule morphology is greatly influenced by both the sodium alginate concentration and spray voltage. To obtain small ( approximately 100 mum) cell-loaded microcapsules with good morphology (i.e., round in shape and uniform in size) and high encapsulation efficiency (>5 cells/microcapsule), the optimal ranges of spray voltage, flow rate, alginate concentration, and cell density are from 1.6-1.8 kV, 1.5-3 ml/h, >1.5% (w/v), and (3-5)x10(6) cells/ml, respectively. Under optimal preparation conditions, cells were found to survive the microencapsulation process well.