Electrostatic Droplet Generation Research Articles

Preparation of Alginate/Poly(L-Arginine)-Chitosan Ternary Complex Microcapsules

Following a polyelectrolytical complex reaction, alginate/poly(L-Arginine)-chitosan ternary complex microcapsules were prepared by coating poly(L-Arginine) and chitosan as membrane materials on calcium alginate beads, which were produced by a high-voltage electrostatic droplet generator. The influences on the diameter and uniformity of the calcium alginate beads were studied, and the optimum operating parameters were selected to produce microcapsules. The in vitro drug release behavior and pH stimuli-response of alginate/poly(L-Arginine)-chitosan ternary complex microcapsules were investigated. In comparison with alginate/chitosan microcapsules, alginate/poly(L-Arginine) microcapsules and their corresponding double-membrane microcapsules, alginate/poly(L-Arginine)-chitosan microcapsules released the macromolecular drug in a more sustained and stable way. It was found that they released 85.7% of the bovine erythrocytes hemoglobin (Hb) in 85 hours by approximate first-order kinetics in pH 6.8 PBS. While in a pH 1.0 HCl solution, only 9.6 % of the Hb was released in the first half hour and then the drug release shifted to a flat stage, which indicated that the alginate/poly(L-Arginine)-chitosan microcapsules possessed a pH stimuli-response property. The results suggest that the alginate/poly(L-Arginine)-chitosan ternary complex microcapsules might be a potential colon-targeted drug delivery system for the encapsulation of proteins.

Bioethanol production from corn meal by simultaneous enzymatic saccharification and fermentation with immobilized cells of Saccharomyces cerevisiae var. ellipsoideus

The simultaneous enzymatic saccharification and fermentation (SSF) of corn meal using immobilized cells of Saccharomyces cerevisiae var. ellipsoideus yeast in a batch system was studied. The yeast cells were immobilized in Ca-alginate by electrostatic droplet generation method. The process kinetics was assessed and determined and the effect of addition of various yeast activators (mineral salts: ZnSO 4 · 7H 2O and MgSO 4 · 7H 2O, and vitamins: Ca-pantothenate, biotin and myo-inositol) separately or mixed, was investigated. Taking into account high values of process parameters (such as ethanol concentration, ethanol yield, percentage of the theoretical ethanol yield, volumetric productivity and utilized glucose) and significant energy savings the SSF process was found to be superior compared to the SHF process. Further improvement in ethanol production was accomplished with the addition of mineral salts as yeast activators which contributed to the highest increase in ethanol production. In this case, the ethanol concentration of 10.23% (w/w), percentage of the theoretical ethanol yield of 98.08%, the ethanol yield of 0.55 g/g and the volumetric productivity of 2.13 g/l·h were obtained.

Bioethanol production by immobilized Sacharomyces cerevisiae var. ellipsoideus cells

Bioethanol can be produced by fermentation of sugars from various waste agricultural materials. Whichever system for bioethanol production is chosen, the attention must be paid to the overall economics and energy consumption. The aim of the present study was to investigate the immobilization of Sacharomyces cerevisiae var. ellipsoideus yeast cells for bioethanol production from corn meal hydrolyzates. For this purpose the biocompatible polymers such as polyvinil alcohol (PVA) and Ca-alginate were assessed. The parameters of ethanol fermentation, such as inoculum concentration in different carriers and the choice of a convenient carrier for the efficient ethanol production were studied. The maximum ethanol concentration of 10.05% (w/w) was obtained in the fermentation of corn meal hydrolyzates by 5% (v/v) of inoculum concentration of the yeast immobilized in Ca-alginate using a method of electrostatic droplet generation. The repeated batch fermentation with the yeast immobilized in Ca-alginate indicated that alginate gels degraded after the second fermentation cycle. PVA carrier exhibited better mechanical properties and stability; however lower ethanol concentrations were achieved during the fermentation.

Abstract 5283: Perfluorocarbon Microcapsules for X-ray Visualization of Mesenchymal Stem Cell Delivery and Engraftment

Mesenchymal stem cell (MSC) transplantation offers an alternative strategy for therapeutic angiogenesis for the management of ischemic cardiovascular disease. However, the poor survival of transplanted cells and lack of sustained engraftment severely limits therapeutic efficacy. We propose a novel cell microencapsulation method utilizing perfluoro-octyl-bromide (PFOB) impregnated alginate-poly-L-lysine-alginate microcapsules (PFOB Caps) that enable noninvasive cell delivery and tracking using conventional clinical X-ray fluoroscopy. Microen-capsulation of rabbit MSCs (1x10 6 cells/ml) combined with PFOB-loaded alginate was performed with an electrostatic droplet generator. Control capsules lacked PFOB. MSC viability post-encapsulation was determined using a microfluorometric assay. X-ray fluoroscopy was performed during direct intramuscular/intramyocardial injection of 2300 capsules/injection in a rabbit peripheral arterial disease (PAD) model (n=2) and a swine reperfused myocardial infarction (MI) model (n=3). Fluoroscopy and angiographic computed tomography (DynaCT) were performed to assess the ability to monitor microcapsule delivery and tracking with X-ray. As compared to control capsules, PFOB Caps showed similar swelling, when subjected to 55 mM sodium citrate incubation (mean diameter increased 5.4% for PFOB vs. 4.5% for control, P=NS), and mechanical strength (broken capsules from osmotic pressure tests: 2/591 for PFOB and 2/603 for control). The PFOB Caps showed a small viability decrease immediately after encapsulation (90±3%) with no significant further viability loss up to 4 weeks in vitro (79±5%). In both PAD and MI animals, successful injection of PFOB Caps could be demonstrated with DynaCT but not with real-time fluoroscopic images. Control capsules were never detected. CT tracking of PFOB Caps was possible up to 5 weeks post-injection. PFOB microcapsules provide an ideal microenvironment for maintaining MSC viability in vitro . In addition, PFOB proves to be a non-toxic, radiopaque agent suitable for cell tracking using conventional fluoroscopy in vivo . PFOB microencapsulation of MSCs may be a novel approach for X-ray tracking therapeutic angiogenesis.

Effect of different fermentation parameters on bioethanol production from corn meal hydrolyzates by free and immobilized cells of Saccharomyces cerevisiae var. ellipsoideus

AbstractBACKGROUND: Bioethanol produced from renewable biomass, such as corn meal, is a biofuel that is both renewable and environmentally friendly. Significant scientific and technological investments will be needed to achieve substitution of conventional fossil fuels with alternative fuels. The ethanol fermentation of enzymatically obtained corn meal hydrolyzates by free and immobilized cells of Saccharomyces cerevisiae var. ellipsoideus yeast in a batch system was studied. The initial glucose and inoculum concentration and the time required for the efficient ethanol production were optimized taking into account parameters such as ethanol concentration, ethanol yield, percentage of the theoretical yield of ethanol and volumetric productivity in both immobilized and free cell systems.RESULTS: The yeast cells were immobilized in Ca–alginate by an electrostatic droplet generation method. An optimal initial inoculum concentration of 2% (v/v) and optimal fermentation time of 38 h for both immobilized and free yeasts were determined. An optimal initial glucose concentration of 150 g L−1 for free system was achieved. At the initial glucose concentration of 176 g L no substrate or product inhibition were achieved with immobilized yeast.CONCLUSION: By immobilization of the yeast into Ca–alginate using the method of electrostatic droplet generation a superior system was realized, which exhibited lower substrate inhibition and higher tolerance to ethanol. The cells of S. cerevisiae var. ellipsoideus yeast entrapped in Ca–alginate showed good physical and chemical stability, and no substrate and product diffusion restrictions were noticed. Copyright © 2008 Society of Chemical Industry

Culture of C3A Cells in Alginate Beads for Fluidized Bed Bioartificial Liver

Extracorporeal bioartificial liver has been designed to sustain the detoxification and synthetic function of the failed liver in patients suffering from acute liver failure until the time of liver allotransplantation or regeneration of their own. A fluidized bed, bioartificial liver improves the mass transfer velocity between the medium and the hepatocytes. Detoxification functions of the liver could be replaced by completely artificial systems, but the synthetic functions of hepatocytes may be obtained only by metabolically active cells. The aim of our study was to investigate the influence of C3A cell culture in alginate beads on synthetic function in a fluidized bed, bioartificial liver. Cells in alginate beads were prepared using an electrostatic droplet generator of our own design using low-viscosity alginate. Beads were cultured for 24 hours then 7 days in static conditions and then 24 hours of fluidization in the bioreactor to assess albumin production. We observed significantly increased albumin production by C3A cells entrapped in alginate beads during static culture. Fluidization increased albumin production compared with static culture. Fluidization performed after 7 days of static culture resulted in a significant increase in albumin synthesis. In conclusion, static culture of alginate beads hosting hepatic cells facilitates restoration of cell function.

Biologic effect and immunoisolating behavior of BMP-2 gene-transfected bone marrow-derived mesenchymal stem cells in APA microcapsules

We investigated the encapsulation of BMP-2 gene-modified mesenchymal stem cells (MSCs) in alginate-poly- l-lysine (APA) microcapsules for the persistent delivery of bone morphogenic protein-2 (BMP-2) to induce bone formation. An electrostatic droplet generator was employed to produce APA microcapsules containing encapsulated β-gal or BMP-2 gene-transfected bone marrow-derived MSCs. We found that X-gal staining was still positive 28 days after encapsulation. Encapsulated BMP-2 gene-transfected cells were capable of constitutive delivery of BMP-2 proteins for at least 30 days. The encapsulated BMP-2 gene-transfected MSCs or the encapsulated non-gene transfer MSCs (control group) were cocultured with the undifferentiated MSCs. The gene products from the encapsulated BMP-2 cells could induce the undifferentiated MSCs to become osteoblasts that had higher alkaline phosphatase (ALP) activity than those in the control group ( p < 0.05). The APA microcapsules could inhibit the permeation of fluorescein isothiocyanate-conjuncted immunoglobulin G. Mixed lymphocyte reaction also indicates that the APA microcapsules could prevent the encapsulated BMP-2 gene-transfected MSCs from initiating the cellular immune response. These results demonstrated that the nonautologous BMP-2 gene-transfected stem cells are of potential utility for enhancement of bone repair and bone regeneration in vivo.

Preparation of protein-loaded microspheres with size ⩽10 μm by electrostatic droplet generation technology

The development of non-injection route for protein drugs, especially oral administration, has been the main focus of controlled release of drugs. To overcome obstacles unsolved such as enzyme degradation and penetration barrier of intestinal epithelium, technologies using microspheres as carrier of protein drugs have been proven potential to realize oral administration. It has been demonstrated that microspheres can not only protect proteins, but also facilitate the penetration and absorption through Peyer’s patches when the size is smaller than 10 μm. Therefore, the objective of this paper is to prepare protein-loaded microspheres with size ⩽ 10 μm. Electrostatic droplet generation technology was used with insulin and hemoglobin as drug models and sodium alginate as microsphere material. By decreasing the surface tension of feed solution by adding surfactant, and improving electric field distribution by changing the shape of container and electrode for gelation solution, protein-loaded microspheres with mean size less than 10 μm were successfully produced through needle with diameter of 400 μm. The microspheres showed good sphericity and narrow size distribution. The mean standard variance of size distribution was 1.61. The encapsulation efficiency of proteins was over 70%. Moreover, the significance analysis of factors influencing the size of protein loaded microspheres was carried out through orthogonal experiments, which showed that output voltage (U), needle diameter (D) and the distance between needle tips to the surface of gelation solution (δ) influenced significantly the size of microspheres. Finally, the statistic analysis showed that when confidence level was α=0.05, and α=0.1, confidence interval of microsphere size can be (6.2545, 10.1735) and (6.6022, 9.8258) correspondingly, suggesting that there is good repeatability and reliability for improving electrostatic droplet generation technology to prepare protein-loaded microspheres with size ⩽10 μm.

Immobilization of cells by electrostatic droplet generation: a model system for potential application in medicine.

The process of electrostatic extrusion as a method for cell immobilization was investigated that could be used for potential applications in medicine. An attempt was made to assess the effects of cell addition and polymer concentration on the overall entrapment procedure, ie, on each stage of immobilization: polymer-cell suspension rheological characteristics, electrostatic extrusion process, and the process ofgelation. The findings should contribute to a better understanding of polymer-cell interactions, which could be crucial in possible medical treatments. Alginate-yeast was used as a model system for carrier-cells. The electrostatic extrusion was considered as a complex two-phase flow system and the effects of cell and alginate concentrations on the resulting microbead size and uniformity were assessed. Under investigated conditions, microbeads 50-600 microm in diameter were produced and the increase in both alginate and cell concentrations resulted in larger microbeads with higher standard deviations in size. We attempted to rationalize the findings by rheological characterization of the cell-alginate suspensions. Rheological characterization revealed non-Newtonian, pseudoplastic behavior of cell-alginate suspensions with higher viscosities at higher alginate concentrations. However, the presence of cells even at high concentrations (5x10(8) and 1x10(9) cells/mL) did not significantly affect the rheological properties of Na-alginate solution. Lastly, we investigated the kinetics of alginate gelation with respect to the quantity of Ca2+ ions and cell presence. The gelation kinetics were examined under conditions of limited supply with Ca2+ ions, which can be essential for immobilization of highly sensitive mammalian cells that require minimal exposure to CaCl2 solution. The molar ratio of G units to Ca2+ ions of 3.8:1 provided complete crosslinking, while the increase in alginate concentration resulted in prolonged gelation times but higher strength of the resulting gel. The cell presence decreased the rate of network formation as well as the strength of the obtained Ca-alginate hydrogel.

Optimization of the electrostatic droplet generation process for controlled microbead production: Single nozzle system

The aim of this study was to optimize the electrostatic extrusion process for producing small, spherical and uniform microbeads with different fluid viscosities by varying the operating parameters in very wide ranges. Alginate was used as a model polymer. Since the rheological behavior of the solution is one of the parameters that affects the flow dynamics during extrusion, viscosity measurements of solutions with different alginate content were performed. The results obtained in this study show that an electrostatic droplet generator can be used for the production of spherical microbeads of narrow size distribution from low- and medium- viscous fluids (0.5, 1, and 2% of alginate). The average microbead diameter for low-viscous solutions was less than 100 micrometers. It was possible to obtain beads smaller than 500 micrometers that were very uniform (standard deviations less than 2.5%) and of spherical (the shape distortion was less than 1%) from medium-viscous alginate solution (2%). By reducing the polymer flowrate to less than 1 ml/h, even smaller microbeads were produced with diameters of about 300 micrometers. The particular contribution of this paper is in exceeding limitations regarding the use of high-viscous polymer solutions. Optimization of the operating conditions that included the use of a very small needle (0.15 mm), enlargement of the electrode distance to more than 20 cm and a severe reduction in the polymer flow rate to lower than 5 ml/h (for 3% alginate) or 1 ml/h (for 4% alginate) enabled the production of small, entirely spherical and uniform microbeads with an average microbead diameter lower than 500 and 700 micrometers in the case of 3 and 4% of alginate, respectively.

Alginate Microbeads as Potential Support for Cultivation of Bone Marrow Stromal Cells

Alginate is currently being employed and explored for a broad range of biomedical and biotechnology applications, due to its biodegradability and simple procedure for cell immobilization. However, cell immobilization was mostly aimed for immunoisolatory and biochemical processing applications and far less is known about potentials of alginate as a substrate for tissue formation. In the present work, isolation, immobilization and cultivation procedures of murine bone marrow stromal cells (BMSC) were studied and standardized in order to establish the alginate-bioreactor culture system for chondrogenic and/or hematopoiesis-supportive tissue progression. Two techniques for cell immobilization based on alginate were investigated: entrapment within gel matrix using electrostatic droplet generation and simple cell adsorption onto gel surfaces. Alginate gels in forms of microbeads and discs with immobilized culture expanded BMSC were cultivated for up to 30 days and analyzed for surface properties, cell concentration, viability, and differentiation.

Effects of cell addition on immobilization by electrostatic droplet generation

In this study, an attempt was made to assess the effects of cell addition and final concentration on the process of electrostatic extrusion as a method for cell immobilization in alginate microbeads. The electrostatic extrusion process is a complex function of several operating parameters, the system geometry, and the properties of the polymer solution, which is being extruded. The addition of cells results in the formation of a two-phase system, adding to the complexity of the process by the associated phenomenon of two-phase flow. This study especially focused on analyzing the effects of cell presence on each stage of the immobilization process. Specifically, the effects of the cell and alginate concentrations on the resulting microbead size and uniformity were assessed. Under the investigated conditions, microbeads, 50-600 ?m in diameter, were produced and the increase in both alginate and cell concentrations resulted in larger microbeads with higher standard deviations in size. We attempted to rationalize the obtained findings by rheological characterization of the cell-alginate suspensions. H-NMR Spectroscopy of the alginate used in this study revealed a high content (67%) of guluronic residues and GG diad blocks (FGG = 55%). The mole fractions of the MM and GM diad sequences, Fmm and Fgm, were 21 and 12%, respectively. Rheological characterization revealed non-Newtonian, pseudoplastic behavior of the cell-alginate suspensions with an increase in viscosity as the alginate concentration was increased. However, the presence of cells even at high concentrations (5 ? 108 and 1 ? 109 cell/ml) did not significantly affect the rheological properties of Na alginate solution. Finally, the effects of the alginate and cell concentrations on the gelation kinetics and the dynamic-mechanical behavior of the obtained hydrogels were investigated. A molar ratio of G units to Ca2+ ions of 3.8 : 1 provided complete crosslinking, while an increase in the alginate concentration resulted in prolonged gelation times, but higher strength of the resulting gel. Cell presence decreased the rate of network formation, as well as the strength of the obtained Ca alginate hydrogel.

Use of ultrathin shell microcapsules of hepatocytes in bioartificial liver-assist device.

We previously encapsulated hepatocytes in ultrathin shell microcapsules and showed them to have enhanced differentiated functions over cells cultured in monolayer. Here we have used these microencapsulated hepatocytes in a bioartificial liver-assisted device (BLAD) with a rat hepatectomy model. Primary rat hepatocytes were encapsulated in 150- to 200-microm microcapsules, using an electrostatic droplet generator. The microencapsulated hepatocytes exhibited good in vitro urea synthesis activity in plasma from rats with fulminant hepatic failure (FHF). The ex vivo hemoperfusion was conducted in FHF rats by perfusing plasma at a rate of 1-2 mL/min through 1.5-2 x 10(8) encapsulated hepatocytes packed into a packed-bed bioreactor. Hemoperfusion with the bioreactor was initiated 5 h after operative induction of liver failure and continued for 7 h. The BLAD-treated rats showed improvements over the control groups in survival time and metabolic indicators, including ammonia and total bilirubin levels. Furthermore, expanded bed adsorption (EBA) detoxification technology using Streamline-SP resin was explored to complement the bioreactor with microencapsulated hepatocytes. In vitro experiments indicated that serum ammonia could be specifically removed in dose-dependent manner, whereas the total serum proteins were unaffected by the resin. In ex vivo experiments, hemoperfusion with the resin was initiated 3 h after operative induction of liver failure and continued for 7 h. The resin-treated rats showed obvious serum ammonia removal with no observable total blood protein and blood cell adsorption. Therefore, Streamline-SP resin can potentially be integrated into a BLAD for improved efficacy.

Alginate-immobilized lipase by electrostatic extrusion for the purpose of palm oil hydrolysis in lecithin/isooctane system

Lipase from Candida rugosa was immobilized in alginate beads for possible application in non-aqueous or microaqueous reaction systems. An electrostatic droplet generation technique was used for production of small diameter (<1 mm) lipase-alginate beads. This technique provided negligible loss of the lipase (immobilization efficiencies were 98.2–99.2%). Under optimal immobilization conditions (applied potential 4.9 kV, needle gauge 21, 2% sodium alginate solution) the lipase-alginate beads, 0.65 mm in diameter, retained enzyme activity equivalent to 75% that of free lipase. The activity of the immobilized lipase was verified in the reaction of palm oil hydrolysis in a lecithin/isooctane system. The reaction rate with alginate-immobilized lipase was lower than with the free enzyme but the final conversions were approximately the same (∼74%). Immobilized lipase could be used for up to three reaction cycles with little loss of activity.

Electrostatic generation of alginate microbeads loaded with brewing yeast

The substantial concern with the possible use of immobilized yeast cells for beer production is reduction of internal mass transfer resistance during continuous fermentation. One way to minimise this problem is to use small-diameter beads. The effects of bead diameters in the range 0.3–2.0 mm on yeast cell immobilization and growth over a short-term cultivation were investigated. Bead diameters in the range 0.5–0.6 mm were optimal and provided rapid cell growth and the highest final cell concentration (2.33×10 9 cells/ml of beads). Electrostatic droplet generation was investigated as a technique for production of alginate microbeads. The effects of applied potential, internal needle diameter and electrode position on bead diameter were assessed. The results have shown that this method can be used for controlled production of small-size microbeads loaded with yeast. Depending on applied conditions it was possible to produce the beads in the range 250 μm–2.0 mm in diameter.

Physico-chemical and mass transfer considerations in microencapsulation.

To gain better insight into mass transfer problems in encapsulated cell systems requires a combination of experimental investigations and mathematical modeling. Specific mass transfer studies are reviewed including oxygen transfer in immobilized animal cell culture bioreactors, modeling of polymer droplet formation and encapsulated animal cell growth, and growth of somatic tissue encapsulated in alginate using electrostatics. Special emphasis is given to electrostatic droplet generation for cell immobilization.

Electrostatic Droplet Generation for Encapsulat ion of Somatic Tissue: Assessment of High‐Voltage Power Supply

AbstractThe production of alginate microbeads with and without somatic tissue was investigated using an electrostatic droplet generator with a custom‐made fixed (5.7 kV) and variable (0–20 kV) high‐voltage power supply. The effects of applied potential, needle size, and alginate concentration were assessed as well as the immobilization of carnation callus cells. The high‐voltage output from the power supply depended on whether the low‐voltage input was increasing or decreasing. This hysteresis effect may be due to the electrical properties of the oscillator in the high‐voltage source. While a short electrode distance and a high needle gauge were important for producing small alginate bead diameters (e.g., 100 μm), alginate concentration in the range 1–3% (w/v) was not a key factor. Somatic tissue encapsulated using 2% sodium alginate retained viability over a 2‐month culture period.

Modulation of protein release from chitosan-alginate microcapsules using the pH-sensitive polymer hydroxypropyl methylcellulose acetate succinate.

The release characteristics of protein from chitosan-alginate microcapsules prepared using an electrostatic droplet generator were evaluated. The release studies were undertaken in-vitro in simulated gastrointestinal fluids covering the pH range 1.2-8. Chitosan-alginate microcapsules showed unsatisfactory release properties, losing 94% of the encapsulated proteins (bovine serum albumin) over a 24 h period at pH 1.2. Incorporation of a pH-sensitive polymer, hydroxypropyl methylcellulose acetate succinate (HPMCAS), in the microcapsules, by coating the capsule membrane as well as blending with the capsule core polymer in varying ratios, produced significant changes in the release profiles of the microcapsules. At pH 1.2, the modified microcapsules retained up to 60% of the encapsulated protein after 24 h. The results obtained highlight the potential of HPMCAS as a release-modifier in chitosan-alginate microcapsules.

Effect of electrode geometry and charge on the production of polymer microbeads by electrostatics

AbstractExperimental parameters which are critical for producing small diameter (i.e. 100‐300 μm) polymer microbeads, using electrostatic droplet generation, were investigated with three types of electrodes; a parallel plate, a positively charged needle and a grounded needle with alginate as the polymer. Electrode spacing was a critical factor controlling microbead size, but only for the parallel plate set‐up. While the applied potential affected droplet size in all three set‐ups, the smallest droplet size was produced with the positively charged needle. In some experiments needle oscillation was observed resulting in even smaller microbeads (i.e. &lt; 100 μm). Calculated microbead diameters agreed well with experimental values.

Electrostatic droplet generation: Mechanism of polymer droplet formation

AbstractThe mechanism of alginate droplet formation and experimental parameters for producing very small polymer microbeads (less than 100 μm dia.) using an electrostatic droplet generator studied showed that the microbead size was a function of needle diameter, charge arrangement (electrode geometry and spacing) and strength of electric field. Perfectly spherical and uniform polymer beads, 170 μm dia., for example, were obtained at a potential difference of 6 kV with a 26‐gauge needle and an electrode distance of 2.5 cm. Increasing the electric field, and thus the surface charge in the vicinity of the needle, by increasing the applied potential, resulted in needle oscillation, giving a bimodal bead size distribution with a large fraction (30–40%) of microbeads with a mean diameter of 50 μm. The process of alginate droplet formation under the influence of electrostatic forces assessed with an image analysis/video system revealed distinct stages. After a voltage was applied, the liquid meniscus at the needle tip was distorted from a spherical shape into an inverted cone‐like shape. Consequently, alginate solution flowed into this cone at an increasing rate causing formation of a neck‐like filament. When this filament broke away, producing small droplets, the meniscus relaxed back to a spherical shape until flow of the polymer caused the process to start again. A large‐scale multineedle device with a processing capacity of 0.7 L/h was also designed and produced uniform 400 ± 150 μm microbeads.