Non-spherical Microparticles Research Articles

Continuous form-dependent focusing of non-spherical microparticles in a highly diluted suspension with the help of microfluidic spirals

Microfluidic spirals are able to focus non-spherical microparticles in diluted suspension due to the Dean effect. A secondary flow establishes in a curved channel, consisting of two counter-rotating vortices, which transport particles to an equilibrium position near the inner wall of the channel. The relevant size parameter, which is responsible for successful focusing, is the ratio between the particle diameter of a sphere and the hydraulic diameter, which is a characteristic of the microfluidic spiral. A non-spherical particle has not one but several different size parameters. This study investigated the minor and major axes, the equivalent spherical diameter, and the maximal rotational diameter as an equivalent to the spherical diameter. Using a polydimethylsiloxane (PDMS)-based microfluidic device with spirals, experiments were conducted with artificial peanut-shaped and ellipsoidal particles sized between 3 and 9 μm as well as with the bacteria Bacillus subtilis. Our investigations show that the equivalent spherical diameter, the major axis, and the maximal rotational diameter of a non-spherical particle can predict successful focusing. The minor axis is not suitable for this purpose. Non-spherical particles focused when the ratio of their equivalent spherical diameter to the hydraulic diameter of the channel was larger than 0.07. The particles also focused when the ratio between the maximal rotational diameter or the major axis and the hydraulic diameter was larger than 0.01. These results may help us to separate non-spherical biological particles, such as circulating tumor cells or pathogenic bacteria, from blood in future experimental studies.

Interaction of a Gas Flow Carrying Nonspherical Microparticles with a Cross Cylinder

A model of the dynamics of the particles-spheroids carried by a gas flow over a cross cylindrical body and rebounding from it has been developed. In this model, the gas flow around the particles is assumed to be viscous, and the reverse action of the particles on the gas and the collisions between them are not taken into account. The coefficients of recovery of the velocity components of the particles rebounded from the cylinder were determined on the basis of the heuristic theory in which the physical and mechanical properties of colliding bodies are considered. The influence of the ratio between the axes of particles-spheroids on the coefficient of wetting of the cylinder by them, the distributions of the mass-flow density of the particles and their velocity components over the cylinder surface, and the spatial distribution of the indicated quantities of the rotating particles rebounded from the cylinder was investigated numerically. The model proposed can be used for estimating the action of ice microcrystals and particles of volcanic ash emissions and dust storms on the structural elements of aircraft engines and small-size flying vehicles.

Controlled Electrospray Generation of Nonspherical Alginate Microparticles.

Electrospraying is a technique used to generate microparticles in a high throughput manner. For biomedical applications, a biocompatible electrosprayed material is often desirable. Using polymers, such as alginate hydrogels, makes it possible to create biocompatible and biodegradable microparticles that can be used for cell encapsulation, to be employed as drug carriers, and for use in 3D cell culturing. Evidence in the literature suggests that the morphology of the biocompatible microparticles is relevant in controlling the dynamics of the microparticles in drug delivery and 3D cell culturing applications. Yet, most electrospray-based techniques only form spherical microparticles, and there is currently no widely adopted technique for producing nonspherical microparticles at a high throughput. Here, we demonstrate the generation of nonspherical biocompatible alginate microparticles by electrospraying, and control the shape of the microparticles by varying experimental parameters such as chemical concentration and the distance between the electrospray tip and the particle-solidification bath. Importantly, we show that these changes to the experimental setup enable the synthesis of different shaped particles, and the systematic change in parameters, such as chemical concentration, result in monotonic changes to the particle aspect ratio. We expect that these results will find utility in many biomedical applications that require biocompatible microparticles of specific shapes.

Numerical Study of Lateral Migration of Elliptical Magnetic Microparticles in Microchannels in Uniform Magnetic Fields

This work reports numerical investigation of lateral migration of a paramagnetic microparticle of an elliptic shape in a plane Poiseuille flow of a Newtonian fluid under a uniform magnetic field by direct numerical simulation (DNS). A finite element method (FEM) based on the arbitrary Lagrangian–Eulerian (ALE) approach is used to study the effects of strength and direction of the magnetic field, particle–wall separation distance and particle shape on the lateral migration. The particle is shown to exhibit negligible lateral migration in the absence of a magnetic field. When the magnetic field is applied, the particle migrates laterally. The migration direction depends on the direction of the external magnetic field, which controls the symmetry property of the particle rotational velocity. The magnitude of net lateral migration velocity over a π cycle is increased with the magnetic field strength when the particle is able to execute complete rotations, expect for α = 45° and 135°. By investigating a wide range of parameters, our direct numerical simulations yield a comprehensive understanding of the particle migration mechanism. Based on the numerical data, an empirical scaling relationship is proposed to relate the lateral migration distance to the asymmetry of the rotational velocity and lateral oscillation amplitude. The scaling relationship provides useful guidelines on design of devices to manipulate nonspherical micro-particles, which have important applications in lab-on-a-chip technology, biology and biomedical engineering.

Effects of l-leucine on PLGA microparticles for pulmonary administration prepared using spray drying: Fine particle fraction and phagocytotic ratio of alveolar macrophages

Recently, non-spherical particles for inhalation have attracted attention. In the previous study, we reported non-spherical nanocomposite particles suitable for transpulmonary administration using amino acids [I. Takeuchi et. al., Colloids Surf. A 529 (2017) 387–393]. In this study, to apply this nanocomposite particle preparation method using amino acid to microparticles for inhalation, the influence of l-leucine on small fine particle fraction (FPF) values of poly(lactic-co-glycolide) (PLGA) microparticles and their phagocytotic ratio of alveolar macrophages was investigated. We prepared non-spherical rifampicin-loaded PLGA microparticles for inhalation using l-leucine and l-aspartic acid. The amino acids were added in aqueous phase, and the microparticles were prepared using a spray dryer via emulsion. Spherical rifampicin-loaded PLGA microparticles were also prepared using a conventional spray drying method for comparison. The FPF below 4.7μm of microparticles prepared using an aqueous phase with a leucine concentration of 0.2% (w/v) increased to 6.9 times (43.4±5.7%) that of conventional microspheres (6.3±4.0%). From the measurement result of the tap density, it was found that the shape of the particle had a large effect on the FPF value in this study. To evaluate the effectiveness of this particle in treating tuberculosis, microparticles phagocytotic ratio of alveolar macrophages (rat alveolar macrophage-derived NR8383 cells) was studied. The phagocytotic ratio of the microparticles prepared using an aqueous phase with a leucine concentration of 0.2% (w/v) was significantly higher than the spherical microparticles, and 0.34±0.16μg/mL of rifampicin concentration in alveolar macrophages was obtained.

Controllable Microfluidic Fabrication of Microstructured Materials from Nonspherical Particles to Helices.

This work reports on a facile and flexible strategy based on the deformation of encapsulated droplets in fiber-like polymeric matrices for template synthesis of controllable microstructured materials from nonspherical microparticles to complex 3D helices. Monodisperse droplets generated from microfluidics are encapsulated into crosslinked polymeric networks via an interfacial crosslinking reaction in microchannel to in situ produce the droplet-containing, fiber-like matrices. By stretching and twining the dried fiber-like matrices, the encapsulated droplets can be flexibly engineered into versatile shapes for template synthesis of controllable nonspherical microparticles and helices. Moreover, magnetic helices can be fabricated by simply dispersing magnetic Fe3 O4 nanoparticles in the droplets to achieve rotational and translational motion under a rotated magnetic field. This work provides a simple and versatile strategy for the template synthesis of advanced functional microstructured materials with flexible shapes.

Shape Measurement of Ellipsoidal Particles in a Cross-Slot Microchannel Utilizing Viscoelastic Particle Focusing.

Shape measurement of nonspherical microparticles by conventional methods such as optical microscopy is challenging owing to particle aggregation or uncertainty regarding the out-of-plane arrangement of particles. In this work, we propose a facile microfluidic method to align particles in-plane utilizing the extensional flow field generated in a cross-slot microchannel. Viscoelastic particle focusing is also harnessed to move particles toward the stagnation point of the cross-slot microchannel. We demonstrate that the shapes of ellipsoidal particles with various aspect ratios can be successfully measured using our novel microfluidic method. This method is expected to be useful in a wide range of applications such as shape measurement of nonspherical cells.

From core-shell to Janus: Microfluidic preparation and morphology transition of Gas/Oil/Water emulsions

In this article, gas-liquid-liquid emulsion drops were firstly generated by one-step method in a coaxial microfluidic device. Based on that, the effects of several parameters on the morphology transition from core-shell to Janus droplets was studied systematically. By tuning flow rates, interfacial tensions and viscosity, we can change the size and morphology of droplets. Furthermore, non-spherical microparticles were obtained by using photo-responsive reagent through solidification. The developed approach offers a novel and simple strategy on the synthesis of Janus emulsions and anisotropic microparticles with controlled morphologies.

A study of the Brownian motion of the non-spherical microparticles on fluctuating lattice Boltzmann method

In this paper, the fluctuating lattice Boltzmann (FLB) model is used to simulate the Brownian motion of spherical and non-spherical particles directly on 3D. The FLB model is validated by comparing the simulation results with theoretical and experimental results. And then the Brownian motion characteristics of different shapes of non-spherical particles are analyzed, which includes some ellipsoidal and cylindrical particles with different aspect ratios. It is found that, although the ellipsoidal and cylindrical particles are anisotropic, they still obey the energy equalization theorem. The velocity and angular velocity autocorrelation functions of the particles still have the “long-time tail” effect. Moreover, the velocity and angular velocity autocorrelation functions are independent of the particle shape, and the diffusion coefficient is insensitive to the shape under a low aspect ratio. This work is a fundamental study for the further research of the motion of microparticles based on Brownian motion.

One-Step Synthesis of Hollow Dimpled Polystyrene Microparticles by Dispersion Polymerization.

The design and preparation of hollow nonspherical microparticles are of great significance for their potential applications, but the development of a facile synthetic method using only one production step remains a great challenge. In the current work, a new template-free method based on dispersion polymerization was successfully developed to produce anisotropic hollow polystyrene (PS) microparticles in a single step. In the synthesis, ammonium persulfate (APS) played a critical role in the formation and growth of highly uniform and stable hollow PS microparticles. By varying the concentration of APS and that of the stabilizer used, polyvinylpyrrolidone, we were able to control the average size of the PS particles and their degree of concavity. Based on our results and observations, a plausible mechanism for formation of these unusually shaped PS microparticles was proposed.

Synthesis of Optically Complex, Porous, and Anisometric Polymeric Microparticles by Templating from Liquid Crystalline Droplets

It is demonstrated that aqueous dispersions of micrometer‐sized liquid crystal (LC) droplets provide the basis of a general and facile methodology for the templated synthesis of spherical and nonspherical polymeric microparticles with complex internal structure and porosity. Specifically, nematic droplets of reactive (RM257)/nonreactive mesogens with distinct internal configurations are prepared using a range of approaches, the reactive mesogens are photopolymerized, and then the nonreactive mesogens are extracted to yield polymeric particles. It is found that LC droplets exhibiting bipolar, radial, axial or preradial configurations template the formation of spindle‐shaped, spherical, spherocylindrical or tear‐shaped polymeric microparticles, respectively. Each type of microparticle exhibits distinct optical signatures indicating the presence of an internal LC‐templated, anisotropic polymer network. In addition, by using a microfluidic system to generate monodisperse LC droplets containing 10%–40% wt/wt of RM257, spindle‐shaped microparticles with tailored aspect ratios ranging from 2.4 to 1.2 are formed. The mass density of spherical microparticles templated from radial LC droplets can be tuned to range from 0.2 to 0.6 g cm−3, revealing the introduction of porosity (confirmed by electron microscopy) with a volume‐average pore diameter of 39 ± 16 nm (obtained from nitrogen sorption isotherms).

Engineering particle morphology with microfluidic droplets

The controlled generation of microparticles with non-spherical features is of increasing importance. Such particles are useful for fundamental studies in areas such as self-assembly, as well as biomedical applications from drug carriers to photonic devices. We propose a simple model that captures the dominating factors controlling the size and morphology of non-spherical particles from phase separated droplets. The validity of our model is verified by comparing the generated non-spherical microparticles by droplet microfluidics. This simple relationship between the dominating factors and the final morphologies enables the production of non-spherical particles with well-defined shapes and tightly-controlled dimensions for a variety of applications from drug delivery vehicles to structural materials.

Shape-tunable wax microparticle synthesis via microfluidics and droplet impact.

Spherical and non-spherical wax microparticles are generated by employing a facile two-step droplet microfluidic process which consists of the formation of molten wax microdroplets in a flow-focusing microchannel and their subsequent off-chip crystallization and deformation via microdroplet impingement on an immiscible liquid interface. Key parameters on the formation of molten wax microdroplets in a microfluidic channel are the viscosity of the molten wax and the interfacial tension between the dispersed and continuous fluids. A cursory phase diagram of wax morphology transition is depicted depending on the Capillary number and the Stefan number during the impact process. A combination of numerical simulation and analytical modeling is carried out to understand the physics underlying the deformation and crystallization process of the molten wax. The deformation of wax microdroplets is dominated by the viscous and thermal effects rather than the gravitational and buoyancy effects. Non-isothermal crystallization kinetics of the wax illustrates the time dependent thermal effects on the droplet deformation and crystallization. The work presented here will benefit those interested in the design and production criteria of soft non-spherical particles (i.e., alginate gels, wax, and polymer particles) with the aid of time and temperature mediated solidification and off-chip crosslinking.

Optical trapping and manipulation of light-absorbing particles by means of a Hermite–Gaussian laser beam

This paper describes simultaneous optical trapping and displacement of several nonspherical light-absorbing microparticles in air by means of a focused Hermite–Gaussian laser beam (laser mode TEM10, radiation wavelength 457 nm). Agglomerations of carbon nanoparticles are displaced in three dimensions by distances of the order of a millimeter. The structure of the Hermite–Gaussian beam used here made it possible to displace microparticles simultaneously along two parallel trajectories in space.

Localized light jets from radially symmetric nonspherical dielectric microparticles

The results of numerical modeling of the near field of light wave scattering (“photonic (nano)jet”—PNJ region) by radially symmetric nonabsorbing dielectric microparticles are presented. It is shown that the homogeneous silica microparticles of different spatial shape and orientation form PNJ of different sizes and amplitudes. Photonic nanojets from hemispheres are of high extent but moderate intensity. Use of microaxicons provides for a record increase in the PNJ length of the order of twenty wavelengths of the incident radiation.

Integrating Multi-Functionalities Into Non-Spherical Microparticles Fabricated by Top-Down Approach

Integrating Multi-Functionalities Into Non-Spherical Microparticles Fabricated by Top-Down Approach

Multi-Compartmental Hydrogel Microparticles Fabricated by Combination of Sequential Electrospinning and Photopatterning.

Multi-compartmental non-spherical hydrogel microparticles were fabricated by combining electrospinning and photopatterning. Sequential electrospinning produced multi-layered fiber matrices with different composition in which each layer became a compartment of the particle. Photopatterning of the hydrogel in the presence of the multi-layered fiber matrix generated multi-compartmental microparticles with different vertical functionalities. While the shapes of the hydrogel microparticles were determined by the design of the photomask, the chemical properties and size of each compartment were independently controlled by changing the molecules incorporated into each fiber matrix and the electrospinning times, respectively. The resultant multi-compartmental hydrogel microparticles could carry out not only the release of different growth factors with independent kinetics but also binding of multiple targets at different compartments.

Clinical Long-Term Outcome and Reinterventional Rate After Uterine Fibroid Embolization with Nonspherical Versus Spherical Polyvinyl Alcohol Particles.

This study was designed to evaluate the long-term clinical outcome and frequency of reinterventions in patients with uterine fibroids treated with embolization at a single center using polyvinyl alcohol microparticles. The study included all patients with symptomatic uterine fibroids treated with uterine fibroid embolization (UFE) with spherical (s-PVA) and nonspherical (ns-PVA) polyvinyl alcohol microparticles during the period January 2001 to January 2011. Clinical success and secondary interventions were examined. Hospital records were reviewed during follow-up, and symptom-specific questionnaires were sent to all patients. In total, 515 patients were treated with UFE and 350 patients (67 %) were available for long-term clinical follow-up. Median time of follow-up was 93 (range 76-120.2) months. Eighty-five patients (72 %) had no reinterventions during follow-up in the group embolized with ns-PVA compared with 134 patients (58 %) treated with s-PVA. Thirty-three patients (28 %) underwent secondary interventions in the ns-PVA group compared with 98 patients (42 %) in s-PVA group (χ(2) test, p < 0.01). Spherical PVA particles 500-700 µm showed high reintervention rate at long-term follow-up, and almost one quarter of the patients underwent secondary interventions, suggesting that this type of particle is inappropriate for UFE.

Capillary-assisted fabrication of biconcave polymeric microlenses from microfluidic ternary emulsion droplets.

In this study, a simple capillary-based approach for producing biconcave polymeric microlenses with uniform size and shape from ternary emulsion droplets is presented. Monodisperse ternary emulsion droplets (0.6-4.0 nL) are produced which contain a photocurable segment of an acrylate monomer and two non-curable segments of silicone oil (SO) by using a microfluidic sheath-flowing droplet generator on a glass chip. The curvature radius of the interfaces separating the droplet segments, as well as the droplet size, and production rate can be flexibly varied by changing the flow conditions of the organic and aqueous phases. Subsequently, off-chip suspension photopolymerization yields non-spherical polymeric microparticles with two spherical concave surfaces templated by two SO segments at random positions. By ultraviolet light irradiation of ternary droplets with two SO segments trapped by the interior wall of a cylindrical microcapillary (internal diameter: 130 μm), biconcave microlenses can be produced with two spherical concave surfaces with a common lens axis. The produced lenses are suitable for use as optical diverging lenses.

Microfluidic conformal coating of non-spherical magnetic particles.

We present the conformal coating of non-spherical magnetic particles in a co-laminar flow microfluidic system. Whereas in the previous reports spherical particles had been coated with thin films that formed spheres around the particles; in this article, we show the coating of non-spherical particles with coating layers that are approximately uniform in thickness. The novelty of our work is that while liquid-liquid interfacial tension tends to minimize the surface area of interfaces-for example, to form spherical droplets that encapsulate spherical particles-in our experiments, the thin film that coats non-spherical particles has a non-minimal interfacial area. We first make bullet-shaped magnetic microparticles using a stop-flow lithography method that was previously demonstrated. We then suspend the bullet-shaped microparticles in an aqueous solution and flow the particle suspension with a co-flow of a non-aqueous mixture. A magnetic field gradient from a permanent magnet pulls the microparticles in the transverse direction to the fluid flow, until the particles reach the interface between the immiscible fluids. We observe that upon crossing the oil-water interface, the microparticles become coated by a thin film of the aqueous fluid. When we increase the two-fluid interfacial tension by reducing surfactant concentration, we observe that the particles become trapped at the interface, and we use this observation to extract an approximate magnetic susceptibility of the manufactured non-spherical microparticles. Finally, using fluorescence imaging, we confirm the uniformity of the thin film coating along the entire curved surface of the bullet-shaped particles. To the best of our knowledge, this is the first demonstration of conformal coating of non-spherical particles using microfluidics.