Pinched flow fractionation: continuous size separation of particles utilizing a laminar flow profile in a pinched microchannel

A concept of "pinched flow fractionation" for the continuous size separation and analysis of particles in microfabricated devices has been proposed and demonstrated. In this method, particles suspended in liquid were continuously introduced into a microchannel having a pinched segment and were aligned to one sidewall in the pinched segment by another liquid flow without particles. The particles were then separated perpendicularly to the flow direction according to their sizes by the spreading flow profile inside the microchannel. Polymer microbeads were successfully separated, and the effects of the flow rate and channel shapes on the separation performance were examined. Also, separated particles were collected independently by making branches at the end of the pinched segment. Since this method utilizes only the laminar flow profile inside a microchannel, complicated outer field control could be eliminated, which is usually required for other kinds of particle separation methods such as field flow fractionation. Also, this method can be applied both for particle size analysis and for preparation of monodispersed particles, since separation can be rapidly and continuously performed.     

Microfluidic particle sorter employing flow splitting and recombining

This paper describes an improved microfluidic device that enables hydrodynamic particle concentration and size-dependent separation to be carried out in a continuous manner. In our previous study, a method for hydrodynamic filtration and sorting of particles was proposed using a microchannel having multiple branch points and side channels, and it was applied for continuous concentration and separation of polymer particles and cells. In the current study, the efficiency of particle sorting was dramatically improved by geometrically splitting fluid flow from a main stream and recombining. With these operations, particles with diameters larger than a specific value move toward one sidewall in the mainstream. This control of particle positions is followed by the perfect particle alignment onto the sidewall, which increases the selectivity and recovery rates without using a liquid that does not contain particles. In this study, a microchannel having one inlet and five outlets was designed and fabricated. By simply introducing particle suspension into the device, concentrations of 2.1-3.0-microm particles were increased 60-80-fold, and they were collected independently from each outlet. In addition, it was demonstrated that the measured flow rates distributed into each side channel corresponded well to the theoretical values when regarding the microchannel network as a resistive circuit.     

Size separation of supermicrometer particles in asymmetrical flow field-flow fractionation. Flow conditions for rapid elution

The performance of lift-hyperlayer asymmetrical flow field-flow fractionation using rapid elution conditions was tested through the separation of standard polystyrene latex particles of diameters from 2 to 20 microm. Optimization of flowrates was studied not only in order to obtain efficient and rapid separation, but also to work under conditions of various shape and steepness of the axial flow velocity gradient. Using extreme flow conditions, the five widely spaced particle sizes, 20.5-, 15.0-, 9.7-, 5.0-, and 2.0-microm diameter, could be resolved in 6 min, whereas for the narrower size range of 20.5-5.0 microm, 1 min was enough. The size selectivity in the size range 9.7-2.0 microm was studied as a function of flowrates and particle size and was found to be constant. A particle trapping device made it possible to separate particles of sizes > 10 microm, which has previously proven to be difficult in asymmetrical channels.     

Continuous dielectrophoretic size-based particle sorting

Continuous-flow dielectrophoretic (DEP) particle separation based on size is demonstrated in a microfluidic device. Polystyrene microspheres suspended in a neutrally buoyant aqueous solution are used as model particles to study DEP induced by an array of slanted, planar, interdigitated electrodes inside of a soft-lithography microchannel. The E-field gradients from the slanted electrodes impart a net transverse force component on the particles that causes them to "ratchet" across the channel. Over the length of the device, larger particles are deflected more than smaller particles according to the balance of hydrodynamic drag and DEP forces. Consequently, a flow-focused particle suspension containing different-sized particles is fractionated as the beads flow and separate down the length of the device. The flow behavior of spherical particles is modeled, and the total transverse particle displacement in the microfluidic device predicts fourth-order size and voltage and second-order inverse flow rate dependences. The model is verified experimentally for a range of flow rates, particle sizes, and E-field strengths.     

Cross-type optical particle separation in a microchannel

A continuous, real-time optical particle separation, which was previously delineated theoretically, is successfully implemented experimentally for the first time. In this method, particles suspended in a flowing fluid are irradiated with a laser beam propagating in a direction perpendicular to direction of fluid flow. Upstream of the laser beam, the particles move parallel to the direction of fluid flow. When the particles pass through the laser beam, the scattering force pushes them in the direction of laser beam propagation, causing the particles to be displaced perpendicular to the fluid flow direction. This displacement, known as the retention distance, depends on the particle size and the laser beam parameters. Finally, the particles escape from the laser beam and maintain their retention distances as they move downstream. In the present work, the trajectories and retention distances of polystyrene latex microspheres with three distinct diameters were monitored and measured using cross-type optical particle separation. The measured retention distances for different-sized particles were in good agreement with theoretical predictions.     

Continuous free-flow electrophoresis of water-soluble monolayer-protected clusters

There has recently been a surge of interest in the properties and applications of monolayer protected clusters (MPCs). MPCs are metal nanoparticles that have unique optical, chemical, and electrochemical properties resulting from their small size. Because the size defines their properties, MPC particle size fractionation is important for control of the MPC characteristics for use in many potential applications. This paper explores the use of continuous free-flow electrophoresis (CFE) for the size fractionation of N-(2-mercaptopropionyl)glycine (tiopronin) monolayer protected gold clusters into monodisperse nanoparticle samples. CFE is a fractionation technique that isolates monodisperse particle sizes into several different collection vials on the tens of milligrams scale. This allows the MPCs to be separated based on their electrophoretic mobilities into isolated, monodisperse particles across a wide range of sizes. CFE separation of water-soluble tiopronin MPCs yielded fractions that varied in color, UV-visible spectra, transmission electron microscopy (TEM) size histograms, and solubility, indicating narrow size dispersity in the isolated fractions. UV-visible spectrophotometry verified the separation of the tiopronin MPCs through the inspection of surface plasmon resonance peak sizes for the different fractions. TEM was also used to verify the narrowed dispersity of MPC samples. The ability to separate water-soluble nanoparticles into 30 or more fractions in a continuous flow process will enable future studies on their size dependent properties.     

On-chip free-flow magnetophoresis: continuous flow separation of magnetic particles and agglomerates

The separation of magnetic microparticles was achieved by on-chip free-flow magnetophoresis. In continuous flow, magnetic particles were deflected from the direction of laminar flow by a perpendicular magnetic field depending on their magnetic susceptibility and size and on the flow rate. Magnetic particles could thus be separated from each other and from nonmagnetic materials. Magnetic and nonmagnetic particles were introduced into a microfluidic separation chamber, and their deflection was studied under the microscope. The magnetic particles were 2.0 and 4.5 microm in diameter with magnetic susceptibilities of 1.12 x 10(-4) and 1.6 x 10(-4) m(3) kg(-1), respectively. The 4.5-microm particles with the larger susceptibility were deflected further from the direction of laminar flow than the 2.0-microm magnetic particles. Nonmagnetic 6-microm polystyrene beads, however, were not deflected at all. Furthermore, agglomerates of magnetic particles were found to be deflected to a larger extent than single magnetic particles. The applied flow rate and the strength and gradient of the applied magnetic field were the key parameters in controlling the deflection. This separation method has a wide applicability since magnetic particles are commonly used in bioanalysis as a solid support material for antigens, antibodies, DNA, and even cells. Free-flow magnetophoretic separations could be hyphenated with other microfluidic devices for reaction and analysis steps to form a micro total analysis system.     

On-chip diamagnetic repulsion in continuous flow

We explore the potential of a microfluidic continuous flow particle separation system based on the repulsion of diamagnetic materials from a high magnetic field. Diamagnetic polystyrene particles in paramagnetic manganese (II) chloride solution were pumped into a microfluidic chamber and their deflection behaviour in a high magnetic field applied by a superconducting magnet was investigated. Two particle sizes (5 and 10 μm) were examined in two concentrations of MnCl₂ (6 and 10%). The larger particles were repelled to a greater extent than the smaller ones, and the effect was greatly enhanced when the particles were suspended in a higher concentration of MnCl₂. These findings indicate that the system could be viable for the separation of materials of differing size and/or diamagnetic susceptibility, and as such could be suitable for the separation and sorting of small biological species for subsequent studies.     

Carrier medium exchange through ultrasonic particle switching in microfluidic channels

This paper describes a method, utilizing acoustic force manipulation of suspended particles, in which particles in a laminar flow microchannel are continuously translated from one medium to another with virtually no mixing of the two media. During the study, 5-microm polyamide spheres suspended in distilled water, spiked (contaminated) with Evans blue, were switched over to clean distilled water. More than 95% of the polyamide spheres could be collected in the clean medium while removing up to 95% of the contaminant. Preliminary experiments to use this method to wash blood were performed. Red blood cells were switched from blood, spiked with Evans blue, to clean blood plasma. At least 95% of the red blood cells (bovine blood) could be collected in clean blood plasma while up to 98% of the contaminant was removed. The obtained results indicate that the presented method can be used as a generic method for particle washing and, more specifically, be applied for both intraoperative and postoperative blood washing.     

RESEARCH ON AN AERODYNAMIC PARTICLE SEPARATOR (THE EPS)

This report presents an account of the research work carried out in support of the development of a new particle separator.* The EPS, as it is designated, produces multiple fractions simultaneously at a high throughput rate. The cut sizes are roughly in the range 10 to 200 µm. The principle is that particles dissimilar with respect to any of size, density, or shape will follow different and distinct trajectories when injected into a uniform laminar flow of air.

The report outlines the theoretical analyses and experimental measurements made to verify the design concepts. A detailed model of the flow field permits the calculation of particle trajectories, and hence the prediction of coarse grade efficiency and sharpness of cut. The measurements made with glass spheres and other irregular particles (e.g., carbon, cement) provide a general verification of the analytical results.

Sharpness of cut values better than 0.8 are achieved down to cut points of about 10µm. Maximum throughput rates are not yet known, but separations have been made at 480 kg/hr in a separation zone 100 mm wide. Scale-up to larger capacity is straightforward.     

On-chip diamagnetic repulsion in continuous flow

Abstract

We explore the potential of a microfluidic continuous flow particle separation system based on the repulsion of diamagnetic materials from a high magnetic field. Diamagnetic polystyrene particles in paramagnetic manganese (II) chloride solution were pumped into a microfluidic chamber and their deflection behaviour in a high magnetic field applied by a superconducting magnet was investigated. Two particle sizes (5 and 10 μm) were examined in two concentrations of MnCl₂ (6 and 10%). The larger particles were repelled to a greater extent than the smaller ones, and the effect was greatly enhanced when the particles were suspended in a higher concentration of MnCl₂. These findings indicate that the system could be viable for the separation of materials of differing size and/or diamagnetic susceptibility, and as such could be suitable for the separation and sorting of small biological species for subsequent studies.     

Gravity Separation of Particulate Solids in Turbulent Fluid Flow

The separation characteristics of particles’ settling velocity, size, density, and shape are introduced, and the equivalent settling condition for laminar, transition, and turbulent flow are explained. A similarity model of particle transport in a turbulent flow field is briefly discussed. Typical operation principles in separation devices for counter current and cross-flow separation are presented. The separation function, cut point, sharpness, and separation stage utilization coefficient are determined to assess the efficiency for process sequences for multistage turbulent cross-flow separation. Satisfactory to very good results were achieved in the difficult separation of a partially liberated aggregate consisting of hardened cement paste rubble with sharpness from 0.66 to 0.94 at separation stage utilization coefficients of 7 to 87%. Specific mass flow rates of 3 to 16 t/(m² · h) and mass related energy consumption of 0.2 to 8 kWh/t were obtained.     

Photophoretic velocimetry for colloid characterization and separation in a cross-flow setup

We introduce photophoretic velocimetry as a new technique for characterization of particulate matter on the basis of optical particle properties. Complementary to well-established techniques, we could show that, by measuring the photophoretic velocity of the single particles, it is possible to distinguish particles of different sizes as well as particles of one size but different refractive indices. The difference in photophoretic migration of particles can be applied to the separation of particles. Polystyrene, melamine, and SiO2 microparticles (0.3-10 mum) suspended in purified water were used as test samples for validation of a cross-flow setup. The particles were pushed perpendicular to a uniform, pulsation-free fluid flow by a focused He-Ne laser (lambda = 633 nm, P = 47 mW, I(max) = 14.0 kW cm(-2)) providing a well-defined Gaussian-shaped flux distribution. The migration behavior was observed by means of a video camera system, and the velocities and displacements were calculated by using an adapted particle imaging velocimetry code as an approach to automatic characterization. The photophoretic displacement depends on both flow conditions and particle properties and can be applied for separation means.     

An analysis of transport phenomena for multi-solid particle systems at higher Reynolds numbers by a 5th order polynomial Karman-Pohlhausen method

Using the concentric spheres free surface model and a 5th order polynomial Karman-Pohlhausen method of the laminar boundary layer theory, the dimensionless tangential stress distributions, the dimensionless pressure distributions around a solid sphere in a swarm and the viscous, form and total drag coefficients for multi-solid sphere systems were numerically computed at higher Reynolds numbers, based on the first assumption that the pressure distribution equals that of potential flow between concentric spheres up to the separation point, and behind the separation point in the wake region the pressure does not recover and keeps constant, and on the second assumption that the pressure distribution varies according to the measurement of Flachsbart.The theoretical drag coefficient of single solid spheres in an infinite medium based on the second assumption agreed with the experimental data in the range of the Reynolds numbers from $\text{3 × 10}{}^2\text{to 10}{}^5$.The friction factor for multi-solid particle systems based on the first assumption is almost the same as that on the 4th order polynomial and agreed with the experimental data of packed and distended beds.The void functions obtained from the drag coefficients for multi-solid particle systems based on both first and second assumptions were almost the same as the one on the 4th order polynomial.Using the velocity profiles based on concentric spheres free surface model and a 5th order polynomial Karman-Pohlhausen method of the laminar boundary layer obtained previously, the diffusion equation was solved numerically at higher Reynolds numbers on the first assumption of the pressure distribution around a solid sphere in a swarm equals that of potential flow between concentric spheres from the frontal stagnation point to the separation one, and the pressure does not recover, but keeps constant behind the separation point in the wake region. The mass transfer rate for multi-solid particle systems so computed was almost the same as that on the 4th order polynominal and agreed with the experimental data of single Solid spheres, and packed and particulate fluidized beds at higher Reynolds numbers.     

Photophoretic velocimetry for the characterization of aerosols

Aerosols are particles in a size range from some nanometers to some micrometers suspended in air or other gases. Their relevance varies as wide as their origin and composition. In the earth's atmosphere they influence the global radiation balance and human health. Artificially produced aerosols are applied, e.g., for drug administration, as paint and print pigments, or in rubber tire production. In all these fields, an exact characterization of single particles as well as of the particle ensemble is essential. Beyond characterization, continuous separation is often required. State-of-the-art separation techniques are based on electrical, thermal, or flow fields. In this work we present an approach to apply light in the form of photophoretic (PP) forces for characterization and separation of aerosol particles according to their optical properties. Such separation technique would allow, e.g., the separation of organic from inorganic particles of the same aerodynamic size. We present a system which automatically records velocities induced by PP forces and does a statistical evaluation in order to characterize the particle ensemble properties. The experimental system essentially consists of a flow cell with rectangular cross section (1 cm(2), length 7 cm), where the aerosol stream is pumped through in the vertical direction at ambient pressure. In the cell, a laser beam is directed orthogonally to the particle flow direction, which results in a lateral displacement of the particles. In an alternative configuration, the beam is directed in the opposite direction to the aerosol flow; hence, the particles are slowed down by the PP force. In any case, the photophoretically induced variations of speed and position are visualized by a second laser illumination and a camera system, feeding a mathematical particle tracking algorithm. The light source inducing the PP force is a diode laser (lambda = 806 nm, P = 0.5 W).     

Gravity-driven microfluidic particle sorting device with hydrodynamic separation amplification

This paper describes a simple microfluidic sorting system that can perform size profiling and continuous mass-dependent separation of particles through combined use of gravity (1 g) and hydrodynamic flows capable of rapidly amplifying sedimentation-based separation between particles. Operation of the device relies on two microfluidic transport processes: (i) initial hydrodynamic focusing of particles in a microchannel oriented parallel to gravity and (ii) subsequent sample separation where positional difference between particles with different mass generated by sedimentation is further amplified by hydrodynamic flows whose streamlines gradually widen out due to the geometry of a widening microchannel oriented perpendicular to gravity. The microfluidic sorting device was fabricated in poly(dimethylsiloxane), and hydrodynamic flows in microchannels were driven by gravity without using external pumps. We conducted theoretical and experimental studies on fluid dynamic characteristics of laminar flows in widening microchannels and hydrodynamic amplification of particle separation. Direct trajectory monitoring, collection, and post-analysis of separated particles were performed using polystyrene microbeads with different sizes to demonstrate rapid (<1 min) and high-purity (>99.9%) separation. Finally, we demonstrated biomedical applications of our system by isolating small-sized (diameter <6 microm) perfluorocarbon liquid droplets from polydisperse droplet emulsions, which is crucial in preparing contrast agents for safe, reliable ultrasound medical imaging, tracers for magnetic resonance imaging, or transpulmonary droplets used in ultrasound-based occlusion therapy for cancer treatment. Our method enables straightforward, rapid, real-time size monitoring and continuous separation of particles in simple stand-alone microfabricated devices without the need for bulky and complex external power sources. We believe that this system will provide a useful tool to separate colloids and particles for various analytical and preparative applications and may hold potential for separation of cells or development of diagnostic tools requiring point-of-care sample preparation or testing.     

Design of an optimized ECCA microchannel for particle manipulation utilizing dean flow coupled elasto-inertial method

In this paper, an Eulerian-Lagrangian simulation was conducted to achieve optimal Expanded-Contracted Cavity Arrays microchannel. First, a new code was developed to solve the viscoelastic flow field, and then the particles were solved by adding appropriate forces to the OpenFOAM Lagrangian solver. This code was then validated for both Eulerian and Lagrangian models. Subsequently, the effect of different parameters such as flow rate, distance from the inlet, cavity depth and distance, and particle size were also studied to obtain the proper geometry for particle focusing. Finally, the selected channel was integrated with a straight channel to separate 4.8 and 13 μm particles. The results of current research can be used to find a proper design of an Expanded-Contracted Cavity Arrays channel to achieve precise focusing and efficient, continuous, and sheathless particle/cell separation, which is much worthy for applications such as high-speed cytometry, cell counting, sorting, and many biological applications.     

The Effect of Frequency Sweeping and Fluid Flow on Particle Trajectories in Ultrasonic Standing Waves

Particle concentration and separation in ultrasonic standing waves through the action of the acoustic radiation force on suspended particles are discussed. The acoustic radiation force is a function of the density and compressibility of the fluid and the suspended particles. A two-dimensional theoretical model is developed for particle trajectory calculations. An electroacoustic model is used to predict the acoustic field in a resonator, driven by a piezoelectric transducer. Second, the results of the linear acoustic model are used to calculate the acoustic radiation force acting on a particle suspended in the resonator. Third, a particle trajectory model is developed that integrates the equation of motion of a particle subjected to a buoyancy force, a fluid drag force, and the acoustic radiation force. Computational fluid dynamics calculations are performed to calculate the velocity field that is subsequently used to calculate fluid drag. For a fixed frequency excitation, the particles are concentrated along the stable node locations of the acoustic radiation force. Through a periodic sweeping of the excitation frequency particle translation is achieved. Two types of frequency sweeps are considered, a ramp approach and a step-change method. Numerical results of particle trajectory calculations are presented for two configurations of flow-through resonators and for two types of frequency sweeping. It is shown that most effective particle separation occurs when the fluid drag force is orthogonal to the acoustic radiation force.     

Acoustophoresis in wet-etched glass chips

Acoustophoresis in microfluidic structures has primarily been reported in silicon microfabricated devices. This paper demonstrates, for the first time, acoustophoresis performed in isotropically etched glass chips providing a performance that matches that of the corresponding silicon microdevices. The resonance mode characteristics of the glass chip were equal to those of the silicon chip at its fundamental resonance. At higher order resonance modes the glass chip displays resonances at lower frequencies than the silicon chip. The cross-sectional profiles of acoustically focused particle streams are also reported for the first time, displaying particles confined in a vertical band in the channel center for both glass and silicon chips. A particle extraction efficiency of 98% at flow rates up to 200 microL/min (2% particle concentration) is reported for the glass chip at the fundamental resonance. The glass and silicon chips displayed equal particle extraction performance when tested for increasing particle concentrations of 2-15%, at a flow velocity of 12.9 cm/s for the glass chip and 14.8 cm/s for the silicon chip.     

Design and numerical investigation of a circular microchannel for particle/cell separation using dielectrophoresis

Precisely separating particles/cells with different sizes and physical properties has been an interest for point-of-care diagnostics and personalized treatment. Dielectrophoresis (DEP) is widely known as a powerful and non-invasive technique to separate particles and cells. This paper presents a comprehensive numerical investigation of particle/cell separation in circular microchannels using DEP. First, the geometrical parameters of the circular microchannel affecting DEP force are determined by performing an analytical solution. Then, by developing a solver in OpenFOAM, the effect of these parameters on particles deflection is investigated. According to the results, two different circular microchannels are presented to investigate the continuous separation of bio-particles (based on their physical properties) and polystyrene particles (based on their size). The results showed that a minimum voltage of 7, 9, and 12 V is required to achieve 100 % purity and separation efficiency for separating red blood cells from MDA-MB-231 cancer cells at the flow rate of 0.5, 1.0, and 1.5 µl/min, respectively. Also, the efficient separation of 5 and 10 µm polystyrene particles at the flow rate of 0.1 µl/min is possible only at the voltage of 9 V. The results of this numerical study can be useful for the fabrication of an optimal microdevice for the continuous DEP separation of particles and cells.