Sheathless Particle Research Articles

Continuous sheathless particle separation in viscoelastic fluids with different rheological properties

Continuous sheathless particle separation in viscoelastic fluids with different rheological properties

A sheathless high precise particle separation chip integrated contraction–expansion channel and deterministic lateral displacement

Cell sorting plays an important role in medical and biological research. This study aimed to propose a novel approach combining a contraction–expansion array (CEA) channel and a deterministic lateral displacement (DLD) array to achieve high-throughput and high-precision particle separation of different sizes. The CEA channel could realize the focusing and preliminary sorting of particles with different sizes under the joint action of inertia force and Dean resistance. The separation purity and efficiency could be further improved by coupling triangular microcolumn DLD. The finite element simulation analysis was carried out using commercial software COMSOL Multiphysics 5.4. The flow field distribution and the particle movement trajectory under the CEA channel and DLD array were simulated, respectively. The simulation results showed that this structure could achieve high-throughput and high-precision particle separation of different sizes. Finally, the separation experiments showed that the separation efficiency of 5 µm polystyrene microspheres as the target particles was more than 99%, and the separation purity was 96.1% under a high flow velocity. The microfluidic chip had the advantages of low cost, simple preparation process, and label-free, sheathless characteristics, thus realizing high-efficiency, high-throughput particle separation of different sizes. In general, the proposed approach provided a new pathway for sheathless particle separation with high precision and high throughput.

Cascaded contraction-expansion channels for bacteria separation from RBCs using viscoelastic microfluidics

Implementation of viscoelasticity-based particle migration techniques has attracted significant interest thanks to its simplicity to achieve particle separation and enrichment at high sensitivity and accuracy for the last decade. Many methods have previously been developed for particle focusing and separation, but they all require long fluidic channels to enable the desired elastic force on particles. Here, a cascade contraction-expansion microfluidic system with a much shorter channel length is presented. Experimental results show that this system achieved continuous, sheathless particle separation in a viscoelastic fluid, and Enterococcus faecalis was successfully separated from red blood cells (RBCs). Thanks to its small size, the system provides extra advantage for its integration into small chips.

Hydrophoresis — A Microfluidic Principle for Directed Particle Migration in Flow

Despite the stereotype that secondary flow fields induced by surface grooves are effective for microfluidic mixing and increase the entropy of different fluid flows, many efforts have been made to utilize the grooves for particle separation and focusing, decreasing the entropy of particle distribution. As part of these efforts, hydrophoresis has been proposed to define deterministic particle trajectories in grooved microchannels. Due to the simple, cloggingfree, and high-throughput characteristics, hydrophoresis has become increasingly promising for blood separation in clinical applications and sheathless particle focusing in flow cytometric applications. In this review, I introduce and summarize the basic physics, design parameters, design principles, and applications of hydrophoresis to improve the fundamental understanding of hydrophoresis and expand its use. I also discuss the challenges of hydrophoresis and forecast its future direction.

Particle Focusing in Microchannel with Multi-Parallel Channels or Porous Orifice

The sheathless particle focusing in a microchannel installing one set of multi-parallel channels or one porous orifice is proposed in this study. Numerical calculations have been carried out by the Lagrange two-phase model (i.e. the particle tracking model) in PHOENICS software for the microchannel including the porous orifice, in simulating both the channels installing the multi-parallel channels and the porous orifice. It becomes clear from calculation results that the particle focusing may be achieved at lower inlet velocities by using the porous orifice. Low velocities correspond to reduction in the sample flow including particles (i.e. cells). It also becomes obvious that the particle focusing is improved if the porous orifice with taper shape is used. Furthermore, particle focusing experiments have been conducted in the channel including the multi-parallel channels. It becomes clear that the particle focusing may be achieved by using the multi-parallel channels.

High-throughput sheathless and three-dimensional microparticle focusing using a microchannel with arc-shaped groove arrays

Sheathless particle focusing which utilises the secondary flow with a high throughput has great potential for use in microfluidic applications. In this work, an innovative particle focusing method was proposed. This method makes use of a mechanism that takes advantage of secondary flow and inertial migration. The device was a straight channel with arrays of arc-shaped grooves on the top surface. First, the mechanism and expected focusing phenomenon are explained using numerical simulation of the flow field and force balance. A simulation of particle trajectories was conducted as a reference, and then a series of experiments was designed and the effects of changes in particle size, flow rate and quantity of the groove structure were discussed. The microscopic images show that this particle focusing method performed well for different size particles, and the results agreed well with the theory and simulated results. Finally, the channel successfully concentrated Jurkat cells, which showed a good compatibility in the biological assay field. In this work, the arc-shaped groove channel was demonstrated to have the ability to achieve high-throughput, sheathless and three-dimensional particle focusing with simple operations.

Sheathless Dean-flow-coupled elasto-inertial particle focusing and separation in viscoelastic fluid

Sheathless particle focusing and separation in viscoelastic fluid is demonstrated using an integrated ECCA (straight channel section with asymmetrical expansion–contraction cavity arrays) straight channel.

Sheathless particle focusing in a microfluidic chamber by using the thermoplasmonic Marangoni effect

We experimentally investigated the modes of the Marangoni flow around a microbubble in a 50-μm-thick water chamber and found a transition flow mode that enables sheathless particle focusing. A temperature gradient was thermoplasmonically induced around the laser spot on a gold nanoisland film, and Marangoni flows were generated around the microbubble to drive submicron particles dispersed in the water. When the laser spot was slightly displaced from the bubble center, the particles were continuously collected by the bubble underneath and leaked in one direction to form a focused particle stream. The generation of the particle-focusing Marangoni flow was attributed to the appropriate balance of the temperature gradient in the perpendicular and horizontal directions of the chamber, which was controlled by the laser spot position against the bubble center. Temporally controlling this flow mode with laser power caused the periodic emission of clustered particles from the bubble underneath. This particle handling method with a thermoplasmonic Marangoni flow can be useful for improving the efficiency of reaction or sensing processes that take place in a microfluidic chamber.

Focusing particles by induced charge electrokinetic flow in a microchannel.

A novel method of sheathless particle focusing by induced charge electrokinetic flow in a microchannel is presented in this paper. By placing a pair of metal plates on the opposite walls of the channel and applying an electrical field, particle focusing is achieved due to the two pairs of vortex that constrain the flow of the particle solution. As an example, the trajectories of particles under different electrical fields with only one metal plate on one side channel wall were numerically simulated and experimentally validated. Other flow focusing effects, such as the focused width ratio (focused width/channel width) and length ratio (focused length/half-length of metal plate) of the sample solution, were also numerically studied. The results show that the particle firstly passes through the gaps between the upstream vortices and the channel walls. Afterwards, the particle is focused to pass through the gap between the two downstream vortices that determine the focused particle position. Numerical simulations show that the focused particle stream becomes thin with the increases in the applied electrical field and the length of the metal plates. As regards to the focused length ratio of the focused stream, however, it slightly increases with the increase in the applied electrical field and almost keeps constant with the increase in the length of the metal plate. The size of the focused sample solution, therefore, can be easily adjusted by controlling the applied electrical field and the sizes of the metal plates.

Continuous inertial microparticle and blood cell separation in straight channels with local microstructures.

Fluid inertia which has conventionally been neglected in microfluidics has been gaining much attention for particle and cell manipulation because inertia-based methods inherently provide simple, passive, precise and high-throughput characteristics. Particularly, the inertial approach has been applied to blood separation for various biomedical research studies mainly using spiral microchannels. For higher throughput, parallelization is essential; however, it is difficult to realize using spiral channels because of their large two dimensional layouts. In this work, we present a novel inertial platform for continuous sheathless particle and blood cell separation in straight microchannels containing microstructures. Microstructures within straight channels exert secondary flows to manipulate particle positions similar to Dean flow in curved channels but with higher controllability. Through a balance between inertial lift force and microstructure-induced secondary flow, we deterministically position microspheres and cells based on their sizes to be separated downstream. Using our inertial platform, we successfully sorted microparticles and fractionized blood cells with high separation efficiencies, high purities and high throughputs. The inertial separation platform developed here can be operated to process diluted blood with a throughput of 10.8 mL min(-1)via radially arrayed single channels with one inlet and two rings of outlets.

Hybrid capillary-inserted microfluidic device for sheathless particle focusing and separation in viscoelastic flow

A novel microfluidic device which consists of two stages for particle focusing and separation using a viscoelastic fluid has been developed. A circular capillary tube was used for three-dimensional particle pre-alignment before the separation process, which was inserted in a polydimethylsiloxane microchannel. Particles with diameters of 5 and 10 μm were focused at the centerline in the capillary tube, and the location of particles was initialized at the first bifurcation. Then, 5 and 10 μm particles were successfully separated in the expansion region based on size-dependent lateral migration, with ∼99% separation efficiency. The proposed device was further applied to separation of MCF-7 cells from leukocytes. Based on the cell size distribution, an approximate size cutoff for separation was determined to be 16 μm. At 200 μl/min, 94% of MCF-7 cells were separated with the purity of ∼97%. According to the trypan blue exclusion assay, high viability (∼90%) could be achieved for the separated MCF-7 cells. The use of a commercially available capillary tube enables the device to be highly versatile in dealing with particles in a wide size range by using capillary tubes with different inner diameters.

Microfluidic device for sheathless particle focusing and separation using a viscoelastic fluid

Continuous sheathless particle separation with high efficiency is essential for various applications such as biochemical analyses and clinical diagnosis. Here, a novel microfluidic device for highly efficient, sheathless particle separation using an elasticity-dominant non-Newtonian fluid is proposed. Our device consists of two stages: sheathless three-dimensional focusing (1 st stage) and separation (2nd stage). It is designed based on the principle of a viscoelasticity-induced particle lateral migration, which promises precise separation of particles in a microfluidic device. Particles of 5- and 10-μm diameters were all focused at the centerline of a circular channel at the 1st stage and successfully separated at the 2nd stage with an efficiency of ∼99.9% using size-based lateral migration of particles induced by the viscoelasticity of the medium. We also demonstrated the capability of our device for separation of blood cells into multiple fractions. The tunability of separable particle size could be achieved by changing the viscoelastic property of the medium and flow rate.

Sheathless Size-Based Acoustic Particle Separation

Particle separation is of great interest in many biological and biomedical applications. Flow-based methods have been used to sort particles and cells. However, the main challenge with flow based particle separation systems is the need for a sheath flow for successful operation. Existence of the sheath liquid dilutes the analyte, necessitates precise flow control between sample and sheath flow, requires a complicated design to create sheath flow and separation efficiency depends on the sheath liquid composition. In this paper, we present a microfluidic platform for sheathless particle separation using standing surface acoustic waves. In this platform, particles are first lined up at the center of the channel without introducing any external sheath flow. The particles are then entered into the second stage where particles are driven towards the off-center pressure nodes for size based separation. The larger particles are exposed to more lateral displacement in the channel due to the acoustic force differences. Consequently, different-size particles are separated into multiple collection outlets. The prominent feature of the present microfluidic platform is that the device does not require the use of the sheath flow for positioning and aligning of particles. Instead, the sheathless flow focusing and separation are integrated within a single microfluidic device and accomplished simultaneously. In this paper, we demonstrated two different particle size-resolution separations; (1) 3 μm and 10 μm and (2) 3 μm and 5 μm. Also, the effects of the input power, the flow rate, and particle concentration on the separation efficiency were investigated. These technologies have potential to impact broadly various areas including the essential microfluidic components for lab-on-a-chip system and integrated biological and biomedical applications.

Sheathless elasto-inertial particle focusing and continuous separation in a straight rectangular microchannel

Particle focusing in planar geometries is essentially required in order to develop cost-effective lab-on-a-chips, such as cell counting and point-of-care (POC) devices. In this study, a novel method for sheathless particle focusing, called "Elasto-Inertial Particle Focusing", was demonstrated in a straight microchannel. The particles were notably aligned along the centerline of the straight channel under a pressure-driven flow without any additional external force or apparatus after the addition of an elasticity enhancer: PEO (poly(ethylene oxide)) (∼O(100) ppm). As theoretically predicted (elasticity number: El≈O(100)), multiple equilibrium positions (centerline and corners) were observed for the viscoelastic flow without inertia, whereas three-dimensional particle focusing only occurred when neither the elasticity nor the inertia was negligible. Therefore, the three-dimensional particle focusing mechanism was attributed to the synergetic combination of the elasticity and the inertia (elasticity number: El≈O(1-10)). Furthermore, from the size dependence of the elastic force upon particles, we demonstrated that a mixture of 5.9 and 2.4 µm particles was separated at the exit of the channel in viscoelastic flows. We expect that this method can contribute to develop the miniaturized flow cytometry and microdevices for cell and particle manipulation.

Particle focusing in microfluidic devices

Focusing particles (both biological and synthetic) into a tight stream is usually a necessary step prior to counting, detecting, and sorting them. The various particle focusing approaches in microfluidic devices may be conveniently classified as sheath flow focusing and sheathless focusing. Sheath flow focusers use one or more sheath fluids to pinch the particle suspension and thus focus the suspended particles. Sheathless focusers typically rely on a force to manipulate particles laterally to their equilibrium positions. This force can be either externally applied or internally induced by channel topology. Therefore, the sheathless particle focusing methods may be further classified as active or passive by the nature of the forces involved. The aim of this article is to introduce and discuss the recent developments in both sheath flow and sheathless particle focusing approaches in microfluidic devices.

Sheathless Hydrophoretic Particle Focusing in a Microchannel with Exponentially Increasing Obstacle Arrays

We present a novel microfluidic device with exponentially increasing obstacle arrays to enable sheathless particle focusing. The anisotropic fluidic resistance of slant obstacles generates transverse flows, along which particles are focused to one sidewall. In the successive channel with exponentially increasing widths, bent obstacles extended from the slant obstacles increase the focusing efficiency of the particles. With the device, we achieved the focusing efficiency of 76%, 94%, and 98% for 6, 10, and 15 microm beads, respectively. The focusing efficiency of the particles can be further improved in the devices with more extension steps. In addition, using the microfluidic devices with the symmetric structure of the slant and bent obstacles, we achieved complete focusing of biological cells to the centerline of a channel within 1.7% coefficient of variation. The results demonstrated the sheathless hydrophoretic focusing of microparticles and cells with the advantages of a sheathless method, passive operation, single channel, and flow rate independence.