High-throughput particle focusing and separation in split-recombination channel

Inertial microfluidic has been widely applied to manipulate particles or bio-sample based on the inertial lift force and Dean Vortices. This technology provides significant advantages over conventional technologies, including simple structure, high throughput and freedom from an external field. Among many inertial microfluidic systems, the straight microchannel is commonly used to produce inertial focusing, which is a phenomenon that particles or cells are aligned and separated based on their size under the influence of inertial lift force. Besides the inertial lift force, flow drag forces induced by the geometrical structures of microchannel can also affect particle focusing. Herein, a split-recombination microchannel, consisting of curved and straight channels, is proposed to focus and separate particles at high flow rate. As compared with the straight channel, the particle focusing in the split-recombination channel is greatly improved, which results from the combined effects of the inertial lift force, the curvature-induced Dean drag force and the structure of split and recombination. Moreover, the distribution of different-sized particles in designed microchannel is investigated. The results indicate that the proposed microchannel not only enhances the particle focusing but also enables the separation of different-sized particles with high throughput. Finally, it is discovered that the larger length of straight channel and curvature radius of curved channel can result in a more efficient particle separation. Another important feature of designed split-recombination microchannel is that it can be arranged in parallel to handle large-volume samples, holding great potential in lab-on-a-chip applications.

Hand-Powered Inertial Microfluidic Syringe-Tip Centrifuge

Conventional sample preparation techniques require bulky and expensive instruments and are not compatible with next-generation point-of-care diagnostic testing. Here, we report a manually operated syringe-tip inertial microfluidic centrifuge (named i-centrifuge) for high-flow-rate (up to 16 mL/min) cell concentration and experimentally demonstrate its working mechanism and performance. Low-cost polymer films and double-sided tape were used through a rapid nonclean-room process of laser cutting and lamination bonding to construct the key components of the i-centrifuge, which consists of a syringe-tip flow stabilizer and a four-channel paralleled inertial microfluidic concentrator. The unstable liquid flow generated by the manual syringe was regulated and stabilized with the flow stabilizer to power inertial focusing in a four-channel paralleled concentrator. Finally, we successfully used our i-centrifuge for manually operated cell concentration. This i-centrifuge offers the advantages of low device cost, simple hand-powered operation, high-flow-rate processing, and portable device volume. Therefore, it holds potential as a low-cost, portable sample preparation tool for point-of-care diagnostic testing.

Instability of a liquid sheet with viscosity contrast in inertial microfluidics

Flows at moderate Reynolds numbers in inertial microfluidics enable high throughput and inertial focusing of particles and cells with relevance in biomedical applications. In the present work, we consider a viscosity-stratified three-layer flow in the inertial regime. We investigate the interfacial instability of a liquid sheet surrounded by a density-matched but more viscous fluid in a channel flow. We use linear stability analysis based on the Orr–Sommerfeld equation and direct numerical simulations with the lattice Boltzmann method (LBM) to perform an extensive parameter study. Our aim is to contribute to a controlled droplet production in inertial microfluidics. In the first part, on the linear stability analysis we show that the growth rate of the fastest growing mode $$\xi ^{*}$$ ξ ∗ increases with the Reynolds number $$\text {Re}$$ Re and that its wavelength $$\lambda ^{*}$$ λ ∗ is always smaller than the channel width w for sufficiently small interfacial tension $$\Gamma $$ Γ . For thin sheets we find the scaling relation $$\xi ^{*} \propto mt^{2.5}_{s}$$ ξ ∗ ∝ m t s 2.5 , where m is viscosity ratio and $$t_{s}$$ t s the sheet thickness. In contrast, for thicker sheets $$\xi ^{*}$$ ξ ∗ decreases with increasing $$t_s$$ t s or m due to the nearby channel walls. Examining the eigenvalue spectra, we identify Yih modes at the interface. In the second part on the LBM simulations, the thin liquid sheet develops two distinct dynamic states: waves traveling along the interface and breakup into droplets with bullet shape. For smaller flow rates and larger sheet thicknesses, we also observe ligament formation and the sheet eventually evolves irregularly. Our work gives some indication how droplet formation can be controlled with a suitable parameter set $$\{\lambda ,t_{s},m,\Gamma ,\text {Re}\}$$ { λ , t s , m , Γ , Re } . Graphical Abstract

Inertial and non-inertial focusing of a deformable capsule in a curved microchannel

A computational study is presented on cross-stream migration and focusing of deformable capsules in curved microchannels of square and rectangular sections under inertial and non-inertial regimes. The numerical methodology is based on immersed boundary methods for fluid–structure coupling, a finite-volume-based flow solver and finite-element method for capsule deformation. Different focusing behaviours in the two regimes are predicted that arise due to the interplay of inertia, deformation, altered shear gradient, streamline curvature effect and secondary flow. In the non-inertial regime, a single-point focusing occurs on the central plane, and at a radial location between the interior face (i.e. face with highest curvature) of the channel and the location of zero shear. The focusing position is nearly independent of capsule deformability (represented by the capillary number, $Ca$ ). A two-step migration is observed that is comprised of a faster radial migration, followed by a slower migration toward the centre plane. The focusing location progressively moves further toward the interior face with increasing curvature and width, but decreasing height. In the inertial regime, single-point focusing is observed near the interior face for channel Reynolds number $Re_{C}\sim {O}(1)$ , that is also highly sensitive to $Re_{C}$ and $Ca$ , and moves progressively toward the exterior face with increasing $Re_{C}$ but decreasing $Ca$ . As $Re_{C}$ increases by an order, secondary flow becomes stronger, and two focusing locations appear close to the centres of the Dean vortices. This location becomes practically independent of $Ca$ at even higher inertia. The inertial focusing positions move progressively toward the exterior face with increasing channel width and decreasing height. For wider channels, the equilibrium location is further toward the exterior face than the vortex centre.

Enhanced Separation Efficiency and Purity of Circulating Tumor Cells Based on the Combined Effects of Double Sheath Fluids and Inertial Focusing

Circulating tumor cells (CTCs) play a crucial role in solid tumor metastasis, but obtaining high purity and viability CTCs is a challenging task due to their rarity. Although various works using spiral microchannels to isolate CTCs have been reported, the sorting purity of CTCs has not been significantly improved. Herein, we developed a novel double spiral microchannel for efficient separation and enrichment of intact and high-purity CTCs based on the combined effects of two-stage inertial focusing and particle deflection. Particle deflection relies on the second sheath to produce a deflection of the focused sample flow segment at the end of the first-stage microchannel, allowing larger particles to remain focused and entered the second-stage microchannel while smaller particles moved into the first waste channel. The deflection of the focused sample flow segment was visualized. Testing by a binary mixture of 10.4 and 16.5 μm fluorescent microspheres, it showed 16.5 μm with separation efficiency of 98% and purity of 90% under the second sheath flow rate of 700 μl min−1. In biological experiments, the average purity of spiked CTCs was 74% at a high throughput of 1.5 × 108 cells min−1, and the recovery was more than 91%. Compared to the control group, the viability of separated cells was 99%. Finally, we validated the performance of the double spiral microchannel using clinical cancer blood samples. CTCs with a concentration of 2–28 counts ml−1 were separated from all 12 patients’ peripheral blood. Thus, our device could be a robust and label-free liquid biopsy platform in inertial microfluidics for successful application in clinical trials.

Pattern Transition on Inertial Focusing of Neutrally Buoyant Particles Suspended in Rectangular Duct Flows

The continuous separation and filtration of particles immersed in fluid flows are important interests in various applications. Although the inertial focusing of particles suspended in a duct flow is promising in microfluidics, predicting the focusing positions depending on the parameters, such as the shape of the duct cross-section and the Reynolds number (Re) has not been achieved owing to the diversity of the inertial-focusing phenomena. In this study, we aimed to elucidate the variation of the inertial focusing depending on Re in rectangular duct flows. We performed a numerical simulation of the lift force exerted on a spherical particle flowing in a rectangular duct and determined the lift-force map within the duct cross-section over a wide range of Re. We estimated the particle trajectories based on the lift map and Stokes drag, and identified the particle-focusing points appeared in the cross-section. For an aspect ratio of the duct cross-section of 2, we found that the blockage ratio changes transition structure of particle focusing. For blockage ratios smaller than 0.3, particles focus near the centres of the long sides of the cross-section at low Re and near the centres of both the long and short sides at relatively higher Re. This transition is expressed as a subcritical pitchfork bifurcation. For blockage ratio larger than 0.3, another focusing pattern appears between these two focusing regimes, where particles are focused on the centres of the long sides and at intermediate positions near the corners. Thus, there are three regimes; the transition between adjacent regimes at lower Re is found to be expressed as a saddle-node bifurcation and the other transition as a supercritical pitchfork bifurcation.

Research on the Inertial Migration Characteristics of Bi-Disperse Particles in Channel Flow

The inertial focusing effect of particles in microchannels shows application potential in engineering practice. In order to study the mechanism of inertial migration of particles with different scales, the motion and distribution of two particles in Poiseuille flow are studied by the lattice Boltzmann method. The effects of particle size ratio, Reynolds number, and blocking rate on particle inertial migration are analyzed. The results show that, at a high blocking rate, after the same scale particles are released at the same height of the channel, the spacing between the two particles increases monotonically, and the change in the initial spacing has little effect on the final spacing of inertial migration. For two different size particles, when the smaller particle is downstream, the particle spacing will always increase and cannot remain stable. When the larger particle is downstream, the particle spacing increases firstly and then decreases, and finally tends to be stable.

Utilization of direct forcing immersed boundary methods for the optimization of inertial focusing microfluidics

Inertial focusing microfluidics have gained significant momentum in the last decade for their ability to separate and filter mixtures of particles and cells based on size [1-3]. However, the most important feature is that the separation is passive, without the need for external forces. At the heart of inertial focusing is the balance between counteracting lift forces: shear and wallinduced lift. Shear-induced lift is a product of the curvature of the fluid flow and the rotation of the particle in the flow, while wall-induced lift is generated by the disturbance of the fluid by the particle near a wall. This phenomenon was first observed by Segre and Silberberg for the focusing of particles in a pipe, and was later extended to the focusing of cells and particle in rectangular channels [4]. Taking advantage of inertial focusing we explore particle capture utilizing an expanded channel microfluidics chip design. By expanding a small region of the straight channel microvortices form in the well, which allows for size selective trapping of particles.

High-resolution particle separation by inertial focusing in high aspect ratio curved microfluidics

The ability to focus, separate and concentrate specific targets in a fluid is essential for the analysis of complex samples such as biological fluids, where a myriad of different particles may be present. Inertial focusing is a very promising technology for such tasks, and specially a recently presented variant, inertial focusing in High Aspect Ratio Curved systems (HARC systems), where the systems are easily engineered and focus the targets together in a stable position over a wide range of particle sizes and flow rates. However, although convenient for laser interrogation and concentration, by focusing all particles together, HARC systems lose an essential feature of inertial focusing: the possibility of particle separation by size. Within this work, we report that HARC systems not only do have the capacity to separate particles but can do so with extremely high resolution, which we demonstrate for particles with a size difference down to 80 nm. In addition to the concept for particle separation, a model considering the main flow, the secondary flow and a simplified expression for the lift force in HARC microchannels was developed and proven accurate for the prediction of the performance of the systems. The concept was also demonstrated experimentally with three different sub-micron particles (0.79, 0.92 and 1.0 µm in diameter) in silicon-glass microchannels, where the resolution in the separation could be modulated by the radius of the channel. With the capacity to focus sub-micron particles and to separate them with high resolution, we believe that inertial focusing in HARC systems is a technology with the potential to facilitate the analysis of complex fluid samples containing bioparticles like bacteria, viruses or eukaryotic organelles.