Particle inertial focusing and its mechanism in a serpentine microchannel

Particle inertial focusing in a curved channel promises a big potential for lab-on-a-chip applications. This focusing concept is usually based on the balance of inertial lift force and the drag of secondary flow. This paper proposes a new focusing concept independent of inertial lift force, relying solely on secondary flow drag and particle centrifugal force. Firstly, a focusing mechanism in a serpentine channel is introduced, and some design considerations are described in order to make the proposed focusing concept valid. Then, numerical modelling based on the proposed focusing mechanism is conducted, and the numerical results agree well with the experimental ones, which verify the rationality of proposed mechanism. Thirdly, the effects of flow condition and particle size on the focusing performance are studied. The effect of particle centrifugal force on particle focusing in a serpentine microchannel is carefully evaluated. Finally, the speed of focussed particles at the outlet is measured by a micro-PIV, which further certifies the focusing positions of particles within the cross section. Our study provides insights into the role of centrifugal force on inertial focusing. This paper demonstrates for the first time that a single focusing streak can be achieved in a symmetric serpentine channel. The simple serpentine microchannel can easily be implemented in a single-layer microfluidic device. No sheath flow or external force field is needed allowing a simple operation in a more complex lab-on-a-chip system.     

Flow rate-insensitive microparticle separation and filtration using a microchannel with arc-shaped groove arrays

Inertial microfluidics can separate microparticles in a continuous and high-throughput manner, and is very promising for a wide range of industrial, biomedical and clinical applications. However, most of the proposed inertial microfluidic devices only work effectively at a limited and narrow flow rate range because the performance of inertial particle focusing and separation is normally very sensitive to the flow rate (Reynolds number). In this work, an innovative particle separation method is proposed and developed by taking advantage of the secondary flow and particle inertial lift force in a straight channel (AR = 0.2) with arc-shaped groove arrays patterned on the channel top surface. Through the simulation results achieved, it can be found that a secondary flow is induced within the cross section of the microchannel and guides different-size particles to the corresponding equilibrium positions. On the other hand, the effects of the particle size, flow rate and particle concentration on particle focusing and separation quality were experimentally investigated. In the experiments, the performance of particle focusing, however, was found relatively insensitive to the variation of flow rate. According to this, a separation of 4.8 and 13 µm particle suspensions was designed and successfully achieved in the proposed microchannel, and the results show that a qualified particle separation can be achieved at a wide range of flow rate. This flow rate-insensitive microfluidic separation (filtration) method is able to potentially serve as a reliable biosample preparation processing step for downstream bioassays.     

Sheathless microfluidic particle focusing technique using slanted microstructure array

This paper proposes a microfluidic channel for particle focusing that uses a microstructure on the bottom of the channel. Particles can be effectively focused in channels with bottom structures because of microvortex induced by the structure. Microchannels with top structures (top type) and bottom structures (bottom type) were fabricated. The focusing ratios in the focusing region (one-eighth of the channel width) were 86 % in top type and 89 % in bottom type at a flow rate of 1 μl/min. When the flow rate was increased to 5 μl/min, particles in top type were barely focused, whereas particles in bottom type were focused with a focusing ratio of approximately 80 %. We also evaluated the effect of a slanted angle for the microstructures. The comparative experiment was conducted with microstructures fabricated at slanted angle intervals of 20° (20°, 40°, 60°, and 80°) and 10°. The results indicated that the slanted angle (20°) required a small number of microstructures to direct the sample to the focusing region. For microstructures with a 20° slanted angle, the sample was focused after passing through 20 microstructures (10 mm). However, microstructures with an angle of 80° needed over 70 microstructures (over 23 mm) to direct the particle. In this sense, a microchannel with microstructures slanted at 20° is applicable to miniaturized devices. These results show that the microchannel with bottom structures slanted 20° can be used to effectively focus samples with advantages of applying various ranges of flow rates and miniaturizing devices.     

Viscosity-difference-induced asymmetric selective focusing for large stroke particle separation

We developed a new approach for particle separation by introducing viscosity difference of the sheath flows to form an asymmetric focusing of sample particle flow. This approach relies on the high-velocity gradient in the asymmetric focusing of the particle flow to generate a lift force, which plays a dominated role in the particle separation. The larger particles migrate away from the original streamline to the side of the higher relative velocity, while the smaller particles remain close to the streamline. Under high-viscosity (glycerol–water solution) and low-viscosity (PBS) sheath flows, a significant large stroke separation between the smaller (1.0 μm) and larger (9.9 μm) particles was achieved in a sample microfluidic device. We demonstrate that the flow rate and the viscosity difference of the sheath flows have an impact on the interval distance of the particle separation that affects the collected purity and on the focusing distribution of the smaller particles that affects the collected concentration. The interval distance of 293 μm (relative to the channel width: 0.281) and the focusing distribution of 112 μm (relative to the channel width: 0.107) were obtained in the 1042-μm-width separation area of the device. This separation method proposed in our work can potentially be applied to biological and medical applications due to the wide interval distance and the narrow focusing distribution of the particle separation, by easy manufacturing in a simple device.     

Inertial focusing of microparticles in curvilinear microchannels with different curvature angles

Inertial microfluidics has become one of the emerging topics due to potential applications such as particle separation, particle enrichment, rapid detection and diagnosis of circulating tumor cells. To realize its integration to such applications, underlying physics should be well understood. This study focuses on particle dynamics in curvilinear channels with different curvature angles (280°, 230°, and 180°) and different channel heights (90, 75, and 60 µm) where the advantages of hydrodynamic forces were exploited. We presented the cruciality of the three-dimensional particle position with respect to inertial lift forces and Dean drag force by examining the focusing behavior of 20 µm (large), 15 µm (medium) and 10 µm (small) fluorescent polystyrene microparticles for a wide range of flow rates (400–2700 µL/min) and corresponding channel Reynolds numbers. Migration of the particles in lateral direction and their equilibrium positions were investigated in detail. In addition, in the light of our findings, we described two different regions: transition region, where the inner wall becomes the outer wall and vice versa, and the outlet region. The maximum distance between the tight particle stream of 20 and 15 µm particles was obtained in the 90 high channel with curvature angle of 280° at Reynolds number of 144 in the transition region (intersection of the turns), which was the optimum condition/configuration for focusing.     

Quantitative characterization of the focusing process and dynamic behavior of differently sized microparticles in a spiral microchannel

In this paper, a spiral microchannel was fabricated to systematically investigate particle dynamics. The focusing process or migration behavior of different-sized particles in the outlet region was presented. Specifically, for focused microparticles, quantitative characterization and analysis of how particles migrate towards the equilibrium positions with the increase in flow rate (De = 0.31–3.36) were performed. For unfocused microparticles, the particle migration behavior and the particle-free region’s formation process were characterized over a wide range of flow rates (De = 0.31–4.58), and the emergence of double particle-free regions was observed at De ≥ 3.36. These results provide insights into the design and operation of high-throughput particle/cell filtration and separation. Furthermore, using the location markers pre-fabricated along with the microchannel structures, the focusing or migration dynamics of different-sized particles along the spiral microchannel was systematically explored. The particle migration length effects on focusing degree and particle-free region width were analyzed. These analyses may be valuable for the optimization of microchannel structures. In addition, this device was successfully used to efficiently filter rare particles from a large-volume sample and separate particles of two different sizes according to their focusing states.     

Inertial particle focusing dynamics in a trapezoidal straight microchannel: application to particle filtration

Inertial microfluidics has emerged recently as a promising tool for high-throughput manipulation of particles and cells for a wide range of flow cytometric tasks including cell separation/filtration, cell counting, and mechanical phenotyping. Inertial focusing is profoundly reliant on the cross-sectional shape of channel and its impacts on not only the shear field but also the wall-effect lift force near the wall region. In this study, particle focusing dynamics inside trapezoidal straight microchannels was first studied systematically for a broad range of channel Re number (20 < Re < 800). The altered axial velocity profile and consequently new shear force arrangement led to a cross-lateral movement of equilibration toward the longer side wall when the rectangular straight channel was changed to a trapezoid; however, the lateral focusing started to move backward toward the middle and the shorter side wall, depending on particle clogging ratio, channel aspect ratio, and slope of slanted wall, as the channel Reynolds number further increased (Re > 50). Remarkably, an almost complete transition of major focusing from the longer side wall to the shorter side wall was found for large-sized particles of clogging ratio K ~ 0.9 (K = a/H_min) when Re increased noticeably to ~ 650. Finally, based on our findings, a trapezoidal straight channel along with a bifurcation was designed and applied for continuous filtration of a broad range of particle size (0.3 < K < 1) exiting through the longer wall outlet with ~ 99% efficiency (Re < 100).     

Experimental observations of bands of suspended colloidal particles subject to shear flow and steady electric field

Manipulating suspended colloidal particles flowing through a microchannel is of interest in microfluidics and nanotechnology. However, the flow itself can affect the dynamics of these suspended particles via wall-normal “lift” forces. The near-wall dynamics of particles suspended in shear flow and subject to a dc electric field was quantified in combined Poiseuille and EO flow through a?~?30 μm deep channel. When the two flows are in opposite directions, the particles are attracted to the wall. They then assemble into very high aspect ratio structures, or concentrated streamwise “bands,” above a minimum electric field magnitude, and, it appears, a minimum near-wall shear rate. These bands only exist over the few micrometers next to the wall and are roughly periodic in the cross-stream direction, although there are no external forces along this direction. Experimental observations and dimensional analysis of the time for the first band to form and the number of bands over a field of view of ~?200 μm are presented for dilute suspensions of polystyrene particles over a range of particle radii, concentrations, and zeta potentials. To our knowledge, there is no theoretical explanation for band assembly, but the results presented here demonstrate that it occurs over a wide range of different particle and flow parameters.     

Improving particle detection sensitivity of a microfluidic resistive pulse sensor by a novel electrokinetic flow focusing method

A novel and simple method of improving the particle detection sensitivity of a microfluidic resistive pulse sensor was presented in this paper. This novel electrokinetic flow focusing method utilizes a focusing solution (with high resistivity) flowing from the upstream focusing channel to the downstream focusing channel. The focusing solution in the sensing gate works like a virtual insulation wall that greatly narrows the gate and thus improves the detection sensitivity. An equation was derived to relate the magnitude of the output signal to the resistivity and the width of the focusing solution. The width of the focused particle solution under different voltages was numerically predicted. The results show that the magnitude of output signal increases with the decrease in the width of the focused particle stream. More importantly, the detection sensitivity can be improved by decreasing the space occupied by the focusing solution in the upstream and downstream channels as much as possible. Detection of 1 μm particle with a sensing gate of 30 × 40 × 10 μm (width × length × height) was successfully achieved. The proposed method is simple and advantageous in detecting smaller particles without fabricating a small sensing gate.     

集成惯性聚焦结构的介电泳微流控芯片的粒子连续分离

设计并制造了一种带有惯性聚焦结构的介电泳微流控芯片,以实现不同介电性质的粒子连续分离.采用MEMS工艺制作了介电泳微流控芯片:通道入口侧壁设置一对梯形结构使经过的粒子受惯性升力的作用聚焦到通道两侧;通道底部光刻一组夹角为90°的倾斜叉指电极产生非均匀电场,利用介电泳力和流体曳力的合力使通道两侧不同的粒子发生角度不同的偏转进入不同通道,从而实现分离.将酵母菌细胞和聚苯乙烯小球作为实验样本,分析了流速和交流电压对分离的影响,确定了二者分离的最优条件并进行分离.实验结果表明,将电导率为20μS/cm的样本溶液以5μL/min的流速注入到通道中,施加6 Vp-p、10 kHz的正弦信号,酵母菌细胞沿电极运动至夹角处后沿通道中心排出,聚苯乙烯小球沿通道两侧排出,成功实现分离,平均分离效率达92.8％、平均分离纯度达90.7％.     

Diamagnetic particle focusing using ferromicrofluidics with a single magnet

Focusing particles into a tight stream is critical to many applications such as microfluidic flow cytometry and particle sorting. Current magnetic field-induced particle focusing techniques rely on the use of a pair of repulsive magnets, which makes the device integration and operation difficult. We develop herein a new approach to focusing nonmagnetic particles in ferrofluid flow through a T-microchannel using a single permanent magnet. Particles are deflected across the suspending ferrofluid by negative magnetophoresis and confined by a water flow to the center plane of the microchannel, leading to a focused particle stream flowing near the bottom channel wall. Such three-dimensional diamagnetic particle focusing is demonstrated in a sufficiently diluted ferrofluid through both the top and side views of the microchannel. As the suspended particles can be visualized in bright field, this magnetic focusing method is expected to find applications to label-free (i.e., no magnetic or fluorescent labeling) cellular focusing in lab-on-a-chip devices.     

Parameters affecting the shape of a hydrodynamically focused stream

Even at low Reynolds numbers, momentum can impact the shape of hydrodynamically focused flow. Both theoretical and experimental characterization of hydrodynamic focusing in microchannels at Reynolds numbers ≤25 revealed the important parameters that affect the shape of the focused layer. A series of symmetric and asymmetric microfluidic channels with two converging streams were fabricated with different angles of confluence at the junction. The channels were used to study the characteristics of Y-type microchannels for flow-focusing. Computational analysis and experimental results gathered using confocal microscopy and particle image velocimetry indicated that the orientation of the sheath and the sample stream inlets, as well as the absolute flow velocities, determine the curvature in the concentration distribution of the focused stream. Decreasing the angle of confluence between sheath and sample, as well as reducing the overall Reynolds number, resulted in a flat interface between sheath and focused fluids. Alignment of the faster flowing sheath fluid channel with the main channel also reduced the inertial effects and produced a focused stream with a flat concentration profile. Control over the shape of the focused stream is important in many biosensors and lab-on-a-chip devices that rely on hydrodynamic focusing for increased detection sensitivity.     

Analysis and experiment of transient filling flow into a rectangular microchannel on a rotating disk

In order to predict the time-dependent behaviors of the moving front in lab-on-a-CD systems or centrifugal pumping, an analytical expression and experimental methods of centrifugal-force-driven transient filling flow into a rectangular microchannel in centrifugal microfluidics are presented in this paper. Considering the effect of surface tension, and neglecting the effect of Coriolis force, the velocity profile, flow rate, the moving front displacement and the pressure distribution along the microchannel are characterized. Experiments are carried out using the image-capturing unit to measure the shift of the flow in rectangular microchannels. The flow characteristics in rectangular microchannels with different cross-sectional dimensions (200, 300 and 400 μm in width and 140, 240 and 300 μm in depth) and length (18 and 25 mm) under different rotational speed are investigated. According to the experimental data, the model can be more reasonable to predict the flow displacement with time, and the errors between theoretical and the experimental will decrease with increasing the cross-section size of the microchannel.     

Inertially focused diamagnetic particle separation in ferrofluids

Continuous flow separation of target particles from a mixture is essential to many chemical and biomedical applications. There has recently been an increasing interest in the integration of active and passive particle separation techniques for enhanced sensitivity and flexibility. We demonstrate herein the proof-of-concept of a ferrofluid-based hybrid microfluidic technique that combines passive inertial focusing with active magnetic deflection to separate diamagnetic particles by size. The two operations take place in series in a continuous flow through a straight rectangular microchannel with a nearby permanent magnet. We also develop a three-dimensional numerical model to simulate the transport of diamagnetic particles during their inertial focusing and magnetic separation processes in the entire microchannel. The predicted particle trajectories are found to be approximately consistent with the experimental observations at different ferrofluid flow rates and ferrofluid concentrations.     

Inertial migration of single particle in a square microchannel over wide ranges of <Emphasis Type="Italic">Re</Emphasis> and particle sizes

Inertial migration of particles has been widely used in inertial microfluidic systems to passively manipulate cells/particles. However, the migration behaviors and the underlying mechanisms, especially in a square microchannel, are still not very clear. In this paper, the immersed boundary-lattice Boltzmann method (IB-LBM) was introduced and validated to explore the migration characteristics and the underlying mechanisms of an inertial focusing single particle in a square microchannel. The grid-independence analysis was made first to highlight that the grid number across the thin liquid film (between a particle and its neighboring channel wall) was of significant importance in accurately capturing the migrating particle’s dynamics. Then, the inertial migration of a single particle was numerically investigated over wide ranges of Reynolds number (Re, from 10 to 500) and particle sizes (diameter-to-height ratio a/H, from 0.16 to 0.5). It was interesting to find that as Re increased, the channel face equilibrium (CFE) position moved outward to channel walls at first, and then inflected inwards to the channel center at high Re (Re?>?200). To account for the physical mechanisms behind this behavior, the secondary flow induced by the inertial focusing single particle was further investigated. It was found that as Re increased, two vortices appeared around the particle and grew gradually, which pushed the particle away from the channel wall at high Re. Finally, a correlation was proposed based on the numerical data to predict the critical length L_c (defined to describe the size of fluid domain that was strongly influenced by the particle) according to the particle size a/H and Re.     

Multiplex Inertio-Magnetic Fractionation (MIMF) of magnetic and non-magnetic microparticles in a microfluidic device

Separation of multiple microparticles at high throughput is highly required in different applications such as diagnostics and immunomagnetic detection. We present a microfluidic device for multiplex (i.e., duplex to fourplex) fractionation of magnetic and non-magnetic microparticles using a novel hybrid technique based on interactions between flow-induced inertial forces and countering magnetic forces in a simple expansion microchannel with a side permanent magnet. Separation of more than two types of particles solely by inertia or magnetic forces in a straight microchannel is challenging due to the inherent limitations of each technique. By combining inertial and magnetic forces in a straight microchannel and addition of a downstream expansion hydrodynamic separator, we overcame these limitations and achieved duplex to fourplex fractionation of magnetic and non-magnetic microparticles with high throughput and efficiency. Particle fractionation performance in our device was first optimized with respect to parameters such as flow rate and aspect ratio of the channel to attain coexistence of inertial and magnetic focusing of particles. Using this scheme, we achieved duplex fractionation of particles at high throughput of 10⁹ particles per hour. Further, we conducted experiments with three magnetic particles (5, 11 and 35 µm) to establish their size-dependent ordering in the device under combined effects of magnetic and inertial forces. We then used the findings for fourplex fractionation of 5, 11 and 35 µm magnetic particles from non-magnetic particles of various sizes (10–19 µm). This Multiplex Inertio-Magnetic Fractionation (MIMF) technique offers a simple tool to handle complex and heterogeneous samples and can be used for affinity-based immunomagnetic separation of multiple biological substances in fluidic specimens in the future.     

Size-dependent microparticles separation through standing surface acoustic waves

This study presents a method that uses a standing surface acoustic wave (SSAW) to continuously separate particles in a size-gradient manner in a microchannel flow. The proposed method was applied to a colloidal suspension containing poly dispersed particles with three different sizes (1, 5, and 10 μm) but the same density and compressibility. Particle suspension was focused hydrodynamically at an entrance region, and particles were forced actively toward the side wall where SSAW-pressure nodes were generated by two interdigital transducers (IDTs) across the channel. The particles placed in the middle stream, in which the shear rate was minimized, were separated successfully in a size-gradient manner by acoustic force. In addition, this study further developed an analytical model to predict the displacement of particles in microchannel flow by considering viscous, acoustic, and diffusive forces. The predicted values of particle displacement showed excellent agreement with the experimental results, and diffusion was found to be important and not negligible. The advantage of this method is to minimize the shear rate on particles, which would be useful for potential applications of shear-dependent cells such as platelets.     

Particle focusing in a contactless dielectrophoretic microfluidic chip with insulating structures

The focusing of biological and synthetic particles in microfluidic devices is a crucial step for the construction of many microstructured materials as well as for medical applications. The present study examines the feasibility of using contactless dielectrophoresis (cDEP) in an insulator-based dielectrophoretic (iDEP) microdevice to effectively focus particles. Particles 10?μm in diameter were introduced into the microchannel and pre-confined hydrodynamically by funnel-shaped insulating structures near the inlet. The particles were repelled toward the center of the microchannel by the negative DEP forces generated by the insulating structures. The microchip was fabricated based on the concept of cDEP. The electric field in the main microchannel was generated using electrodes inserted into two conductive micro-reservoirs, which were separated from the main microchannel by 20-μm-thick insulating barriers made of polydimethylsiloxane (PDMS). The impedance spectrum of the thin insulating PDMS barrier was measured to investigate its capacitive behavior. Experiments employing polystyrene particles were conducted to demonstrate the feasibility of the proposed microdevice. Results show that the particle focusing performance increased with increasing frequency of the applied AC voltage due to the reduced impedance of PDMS barriers at high frequencies. When the frequency was above 800?kHz, most particles were focused into a single file. The smallest width of focused particles distributed at the outlet was about 13.1?μm at a frequency of 1?MHz. Experimental results also show that the particle focusing performance improved with increasing applied electric field strength and decreasing inlet flow rate. The usage of the cDEP technique makes the proposed microchip mechanically robust and chemically inert.     

Microfluidic counterflow centrifugal elutriation system for sedimentation-based cell separation

We present a centrifugal microfluidic system for precise cell/particle sorting using the concept of counterflow centrifugal elutriation (CCE). A conventional CCE system uses a rotor device incorporating a flow-through separation chamber, in which the balance of centrifugal and counterflow drag forces exerted on particles is gradually shifted by changing the flow rate and/or the rotation speed. In the present system, both the centrifugal and the fluid forces are generated through microdevice rotation in order to significantly simplify the setup of the conventional CCE. In addition, the density gradient of the medium is employed to elute particles/cells of different sedimentation velocities stepwise from the separation chamber instead of changing the rotation speed. We successfully separated polymer particles with diameters of 1.0–5.0 μm using a branched loading channel for focusing particles to the center of the separation chamber. We also demonstrated the sorting of blood cells for biological applications. This system may provide a versatile means for cell/particle sorting in a general biological laboratory and function as a unit operation in various centrifugal microfluidic platforms for biochemical experiments and clinical diagnosis.     

Control of secondary flow in concentrically traveling flow on centrifugal microfluidics

This paper reports a fundamental study of the stripe laminar flow pattern on a centrifugal microfluidic device with the goal of realizing a sedimentation-based, continuous mode particle separation technique. Microfluidic channels were designed with a concentrically integrated microchannel, and the patterning of the flow in the channel was investigated. A significant secondary flow was observed as a preliminary result. We conclude that the origin of this secondary flow was not the Dean force, because it was observed in a straight microchannel, but was not observed in curved channel during the spinning of the system at rest. The transition of the pattern was investigated using a simulation and experiment, and the flow pattern’s dependence on the rotational speed was determined, which suggested that the origin of the secondary flow was the Coriolis force. The significance of the secondary flow was controlled by adjusting the rotational speed of the disk, and the flow rate and laminar flow patterns were controlled by the stripe flow pattern.