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1.
The need for cell and particle sorting in human health care and biotechnology applications is undeniable. Inertial microfluidics has proven to be an effective cell and particle sorting technology in many of these applications. Still, only a limited understanding of the underlying physics of particle migration is currently available due to the complex inertial and impact forces arising from particle–particle and particle–wall interactions. Thus, even though it would likely enable significant advances in the field, very few studies have tried to simulate particle-laden flows in inertial microfluidic devices. To address this, this study proposes new codes (solved in OpenFOAM software) that capture all the salient inertial forces, including the four-way coupling between the conveying fluid and the suspended particles traveling a spiral microchannel. Additionally, these simulations are relatively (computationally) inexpensive since the arbitrary Lagrangian–Eulerian formulation allows the fluid elements to be much larger than the particles. In this study, simulations were conducted for two different spiral microchannel cross sections (e.g., rectangular and trapezoidal) for comparison against previously published experimental results. The results indicate good agreement with experiments in terms of (monodisperse) particle focusing positions, and the codes can readily be extended to simulate two different particle types. This new numerical approach is significant because it opens the door to rapid geometric and flow rate optimization in order to improve the efficiency and purity of cell and particle sorting in biotechnology applications.  相似文献   

2.
Particle focusing is an essential step in a wide range of applications such as cell counting and sorting. Recently, viscoelastic particle focusing, which exploits the spatially non-uniform viscoelastic properties of a polymer solution under Poiseuille flow, has attracted much attention because the particles are focused along the channel centerline without any external force. Lateral particle migration in polymer solutions in square channels has been studied due to its practical importance in lab-on-a-chip applications. However, there are still many questions about how the rheological properties of the medium alter the equilibrium particle positions and about the flow rate ranges for particle focusing. In this study, we investigated lateral particle migration in a viscoelastic flow of DNA solution in a square microchannel. The elastic property is relevant due to the long relaxation time of a DNA molecule, even when the DNA concentration is extremely low. Further, the shear viscosity of the solution is essentially constant irrespective of shear rate. Our current results demonstrate that the particles migrate toward the channel centerline and the four corners of a square channel in the dilute DNA solution when the inertia is negligible (elasticity-dominant flow). As the flow rate increases, the multiple equilibrium particle positions are reduced to a single file along the channel centerline, due to the elasto-inertial particle focusing mechanism. The current results support that elasto-inertial particle focusing mechanism is a universal phenomenon in a viscoelastic fluid with constant shear viscosity (Boger fluid). Also, the effective flow rate ranges for three-dimensional particle focusing in the DNA solution were significantly higher and wider than those for the previous synthetic polymer solution case, which facilitates high throughput analysis of particulate systems. In addition, we demonstrated that the DNA solution can be applied to focus a wide range of particle sizes in a single channel and also align red blood cells without any significant deformation.  相似文献   

3.
In this paper, we use a spiral channel inertial focusing device for isolation and purification of chromosomes, which are highly asymmetric. The method developed is proposed as a sample preparation process for transchromosomic research. The proposed microfluidics-based chromosome separation approach enables rapid, label-free isolation of bioactive chromosomes and is compatible with chromosome buffer. As part of this work, particle force analysis during the separation process is performed utilizing mathematic models to estimate the expected behavior of chromosomes in the channel and the model validated with experiments employing fluorescent beads. The chromosome sample is further divided into subtypes utilizing fluorescent activated cell sorting , including small condensed chromosomes, single chromosomes, and groups of two chromosomes (four sister chromatids). The separation of chromosome subtypes is realized based on their shape differences in the spiral channel device under high flow rate conditions. When chromosomes become aligned in the shear flow, the balance between the inertial focusing force and the Dean flow drag force is determined by the chromosome projection area and aspect ratio, or shape difference, leading to different focusing locations in the channel. The achieved results indicate a new separation regime in inertial microfluidics that can be used for the separation of non-spherical particles based on particle aspect ratios, which could potentially be applied in fields such as bacteria subtype separation and chromosome karyotyping.  相似文献   

4.
Inertial microfluidics has brought enormous changes in the conventional cell/particle detection process and now become the main trend of sample pretreatment with outstanding throughput, low cost, and simple control method. However, inertial microfluidics in a straight microchannel is not enough to provide high efficiency and satisfying performance for cell/particle separation. A contraction–expansion microchannel is a widely used and multifunctional channel pattern involving inertial microfluidics, secondary flow, and the vortex in the chamber. The strengthened inertial microfluidics can help us to focus particles with a shorter channel length and less processing time. Both the vortex in the chamber and the secondary flow in the main channel can trap the target particles or separate particles based on their sizes more precisely. The contraction–expansion microchannels are also capable of combining with a curved, spiral, or serpentine channel to further improve the separation performance. Some recent studies have focused on the viscoelastic fluid that utilizes both elastic forces and inertial forces to separate different size particles precisely with a relatively low flow rate for the vulnerable cells. This article comprehensively reviews various contraction–expansion microchannels with Newtonian and viscoelastic fluids for particle focusing, separation, and microfluid mixing and provides particle manipulation performance data analysis for the contraction–expansion microchannel design.  相似文献   

5.
Integrating different steps on a chip for cell manipulations and sample preparation is of foremost importance to fully take advantage of microfluidic possibilities, and therefore make tests faster, cheaper and more accurate. We demonstrated particle manipulation in an integrated microfluidic device by applying hydrodynamic, electroosmotic (EO), electrophoretic (EP), and dielectrophoretic (DEP) forces. The process involves generation of fluid flow by pressure difference, particle trapping by DEP force, and particle redirect by EO and EP forces. Both DC and AC signals were applied, taking advantages of DC EP, EO and AC DEP for on-chip particle manipulation. Since different types of particles respond differently to these signals, variations of DC and AC signals are capable to handle complex and highly variable colloidal and biological samples. The proposed technique can operate in a high-throughput manner with thirteen independent channels in radial directions for enrichment and separation in microfluidic chip. We evaluated our approach by collecting Polystyrene particles, yeast cells, and E. coli bacteria, which respond differently to electric field gradient. Live and dead yeast cells were separated successfully, validating the capability of our device to separate highly similar cells. Our results showed that this technique could achieve fast pre-concentration of colloidal particles and cells and separation of cells depending on their vitality. Hydrodynamic, DC electrophoretic and DC electroosmotic forces were used together instead of syringe pump to achieve sufficient fluid flow and particle mobility for particle trapping and sorting. By eliminating bulky mechanical pumps, this new technique has wide applications for in situ detection and analysis.  相似文献   

6.
Selection of particles or cells of specific shapes from a complex mixture is an essential procedure for various biological and industrial applications, including synchronization of the cell cycle, classification of environmental bacteria, and elimination of aggregates from synthesized particles. Here, we investigate the separation behaviors of nonspherical and spherical particles∕cells in the hydrodynamic filtration (HDF) scheme, which was previously developed for continuous size-dependent particle∕cell separation. Nonspherical particle models were prepared by coating the hemisphere of spherical polymer particles with a thin Au layer and by bonding the Janus particles to form twins and triplets resembling dividing and aggregating cells, respectively. High-speed imaging revealed a difference in the separation behaviors of spherical and nonspherical particles at a branch point; nonspherical particles showed rotation behavior and did not enter the branch channel even when their minor axis was smaller than the virtual width of the flow region entering the branch channel, w(1). The confocal-laser high-speed particle intensity velocimetry system visualized the flow profile inside the HDF microchannel, demonstrating that the steep flow-velocity distribution at the branch point is the main factor causing the rotation behavior of nonspherical particles. As applications, we successfully separated spherical and nonspherical particles with various major∕minor lengths and also demonstrated the selection of budding∕single cells from a yeast cell mixture. We therefore conclude that the HDF scheme can be used for continuous shape-based particle∕cell separation.  相似文献   

7.
Increasingly, invitro culture of adherent cell types utilizes three-dimensional (3D) scaffolds or aggregate culture strategies to mimic tissue-like, microenvironmental conditions. In parallel, new flow cytometry-based technologies are emerging to accurately analyze the composition and function of these microtissues (i.e., large particles) in a non-invasive and high-throughput way. Lacking, however, is an accessible platform that can be used to effectively sort or purify large particles based on analysis parameters. Here we describe a microfluidic-based, electromechanical approach to sort large particles. Specifically, sheath-less asymmetric curving channels were employed to separate and hydrodynamically focus particles to be analyzed and subsequently sorted. This design was developed and characterized based on wall shear stress, tortuosity of the flow path, vorticity of the fluid in the channel, sorting efficiency and enrichment ratio. The large particle sorting device was capable of purifying fluorescently labelled embryoid bodies (EBs) from unlabelled EBs with an efficiency of 87.3% ± 13.5%, and enrichment ratio of 12.2 ± 8.4 (n = 8), while preserving cell viability, differentiation potential, and long-term function.  相似文献   

8.
Focusing and sorting cells and particles utilizing microfluidic phenomena have been flourishing areas of development in recent years. These processes are largely beneficial in biomedical applications and fundamental studies of cell biology as they provide cost-effective and point-of-care miniaturized diagnostic devices and rare cell enrichment techniques. Due to inherent problems of isolation methods based on the biomarkers and antigens, separation approaches exploiting physical characteristics of cells of interest, such as size, deformability, and electric and magnetic properties, have gained currency in many medical assays. Here, we present an overview of the cell/particle sorting techniques by harnessing intrinsic hydrodynamic effects in microchannels. Our emphasis is on the underlying fluid dynamical mechanisms causing cross stream migration of objects in shear and vortical flows. We also highlight the advantages and drawbacks of each method in terms of throughput, separation efficiency, and cell viability. Finally, we discuss the future research areas for extending the scope of hydrodynamic mechanisms and exploring new physical directions for microfluidic applications.  相似文献   

9.
In this work, we design and fabricate a miniaturized spiral-shaped microchannel device which can be used for high-throughput particle/cell ordering, enrichment, and purification. To probe into the flow rate regulation mechanism, an experimental investigation is carried out on the focusing behaviors of particles with significantly different sizes in this device. A complete picture of the focusing position shifting process is unfolded to clarify the confusing results obtained from flow regimes with different dominant forces in past research. Specifically, with the increase of the flow rate, particles are observed to first move towards the inner wall under the dominant inertial migration, then stabilize at a specific position and finally shift away from the inner wall due to the alternation of the dominant force. Novel phenomena of focusing instability, co-focusing, and focusing position interchange of differently sized particles are also observed and investigated. Based on the obtained experimental data, we develop and validate, for the first time, a five-stage model of the particle focusing process with increasing flow rate for interpreting particle behaviors in terms of the competition between inertial lift and Dean drag forces. These new experimental findings and the proposed process model provide an important supplement to the existing mechanism of inertial particle flow and enable more flexible and precise particle manipulation. Additionally, we examine the focusing behaviors of bioparticles with a polydisperse size distribution to validate the explored mechanisms and thus help realize efficient enrichment and purification of these particles.  相似文献   

10.
The ability to confine flows and focus particle streams has become an integral component of the design of microfluidic systems for the analysis of a wide range of samples. Presented here is the implementation of a 3D microfluidic nozzle capable of both focusing particles as well as dynamically positioning those particles in selected flow lamina within the downstream analysis channel. Through the independent adjustment of the three sheath inlet flows, the nozzle controlled the size of a focused stream for 6, 10, and 15 μm polystyrene microparticles. Additional flow adjustment allowed the nozzle to dynamically position the focused particle stream to a specific area within the downstream channel. This unique ability provides additional capability and sample flexibility to the system. In order to gain insight into the fluidic behavior of the system, experimental conditions and results were duplicated within 4.75 μm using a COMSOL Multiphysics® model to elucidate the structure, direction, proportion, and fate of fluid lamina throughout the nozzle region. The COMSOL Multiphysics model showed that the position and distribution of particles upon entering the nozzle have negligible influence over its focusing ability, extending the experimental results into a wider range of particle sizes and system flow rates. These results are promising for the application of this design to allow for a relatively simple, fast, fully fluidically controlled nozzle for selective particle focusing and positioning for further particle analysis and sorting.  相似文献   

11.
In this paper, 3D particle focusing in a straight channel with asymmetrical expansion–contraction cavity arrays (ECCA channel) is achieved by exploiting the dean-flow-coupled elasto-inertial effects. First, the mechanism of particle focusing in both Newtonian and non-Newtonian fluids was introduced. Then particle focusing was demonstrated experimentally in this channel with Newtonian and non-Newtonian fluids using three different sized particles (3.2 μm, 4.8 μm, and 13 μm), respectively. Also, the effects of dean flow (or secondary flow) induced by expansion–contraction cavity arrays were highlighted by comparing the particle distributions in a single straight rectangular channel with that in the ECCA channel. Finally, the influences of flow rates and distances from the inlet on focusing performance in the ECCA channel were studied. The results show that in the ECCA channel particles are focused on the cavity side in Newtonian fluid due to the synthesis effects of inertial and dean-drag force, whereas the particles are focused on the opposite cavity side in non-Newtonian fluid due to the addition of viscoelastic force. Compared with the focusing performance in Newtonian fluid, the particles are more easily and better focused in non-Newtonian fluid. Besides, the Dean flow in visco-elastic fluid in the ECCA channel improves the particle focusing performance compared with that in a straight channel. A further advantage is three-dimensional (3D) particle focusing that in non-Newtonian fluid is realized according to the lateral side view of the channel while only two-dimensional (2D) particle focusing can be achieved in Newtonian fluid. Conclusively, this novel Dean-flow-coupled elasto-inertial microfluidic device could offer a continuous, sheathless, and high throughput (>10 000 s−1) 3D focusing performance, which may be valuable in various applications from high speed flow cytometry to cell counting, sorting, and analysis.  相似文献   

12.
Passive particle focusing based on inertial microfluidics was recently introduced as a high-throughput alternative to active focusing methods that require an external force field to manipulate particles. In inertial microfluidics, dominant inertial forces cause particles to move across streamlines and occupy equilibrium positions along the faces of walls in flows through straight micro channels. In this study, we systematically analyzed the addition of secondary Dean forces by introducing curvature and show how randomly distributed particles entering a simple u-shaped curved channel are focused to a fixed lateral position exiting the curvature. We found the lateral particle focusing position to be fixed and largely independent of radius of curvature and whether particles entering the curvature are pre-focused (at equilibrium) or randomly distributed. Unlike focusing in straight channels, where focusing typically is limited to channel cross-sections in the range of particle size to create single focusing point, we report here particle focusing in a large cross-section area (channel aspect ratio 1:10). Furthermore, we describe a simple u-shaped curved channel, with single inlet and four outlets, for filtration applications. We demonstrate continuous focusing and filtration of 10 μm particles (with >90% filtration efficiency) from a suspension mixture at throughputs several orders of magnitude higher than flow through straight channels (volume flow rate of 4.25 ml/min). Finally, as an example of high throughput cell processing application, white blood cells were continuously processed with a filtration efficiency of 78% with maintained high viability. We expect the study will aid in the fundamental understanding of flow through curved channels and open the door for the development of a whole set of bio-analytical applications.  相似文献   

13.
Zhao C  Cheng X 《Biomicrofluidics》2011,5(3):32004-3200410
Clinical analysis of acute viral infection in blood requires the separation of viral particles from blood cells, since the cytoplasmic enzyme inhibits the subsequent viral detection. To facilitate this procedure in settings without access to a centrifuge, we present a microfluidic device to continuously purify bionanoparticles from cells based on their different intrinsic movements on the microscale. In this device, a biological sample is layered on top of a physiological buffer, and both fluids are transported horizontally at the same flow rate in a straight channel under laminar flow. While the micron sized particles such as cells sediment to the bottom layer with a predictable terminal velocity, the nanoparticles move vertically by diffusion. As their vertical travel distances have a different dependence on time, the micro- and nanoparticles can preferentially reside in the bottom and top layers respectively after certain residence time, yielding purified viruses. We first performed numerical analysis to predicate the particle separation and then tested the theory using suspensions of synthetic particles and biological samples. The experimental results using dilute synthetic particles closely matched the numerical analysis of a two layer flow system containing different sized particles. Similar purification was achieved using diluted blood spiked with human immunodeficiency virus. However, viral purification in whole blood is compromised due to extensive bioparticle collisions. With the parallelization and automation potential offered by microfluidics, this device has the potential to function as an upstream sample preparation module to continuously provide cell depleted bio-nanoparticles for downstream analysis.  相似文献   

14.
A spiral inertial filtration (SIFT) device that is capable of high-throughput (1 ml/min), high-purity particle separation while concentrating recovered target particles by more than an order of magnitude is reported. This device is able to remove large fractions of sample fluid from a microchannel without disruption of concentrated particle streams by taking advantage of particle focusing in inertial spiral microfluidics, which is achieved by balancing inertial lift forces and Dean drag forces. To enable the calculation of channel geometries in the SIFT microsystem for specific concentration factors, an equivalent circuit model was developed and experimentally validated. Large particle concentration factors were then achieved by maintaining either the average fluid velocity or the Dean number throughout the entire length of the channel during the incremental removal of sample fluid. The SIFT device was able to separate MCF7 cells spiked into whole blood from the non-target white blood cells (WBC) with a recovery of nearly 100% while removing 93% of the sample volume, which resulted in a concentration enhancement of the MCF7 cancer cells by a factor of 14.  相似文献   

15.
High-throughput size-based rare cell enrichment using microscale vortices   总被引：2，自引：0，他引：2  
Cell isolation in designated regions or from heterogeneous samples is often required for many microfluidic cell-based assays. However, current techniques have either limited throughput or are incapable of viable off-chip collection. We present an innovative approach, allowing high-throughput and label-free cell isolation and enrichment from heterogeneous solution using cell size as a biomarker. The approach utilizes the irreversible migration of particles into microscale vortices, developed in parallel expansion-contraction trapping reservoirs, as the cell isolation mechanism. We empirically determined the critical particle∕cell diameter D(crt) and the operational flow rate above which trapping of cells∕particles in microvortices is initiated. Using this approach we successfully separated larger cancer cells spiked in blood from the smaller blood cells with processing rates as high as 7.5×10(6) cells∕s. Viable long-term culture was established using cells collected off-chip, suggesting that the proposed technique would be useful for clinical and research applications in which in vitro culture is often desired. The presented technology improves on current technology by enriching cells based on size without clogging mechanical filters, employing only a simple single-layered microfluidic device and processing cell solutions at the ml∕min scale.  相似文献   

16.
Separation and sorting of biological entities (viruses, bacteria, and cells) is a critical step in any microfluidic lab-on-a-chip device. Acoustofluidics platforms have demonstrated their ability to use physical characteristics of cells to perform label-free separation. Bandpass-type sorting methods of medium-sized entities from a mixture have been presented using acoustic techniques; however, they require multiple transducers, lack support for various target populations, can be sensitive to flow variations, or have not been verified for continuous flow sorting of biological cells. To our knowledge, this paper presents the first acoustic bandpass method that overcomes all these limitations and presents an inherently reconfigurable technique with a single transducer pair for stable continuous flow sorting of blood cells. The sorting method is first demonstrated for polystyrene particles of sizes 6, 10, and 14.5 μm in diameter with measured purity and efficiency coefficients above 75 ± 6% and 85 ± 9%, respectively. The sorting strategy was further validated in the separation of red blood cells from white blood cells and 1 μm polystyrene particles with 78 ± 8% efficiency and 74 ± 6% purity, respectively, at a flow rate of at least 1 μl/min, enabling to process finger prick blood samples within minutes.  相似文献   

17.
For passive sheathless particles focusing in microfluidics, the equilibrium positions of particles are typically controlled by micro channels with a V-shaped obstacle array (VOA). The design of the obstacles is mainly based on the distribution of flow streamlines without considering the existence of particles. We report an experimentally verified particle trajectory simulation using the arbitrary Lagrangian-Eulerian (ALE) fluid-particle interaction method. The particle trajectory which is strongly influenced by the interaction between the particle and channel wall is systematically analyzed. The numerical experiments show that the streamline is a good approximation of particle trajectory only when the particle locates on the center of the channel in depth. As the advantage of fluid-particle interaction method is achieved at a high computational cost and the streamline analysis is complex, a heuristic dimensionless design objective based on the Faxen''s law is proposed to optimize the VOA devices. The optimized performance of particle focusing is verified via the experiments and ALE method.  相似文献   

18.
Ultrafast microfluidics using surface acoustic waves   总被引：2，自引：0，他引：2  
We demonstrate that surface acoustic waves (SAWs), nanometer amplitude Rayleigh waves driven at megahertz order frequencies propagating on the surface of a piezoelectric substrate, offer a powerful method for driving a host of extremely fast microfluidic actuation and micro∕bioparticle manipulation schemes. We show that sessile drops can be translated rapidly on planar substrates or fluid can be pumped through microchannels at 1–10 cm∕s velocities, which are typically one to two orders quicker than that afforded by current microfluidic technologies. Through symmetry-breaking, azimuthal recirculation can be induced within the drop to drive strong inertial microcentrifugation for micromixing and particle concentration or separation. Similar micromixing strategies can be induced in the same microchannel in which fluid is pumped with the SAW by merely changing the SAW frequency to rapidly switch the uniform through-flow into a chaotic oscillatory flow by exploiting superpositioning of the irradiated sound waves from the sidewalls of the microchannel. If the flow is sufficiently quiescent, the nodes of the transverse standing wave that arises across the microchannel also allow for particle aggregation, and hence, sorting on nodal lines. In addition, the SAW also facilitates other microfluidic capabilities. For example, capillary waves excited at the free surface of a sessile drop by the SAW underneath it can be exploited for micro∕nanoparticle collection and sorting at nodal points or lines at low powers. At higher powers, the large accelerations off the substrate surface as the SAW propagates across drives rapid destabilization of the drop free surface giving rise to inertial liquid jets that persist over 1–2 cm in length or atomization of the entire drop to produce 1–10 μm monodispersed aerosol droplets, which can be exploited for ink-jet printing, mass spectrometry interfacing, or pulmonary drug delivery. The atomization of polymer∕protein solutions can also be used for the rapid synthesis of 150–200 nm polymer∕protein particles or biodegradable polymeric shells in which proteins, peptides, and other therapeutic molecules are encapsulated within for controlled release drug delivery. The atomization of thin films behind a translating drop containing polymer solutions also gives rise to long-range spatial ordering of regular polymer spots whose size and spacing are dependent on the SAW frequency, thus offering a simple and powerful method for polymer patterning without requiring surface treatment or physical∕chemical templating.  相似文献   

19.
We report the development and results of a two-step method for sorting cells and small particles in a microfluidic device. This approach uses a single microfluidic channel that has (1) a microfabricated sieve which efficiently focuses particles into a thin stream, followed by (2) a dielectrophoresis (DEP) section consisting of electrodes along the channel walls for efficient continuous sorting based on dielectric properties of the particles. For our demonstration, the device was constructed of polydimethylsiloxane, bonded to a glass surface, and conductive agarose gel electrodes. Gold traces were used to make electrical connections to the conductive gel. The device had several novel features that aided performance of the sorting. These included a sieving structure that performed continuous displacement of particles into a single stream within the microfluidic channel (improving the performance of downstream DEP, and avoiding the need for additional focusing flow inlets), and DEP electrodes that were the full height of the microfluidic walls (“vertical electrodes”), allowing for improved formation and control of electric field gradients in the microfluidic device. The device was used to sort polymer particles and HeLa cells, demonstrating that this unique combination provides improved capability for continuous DEP sorting of particles in a microfluidic device.  相似文献   

20.
Concurrent droplet charging and sorting by electrostatic actuation   总被引：1，自引：0，他引：1  
This paper presents a droplet-based microfluidic device for concurrent droplet charging and sorting by electrostatic actuation. Water-in-oil droplets can be charged on generation by synchronized electrostatic actuation. Then, simultaneously, the precharged droplets can be electrostatically steered into any designated laminar streamline, thus they can be sorted into one of multiple sorting channels one by one in a controlled fashion. In this paper, we studied the size dependence of the water droplets under various relative flow rates of water and oil. We demonstrated the concurrent charging and sorting of up to 600 droplets∕s by synchronized electrostatic actuation. Finally, we investigated optimized voltages for stable droplet charging and sorting. This is an essential enabling technology for fast, robust, and multiplexed sorting of microdroplets, and for the droplet-based microfluidic systems.  相似文献   

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