Dean Drag Force Research Articles

A Novel Size-Based Centrifugal Microfluidic Design to Enrich and Magnetically Isolate Circulating Tumor Cells from Blood Cells through Biocompatible Magnetite-Arginine Nanoparticles.

This paper presents a novel centrifugal microfluidic approach (so-called lab-on-a-CD) for magnetic circulating tumor cell (CTC) separation from the other healthy cells according to their physical and acquired chemical properties. This study enhances the efficiency of CTC isolation, crucial for cancer diagnosis, prognosis, and therapy. CTCs are cells that break away from primary tumors and travel through the bloodstream; however, isolating CTCs from blood cells is difficult due to their low numbers and diverse characteristics. The proposed microfluidic device consists of two sections: a passive section that uses inertial force and bifurcation law to sort CTCs into different streamlines based on size and shape and an active section that uses magnetic forces along with Dean drag, inertial, and centrifugal forces to capture magnetized CTCs at the downstream of the microchannel. The authors designed, simulated, fabricated, and tested the device with cultured cancer cells and human cells. We also proposed a cost-effective method to mitigate the surface roughness and smooth surfaces created by micromachines and a unique pulsatile technique for flow control to improve separation efficiency. The possibility of a device with fewer layers to improve the leaks and alignment concerns was also demonstrated. The fabricated device could quickly handle a large volume of samples and achieve a high separation efficiency (93%) of CTCs at an optimal angular velocity. The paper shows the feasibility and potential of the proposed centrifugal microfluidic approach to satisfy the pumping, cell sorting, and separating functions for CTC separation.

A numerical study of Elasto-inertial particle-focusing in straight and serpentine microchannels

Microfluidic devices have gained popularity in recent years due to their low cost and simplicity. Cell focusing linked with cell counting and cell separation used in clinical tests and point-of-care devices stands towards the top of every list of microfluidic applications. To focus and manipulate particles in a Newtonian medium, inertial microfluidics has been widely used. There is a requirement to replace a significantly more efficient approach given various particle-focusing positions near the channel walls recorded by inertial microfluidics. Here, the synergetic effect of elastic and inertial forces in relatively low-concentration viscoelastic fluids was investigated numerically. Utilizing particle-focusing behavior in straight and serpentine channels with different corner angles, by applying the numerical results obtained using the developed direct numerical simulation method (DNS) for elastic and inertial forces, we created a microchannel with a remarkable performance. As the flow regime transitions to elasto-inertial, where inertial forces are comparable to elastic forces in a straight microchannel, particles tend to concentrate at the channel centerline. As the flow rate increases, however, particle defocusing develops, and shear gradient lift forces ultimately overcome elastic forces in the channel's central region. Given that fluid flows at a higher velocity in the serpentine channel with a corner angle of 75° than in other channels, the Dean drag force induced by secondary flow serves to reduce particle defocusing rate at a given flow rate, making this channel a desirable platform for Elasto-inertial microfluidics. Particle focusing in a vertical direction was noticed as a benefit of elasto-inertial microfluidics, regardless of the geometry or flow rate of the particles passing through the channel. Finally, the impact of particle diameter on focusing behavior was studied. As particle diameter decreases, focusing width decreases and the focusing band shifts to the left side of the cross-section. We expect that the numerical evaluation of using viscoelastic medium in complex geometries can contribute to accelerate the three dimensional particle-focusing mechanism and enhance the efficiency of microdevices for cell and particle manipulation.

Enhancing particle focusing: a comparative experimental study of modified square wave and square wave microchannels in lift and Dean vortex regimes

Serpentine microchannels are known for their effective particle focusing through Dean flow-induced rotational effects, which are used in compact designs for size-dependent focusing in medical diagnostics. This study explores square serpentine microchannels, a geometry that has recently gained prominence in inertial microfluidics, and presents a modification of square wave microchannels for improved particle separation and focusing. The proposed modification incorporates an additional U-shaped unit to convert the square wave microchannel into a non-axisymmetric structure, which enhances the Dean flow and consequently increases the Dean drag force. Extensive experiments were conducted covering a wide range of Reynolds numbers and particle sizes (2.45 µm to 12 µm). The particle concentration capability and streak position dynamics of the two structures were compared in detail. The results indicate that the modified square-wave microchannel exhibits efficient particle separation in the lower part of the Dean vortex-dominated regime. With increasing Reynolds number, the particles are successively focused into two streaks in the lift force-dominated regime and into a single streak in the Dean vortex-dominated regime, in this modified square wave geometry. These streaks have a low standard deviation around a mean value. In the Dean vortex-dominated regime, the location of the particle stream is highly dependent on the particle size, which allows good particle separation. Particle focusing occurs at lower Reynolds numbers in both the lift-dominated and lift/Dean drag-dominated regions than in the square wave microchannel. The innovative serpentine channel is particularly useful for the Dean drag-dominated regime and introduces a unique asymmetry that affects the particle focusing dynamics. The proposed device offers significant advantages in terms of efficiency, parallelization, footprint, and throughput over existing geometries.

Twisted fiber microfluidics: a cutting-edge approach to 3D spiral devices.

The development of 3D spiral microfluidics has opened new avenues for leveraging inertial focusing to analyze small fluid volumes, thereby advancing research across chemical, physical, and biological disciplines. While traditional straight microchannels rely solely on inertial lift forces, the novel spiral geometry generates Dean drag forces, eliminating the necessity for external fields in fluid manipulation. Nevertheless, fabricating 3D spiral microfluidics remains a labor-intensive and costly endeavor, hindering its widespread adoption. Moreover, conventional lithographic methods primarily yield 2D planar devices, thereby limiting the selection of materials and geometrical configurations. To address these challenges, this work introduces a streamlined fabrication method for 3D spiral microfluidic devices, employing rotational force within a miniaturized thermal drawing process, termed as mini-rTDP. This innovation allows for rapid prototyping of twisted fiber-based microfluidics featuring versatility in material selection and heightened geometric intricacy. To validate the performance of these devices, we combined computational modeling with microtomographic particle image velocimetry (μTPIV) to comprehensively characterize the 3D flow dynamics. Our results corroborate the presence of a steady secondary flow, underscoring the effectiveness of our approach. Our 3D spiral microfluidics platform paves the way for exploring intricate microflow dynamics, with promising applications in areas such as drug delivery, diagnostics, and lab-on-a-chip systems.

Efficient separation of large particles and giant cancer cells using an isosceles trapezoidal spiral microchannel.

Polyploid giant cancer cells (PGCCs) contribute to the genetic heterogeneity and evolutionary dynamics of tumors. Their size, however, complicates their isolation from mainstream tumor cell populations. Standard techniques like fluorescence-activated cell sorting (FACS) rely on fluorescent labeling, introducing potential challenges in subsequent PGCC analyses. In response, we developed the Isosceles Trapezoidal Spiral Microchannel (ITSμC), a microfluidic device optimizing the Dean drag force (FD) and exploiting uniform vortices for enhanced separation. Numerical simulations highlighted ITSμC's advantage in producing robust FD compared to rectangular and standard trapezoidal channels. Empirical results confirmed its ability to segregate larger polystyrene (PS) particles (avg. diameter: 50 μm) toward the inner wall, while directing smaller ones (avg. diameter: 23 μm) outward. Utilizing ITSμC, we efficiently isolated PGCCs from doxorubicin-resistant triple-negative breast cancer (DOXR-TNBC) and patient-derived cancer (PDC) cells, achieving outstanding purity, yield, and viability rates (all greater than 90%). This precision was accomplished without fluorescent markers, and the versatility of ITSμC suggests its potential in differentiating a wide range of heterogeneous cell populations.

Numerical study of bacteria removal from microalgae solution using an asymmetric contraction-expansion microfluidic device: A parametric analysis approach

Microalgae have been remarkably taken into account due to their wide applications in the biopharmaceutical, nutraceutical and bio-energy fields. However, contamination of microalgae with bacteria still appears to be a concern, adversely impacting products’ quality and process efficiency. Microalgae decontamination with conventional techniques is usually expensive and time-consuming. Moreover, damage to microalgae cells is highly possible. Asymmetric contraction-expansion microchannels (Asym-CEMCs) are promising passive microfluidic devices that can overcome conventional techniques' drawbacks with their standing-out features. However, the flexibility of Asym-CEMCs performance arising from their various tunable geometrical parameters results in the fact that their performance for separating a target particle cannot be predicted without an investigation. In this work, for the first time, Asym-CEMCs were numerically studied for the removal of a very conventional bacteria, B. subtilis (1 μm), from one of the most popular microalgae, C. vulgaris (5.7 μm). The influences of the microchannel aspect ratio, length and width ratios of the expansion-to-contraction zones, and the total flow rate on the separation resolution and focusing width of the particles were investigated by a 3D numerical model. The aspect ratio had the strongest influence on the Asym-CEMC performance, however, the length ratio had no considerable effect on the results. A decrease in the aspect ratio augmented the shear-induced lift force and Dean drag force, leading to a significant separation resolution improvement. Microalgae decontamination was also enhanced by an increase in the total flow rate and expansion-to-contraction width ratio. Finally, a locally optimized Asym-CEMC with an aspect ratio of one and expansion-to-contraction width and length ratios of 4.7 and 2.07, respectively, was proposed, leading to complete microalgae decontamination with a high normalized separation resolution of 0.6. In a word, Asym-CEMCs with tailored dimensions are promising for successfully decontaminating microalgae from bacteria.

A review on inertial microfluidic fabrication methods.

In recent decades, there has been significant interest in inertial microfluidics due to its high throughput, ease of fabrication, and no need for external forces. The focusing efficiency of inertial microfluidic systems relies entirely on the geometrical features of microchannels because hydrodynamic forces (inertial lift forces and Dean drag forces) are the main driving forces in inertial microfluidic devices. In the past few years, novel microchannel structures have been propounded to improve particle manipulation efficiency. However, the fabrication of these unconventional structures has remained a serious challenge. Although researchers have pushed forward the frontiers of microfabrication technologies, the fabrication techniques employed for inertial microfluidics have not been discussed comprehensively. This review introduces the microfabrication approaches used for creating inertial microchannels, including photolithography, xurography, laser cutting, micromachining, microwire technique, etching, hot embossing, 3D printing, and injection molding. The advantages and disadvantages of these methods have also been discussed. Then, the techniques are reviewed regarding resolution, structures, cost, and materials. This review provides a thorough insight into the manufacturing methods of inertial microchannels, which could be helpful for future studies to improve the harvesting yield and resolution by choosing a proper fabrication technique.

Microparticles’ Lateral Oscillation Motion in Serpentine Micro-Channels without Inertial Lift Effects

Micro-particle manipulation, based solely on the Dean drag force, has begun to be advocated for with the goal of lowering the pumping pressure and simplifying the complexity of the coupling effects of the inertial lift force and the Dean drag force, thus reducing the difficulty of theoretically predicting particle motion. We employed the CFD-DEM two-way coupling method in this work to quantitatively study the lateral (z in axis) motion of particles (7–10 μm), in square or half-circle segment serpentine microchannels, that was only reliant on Dean drag with the blockage ratio dDh= 0.04 (the inertial lift effects show at dDh>0.07). In the square-segment serpentine channel, under the conditions of single-side-wall sheath flow and sedimentation, we discovered that the particles exhibit a twist-type lateral trajectory around each turn, with the larger particles always twisting in the opposite direction of the smaller particles, as a result of the four-grid-pattern distribution of the lateral velocity values at each turn. The large and small particles are separated at the channel’s exit at Re = 56.7, De = 17.8, indicating the likelihood of separation only due to the Dean drag. This separation efficiency decreases as Re and De decreases. The lateral position and velocity values of the particles oscillate, as time passes, due to the twist trajectory, with the oscillation amplitude increasing as Re or De decreases and deflecting toward the inner side of z. In the cases of the two-side-wall-symmetric sheath flow, the particles exhibit only a little lateral deflection, and particle separation is not achieved. The deflection of the oscillation is uncertain and does not change regularly with any physical quantity.

Investigation on a cascaded inertial and acoustic microfluidic device for sheathless and label-free separation of circulating tumor cells

High-precision and high-purity acquisition of tumor cells from whole blood is vital for early disease detection and diagnosis. Here, we investigated a cascaded inertial and acoustic microfluidic device for sheathless and label-free separation of circulating tumor cells (CTCs) from the blood through numerical methods. We introduced a spiral microfluidics channel in the first stage (1st) for cell focusing and rough sorting to improve chip integration and reduce the dependence on sheath flow and extra syringe pumps. In the 1st, we simulated the spiral microfluidic with a rectangular cross section to determine the key parameters affecting the migration kinetics of blood cells and tumor cells. Under the influence of Dean drag force and inertial lift force, blood cells migrate toward the inner side of the channel, while CTCs flow out close to the outer side. A flow rate of 400 μl/min was optimized for the operating flow rate. To improve and further enhance the 1st sorting efficiency and purity, we introduced tilted angle standing surface acoustic wave (SSAW) in the second stage (2st). Based on the parametric study, the SSAW with 33.3 MHz, tilted angle with 5°, and acoustic pressure amplitude with 0.7 MPa was selected as the operating parameter. The product of the 1st is used as input for the 2st acoustofluidic unit, enabling a more accurate separation process to obtain CTCs. The simulation results show that the inertial microfluidic units arranged in the first stage help to improve throughput and assist in 2st acoustofluidic separation, and the cascaded chip has accomplished a separation performance of nearly 100% in terms of purity and efficiency.

Design of a novel integrated microfluidic chip for continuous separation of circulating tumor cells from peripheral blood cells

Cancer is one of the foremost causes of death globally. Late-stage presentation, inaccessible diagnosis, and treatment are common challenges in developed countries. Detection, enumeration of Circulating Tumor Cells (CTC) as early as possible can reportedly lead to more effective treatment. The isolation of CTC at an early stage is challenging due to the low probability of its presence in peripheral blood. In this study, we propose a novel two-stage, label-free, rapid, and continuous CTC separation device based on hydrodynamic inertial focusing and dielectrophoretic separation. The dominance and differential of wall-induced inertial lift force and Dean drag force inside a curved microfluidic channel results in size-based separation of Red Blood Cells (RBC) and platelets (size between 2–4 µm) from CTC and leukocytes (9–12.2 µm). A numerical model was used to investigate the mechanism of hydrodynamic inertial focusing in a curvilinear microchannel. Simulations were done with the RBCs, platelets, CTCs, and leukocytes (four major subtypes) to select the optimized value of the parameters in the proposed design. In first stage, the focusing behavior of microscale cells was studied to sort leukocytes and CTCs from RBCs, and platelets while viable CTCs were separated from leukocytes based on their inherent electrical properties using dielectrophoresis in the second stage. The proposed design of the device was evaluated for CTC separation efficiency using numerical simulations. This study considered the influence of critical factors like aspect ratio, dielectrophoretic force, channel size, flow rate, separation efficiency, and shape on cell separation. Results show that the proposed device yields viable CTC with 99.5% isolation efficiency with a throughput of 12.2 ml/h.

Computational Inertial Microfluidics: Optimal Design for Particle Separation

Following the emergence of many blood transfusion-associated diseases, novel passive cell separation technologies, such as microfluidic devices, are increasingly designed and optimized to separate red blood cells (RBCs) and white blood cells (WBCs) from whole blood. These systems allow for the rapid diagnosis of diseases without relying on complicated and expensive hematology instruments such as flow microscopes, coagulation analyzers, and cytometers. The inertia effect and the impact of intrinsic hydrodynamic forces, the Dean drag force (FD), and the inertial lift force (FL) on the migration of particles within curved and complex confined channels have been explored theoretically, computationally, and experimentally. This study aimed to optimize the dimensions of a microfluidic channel for fast particle propagation and separation. Several spiral geometries with different cross-sections were tested using computational fluid dynamics (CFD) to separate two particle types representing RBCs and WBCs. The chosen three geometries consist of a single inlet, two outlets, and three spiral turns, each having a different cross-sectional height (120, 135, and 150 µm). Particle separation was successfully achieved in the 135 µm-height microchannel, while other microchannels demonstrated mixed particle types at the outlets.

Comparison of logarithmic, elliptic, and conical helical spiral for isolation of circulating tumor cells based on inertial method

Cancer is one of the most significant causes of death in the world. It has been shown that the role of circulating tumor cells (CTCs) in the early detection of cancer is crucial. Since the number of these cancerous cells in blood is very rare, the inertial microfluidic devices are one of the best candidates for the isolation of CTCs because they result in a high throughput process. Consequently, they can process a large volume of blood in a short time. Despite extensive computational and experimental studies on inertial microfluidic platforms, the impact of the curvature has not been thoroughly investigated during separation. In this paper, the feasibility of isolation of CTCs for logarithmic, elliptical, and conical helical spirals has been examined using a computational approach. In addition, the effect of geometrical parameters (i.e., the radius of curvature, aspect ratio, number of turns, and pitch) and operational parameters (i.e., sample and sheath flow velocity) has been studied. While the results showed that all three geometries could isolate CTCs with 100% purity and efficiency, the elliptical spiral was nominated as an optimal geometry since the inertial migration of particles can be completed faster as a result of forming alternating Dean drag forces in this geometry.

Dean flow velocity of shear-thickening SiO2 nanofluids in curved microchannels

We report the effects of a curvilinear microchannel width, height, and radius of curvature, as well as the kinematic viscosity and axial velocity of shear-thickening nanofluids, on the average Dean velocity (VDe) of the secondary flow in the microchannel. Manipulation of inertial and Dean drag forces in curvilinear microchannels has enabled high-throughput and high-resolution size-based separation of microparticles and cells in various biomedical applications. VDe plays a deterministic role in the estimation of the Dean drag force and the design of these microfluidic devices. Despite the previous numerical and experimental studies on VDe of Newtonian and shear-thinning viscoelastic fluids, VDe of shear-thickening metallic nanofluids, such as SiO2 nanoparticles in water, in curved microchannels is still unknown. Such shear-thickening fluids are being used in thermal microsystem applications and are on the verge of entering the field of inertial microfluidics for particle and cell sorting. Our investigations have shown that VDe of shear-thickening SiO2–water nanofluids scales directly with the channel width and the fluid axial velocity, while being inversely proportional with the SiO2 concentration and the channel radius of curvature. Our non-dimensional analysis has led to the development of an empirical correlation that relates VDe-based Reynolds number of the nanofluid to the Dean number and the normalized kinematic viscosity of the nanofluid. It provides a significant accuracy in estimating VDe of shear-thickening fluids, compared to application of Newtonian or shear-thinning equations in the literature, which could be useful toward future design of particle and cell sorting and washing microdevices.

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.

A portable purification system for the rapid removal of microplastics from environmental samples

The use of plastic products has become an indispensable part of our lives. However, due to improper discharge into the ocean and their prevalence in food storage use, humans ingest microplastics (MP) from consuming seafood or drinking water, which poses safety hazards. Furthermore, the existing MP separation methods, such as density separation and filtration, are limited by low efficiency. For micro-particle separation, inertial microfluidics using spiral channels has attracted great interest because of its excellent ability to concentrate particles of specific sizes with the balance of inertial lift force and Dean drag force in a fully enclosed system. Here, we designed and optimized an MP concentrator (MPC) to simultaneously enrich and remove MP for environmental research and water purification. The MPC achieves >90% recovery of MPs from seawater samples and polypropylene food container extracts and also obtained MP counts (per gram wet sediment) for environmental ocean floor samples within the range previously achieved via filtration methods. Moreover, the MPC can purify the sample by concentrating MP to a minimal volume at an output by introducing a feedback loop. Overall, our study provides an innovative technology that simultaneously enriches and filters MP from various samples with minimal equipment requirements, thereby providing a low-cost and convenient method compatible with on-site applications, and has the potential for routine use in MP research, especially for areas with limited resources.

Microdevice based on centrifugal effect and bifurcation law for separation of plasma from on-line diluted whole blood.

In recent decades, scientific interest in the development of devices capable of performing routine clinical analyses through the application of standardized traditional laboratory protocols in a miniaturized lab-on-a-chip device has increased. In the present work, an innovative microdevice for the on-line whole blood dilution with a phosphate buffer solution (PBS) and separation of plasma was designed, manufactured, and characterized. The microdevice was constructed with a rectangular cross-section and spiral-shaped microchannels by photolithography and soft litography. Also, the widths of the diluted plasma and the remaining blood outlet microchannels were different to create a difference in the outlet flow rates to facilitate and achieve the plasma separation based on the combination of centrifugal effect (Dean drag force) and bifurcation law (Zweifach-Fung effect). The separation purity (α) under the separation conditions (total flow rates between 25 and 100 μL/min, entrance flow rate ratio PBS/whole blood between 4 and 10, and hematocrit (% HCT) between 3 and 8) was around 100% for fresh blood samples, while the separation efficiency (β) was between 8 and 13%. The concentration in the separated diluted plasma was between 0.1 and 0.7% (v/v) with plasma flow rates between 3 and 7 μL/min, respectively. The quality of the diluted and separated plasma from micordevice was corroborated from a blood sample from a patient diagnosed with rheumatoid arthritis through the quantification of anti-cyclic citrullinated peptide (anti-CCP) antibodies employing a microdevice immunoassay. The developed microdevice has a high potential to be coupled with the on-line detection of biomarkers.

High throughput viscoelastic particle focusing and separation in spiral microchannels

Passive particle manipulation using inertial and elasto-inertial microfluidics have received substantial interest in recent years and have found various applications in high throughput particle sorting and separation. For separation applications, elasto-inertial microfluidics has thus far been applied at substantial lower flow rates as compared to inertial microfluidics. In this work, we explore viscoelastic particle focusing and separation in spiral channels at two orders of magnitude higher Reynolds numbers than previously reported. We show that the balance between dominant inertial lift force, dean drag force and elastic force enables stable 3D particle focusing at dynamically high Reynolds numbers. Using a two-turn spiral, we show that particles, initially pinched towards the inner wall using an elasticity enhancer, PEO (polyethylene oxide), as sheath migrate towards the outer wall strictly based on size and can be effectively separated with high precision. As a proof of principle for high resolution particle separation, 15 µm particles were effectively separated from 10 µm particles. A separation efficiency of 98% for the 10 µm and 97% for the 15 µm particles was achieved. Furthermore, we demonstrate sheath-less, high throughput, separation using a novel integrated two-spiral device and achieved a separation efficiency of 89% for the 10 µm and 99% for the 15 µm particles at a sample flow rate of 1 mL/min—a throughput previously only reported for inertial microfluidics. We anticipate the ability to precisely control particles in 3D at extremely high flow rates will open up several applications, including the development of ultra-high throughput microflow cytometers and high-resolution separation of rare cells for point of care diagnostics.

Vortex chip incorporating an orthogonal turn for size-based isolation of circulating cells

Size-based label-free separation of rare cells such as CTCs is attractive due to its wider applicability, simpler sample preparation, faster turnaround and better efficiency. Amongst such methods, vortex-trapping based techniques offer high throughput but operate at high flow velocities where the resulting hydrodynamic shear stress is likely to damage cells and compromise their viability for subsequent assays. We present here an orthogonal vortex chip which can carry out size-differentiated trapping at significantly lower (38% of previously reported) velocities. Composed of entry-exit channels that couple orthogonally to a trapping chamber, fluid flow in such configuration results in formation of a vortex which selectively traps larger particles above a critical velocity while smaller particles get ejected with the flow. We call this phenomenon the turn-effect. Critical velocities and optimal architectures for trapping of cells and particles of different sizes are characterized. We explain how shear-gradient lift, centrifugal and Dean flow drag forces contribute to the turn-effect by pushing particles into specific vortex orbits in a size- and velocity-dependent fashion. Selective trapping of human breast cancer cells mixed with whole blood at low concentration is demonstrated. The device shows promising results for gentle isolation of rare cells from blood.

A density-based threshold model for evaluating the separation of particles in heterogeneous mixtures with curvilinear microfluidic channels

Particle separation techniques play an important role in biomedical research. Inertial focusing based microfluidics using nonlinear channels is one of the promising label-free technologies for biological applications. The particle separation is achieved as a result of the combination of inertial lift force (FL) and Dean drag force (FD). Although the mathematical expressions of FL and FD have been well derived in prior studies, they are still complicated, which limits their popularity in practice. Recent studies modified these expressions through experiments and proposed a threshold model, which assumes that only particles larger than the threshold will be well focused. Although this threshold model has been used in recent studies, two varying versions of the threshold model (TM1 and TM2) prevents standardisation in practice. In addition, both models were developed with regular low-density particles and may not be applicable to samples with higher density or samples with irregular shapes. Here, we evaluated the threshold models with samples of different densities. Based on these evaluations, we derived a modified model (TM4), which additionally considers the factor of particle density to improve the accuracy of existing models. Our results demonstrated that TM4 could more reliably predict the sorting efficiency of samples within a wider density range.

Dean flow velocity of viscoelastic fluids in curved microchannels

Curved microchannels take advantage of inertial and Dean drag forces to achieve size-based separation of particles and cells. Despite the reported numerical and experimental correlations for Dean velocity (VDe) of Newtonian fluids, comprehensive studies and correlations are still required for the flow of viscoelastic fluids in curved microchannels. In this paper, the effects of curved channel height, radius of curvature, and kinematic viscosity were investigated to derive an empirical correlation for VDe of viscoelastic water. The developed knowledge of viscoelastic Dean flow velocity will be vital in design of elasto-inertial microfluidic devices for determination of lateral displacement of fluids in fluid exchange and Dean drag force in particle focusing and separation applications.