A stepwise multi-stage continuous dielectrophoresis separation microfluidic chip with microfilter structures.

The separation of target microparticles using microfluidic systems owns extensive applications in biomedical, chemical, and materials science fields. Integration of microfluidic sorting systems employing dielectrophoresis (DEP) technology has been widely investigated. However, enhancing separation efficiency, purity, stability, and integration remains a pressing issue. This study proposes a stepwise multi-stage continuous DEP separation microfluidic chip with a microfilter structure. By leveraging a stepwise electrode configuration, a gradient electric field is generated to drive target microparticles along the electric field gradient, thereby enhancing separation efficiency. Innovative integration of a microfilter structure facilitates simultaneous filtration and improves flow field distribution, thus enhancing system stability. Through the synergistic effect of stepwise electrodes and the microfilter structure, superior coupling of electric and flow fields is achieved, consequently improving the sorting purity, separation efficiency, and system stability of the DEP-based microfluidic sorting system. Validation through simulation and separation of polystyrene microspheres demonstrates the excellent particle separation performance of the proposed system. It evidently shows potential for seamless extension to various biological microparticle sorting applications, harboring significant prospects in the biomedical domain field.

Dielectrophoretic separation and purification: From colloid and biological particles to droplets.

It is indispensable to realize the high level of purification and separation, so that objective particles, such as malignant cells, harmful bacteria, and special proteins or biological molecules, could satisfy the high precise measurement in the pharmaceutical analysis, clinical diagnosis, targeted therapy, and food defense. In addition, this could reveal the intrinsic nature and evolution mechanisms of individual biological variations. Consequently, many techniques related to optical tweezers, microfluidics, acoustophoresis, and electrokinetics can be broadly used to achieve micro- and nano-scale particle separations. Dielectrophoresis (DEP) has been used for various manipulation, concentration, transport, and separation processes of biological particles owing to its early development, mature theory, low cost, and high throughput. Although numerous reviews have discussed the biological applications of DEP techniques, comprehensive descriptions of micro- and nano-scale particle separations feature less frequently in the literature. Therefore, this review summarizes the current state of particle separation attention to relevant technological developments and innovation, including theoretical simulation, microchannel structure, electrode material, pattern and its layout. Moreover, a brief overview of separation applications using DEP in combination with other technologies is also provided. Finally, conclusions, future guidelines, and suggestions for potential promotion are highlighted.

Light-Induced Material Motion Fingerprint - A Tool Toward Selective Interfacial Sensitive Fractioning of Microparticles via Microfluidic Methods.

In this article, a novel strategy is presented to selectively separate a mixture of equally sized microparticles but differences in material composition and surface properties. The principle relies on a photosensitive surfactant, which makes particles under light illumination phoretically active. The latter hovers microparticles from a planar interface and together with a superimposed fluid flow, particles experience a drift motion characteristic to its interfacial properties. The drift motion is investigated as a function of applied wavelength, demonstrating that particles composed of different material show a unique spectrally resolved light-induced motion profile. Differences in those motion profile allow a selective fractioning of a desired particle from a complex particle mixture made out of more than two equally sized different particle types. Besides that, the influence of applied wavelength is systematically studied, and discussed the origin of the spectrally resolved chemical activity of microparticles from measured photo-isomerization rates.

Geometry Scaling for Externally Balanced Cascade Deterministic Lateral Displacement Microfluidic Separation of Multi-Size Particles.

To non-invasively monitor personal biological and environmental samples in Internet of Things (IoT)-based wearable microfluidic sensing applications, the particle size could be key to sensing, which emphasizes the need for particle size fractionation. Deterministic lateral displacement (DLD) is a microfluidic structure that has shown great potential for the size fractionation of micro- and nano-sized particles. This paper introduces a new externally balanced multi-section cascade DLD approach with a section-scaling technique aimed at expanding the dynamic range of particle size separation. To analyze the design tradeoffs of this new approach, a robust model that also accounts for practical fabrication limits is presented, enabling designers to visualize compromises between the overall device size and the achievement of various performance goals. Furthermore, results show that a wide variety of size fractionation ranges and size separation resolutions can be achieved by cascading multiple sections of an increasingly smaller gap size and critical separation dimension. Model results based on DLD theoretical equations are first presented, followed by model results that apply the scaling restrictions associated with the second order of effects, including practical fabrication limits, the gap/pillar size ratio, and pillar shape.

Enhancing the Yield of a Lab-on-a-Disk-Based Single-Image Parasite Quantification Device.

The recently proposed single-image parasite quantification (SIMPAQ) platform based on a Lab-on-a-Disc (LOD) device was previously successfully tested in field conditions, demonstrating its efficiency in soil-transmitted helminth (STH) egg detection and analysis on the level delivered by the current state-of-the-art methods. Furthermore, the SIMPAQ provides relatively quick diagnostics and requires small amounts of sample and materials. On the other hand, in a recent related study, it was revealed that the performance of the SIMPAQ method can be limited due to the action of the tangential Euler and Coriolis forces, and the interaction of the moving eggs with the walls of the LOD chamber. Here, we propose a new improved design that allows us to overcome these limitations and enhance the yield of the SIMPAQ LOD device, as demonstrated in experiments with a synthetic particle model system and real parasite eggs. Despite the simplicity, the proposed design modification is demonstrated to allow a substantial improvement in the yield of the SIMPAQ device, i.e., above 90% of parasite eggs and 98% of synthetic model particles were transported to the field of view. The new design proposed here will be further examined in the new generation of SIMPAQ devices within ongoing research on STH egg detection in field conditions.

Particle Separation in a Microchannel with a T-Shaped Cross-Section Using Co-Flow of Newtonian and Viscoelastic Fluids.

In this study, we investigated the particle separation phenomenon in a microchannel with a T-shaped cross-section, a unique design detailed in our previous study. Utilizing a co-flow system within this T-shaped microchannel, we examined two types of flow configuration: one where a Newtonian fluid served as the inner fluid and a viscoelastic fluid as the outer fluid (Newtonian/viscoelastic), and another where both the inner and outer fluids were Newtonian fluids (Newtonian/Newtonian). We introduced a mixture of three differently sized particles into the microchannel through the outer fluid and observed that the co-flow of Newtonian/viscoelastic fluids effectively separated particles based on their size compared with Newtonian/Newtonian fluids. In this context, we evaluated and compared the particle separation efficiency, recovery rate, and enrichment factor across both co-flow configurations. The Newtonian/viscoelastic co-flow system demonstrated a superior efficiency and recovery ratio when compared with the Newtonian/Newtonian system. Additionally, we assessed the influence of the flow rate ratio between the inner and outer fluids on particle separation within each co-flow system. Our results indicated that increasing the flow rate ratio enhanced the separation efficiency, particularly in the Newtonian/viscoelastic co-flow configuration. Consequently, this study substantiates the potential of utilizing a Newtonian/viscoelastic co-flow system in a T-shaped straight microchannel for the simultaneous separation of three differently sized particles.

Mesoscopic simulation of multi-scheme particle separation in deterministic lateral displacement devices using two-piece hybrid pillars.

Pillar shape exploration in deterministic lateral displacement (DLD) technique holds great promise for developing high-performance microfluidic devices with versatile sorting schemes. A recent innovative design using filter-like micropillars was proposed to improve cell separation, but its significance might be greatly underestimated due to an inaccurate understanding of the underlying mechanism. In this study, we employ mesoscopic hydrodynamic simulations to explore the movement and separation of rigid spherical particles in DLD arrays using various two-piece hybrid (TPH) pillars, where each pillar consists of two individual pieces separated by a tunable inter-piece channel. In comparison with the conventional one-piece pillars, the back piece of TPH-pillars is found to hierarchically tailor the flow profile of the front piece on the basis of the row shift fraction and the inter-piece channel width, resulting in unique tunable multi-scheme separation at low, intermediate, and high row shift fractions, respectively. At the intermediate regime, in particular, the first flow lane that determines the critical separation size could be physically fenced out by the inter-piece channel, and a delicate coupling of hydrodynamic filtration and DLD has been revealed to induce a constant critical size in the whole regime. This work theoretically demonstrates the feasibility and significance of TPH-pillars, which may open up a new direction of the geometry design by exploiting rich multi-piece hybrid structures to expand the versatility of the DLD technique.

Rapid and Efficient Computation of Cell Paths During Ultrasonic Focusing.

This biophysical analysis explores the first-principles physics of movement of white blood cell sized particles, suspended in an aqueous fluid and experiencing progressive or standing waves of acoustic pressure. In many current applications the cells are gradually nudged or herded toward the nodes of the standing wave, providing a degree of acoustic focusing and concentration of the cells in layers perpendicular to the direction of sound propagation. Here the underlying biomechanics of this phenomenon are analyzed specifically for the viscous regime of water and for small diameter microscopic spheroids such as living cells. The resulting mathematical model leads to a single algebraic expression for the creep or drift velocity as a function of sound frequency, amplitude, wavelength, fluid viscosity, boundary dimensions, and boundary reflectivity. This expression can be integrated numerically by a simple and fast computer algorithm to demonstrate net movement of particles as a function of time, providing a guide to optimization in a variety of emerging applications of ultrasonic cell focusing.

Numerical investigation of ternary particle separation in a microchannel with a wall-mounted obstacle using dielectrophoresis.

In recent years, microfluidic-based particle/cell manipulation techniques have catalyzed significant advances in several fields of science. As an efficient, precise, and label-free particle/cell manipulation technique, dielectrophoresis (DEP) has recently attracted widespread attention. This paper presents the design and investigation of a straight sheathless 3D microchannel with a wall-mounted trapezoidal obstacle for continuous-flow separation of three different populations of polystyrene (PS) particles (5, 10 and 20 µm) using DEP. An OpenFOAM code is developed to simulate and investigate the movement of particles in the microchannel. Then, the code is validated by performing various experimental tests using a microdevice previously fabricated in our lab. By comparing the numerical simulation results with the experimental tests, it can be claimed that the newly developed solver is highly accurate, and its results agree well with experimental tests. Next, the effect of various operational and geometrical parameters such as obstacle height, applied voltage, electrode pairs angle, and flow rate on the efficient focusing and separation of particles are numerically investigated. The results showed that efficient particle separation could only be achieved for obstacle heights of more than 350 µm. Furthermore, the appropriate voltage range for efficient particle separation is increased by decreasing the electrode angle as well as increasing the flow rate. Moreover, the results showed that by employing the appropriate channel design and operational conditions, at a maximum applied voltage of 10V, a sample flow rate of 2.5µL/min could be processed. The proposed design can be beneficial for integrating with lab-on-a-chip and clinical diagnosis applications due to advantages, such as simple design, no need for sheath flow, the simultaneous ternary separation of particles, and providing precise particle separation.

Continuous Flow Separation of Red Blood Cells and Platelets in a Y-Microfluidic Channel Device with Saw-Tooth Profile Electrodes via Low Voltage Dielectrophoresis.

Cell counting and sorting is a vital step in the purification process within the area of biomedical research. It has been widely reported and accepted that the use of hydrodynamic focusing in conjunction with the application of a dielectrophoretic (DEP) force allows efficient separation of biological entities such as platelets from red blood cell (RBC) samples due to their size difference. This paper presents computational results of a multiphysics simulation modelling study on evaluating continuous separation of RBCs and platelets in a microfluidic device design with saw-tooth profile electrodes via DEP. The theoretical cell particle trajectory, particle cell counting, and particle separation distance study results reported in this work were predicted using COMSOL v6.0 Multiphysics simulation software. To validate the numerical model used in this work for the reported device design, we first developed a simple y-channel microfluidic device with square "in fluid" electrodes similar to the design reported previously in other works. We then compared the obtained simulation results for the simple y-channel device with the square in fluid electrodes to the reported experimental work done on this simple design which resulted in 98% agreement. The design reported in this work is an improvement over existing designs in that it can perform rapid separation of RBCs (estimated 99% purification) and platelets in a total time of 6-7 s at a minimum voltage setting of 1 V and at a minimum frequency of 1 Hz. The threshold for efficient separation of cells ends at 1000 kHz for a 1 V setting. The saw-tooth electrode profile appears to be an improvement over existing designs in that the sharp corners reduced the required horizontal distance needed for separation to occur and contributed to a non-uniform DEP electric field. The results of this simulation study further suggest that this DEP separation technique may potentially be applied to improve the efficiency of separation processes of biological sample scenarios and simultaneously increase the accuracy of diagnostic processes via cell counting and sorting.

Recent advances in multimode microfluidic separation of particles and cells.

Microfluidic separation of particles and cells is crucial to lab-on-a-chip applications in the fields of science, engineering, and industry. The continuous-flow separation methods can be classified as active or passive depending on whether the force involved in the process is externally imposed or internally induced. The majority of current separations have been realized using only one of the active or passive methods. Such a single-mode process is usually limited to one-parameter separation, which often becomes less effective or even ineffective when dealing with real samples because of their inherent heterogeneity. Integrating two or more separation methods of either type has been demonstrated to offer several advantages like improved specificity, resolution, and throughput. This article reviews the recent advances of such multimode particle and cell separations in microfluidic devices, including the serial-mode prefocused separation, serial-mode multistage separation, and parallel-mode force-tuned separation.

Versatile Microfluidics Separation of Colloids by Combining External Flow with Light-Induced Chemical Activity.

Separation of particles by size, morphology, or material identity is of paramount importance in fields such as filtration or bioanalytics. Up to now separation of particles distinguished solely by surface properties or bulk/surface morphology remains a very challenging process. Here a combination of pressure-driven microfluidic flow and local self-phoresis/osmosis are proposed via the light-induced chemical activity of a photoactive azobenzene-surfactant solution. This process induces a vertical displacement of the sedimented particles, which depends on their size and surface properties . Consequently, different colloidal components experience different regions of the ambient microfluidic shear flow. Accordingly, a simple, versatile method for the separation of such can be achieved by elution times in a sense of particle chromatography. The concepts are illustrated via experimental studies, complemented by theoretical analysis, which include the separation of bulk-porous from bulk-compact colloidal particles and the separation of particles distinguished solely by slight differences in their surface physico-chemical properties.

Elasto-Inertial Focusing Mechanisms of Particles in Shear-Thinning Viscoelastic Fluid in Rectangular Microchannels.

Growth of the microfluidics field has triggered numerous advances in focusing and separating microparticles, with such systems rapidly finding applications in biomedical, chemical, and environmental fields. The use of shear-thinning viscoelastic fluids in microfluidic channels is leading to evolution of elasto-inertial focusing. Herein, we showed that the interplay between the elastic and shear-gradient lift forces, as well as the secondary flow transversal drag force that is caused by the non-zero second normal stress difference, lead to different particle focusing patterns in the elasto-inertial regime. Experiments and 3D simulations were performed to study the effects of flowrate, particle size, and the shear-thinning extent of the fluid on the focusing patterns. The Giesekus constitutive equation was used in the simulations to capture the shear-thinning and viscoelastic behaviors of the solution used in the experiments. At low flowrate, with Weissenberg number Wi ~ O(1), both the elastic force and secondary flow effects push particles towards the channel center. However, at a high flowrate, Wi ~ O(10), the elastic force direction is reversed in the central regions. This remarkable behavior of the elastic force, combined with the enhanced shear-gradient lift at the high flowrate, pushes particles away from the channel center. Additionally, a precise prediction of the focusing position can only be made when the shear-thinning extent of the fluid is correctly estimated in the modeling. The shear-thinning also gives rise to the unique behavior of the inertial forces near the channel walls which is linked with the 'warped' velocity profile in such fluids.

Biomedical Applications of Microfluidic Devices: A Review.

Both passive and active microfluidic chips are used in many biomedical and chemical applications to support fluid mixing, particle manipulations, and signal detection. Passive microfluidic devices are geometry-dependent, and their uses are rather limited. Active microfluidic devices include sensors or detectors that transduce chemical, biological, and physical changes into electrical or optical signals. Also, they are transduction devices that detect biological and chemical changes in biomedical applications, and they are highly versatile microfluidic tools for disease diagnosis and organ modeling. This review provides a comprehensive overview of the significant advances that have been made in the development of microfluidics devices. We will discuss the function of microfluidic devices as micromixers or as sorters of cells and substances (e.g., microfiltration, flow or displacement, and trapping). Microfluidic devices are fabricated using a range of techniques, including molding, etching, three-dimensional printing, and nanofabrication. Their broad utility lies in the detection of diagnostic biomarkers and organ-on-chip approaches that permit disease modeling in cancer, as well as uses in neurological, cardiovascular, hepatic, and pulmonary diseases. Biosensor applications allow for point-of-care testing, using assays based on enzymes, nanozymes, antibodies, or nucleic acids (DNA or RNA). An anticipated development in the field includes the optimization of techniques for the fabrication of microfluidic devices using biocompatible materials. These developments will increase biomedical versatility, reduce diagnostic costs, and accelerate diagnosis time of microfluidics technology.

A simplified three-dimensional numerical simulation approach for surface acoustic wave tweezers.

Standing surface acoustic waves (SSAWs) have been extensively used as acoustic tweezers to manipulate, transport, and separate microparticles and biological cells in a microscale fluidic environment, with great potentials for biomedical sensing, genetic analysis, and therapeutics applications. Currently, there lacks an accurate, reliable, and efficient three-dimensional (3D) modeling platform to simulate behaviors of micron-size particles/cells in acoustofluidics, which is crucial to provide the guidance for the experimental studies. The major challenge for achieving this is the computational complexity of 3D modeling. Herein, a simplified but effective 3D SSAW microfluidic model was developed to investigate the separation and manipulation of particles. This model incorporates propagation attenuation of the surface waves to increase the modeling accuracy, while simplifies the modeling of piezoelectric substrates and the wall of microchannel by determining the effective propagation region of the substrate. We have simulated the SSAWs microfluidics device, and systematically analyzed effects of voltage, tilt angle, and flow rate on the separation of the particles under the SSAWs. The obtained simulation results are compared with those obtained from the experimental studies, showing good agreements. This simplified modeling platform could become a convenient tool for acoustofluidic research.

Simple and rapid separation of Haematococcus pluvialis and ciliate based on the dean-coupled inertial microfluidics.

Astaxanthin with high antioxidant activity is of great practical value and Haematococcus pluvialis is recognized as the best natural astaxanthin producer. The yield of Haematococcus pluvialis was often affected by the ciliate during its production, however, the use of biochemical pesticides might have a great impact on Haematococcus pluvialis. Therefore, a simple microfluidic chip with the spiral microchannel was developed for continuous-flow physical separation of ∼10 µm ciliate from ∼30 µm Haematococcus pluvialis since their different sizes resulted in different equilibrium positions in the channel due to the Dean-coupled inertial migration. First, a spiral microchannel with a width of 700 µm and a height of 130 µm in the microfluidic chip was developed using three-dimensional printing and verified to completely separate polystyrene particles of 10 µm from those of 30 µm. Then, this microfluidic chip was used to separate the actual sample, and experimental results showed that ∼80% of ciliate was continuously separated from Haematococcus pluvialis at a flow rate of 2.8 ml/min. More importantly, no additional biochemical reagents were used and the activity of Haematococcus pluvialis was not affected. This microfluidic chip featured with simple design, automatic operation, and small size is promising for purification and breeding of Haematococcus pluvialis.

A Novel Perturbed Spiral Sheathless Chip for Particle Separation Based on Traveling Surface Acoustic Waves (TSAW).

The combination of the new perturbed spiral channel and a slanted gold interfingered transducer (IDT) is designed to achieve precise dynamic separation of target particles (20 µm). The offset micropillar array solves the defect that the high-width flow (avoiding the occurrence of channel blockage) channel cannot realize the focusing of small particles (5 µm, 10 µm). The relationship between the maximum design gap of the micropillar (Smax) and the particle radius (a) is given: Smax = 4a, which not only ensures that small particles will not pass through the micropillar gap, but also is compatible with the appropriate flow rates. A non-offset micropillar array was used to remove 20 µm particles in the corner area. The innovation of a spiral channel structure greatly improves the separation efficiency and purity of the separation chip. The separation chip designed by us achieves deflection separation of 20 µm particles at 24.95-41.58 MHz (κ = 1.09-1.81), at a flow rate of 1.2 mL per hour. When f = 33.7 MHz (κ = 1.47), the transverse migration distance of 20 µm particles is the smallest, and the separation purity and efficiency are as high as 92% and 100%, respectively.

Neural Network-Based Optimization of an Acousto Microfluidic System for Submicron Bioparticle Separation.

The advancement in microfluidics has provided an excellent opportunity for shifting from conventional sub-micron-sized isolation and purification methods to more robust and cost-effective lab-on-chip platforms. The acoustic-driven separation approach applies differential forces acting on target particles, guiding them towards different paths in a label-free and biocompatible manner. The main challenges in designing the acoustofluidic-based isolation platforms are minimizing the reflected radio frequency signal power to achieve the highest acoustic radiation force acting on micro/nano-sized particles and tuning the bandwidth of the acoustic resonator in an acceptable range for efficient size-based binning of particles. Due to the complexity of the physics involved in acoustic-based separations, the current existing lack in performance predictive understanding makes designing these miniature systems iterative and resource-intensive. This study introduces a unique approach for design automation of acoustofluidic devices by integrating the machine learning and multi-objective heuristic optimization approaches. First, a neural network-based prediction platform was developed to predict the resonator's frequency response according to different geometrical configurations of interdigitated transducers In the next step, the multi-objective optimization approach was executed for extracting the optimum design features for maximum possible device performance according to decision-maker criteria. The results show that the proposed methodology can significantly improve the fine-tuned IDT designs with minimum power loss and maximum working frequency range. The examination of the power loss and bandwidth on the alternation and distribution of the acoustic pressure inside the microfluidic channel was carried out by conducting a 3D finite element-based simulation. The proposed methodology improves the performance of the acoustic transducer by overcoming the constraints related to bandwidth operation, the magnitude of acoustic radiation force on particles, and the distribution of pressure acoustic inside the microchannel.

Viscoelastic Particle Focusing and Separation in a Spiral Channel.

As one type of non-Newtonian fluid, viscoelastic fluids exhibit unique properties that contribute to particle lateral migration in confined microfluidic channels, leading to opportunities for particle manipulation and separation. In this paper, particle focusing in viscoelastic flow is studied in a wide range of polyethylene glycol (PEO) concentrations in aqueous solutions. Polystyrene beads with diameters from 3 to 20 µm are tested, and the variation of particle focusing position is explained by the coeffects of inertial flow, viscoelastic flow, and Dean flow. We showed that particle focusing position can be predicted by analyzing the force balance in the microchannel, and that particle separation resolution can be improved in viscoelastic flows.

Biotechnology Approach to Mineral Separation via Phage Flotation Collectors.

A long-standing challenge in the mining industry is the separation of mineral particles that have similar surface characteristics for which surfactant-based flotation collectors cannot discriminate. In Florida phosphate mining, this problem occurs in the separation of dolomite [CaMg(CO3)2] contaminants from the desired francolite mineral {a fluorapatite [Ca5(PO4)3(F,OH)]}. In this study, phage display techniques were used to select phage clones with specific binding affinity to francolite, which were then tested in a benchtop bubbler flotation apparatus for their ability to selectively float francolite particles from mixtures containing dolomite. Contact angles measured with the captive bubble technique were used to examine changes in the surface character of the mineral particles upon adsorption of the phage, which showed that the most selective phage led to an increase in the contact angle from 16 to 50°. Although this is below the level considered hydrophobic, the correlation between contact angles and increased flotation recovery suggests that the phage coat proteins are behaving as efficient bioamphiphiles for the attachment of the particles to air bubbles, demonstrating a new and environmentally friendly type of biocollector system. The chemical and physical characteristics of the phage "tail" peptides were evaluated to offer an explanation for the specificity of phage binding. We conclude with a discussion of the potential benefits of this biotechnology approach, even for commodity industries such as mining or other particle separation systems, when costs and sustainability are considered.