Special Issue "Particles Separation in Microfluidic Devices"

A special issue of Micromachines (ISSN 2072-666X). This special issue belongs to the section "C:Chemistry".

Deadline for manuscript submissions: closed (20 May 2019).

Special Issue Editors

Dr. Takasi Nisisako
Website
Guest Editor
Tokyo Institute of Technology, R2-9, 4259 Nagatsuta-cho, Midori-ku, Yokohama, Kanagawa 226-8503, Japan
Interests: droplet microfluidics; microreactors; microfabrication; particles synthesis
Special Issues and Collections in MDPI journals
Dr. Naotomo Tottori
Website
Guest Editor
Department of Mechanical Engineering, Kyushu University, W4-729, 744, Motooka, Nishi-ku, Fukuoka 819-0395, Japan
Interests: particles separation; lab on a chip; nanofabrication
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

Microfluidic platforms are increasingly being used for separating a wide variety of particles based on their physical and chemical properties. In the past two decades, many practical applications have been found in the chemical and biological sciences, including single cell analysis, clinical diagnostics, regenerative medicine, nanomaterials synthesis, environmental monitoring, etc.

In this Special Issue, we invite contributions to report the state-of-the art developments in the fields of micro- and nanofluidic separation, fractionation, sorting, and purification of all classes of particles, including, but not limited to, active devices using electric, magnetic, optical, and acoustic forces, passive devices using geometries and hydrodynamic effects at micro/nanoscale, confined and open platforms, label-based and label-free technology, separation of bioparticles (including blood cells), circulating tumor cells, live/dead cells, exosomes, DNAs, and non-bioparticles, including polymeric or inorganic micro- and nanoparticles, droplets, bubbles, etc. Practical devices that demonstrate capabilities to solve real-world problems are of particular interest.

Prof. Takasi Nisisako
Dr. Naotomo Tottori
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Micromachines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Microfluidics
  • Nanofluidics
  • Particles separation
  • Lab on a chip
  • Micro total analysis systems

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Published Papers (14 papers)

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Editorial

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Open AccessEditorial
Editorial for the Special Issue on Particles Separation in Microfluidic Devices
Micromachines 2020, 11(6), 602; https://doi.org/10.3390/mi11060602 - 22 Jun 2020
Abstract
The separation and sorting of micro- and nano-sized particles is an important step in chemical, biological, and medical analyses [...] Full article
(This article belongs to the Special Issue Particles Separation in Microfluidic Devices)

Research

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Open AccessArticle
Modeling a Dielectrophoretic Microfluidic Device with Vertical Interdigitated Transducer Electrodes for Separation of Microparticles Based on Size
Micromachines 2020, 11(6), 563; https://doi.org/10.3390/mi11060563 - 31 May 2020
Cited by 1
Abstract
This article conceptualizes and mathematically models a dielectrophoretic microfluidic device with two sets of interdigitated transducer vertical electrodes for separation of a binary heterogeneous mixture of particles based on size; each set of electrodes is located on the sidewalls and independently controllable. To [...] Read more.
This article conceptualizes and mathematically models a dielectrophoretic microfluidic device with two sets of interdigitated transducer vertical electrodes for separation of a binary heterogeneous mixture of particles based on size; each set of electrodes is located on the sidewalls and independently controllable. To achieve separation in the proposed microfluidic device, the small microparticles are subjected to positive dielectrophoresis and the big microparticles do not experience dielectrophoresis. The mathematical model consists of equations describing the motion of each microparticle, fluid flow profile, and electric voltage and field profiles, and they are solved numerically. The equations of motion take into account the influence of phenomena, such as inertia, drag, dielectrophoresis, gravity, and buoyancy. The model is used for a parametric study to understand the influence of parameters on the performance of the microfluidic device. The parameters studied include applied electric voltages, electrode dimensions, volumetric flow rate, and number of electrodes. The separation efficiency of the big and small microparticles is found to be independent of and dependent on all parameters, respectively. On the other hand, the separation purity of the big and small microparticles is found to be dependent on and independent of all parameters, respectively. The mathematical model is useful in designing the proposed microfluidic device with the desired level of separation efficiency and separation purity. Full article
(This article belongs to the Special Issue Particles Separation in Microfluidic Devices)
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Open AccessFeature PaperArticle
Evaluation of Performance and Tunability of a Co-Flow Inertial Microfluidic Device
Micromachines 2020, 11(3), 287; https://doi.org/10.3390/mi11030287 - 10 Mar 2020
Cited by 3
Abstract
Microfluidics has gained a lot of attention for biological sample separation and purification methods over recent years. From many active and passive microfluidic techniques, inertial microfluidics offers a simple and efficient method to demonstrate various biological applications. One prevalent limitation of this method [...] Read more.
Microfluidics has gained a lot of attention for biological sample separation and purification methods over recent years. From many active and passive microfluidic techniques, inertial microfluidics offers a simple and efficient method to demonstrate various biological applications. One prevalent limitation of this method is its lack of tunability for different applications once the microfluidic devices are fabricated. In this work, we develop and characterize a co-flow inertial microfluidic device that is tunable in multiple ways for adaptation to different application requirements. In particular, flow rate, flow rate ratio and output resistance ratio are systematically evaluated for flexibility of the cutoff size of the device and modification of the separation performance post-fabrication. Typically, a mixture of single size particles is used to determine cutoff sizes for the outlets, yet this fails to provide accurate prediction for efficiency and purity for a more complex biological sample. Thus, we use particles with continuous size distribution (2–32 μm) for separation demonstration under conditions of various flow rates, flow rate ratios and resistance ratios. We also use A549 cancer cell line with continuous size distribution (12–27 μm) as an added demonstration. Our results indicate inertial microfluidic devices possess the tunability that offers multiple ways to improve device performance for adaptation to different applications even after the devices are prototyped. Full article
(This article belongs to the Special Issue Particles Separation in Microfluidic Devices)
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Open AccessArticle
Nucleotide Identification in DNA Using Dielectrophoresis Spectroscopy
Micromachines 2020, 11(1), 39; https://doi.org/10.3390/mi11010039 - 28 Dec 2019
Cited by 2
Abstract
We show that negative dielectrophoresis (DEP) spectroscopy is an effective transduction mechanism of a biosensor for the detection of single nucleotide polymorphism (SNP) in a short DNA strand. We observed a frequency dependence of the negative DEP force applied by interdigitated electrodes to [...] Read more.
We show that negative dielectrophoresis (DEP) spectroscopy is an effective transduction mechanism of a biosensor for the detection of single nucleotide polymorphism (SNP) in a short DNA strand. We observed a frequency dependence of the negative DEP force applied by interdigitated electrodes to polystyrene microspheres (PM) with respect to changes in both the last and the second-to-last nucleotides of a single-strand DNA bound to the PM. The drift velocity of PM functionalized to single-strand DNA, which is proportional to the DEP force, was measured at the frequency range from 0.5 MHz to 2 MHz. The drift velocity was calculated using a custom-made automated software using real time image processing technique. This technology for SNP genotyping has the potential to be used in the diagnosis and the identification of genetic variants associated with diseases. Full article
(This article belongs to the Special Issue Particles Separation in Microfluidic Devices)
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Open AccessArticle
Numerical Study of Paramagnetic Elliptical Microparticles in Curved Channels and Uniform Magnetic Fields
Micromachines 2020, 11(1), 37; https://doi.org/10.3390/mi11010037 - 28 Dec 2019
Cited by 1
Abstract
We numerically investigated the dynamics of a paramagnetic elliptical particle immersed in a low Reynolds number Poiseuille flow in a curved channel and under a uniform magnetic field by direct numerical simulation. A finite element method, based on an arbitrary Lagrangian-Eulerian approach, analyzed [...] Read more.
We numerically investigated the dynamics of a paramagnetic elliptical particle immersed in a low Reynolds number Poiseuille flow in a curved channel and under a uniform magnetic field by direct numerical simulation. A finite element method, based on an arbitrary Lagrangian-Eulerian approach, analyzed how the channel geometry, the strength and direction of the magnetic field, and the particle shape affected the rotation and radial migration of the particle. The net radial migration of the particle was analyzed after executing a π rotation and at the exit of the curved channel with and without a magnetic field. In the absence of a magnetic field, the rotation is symmetric, but the particle-wall distance remains the same. When a magnetic field is applied, the rotation of symmetry is broken, and the particle-wall distance increases as the magnetic field strength increases. The causation of the radial migration is due to the magnetic angular velocity caused by the magnetic torque that constantly changes directions during particle transportation. This research provides a method of magnetically manipulating non-spherical particles on lab-on-a-chip devices for industrial and biological applications. Full article
(This article belongs to the Special Issue Particles Separation in Microfluidic Devices)
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Open AccessArticle
Accelerated Particle Separation in a DLD Device at Re > 1 Investigated by Means of µPIV
Micromachines 2019, 10(11), 768; https://doi.org/10.3390/mi10110768 - 11 Nov 2019
Cited by 3
Abstract
A pressure resistant and optically accessible deterministic lateral displacement (DLD) device was designed and microfabricated from silicon and glass for high-throughput fractionation of particles between 3.0 and 7.0 µm comprising array segments of varying tilt angles with a post size of 5 µm. [...] Read more.
A pressure resistant and optically accessible deterministic lateral displacement (DLD) device was designed and microfabricated from silicon and glass for high-throughput fractionation of particles between 3.0 and 7.0 µm comprising array segments of varying tilt angles with a post size of 5 µm. The design was supported by computational fluid dynamic (CFD) simulations using OpenFOAM software. Simulations indicated a change in the critical particle diameter for fractionation at higher Reynolds numbers. This was experimentally confirmed by microparticle image velocimetry (µPIV) in the DLD device with tracer particles of 0.86 µm. At Reynolds numbers above 8 an asymmetric flow field pattern between posts could be observed. Furthermore, the new DLD device allowed successful fractionation of 2 µm and 5 µm fluorescent polystyrene particles at Re = 0.5–25. Full article
(This article belongs to the Special Issue Particles Separation in Microfluidic Devices)
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Open AccessArticle
Nozzle-Shaped Electrode Configuration for Dielectrophoretic 3D-Focusing of Microparticles
Micromachines 2019, 10(9), 585; https://doi.org/10.3390/mi10090585 - 31 Aug 2019
Cited by 3
Abstract
An experimentally validated mathematical model of a microfluidic device with nozzle-shaped electrode configuration for realizing dielectrophoresis based 3D-focusing is presented in the article. Two right-triangle shaped electrodes on the top and bottom surfaces make up the nozzle-shaped electrode configuration. The mathematical model consists [...] Read more.
An experimentally validated mathematical model of a microfluidic device with nozzle-shaped electrode configuration for realizing dielectrophoresis based 3D-focusing is presented in the article. Two right-triangle shaped electrodes on the top and bottom surfaces make up the nozzle-shaped electrode configuration. The mathematical model consists of equations describing the motion of microparticles as well as profiles of electric potential, electric field, and fluid flow inside the microchannel. The influence of forces associated with inertia, gravity, drag, virtual mass, dielectrophoresis, and buoyancy are taken into account in the model. The performance of the microfluidic device is quantified in terms of horizontal and vertical focusing parameters. The influence of operating parameters, such as applied electric potential and volumetric flow rate, as well as geometric parameters, such as electrode dimensions and microchannel dimensions, are analyzed using the model. The performance of the microfluidic device enhances with an increase in applied electric potential and reduction in volumetric flow rate. Additionally, the performance of the microfluidic device improves with reduction in microchannel height and increase in microparticle radius while degrading with increase in reduction in electrode length and width. The model is of great benefit as it allows for generating working designs of the proposed microfluidic device with the desired performance metrics. Full article
(This article belongs to the Special Issue Particles Separation in Microfluidic Devices)
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Open AccessFeature PaperArticle
Real Time Electronic Feedback for Improved Acoustic Trapping of Micron-Scale Particles
Micromachines 2019, 10(7), 489; https://doi.org/10.3390/mi10070489 - 21 Jul 2019
Cited by 3
Abstract
Acoustic differential extraction has been previously reported as a viable alternative to the repetitive manual pipetting and centrifugation steps for isolating sperm cells from female epithelial cells in sexual assault sample evidence. However, the efficiency of sperm cell isolation can be compromised in [...] Read more.
Acoustic differential extraction has been previously reported as a viable alternative to the repetitive manual pipetting and centrifugation steps for isolating sperm cells from female epithelial cells in sexual assault sample evidence. However, the efficiency of sperm cell isolation can be compromised in samples containing an extremely large number of epithelial cells. When highly concentrated samples are lysed, changes to the physicochemical nature of the medium surrounding the cells impacts the acoustic frequency needed for optimal trapping. Previous work has demonstrated successful, automated adjustment of acoustic frequency to account for changes in temperature and buffer properties in various samples. Here we show that, during acoustic trapping, real-time monitoring of voltage measurements across the piezoelectric transducer correlates with sample-dependent changes in the medium. This is achieved with a wideband peak detector circuit, which identifies the resonant frequency with minimal disruption to the applied voltage. We further demonstrate that immediate, corresponding adjustments to acoustic trapping frequency provides retention of sperm cells from high epithelial cell-containing mock sexual assault samples. Full article
(This article belongs to the Special Issue Particles Separation in Microfluidic Devices)
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Open AccessArticle
Microfluidic In-Flow Decantation Technique Using Stepped Pillar Arrays and Hydraulic Resistance Tuners
Micromachines 2019, 10(7), 471; https://doi.org/10.3390/mi10070471 - 15 Jul 2019
Cited by 1
Abstract
Separating the particles from the liquid component of sample solutions is important for several microfluidic-based sample preparations and/or sample handling techniques, such as plasma separation from whole blood, sheath-free flow focusing, particle enrichment etc. This paper presents a microfluidic in-flow decantation technique that [...] Read more.
Separating the particles from the liquid component of sample solutions is important for several microfluidic-based sample preparations and/or sample handling techniques, such as plasma separation from whole blood, sheath-free flow focusing, particle enrichment etc. This paper presents a microfluidic in-flow decantation technique that provides the separation of particles from particle-free fluid while in-flow. The design involves the expansion of sample fluid channel in lateral and depth directions, thereby producing a particle-free layer towards the walls of the channel, followed by gradual extraction of this particle-free fluid through a series of tiny openings located towards one-end of the depth-direction. The latter part of this design is quite crucial in the functionality of this decantation technique and is based on the principle called wee-extraction. The design, theory, and simulations were presented to explain the principle-of-operation. To demonstrate the proof-of-principle, the experimental characterization was performed on beads, platelets, and blood samples at various hematocrits (2.5%–45%). The experiments revealed clog-free separation of particle-free fluid for at least an hour of operation of the device and demonstrated purities close to 100% and yields as high as 14%. The avenues to improve the yield are discussed along with several potential applications. Full article
(This article belongs to the Special Issue Particles Separation in Microfluidic Devices)
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Open AccessArticle
Hydrodynamic Microparticle Separation Mechanism Using Three-Dimensional Flow Profiles in Dual-Depth and Asymmetric Lattice-Shaped Microchannel Networks
Micromachines 2019, 10(6), 425; https://doi.org/10.3390/mi10060425 - 25 Jun 2019
Cited by 5
Abstract
We herein propose a new hydrodynamic mechanism of particle separation using dual-depth, lattice-patterned asymmetric microchannel networks. This mechanism utilizes three-dimensional (3D) laminar flow profiles formed at intersections of lattice channels. Large particles, primarily flowing near the bottom surface, frequently enter the shallower channels [...] Read more.
We herein propose a new hydrodynamic mechanism of particle separation using dual-depth, lattice-patterned asymmetric microchannel networks. This mechanism utilizes three-dimensional (3D) laminar flow profiles formed at intersections of lattice channels. Large particles, primarily flowing near the bottom surface, frequently enter the shallower channels (separation channels), whereas smaller particles flowing near the microchannel ceiling primarily flow along the deeper channels (main channels). Consequently, size-based continuous particle separation was achieved in the lateral direction in the lattice area. We confirmed that the depth of the main channel was a critical factor dominating the particle separation efficiencies, and the combination of 15-μm-deep separation channels and 40-μm-deep main channels demonstrated the good separation ability for 3–10-μm particles. We prepared several types of microchannels and successfully tuned the particle separation size. Furthermore, the input position of the particle suspension was controlled by adjusting the input flow rates and/or using a Y-shaped inlet connector that resulted in a significant improvement in the separation precision. The presented concept is a good example of a new type of microfluidic particle separation mechanism using 3D flows and may potentially be applicable to the sorting of various types of micrometer-sized objects, including living cells and synthetic microparticles. Full article
(This article belongs to the Special Issue Particles Separation in Microfluidic Devices)
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Open AccessArticle
Two-dimensional Simulation of Motion of Red Blood Cells with Deterministic Lateral Displacement Devices
Micromachines 2019, 10(6), 393; https://doi.org/10.3390/mi10060393 - 12 Jun 2019
Cited by 2
Abstract
Deterministic lateral displacement (DLD) technology has great potential for the separation, enrichment, and sorting of red blood cells (RBCs). This paper presents a numerical simulation of the motion of RBCs using DLD devices with different pillar shapes and gap configurations. We studied the [...] Read more.
Deterministic lateral displacement (DLD) technology has great potential for the separation, enrichment, and sorting of red blood cells (RBCs). This paper presents a numerical simulation of the motion of RBCs using DLD devices with different pillar shapes and gap configurations. We studied the effect of the pillar shape, row shift, and pillar diameter on the performance of RBC separation. The numerical results show that the RBCs enter “displacement mode” under conditions of low row-shift (∆λ < 1.4 µm) and “zigzag mode” with large row shift (∆λ > 1.5 µm). RBCs can pass the pillar array when the size of the pillar (d > 6 µm) is larger than the cell size. We show that these conclusions can be helpful for the design of a reliable DLD microfluidic device for the separation of RBCs. Full article
(This article belongs to the Special Issue Particles Separation in Microfluidic Devices)
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Open AccessArticle
Evaluation of Positive and Negative Methods for Isolation of Circulating Tumor Cells by Lateral Magnetophoresis
Micromachines 2019, 10(6), 386; https://doi.org/10.3390/mi10060386 - 08 Jun 2019
Cited by 9
Abstract
We developed an epithelial cell adhesion molecule (EpCAM)-based positive method and CD45/CD66b-based negative method for isolating circulating tumor cells (CTCs) by lateral magnetophoresis. The CTC recovery rate, white blood cell depletion rate, and purity of CTCs isolated using the positive and negative methods [...] Read more.
We developed an epithelial cell adhesion molecule (EpCAM)-based positive method and CD45/CD66b-based negative method for isolating circulating tumor cells (CTCs) by lateral magnetophoresis. The CTC recovery rate, white blood cell depletion rate, and purity of CTCs isolated using the positive and negative methods were analyzed using blood samples spiked with cancer cells with different expression levels of EpCAM. The aim was to assess the strengths and weaknesses of the positive and negative isolation methods for CTC-based diagnostics, prognostics, and therapeutics for cancer. The EpCAM-based positive method yielded CTCs of high purity, while the CD45/CD66b-based negative method yielded a large number of CTCs. In conclusion, the positive method shows promise for detecting somatic oncogenic mutations and the negative method shows promise for discovery of cellular and transcriptomic biomarkers of cancer. Full article
(This article belongs to the Special Issue Particles Separation in Microfluidic Devices)
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Review

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Open AccessReview
Sorting of Particles Using Inertial Focusing and Laminar Vortex Technology: A Review
Micromachines 2019, 10(9), 594; https://doi.org/10.3390/mi10090594 - 10 Sep 2019
Cited by 9
Abstract
The capability of isolating and sorting specific types of cells is crucial in life science, particularly for the early diagnosis of lethal diseases and monitoring of medical treatments. Among all the micro-fluidics techniques for cell sorting, inertial focusing combined with the laminar vortex [...] Read more.
The capability of isolating and sorting specific types of cells is crucial in life science, particularly for the early diagnosis of lethal diseases and monitoring of medical treatments. Among all the micro-fluidics techniques for cell sorting, inertial focusing combined with the laminar vortex technology is a powerful method to isolate cells from flowing samples in an efficient manner. This label-free method does not require any external force to be applied, and allows high throughput and continuous sample separation, thus offering a high filtration efficiency over a wide range of particle sizes. Although rather recent, this technology and its applications are rapidly growing, thanks to the development of new chip designs, the employment of new materials and microfabrication technologies. In this review, a comprehensive overview is provided on the most relevant works which employ inertial focusing and laminar vortex technology to sort particles. After briefly summarizing the other cells sorting techniques, highlighting their limitations, the physical mechanisms involved in particle trapping and sorting are described. Then, the materials and microfabrication methods used to implement this technology on miniaturized devices are illustrated. The most relevant evolution steps in the chips design are discussed, and their performances critically analyzed to suggest future developments of this technology. Full article
(This article belongs to the Special Issue Particles Separation in Microfluidic Devices)
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Open AccessReview
Fiber Optofluidic Technology Based on Optical Force and Photothermal Effects
Micromachines 2019, 10(8), 499; https://doi.org/10.3390/mi10080499 - 26 Jul 2019
Cited by 3
Abstract
Optofluidics is an exciting new area of study resulting from the fusion of microfluidics and photonics. It broadens the application and extends the functionality of microfluidics and has been extensively investigated in biocontrol, molecular diagnosis, material synthesis, and drug delivery. When light interacts [...] Read more.
Optofluidics is an exciting new area of study resulting from the fusion of microfluidics and photonics. It broadens the application and extends the functionality of microfluidics and has been extensively investigated in biocontrol, molecular diagnosis, material synthesis, and drug delivery. When light interacts with a microfluidic system, optical force and/or photothermal effects may occur due to the strong interaction between light and liquid. Such opto-physical effects can be used for optical manipulation and sensing due to their unique advantages over conventional microfluidics and photonics, including their simple fabrication process, flexible manipulation capability, compact configuration, and low cost. In this review, we summarize the latest progress in fiber optofluidic (FOF) technology based on optical force and photothermal effects in manipulation and sensing applications. Optical force can be used for optofluidic manipulation and sensing in two categories: stable single optical traps and stable combined optical traps. The photothermal effect can be applied to optofluidics based on two major structures: optical microfibers and optical fiber tips. The advantages and disadvantages of each FOF technology are also discussed. Full article
(This article belongs to the Special Issue Particles Separation in Microfluidic Devices)
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