Microfluidic-chip platform for cell sorting
13 Apr 2016-Vol. 1724, Iss: 1, pp 020038
TL;DR: In this article, a microfluidic device is fabricated to separate polystyrene beads of size 1'µm, 5', 5', 10', 15', 20', and 20' µm. The actual dimensions of blood corpuscles were kept in mind while deciding the particle size of polystrene beads which are used as a model particles for study.
Abstract: Cell sorting and separation are considered to be very crucial preparatory steps for numerous clinical diagnostics and therapeutics applications in cell biology research arena. Label free cell separation techniques acceptance rate has been increased to multifold by various research groups. Size based cell separation method focuses on the intrinsic properties of the cell which not only avoids clogging issues associated with mechanical and centrifugation filtration methods but also reduces the overall cost for the process. Consequentially flow based cell separation method for continuous flow has attracted the attention of millions. Due to the realization of structures close to particle size in micro dimensions, the microfluidic devices offer precise and rapid particle manipulation which ultimately leads to an extraordinary cell separation results. The proposed microfluidic device is fabricated to separate polystyrene beads of size 1 µm, 5 µm, 10 µm and 20 µm. The actual dimensions of blood corpuscles were kept in mind while deciding the particle size of polystyrene beads which are used as a model particles for study.
References
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TL;DR: In this study, concentrations of polymer microspheres with diameters of 1-3 microm were increased 20-50-fold, and they were collected independently according to size, and selective enrichment of leukocytes from blood was successfully performed.
Abstract: We propose here a new method for continuous concentration and classification of particles in microfluidic devices, named hydrodynamic filtration. When a particle is flowing in a microchannel, the center position of the particle cannot be present in a certain distance from sidewalls, which is equal to the particle radius. The proposed method utilizes this fact, and is performed using a microchannel having multiple side branch channels. By withdrawing a small amount of liquid repeatedly from the main stream through the side channels, particles are concentrated and aligned onto the sidewalls. Then the concentrated and aligned particles can be collected according to size through other side channels (selection channels) in the downstream of the microchannel. Therefore, continuous introduction of a particle suspension into the microchannel enables both particle concentration and classification at the same time. In this method, the flow profile inside a precisely fabricated microchannel determines the size limit of the filtered substances. So the filtration can be performed even when the channel widths are much larger than the particle size, without the problem of channel clogging. In this study, concentrations of polymer microspheres with diameters of 1–3 µm were increased 20–50-fold, and they were collected independently according to size. In addition, selective enrichment of leukocytes from blood was successfully performed.
491 citations
TL;DR: The separation of magnetic microparticles was achieved by on-chip free-flow magnetophoresis with wide applicability since magnetic particles are commonly used in bioanalysis as a solid support material for antigens, antibodies, DNA, and even cells.
Abstract: The separation of magnetic microparticles was achieved by on-chip free-flow magnetophoresis. In continuous flow, magnetic particles were deflected from the direction of laminar flow by a perpendicular magnetic field depending on their magnetic susceptibility and size and on the flow rate. Magnetic particles could thus be separated from each other and from nonmagnetic materials. Magnetic and nonmagnetic particles were introduced into a microfluidic separation chamber, and their deflection was studied under the microscope. The magnetic particles were 2.0 and 4.5 microm in diameter with magnetic susceptibilities of 1.12 x 10(-4) and 1.6 x 10(-4) m(3) kg(-1), respectively. The 4.5-microm particles with the larger susceptibility were deflected further from the direction of laminar flow than the 2.0-microm magnetic particles. Nonmagnetic 6-microm polystyrene beads, however, were not deflected at all. Furthermore, agglomerates of magnetic particles were found to be deflected to a larger extent than single magnetic particles. The applied flow rate and the strength and gradient of the applied magnetic field were the key parameters in controlling the deflection. This separation method has a wide applicability since magnetic particles are commonly used in bioanalysis as a solid support material for antigens, antibodies, DNA, and even cells. Free-flow magnetophoretic separations could be hyphenated with other microfluidic devices for reaction and analysis steps to form a micro total analysis system.
484 citations
TL;DR: The influence of channel height, particle size, buffer composition, electric field, strength and frequency on the dielectrophoretic force and the effectiveness of dielectophoretic deflection structures were determined.
Abstract: Microfluidic devices with three-dimensional (3-D) arrays of microelectrodes embedded in microchannels have been developed to study dielectrophoretic forces acting on synthetic micro- and nanoparticles. In particular, so-called deflector structures were used to separate particles according to their size and to enable accumulation of a fraction of interest into a small sample volume for further analysis. Particle velocity within the microchannels was measured by video microscopy and the hydrodynamic friction forces exerted on deflected particles were determined according to Stokes law. These results lead to an absolute measure of the dielectrophoretic forces and allowed for a quantitative test of the underlying theory. In summary, the influence of channel height, particle size, buffer composition, electric field, strength and frequency on the dielectrophoretic force and the effectiveness of dielectrophoretic deflection structures were determined. For this purpose, microfluidic devices have been developed comprising pairs of electrodes extending into fluid channels on both top and bottom side of the microfluidic channels. Electrodes were aligned under angles varying from 0 to 75 degrees with respect to the direction of flow. Devices with channel height varying between 5 and 50 microm were manufactured. Fabrication involved a dedicated bonding technology using a mask aligner and UV-curing adhesive. Particles with radius ranging from 250 nm to 12 microm were injected into the channels using aqueous buffer solutions.
250 citations
TL;DR: In this paper, a modular micro chemical analysis system fabricated on silicon wafers using semiconductor technology is presented, which is designed to handle particle containing solutions allowing novel applications in biochemical and cytochemical analysis.
206 citations
TL;DR: A microfabricated field flow fractionation device for continuous separation of subcellular organelles by isoelectric focusing provides fast separation in very small samples while avoiding large voltages and heating effects typically associated with conventional electrophoresis-based devices.
Abstract: We report a microfabricated field flow fractionation device for continuous separation of subcellular organelles by isoelectric focusing The microdevice provides fast separation in very small samples while avoiding large voltages and heating effects typically associated with conventional electrophoresis-based devices The basis of the separation is the presence of membrane proteins that give rise to the effective isoelectric points of the organelles Simulations of isoelectric focusing of mitochondria in microchannels are used to assess design parameters, such as dimensions and time scales In addition, a model of Joule heating effects in the microdevice during operation indicates that there is no significant heating, even without active cooling The device is fabricated using a combination of photolithography, thin-film metal deposition/patterning, and electroplating techniques We demonstrate that in the microfluidic devices, mitochondria from cultured cells migrate under the influence of an electric field into a focused band in less than 6 min, consistent with model predictions We also illustrate separation of mitochondria from whole cells and nuclei as well as the separation of two mitochondrial subpopulations When automated and operated in parallel, these microdevices should facilitate high-throughput analysis in studies requiring separation of organelles
133 citations