WO2017116214A1 - 미세입자 분리 또는 정렬 장치, 및 이를 이용한 미세입자 분리 또는 정렬 방법 - Google Patents
미세입자 분리 또는 정렬 장치, 및 이를 이용한 미세입자 분리 또는 정렬 방법 Download PDFInfo
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- WO2017116214A1 WO2017116214A1 PCT/KR2016/015592 KR2016015592W WO2017116214A1 WO 2017116214 A1 WO2017116214 A1 WO 2017116214A1 KR 2016015592 W KR2016015592 W KR 2016015592W WO 2017116214 A1 WO2017116214 A1 WO 2017116214A1
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- fine particles
- separating
- aligning
- fluid
- chip
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/483—Physical analysis of biological material
- G01N33/487—Physical analysis of biological material of liquid biological material
- G01N33/49—Blood
- G01N33/491—Blood by separating the blood components
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502746—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means for controlling flow resistance, e.g. flow controllers, baffles
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502753—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502761—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/08—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/06—Fluid handling related problems
- B01L2200/0636—Focussing flows, e.g. to laminate flows
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/06—Fluid handling related problems
- B01L2200/0647—Handling flowable solids, e.g. microscopic beads, cells, particles
- B01L2200/0652—Sorting or classification of particles or molecules
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0809—Geometry, shape and general structure rectangular shaped
- B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0848—Specific forms of parts of containers
- B01L2300/0851—Bottom walls
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0848—Specific forms of parts of containers
- B01L2300/0858—Side walls
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
- B01L2300/0864—Configuration of multiple channels and/or chambers in a single devices comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2400/00—Moving or stopping fluids
- B01L2400/08—Regulating or influencing the flow resistance
- B01L2400/084—Passive control of flow resistance
- B01L2400/086—Passive control of flow resistance using baffles or other fixed flow obstructions
Definitions
- Fine particle separation or alignment device and fine particle separation or alignment method using the same
- the present invention relates to a microparticle separation and / or alignment apparatus and a method for separating and / or sorting the microparticles using the same. More specifically, the present invention by forming a predetermined pattern in the flow passage of the fluid containing the microparticles,
- a device and method for separating and / or aligning microparticles are provided.
- a pretreatment process for extracting or removing a specific substance is required to analyze diagnostic factors such as cells.
- a separation method using a centrifuge is mainly used as a method for extracting or removing a specific substance.
- the separation process using a centrifuge requires an expensive centrifuge device, is difficult to carry and thus the use conditions are limited, and continuous separation of particles is impossible.
- the disadvantage is that it must go through.
- cell separation devices based on microfluidic dynamics such as inertial fluid devices and dielectric electrophoretic devices have been developed.
- these cell separation devices have only a specific dilution ratio under the specific conditions.
- the disadvantage is that the efficiency varies depending on the flow rate of the working or fluid. For example, in the case of an electrophoretic device, the higher the flow rate, the lower the cell separation efficiency, and in the case of an inertial fluid element, the lower the flow rate, the lower the cell separation efficiency. Also, above
- microparticle separation and alignment apparatus In the microparticle separation and alignment apparatus according to an embodiment of the present invention, a technique for separating and / or aligning specific microparticles from a fluid sample in a desired direction based on pattern shape control is cheaper and simpler.
- It provides a chip for separation or alignment of fine particles comprising a.
- At least one groove is formed to be inclined at an angle of more than 0 ° and less than 90 ° with a line perpendicular to both sides, and one side surface portion at which the fine particle discharge part is located is inclined direction It may be a side portion of the passage portion located in the direction perpendicular to the other end portion connected to the side, or a corner portion to which the side and the other end portion are connected.
- Another example provides an apparatus for separating or aligning fine particles, comprising two or more chips for separating or aligning the fine particles.
- the separation or alignment chips of the two or more fine particles may be arranged in parallel.
- Another example is
- Other examples include chips for separating or aligning the fine particles or devices for separating or aligning the fine particles; And a fluid supply connected to the chip for separating or aligning the fine particles or the inlet of the device for separating or aligning the fine particles.
- the separation or alignment of the fine particles or separation of the fine particles Or a device for sorting, a kit for separating or aligning fine particles, or a method for separating or aligning with fine particles is useful for separating leukocytes from blood, separating and / or purifying proteins or peptides such as antibodies, or aligning specific cells.
- a device for sorting, a kit for separating or aligning fine particles, or a method for separating or aligning with fine particles is useful for separating leukocytes from blood, separating and / or purifying proteins or peptides such as antibodies, or aligning specific cells.
- a chip for separating and / or aligning microparticles capable of separating and / or aligning microparticles from a fluid with high separation efficiency and / or accuracy more simply and quickly, and for separating and / or aligning the microparticles
- An apparatus for separating and / or aligning fine particles comprising a chip, and a method for separating and / or aligning fine particles using a chip or device for separating or aligning the fine particles are proposed.
- It provides a chip for separation and / or alignment of fine particles comprising a.
- the humb is a structure (concave groove) that forms a recessed fine space in the interior space of the passage, and means a groove formed inclined with both sides or both ends of the passage.
- the groove formed on one surface of the passage portion is formed to be inclined
- One side of the inclined groove may be one of the inlet (one end), the outlet (the other end) and the surfaces (lower and upper surfaces) except for both sides of the chip.
- One or more, two or more, three or more or four or more inclined grooves may be inclined at an angle of more than 0 ° and less than 90 ° with a line perpendicular to both sides of the passage part. More specifically, the inclined groove is one or more or two or more in the inclined direction, and / or the other end direction (ie, at one end where the inlet of the fluid is located) One or more than two in the main direction of movement of the fluid in the passage portion).
- One side surface portion in which the fine particle discharge portion is located is a side surface of the passage portion located in a direction perpendicular to the inclination direction (in the main movement direction of the fluid) (more specifically, the portion opposite to the inflow portion of the side surface, which is the same below) It may be a terminal portion connected to the side (part of the other end on the basis of one end where the inlet is located; the other end portion), or a corner portion where the side and the other end portion are connected.
- the fine particles mean particles having a predetermined size and volume, and have an average diameter of about 100 ⁇ m or less, about 500 ⁇ m or less, about 100 ⁇ m or less, 50 ⁇ m or less, 30 ⁇ m or less, 20 urn or less, 15 ⁇ m or less, or 10 ⁇ m or less. Particles (the average diameter cannot be zero, so the lower limit of the numerical range can be selected from values above zero).
- the fine particles may be spherical, elliptical, amorphous, or the like, but are not limited thereto.
- the fine particles are one selected from the group consisting of blood cells such as red blood cells, white blood cells, cancer cells, stem cells, and cells, including normal cells, beads, liposomes, micelles, or the like, to which protein particles, proteins or peptides are attached It may be abnormal.
- the fluid may be a fluid containing the fine particles described above (eg, suspensions, dispersions, colloidal solutions, etc.).
- the fluid may be viscous or have a flowable viscosity, for example, the fluid may be a fluid having a viscosity up to a level similar to the viscosity (viscosity) of the blood, but is not limited thereto. It is not.
- the fluid comprises two or more fine particles having different average diameters
- the fine particles that can be separated and / or aligned by the fine particle separation and / or alignment techniques provided herein may be particles having the largest average diameter.
- the fine particles to be separated may be leukocytes
- the fluid may be blood.
- the blood may be blood diluted 1 to 20 times based on whole blood or whole blood volume.
- the fine particles to be isolated are proteins (eg antibodies) or beads to which the proteins (or antibodies) are attached.
- the fluid may be a suspension comprising the beads.
- the alignment chip or device including the same may be for separating or removing white blood cells from blood.
- the chip for separating and / or aligning the microparticles or a device including the same may be for use in antibody purification.
- the chip for separating and / or aligning the fine particles or a device including the same may be for separating and / or sorting the cells.
- the chip for separating and / or aligning the fine particles may have a side surface opposite to the fine particle discharge portion, that is, an opposite side of one side where the fine particle discharge portion is located (more specifically, a portion opposite the inlet portion of the opposite side, hereinafter the same).
- the other end portion connected to the side, or the edge portion is connected to the side and the other end portion may further include a fluid discharge portion for separating the fluid from which the fine particles are removed.
- the fine particles to be separated are white blood cells and the fluid is blood
- the white blood cells are separated and / or aligned in the fine particle discharge portion of the chip for separating and / or aligning the fine particles.
- Leukocyte free blood may be collected.
- the space in which the fluid flows in the passage portion may be the inlet portion (which may be formed as a separate space or may be an upper surface of the passage portion (the surface where the fluid flow starts)), and a space enclosed at a portion other than the discharge portion. It may be, may be formed integrally so that the fluid introduced from the inlet flows to the outlet.
- the passage portion is an integral structure in communication with the inlet portion and the outlet portion, but may have a straight shape or a shape including one or more curved portions, but is not limited thereto.
- the inclined groove refers to a region that forms an engraved space (concave groove) in the inner space of the passage portion through which the fluid flows. That is, either the upper or lower plate of the passage portion (the surfaces except for both ends and both sides on which the inlet and outlet are located) is partially structured with unevenness.
- the shape of the inclined groove is not limited, for example, polygons (e.g., rectangular, square, rhombus, trapezoidal, triangular, etc.) in which the cross-sectional shape in the horizontal or vertical direction is voluminous, concave polygons (e.g., star shape), circular, elliptical And so on.
- a region in which the inclined groove is not formed in the passage portion that is, the region between the inclined groove (s) closest to the inlet portion, the region between the inclined grooves formed at least one in the inclined direction, at the inlet end
- the area including the area between the inclined grooves formed at least one in the other end direction and the area between the discharge part and the inclined groove (s) closest to the discharge part may be referred to as a channel part.
- the passage portion in which the inclined groove is formed is the height of the channel portion (depth: h c ) and the height of the tracing and groove (if the inclined groove is formed in the upper plate of the passage portion) or the depth (in the case of the inclined groove formed in the lower plate of the passage portion) () Will have the internal space of the height (depth: h).
- the inclined grooves are imaginary lines perpendicular to both sides of the passage (Fig. 4a and
- B-B in 4b If both sides are not parallel or curved, they may be represented by a line perpendicular to the other end direction at one end where the inlet is located) and at an angle greater than 0 ° and less than 90 ° (marked ⁇ in FIG. 4A). It is characterized by one or more formed two or more.
- C denotes a main direction of movement of the fluid
- D denotes a direction perpendicular to the inclined direction in which the inclined groove is formed and the main o) direction of the fluid, that is, the direction in which the fine particles move (the direction in which the fine particle outlet is located).
- FIG. 4B is a cross-sectional view in the A-A direction having an angle ⁇ with B-B of FIG. 4A
- the inclination angle of the inclined groove is a line perpendicular to both side surfaces of the passage (or a line perpendicular to the other end direction at one end where the inflow is located) and a center line of the groove.
- the inclination angle of the inclined groove may be determined in consideration of the direction in which the fine particles are to be collected.
- the inclination angle of the inclined groove is a line perpendicular to both side surfaces of the passage (or a line perpendicular to the other end direction at one end where the inlet is located) and the center line of the groove.
- one or more, two or more, three or more or four inclined grooves may be formed in an inclined direction of a line perpendicular to both sides and an angle of more than 0 ° and less than 90 °. More specifically, one or more inclined grooves are formed in the inclined direction and at least one inclined direction at one end where the inlet is located (ie, the main direction of movement of the fluid; denoted by C in FIG. 4A). Or two or more may be formed.
- the passage portion is configured to communicate at all portions including the at least one inclined groove to allow fluid to pass through all portions of the passage portion.
- the one or more formed inclined groove (s) may not be parallel to each other as long as the above angular conditions are satisfied, and in one example, in order to further increase the fine particle separation and / or alignment efficiency, parallel to each other or 0 ° to 30 °. , 0 ° to 25 °, 0 ° to 20 °, 0 ° to 15 °, 0 ° to 10 °, 0 ° to 5 °, or 0 ⁇ to 3 ° to form an angle, but is not limited thereto. .
- one or more formed inclined groove (s) satisfy the angular conditions and
- FIG. 9 shows an example of an arrangement of at least one inclined groove formed (inclined grooves are indicated in dark colors; hollow arrows indicate the other end direction (main direction of fluid movement) at one end where the inlet is located; Filled arrows indicate the direction of fine particle movement).
- the centers of the one or more inclined grooves may be arranged in a straight line in a direction perpendicular to the inclined surface.
- one or more inclined grooves located in a row adjacent to each other in the direction of the other end (the hollow arrow) from one end where the inflow part is located may be fine with respect to the center position of the groove. It may be arranged to move in the direction of particle movement (fine particle discharge side side direction; filled arrow).
- one or more inclined grooves located in a row adjacent to each other in the direction of the other end (the hollow arrow) from one end where the inlet is located may be referred to as the center position of the groove. It may be arranged to move in a direction opposite to the direction of fine particle movement (the direction of the fine particle discharge; the filled arrow).
- the separation efficiency of the fine particles is the best.
- the fine particle separation efficiency may be excellent.
- the inclined groove may move in the direction of the fine particle movement. The distance traveled is within the length of the inclined groove in the direction of inclination (l r of FIG. 4B), which may include 0, for example, within 4/5 of the length of the inclined groove in the direction of inclination, within 3/5, Within 3/4, 2/3. Or less than or equal to 1/2 (which may include zero).
- the fine particle separation efficiency may be somewhat lower than that of (A) and (B).
- the fine particles contained in the fluid are different from the channel portion. And size) to gather in one direction while the motion of the fine particles changes.
- the inclined grooves are not easily entered against the movement of the fluid generated as the fine particles to be separated from the inlet portion pass through the channel portion. It must be a space of.
- the height or depth of the inclined groove (denoted by! ⁇ In Fig. 4A), the width in the direction perpendicular to the inclined plane (inclined direction) (indicated by ⁇ in Fig. 4A), and the inclination
- the length in the direction (indicated by ⁇ in FIG. 4B) may be appropriately adjusted to the size of the fine particles to be separated.
- the techniques described herein can separate and / or align the fine particles having the largest average particle diameter.
- the inclined grooves are blood cells smaller than leukocytes (red blood cells, platelets, etc.) and plasma, which flow back from the inflow portion through the channel portion.
- the white blood cells can enter, but the space is not easy to enter, the white blood cells are separated from the blood components except this to move in a direction perpendicular to the inclined direction in which the inclined groove is formed.
- the heights (depth h r ) of the one or more inclined grooves may be the same or different from each other.
- the height (or depth) of the inclined groove is 0.5 to 10 times, 0.5 to 7 times, ( ) .5 to 5 times, 0.5 times the average diameter of the fine particles to be separated and / or aligned.
- the average diameter of red blood cells is about 8-10 ⁇ m
- the thickness is about 2-3 ⁇ m
- the average diameter of white blood cells is about I5.
- the depth (h g ) of the inclined groove is 7 to 150 um, 7 to 105 um, 7 to 75 um, 7 to 60 um, 7 to 45 um, 7 to 30 um, 7 to 23 um , 7-15 um, 10-150 um, 10-105 um, 10-75 um, 10-60 um, 10-45 um, 10-30 um, 10-23 um, 10-15 um, 15-150 um , 15 to 105 um, 15 to 75 um, 15 to 60 um, 15 to 45 um, 15 to 30 um, 15 to 23 um, 22 to 150 um, 22 to 105 um, 22 to 75 um, 22 to 60 um , 22 to 45 um, or 22 to 30 um.
- the width w r in the direction perpendicular to the inclined surface of the inclined groove may be equal to or different from the depth () of the groove.
- the width of one or more formed inclined grooves is the same or can be different.
- the width in the vertical direction of the inclined surface of the inclined groove is 0.5 to 10 times, 0.5 to 7 times, 0.5 to 5 times, 0.5 to 4 times the average diameter of the fine particles to be separated and / or aligned Pear, 0.5 to 3 times, 0.5 to 2 times, 0.5 to 1.5 times, 0.5 to 1 times, 0.7 to 10 times, 0.7 times.
- the channel portion height (indicated by h c in FIG. 4A) is 0.5 to 10 times, 0.5 to 7 times, 0.5 to 5 times, 0.5 to 4 times, 0.5 to 3 times the average diameter of the fine particles, 5 times to 2 times, 0.5 times to 1.5 times, 0.5 times to 1 times, 0.7 times to 10 times, 0.7 times to 7 times, 0.7 times to 5 times, 0.7 times to 4 times, 0 times to 3 times , 0.7 rain! To 2 times, to 0.7 times
- 1.5 times 1.5 times, 0.7 times to 1 times, 1 times to 10 times, 1 times to 7 times, 1 times to 5 times, 1 times to 4 times 1 times to 3 times, 1 times to 2 times, 1 times to 1.5 times, 1.5 times to 10 times, 1.5 times to 7 times, 1.5 times to 5 times, 1.5 times to 4 times, 1.5 times to 3 times, or 1.5 times to 2 times, but is not limited thereto.
- the channel portion height is a blood cell component, for example, red blood cells (large cells are larger than erythrocytes in the case of white blood cells but are amorphous so that they can be modified to fit the channel portion height by the flow rate of blood and pass through the channel). It is enough to pass and large enough and there are no special restrictions.
- the channel portion height is 2 to 20um, 2 to 17um, 2 to 15um, 2 to 12um, 5 to 20um, 5 to 17um, 5 to 15um, 5 to 12um, 7 to 20um, and 7 to 17um, 7-15um, 7-12um, 10-20um, 10-17um, 10-15um, or 10-12um, but is not limited thereto.
- the spacing between the inclined grooves formed at least one from one end where the inlet of the passage part is located to the other end is not particularly limited, and is appropriately selected from, for example, the inclined surface of the inclined groove and the width in the vertical direction as described above. Can be.
- each interval may be the same or different.
- the length of the inclined groove in the inclined direction is not particularly limited, but depends on the passage portion size (ie, the size of the chip) and / or the number of one inclined groove in the inclined direction. Can be adjusted.
- the number of at least one inclined groove formed in the inclined direction may be adjusted according to the size of the passage portion (that is, the size of the chip) and / or the length of the inclined groove in the inclined direction.
- the length of the at least one formed inclined groove in the inclined direction may be the same or different from each other.
- the length of the inclined groove in the inclined direction is at least 1 times, at least 1.5 times at least 2 times, at least 2.5 times, at least 3 times, at least 3.5 times, at least 4 times the average diameter of the fine particles to be separated, or It may be 4.5 times or more, for example, 1 to 20 times, 1.5 times to 20 times, 2 times to 20 times, 2.5 times to 20 times, 3 times to 20 times, 3.5 times to 20 times, 4 times the average diameter of red blood cells.
- the interval in the inclined direction between the inclined grooves may be equal to or greater than a minimum interval capable of physically dividing the inclined grooves into two or more, and there is no particular limitation on the upper limit. Considering the efficiency may be shorter than the length of the inclined groove.
- the interval between the inclined grooves may be at least 0.0 times, at least 0.01 times, or at least one times the average diameter of the fine particles to be separated, for example, 0.001 times to 10 times the average diameter of the fine particles to be separated. Pear, 0.001 to 5 times, 0.0 to 2-3 times, 0.0 () 1 to 2 times, 0.001 to 1 times, 0. times to
- the inflow portion is a portion in which fluid is introduced and / or supplies the introduced fluid to the passage portion.
- the inlet is directly connected to the passage or optionally with the inlet. It may be connected to the passageway through a cavity including a void space in communication with the passageway.
- the inlet may be located at one end of the passage, where one end refers to an upstream region where fluid flow begins in the passage.
- the fine particle outlet is the site where the fine particles are separated and / or aligned.
- the side of the passage section having an angle formed by a line perpendicular to both sides and an inclined groove (the center line in the longitudinal direction of the inclined groove), and a portion of the end connected to the side (that is, the other end relative to one end where the inlet is located). Part; the other end portion), or a corner portion where the side and the other end portion is connected.
- the fluid discharge portion from which the fine particles are separated (removed) is discharged, the opposite side (the other side) of one side where the fine particle discharge is located, and a part of the end connected to the other side (that is, the one end where the inlet is located).
- the microparticle outlet and the fluid outlet may be connected directly to the passageway, or may optionally be connected to the passageway via a cavity including a void space in communication with the outlet and the passageway.
- Said side means both sides relative to the main direction of movement of the fluid in the passage (from one end to the other end where the inlet is located).
- the chip for separating and / or aligning the fine particles may be a substrate (surface with no irregularities; 200 as shown in FIGS. 4A and 4B), a surface with irregularities (surface formed with at least one inclined groove), And it may be a structure comprising both sides. One end and the other end where the inlet is located may be a fully open or partially open structure.
- the substrate, both sides, and the surface on which the unevenness is formed may be made of the same or different materials of the solid, the specific material is not particularly limited.
- the substrate, both sides, and the surface on which the unevenness is formed may be polystyrene (PS),
- PC polycarbonate
- PMMA polymethylmethacrylate
- PET polyethylene terephthalate
- PDMS polydimethylsiloxane
- SU-8 PEG-DA photoresist materials such as polyethylene glycol diacrylate
- Metals such as aluminum, iron, platinum and copper
- Soft solids such as silicon
- It may be made of a material independently selected from the group consisting of glass, but is not limited thereto.
- the size of the chip for separating and / or aligning the fine particles is not particularly limited.
- the length (from one end to the other end direction: the main direction of movement of the fluid) is ⁇ lmm to about 100 mm, about lmm to about 50 mm, about 1 mm to about 30 mm, about lmm to about 20 mm : or about lmm to about 10 mm, about 100 um to about 2000 um, about 100 um to about 1800 um, about 100 um to about 1500 um, about 100 um to about 1300 um, About 100 um to about lOOOOum, about 300 um to about 2000um, about 300 um to about 1800um, about 300 um to about 1500um, about 300 um to about 1300um, or about 300 um to about lOOOOum, but is not limited thereto. no.
- Another example is a device for separating and / or aligning fine particles comprising at least one, eg, at least two, at least four, at least six, or at least eight chips for separating and / or aligning the fine particles described above. to provide.
- the upper limit of the number of chips included in the device for separating and / or aligning the fine particles is not limited, and may be included in a number that allows the spatial conditions of the device for separating and / or aligning the fine particles.
- 1 to 100, 1 to 80, 1 to 60, 1 to 50, 1 to 40, 1 to 30, of the number of chips included in the device for separating and / or aligning the fine particles 1 to 20, 1 to 10, 2 to 100, 2 to 80, 2 to 60, 2 to 50, 2 to 40, 2 to 30, 2 to 20, 2 to 10, 4 to 100, 4 to 80, 4 to 60, 4 to 50, 4 to 40, 4 to 30, 4 to 20, 4 to 10, 6 to 100, 6 to 80, 6 to 60, 6 to 50, 6 to 40, 6 to 30, 6 to 20, 6 to 10, 8 to 100, 8 to 80, 8 to 60, 8 to 50, It may be 8 to 40, 8 to 30, 8 to 20, or 8 to 10, but is not limited thereto.
- the amount of fluid that can be processed in the device for separating and / or aligning one fine particle is determined by the chip for separating and / or aligning the fine particles contained in the device for separating and / or aligning the fine particles.
- Chips for separating and / or aligning the two or more fine particles included in the device for separating and / or aligning the fine particles may be connected in parallel.
- the device for separating and / or aligning the fine particles may comprise at least one cavity connected to the inlet of each chip. Inlet (designed to supply fluid to the inlet of each chip) and / or one or more cavity fine particle outlets connected to the outlet of each chip (designed to collect fine particles separated at each fine particle outlet) It may be to further include.
- At least one of the two or more fine particle separation and / or alignment chips included in the device for separating and / or aligning the fine particles has a side portion opposite to the fine particle discharge, that is, the fine particle discharge.
- the alignment device may further comprise a fluid outlet in a cavity connected with the one or more fluid outlets (designed to collect fluid from which fine particles collected at each fluid outlet are removed).
- the fine particles to be separated are white blood cells and the fluid is blood
- the white blood cells are collected in the fine particle discharge portion or the cavity fine particle discharge portion of the device for separating and / or aligning the fine particles
- Blood from the leukocytes may be collected at the fluid outlet of the cavity.
- the apparatus for separating and / or aligning the fine particles may include storing and / or storing the fine particles discharged from the chip for separating and / or aligning two or more fine particles and / or a fluid from which the fine particles have been removed. And / or fluid reservoirs may be further included.
- the chip for separating and / or aligning the fine particles, and / or the device may be used so that the fluid flows from one end to the opposite end where the injection part is located by the injection flow rate of the fluid.
- the injection flow rate of the fluid may be used so that the fluid flows from one end to the opposite end where the injection part is located by the injection flow rate of the fluid.
- the injection flow rate of the fluid per chip for separating and / or aligning the fine particles is about lOul / min, about 20 ul / min, about 30 ul / min, about 40 ul / min, about 50 ul / min or more, about 60 ul / min or more, 70 ul / min or more, or about 80 ul / min or more, with an upper limit of about 1000 ul / min, about 900 ul / min : about 800 ul / min, about 700 ul / min, about 600 ul / min, about 500 ul / min, about 450 ul / min, about 400 ul / min ; It may be about 350 ul / min, about 300 ul / min, about 250 ul / min, about 200 ul / min, about 150 ul / min, or about 120 ul / min, but is not limited thereto.
- the fluid injection rate of the device for separating and / or aligning the fine particles can be used for separating and / or aligning the fine particles contained therein.
- Fluid injection of the chip for separating and / or aligning the fine particles according to the number of chips. Can be set to increase in multiples of speed.
- the chip for separating and / or aligning the fine particles and / or the device for separating and / or aligning the fine particles may be used in connection with a supply capable of supplying a fluid to the fluid inlet.
- a fluid supply connected to the fluid inlet of the chip for separating and / or sorting the fine particles and / or the device for separating and / or sorting the fine particles
- kit for separation and / or alignment of fine particles comprising a.
- the fluid supply unit may serve to apply an injection flow rate of the fluid to the storage and / or air compression of the fluid, for example, a syringe, a pipette, a piston pump, a syringe pump, a diaphragm pump, a tube-linked pump, or the like. It may be one or more selected from the group consisting of.
- the fluid inlet of the device for separating and / or aligning the fine particles may be used in a form connected to the syringe needle.
- Another example provides a method for separating and / or aligning fine particles using the chip for separating and / or aligning the fine particles and / or the device for separating and / or aligning the fine particles.
- Separation of the fine particles when the chip for separating and / or aligning the fine particles and / or the device for separating and / or aligning the fine particles further includes a fluid discharge part for discharging the fluid from which the fine particles have been removed.
- / or the sorting method is for separating and / or sorting the chips and / or sorting and / or sorting the particles and / or sorting the particles and / or the fluid # , after the feeding step and before or after the collecting the particles. And collecting the fluid from which the fine particles are discharged from the fluid outlet of the device.
- the fine particles are leukocytes and the fluid is blood
- blood is introduced to the inlet of the chip for separating and / or aligning the fine particles and / or for separating and / or aligning the fine particles.
- the chip for separating and / or aligning the fine particles and / or the device for separating and / or aligning the fine particles further comprises a fluid outlet from which the fine particles have been removed, wherein the fine particles are leukocytes, If blood,
- the method for isolating and / or removing leukocytes from the blood, or for obtaining leukocyte-depleted blood is characterized by whole blood or relatively high blood cell concentration.
- the leukocytes can be separated from the blood with high efficiency.
- the injected blood may be whole blood or blood (1 to 1/20 concentration) diluted 1 to 20 times by volume, but is not limited thereto.
- the recovery rate of the fine particles from the fluid is about 10% or more and about 30% or more based on the total number of particles contained in the fluid before supplying the chip or device. , At least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 92%, at least about 95%, at least about 96%, at least about 9 7 %, about 98% Or at least about 99%, at least 99.5%, or at least 99.9%.
- the fine particle loss rate ([(the total number of particles contained in the fluid before supply to the chip or device ⁇ Total number of fine particles separated) / total number of particles contained in the fluid before supply to the chip or device] * 100) is about 90% or less, about 70% or less, about 50% or less, about 40% or less, about 30% Or less, about 20% or less, about 10% or less, about 8% or less, about 5% or less, about 4% or less, about 3% or less, about 2% or less, about 1% or less, about 0.5% or less, or about 0.1 It may be less than or equal to%.
- the recovery rate of the white blood cells from the blood is originally included in the blood. At least about 10%, at least about 30%, at least about 50%, at least about 60%, at least about 70%, at least about 80% : at least about 90%, at least 92%, about 95 Or at least about 96%, at least about 97%, at least about 98% : at least about 99%, at least 99.5%, or at least 99.9%.
- the loss rate of the white blood cells is about 90% or less, about 70% or less, about 50% or less, about 40% or less, about 30% or less, about 20% or less, about 10% or less, about 8% or less, about 5% Or about 4% or less, about 3% or less, about 2% or less, about 1% or less, about 0.5% or less, or about 0.1% or less.
- the leukocyte separation efficiency may be related to the blood injection amount (eg, the smaller the blood injection amount, the higher the leukocyte separation efficiency may be), and to increase the leukocyte separation efficiency, the injection amount of blood applied to one chip (injection Flow rate) is about 10 to about lOOOOul / min, about 10 to about 900ul / min, about 10 to about 800ul / mm, about 10 to about 700ul / min, about 10 to about 600ul / min, about 10 to about 500ul / min , About 10 to about
- a method for isolating and / or removing leukocytes from said blood, or for obtaining leukocyte-free blood, and / or for separating and / or aligning microparticles and / or for sorting fine particles and / or fine particles used therein, and And / or the device for sorting may remove leukocytes from the patient's blood when it is necessary to remove leukocytes from blood donated by blood transfusion. It can be usefully applied when leukocytes isolated from the patient's blood are needed for separate use for testing or diagnosis.
- Fine particle separation and / or sorting come for the purpose of separation and arranged in the desired direction.
- the fine particle separation and alignment device according to an embodiment of the present invention, the purpose of separating and aligning the fine particles in a desired direction in a cheaper, more convenient way through a pattern shape.
- FIG. 1 is a view schematically showing the configuration of a fine particle separation and alignment apparatus according to an embodiment of the present invention.
- FIG. 2 is a flowchart illustrating a method for separating and aligning microparticles according to an embodiment of the present invention.
- FIG. 3 is a view showing a fine particle separation and alignment apparatus according to an embodiment of the present invention.
- Figure 4a is a view illustrating a passage portion of the microparticle separation and alignment apparatus according to an embodiment of the present invention
- Figure 4b is a cross-sectional view in the AA direction of Figure 4a (200: substrate without the inclined groove; AA: inclination Cross section; aa: cross section perpendicular to the inclined cross section; BB: line perpendicular to both sides; ⁇ : angle between the A- ⁇ and ⁇ - ⁇ (inclined angle); C: main direction of fluid movement (fluid injection direction) D: direction of fine particle movement (the direction perpendicular to the ⁇ - ⁇ inclined cross section and the main movement direction of the fluid); hr: height (depth) of the inclined groove; wr: width of the inclined groove perpendicular to the inclined plane; he : Height of the channel portion; lr: length of the inclined groove in the inclined groove: lr ' : distance in the inclined direction between the inclined grooves).
- Figure 5a is a diagram showing an example of the use of the microparticle separation and alignment apparatus according to an embodiment of the present invention.
- Figure 5b is a diagram showing an example of the use of microparticle separation and alignment apparatus according to an embodiment of the present invention.
- Figure 5c is a view showing an example of using the microparticle separation and alignment apparatus according to an embodiment of the present invention.
- Figure 5d is a graph showing the microparticle separation according to the use example of the microparticle separation and alignment apparatus according to an embodiment of the present invention.
- Figure 6a is a view showing an example of using the microparticle separation and alignment apparatus according to another embodiment of the present invention.
- Figure 6b is a view showing an example of using the microparticle separation and alignment apparatus according to another embodiment of the present invention.
- Figure 7a is a view showing a fine particle separation and alignment apparatus according to another embodiment of the present invention.
- Figure 7b is a view showing in detail the passage portion of the microparticle separation and alignment apparatus according to another embodiment of the present invention.
- Figure 7c is a view showing an example of the use of the microparticle separation and alignment apparatus according to another embodiment of the present invention.
- Figure 7d is a diagram showing an example of the use of the microparticle separation and alignment apparatus according to another embodiment of the present invention.
- Figure 8a is a diagram showing a practical use example of the microparticle separation and alignment apparatus according to an embodiment of the present invention.
- Figure 8b is a view showing the actual use of the microparticle separation and alignment apparatus according to another embodiment of the present invention.
- Figure 9 shows an example of an arrangement of at least one inclined groove formed (inclined grooves are shown in dark colors; hollow arrows indicate the other end direction (main direction of fluid movement) at one end where the inlet is located; Filled arrows indicate the direction of movement of fine particles discharged).
- injection part 120 passage part
- fine particle acquisition unit 210 white blood cell 220: red blood cell
- the terms “comprise” or “have” are intended to indicate that there is a feature, number, step, operation, component, part, or combination thereof described on the specification, and one or more other It is to be understood that the present invention does not exclude the possibility of the presence or the addition of features, features, steps, operations, components, components, or a combination thereof.
- the microparticle separation and alignment apparatus 100 may include an injection unit (inlet unit: 110), a passage unit 120, and a microparticle acquisition unit (fine particle discharge unit: 130).
- the fluid containing the fine particles to be obtained is
- the injected fluid may be injected through the injection unit 1 10, and the injected fluid flows through the passage unit 120, and the fine particles are concentrated in one direction.
- the fluid containing the microparticles may be concentrated in the microparticle acquisition unit 130.
- the injection unit 110, the passage unit 120 and the fine particle acquisition unit 130 will be described in more detail.
- the injection unit 1 10 may be injected with a fluid containing fine particles.
- the injection may be made via a lyub, syringe, pipette, etc., and the fluid may include whole blood for the purpose of obtaining leukocytes.
- the passage part 120 may separate the microparticles in a specific direction while the injected fluid flows. More specifically, through the injection unit 110 The injected fluid, the fine particles may be separated in a predetermined direction in the process of flowing the passage portion 120 flows. Therefore, at the end of the predetermined direction
- the fine particle separation may be formed in the passage portion 120 through a predetermined pattern having an inclination at a predetermined angle with respect to a direction perpendicular to the main flow direction of the fluid, wherein the inclination of the pattern is the fluid It can be determined according to the main direction of movement of the and the specific direction to separate the fine particles.
- the passage part 120 pattern may have an inclination inclined opposite to the specific direction in which the microparticles are to be separated, based on a direction perpendicular to the main flow direction of the fluid. It may comprise an inclination within 45 degrees with respect to the main flow direction of the fluid.
- the pattern in the passage part 120 may include a groove shape, and at least one of the groove shape of the pattern, that is, the height, the width, the length of the groove, and the height of the passage part may be defined by the fine particles. It depends on the type.
- the height and width of the groove is within 0.5 to 2 times the diameter of the microparticles
- the length of the groove is within 3 to 5 times the diameter of the microparticles
- the height of the passage portion of the diameter of the microparticles It may be within 1.5 to 2 times.
- the diameter includes the average diameter of the microparticles.
- the pattern in the passage portion 120 may include that the grooves are arranged at a predetermined interval, the predetermined interval may include about 50um (micromete r ).
- the shape of the groove may be at least one of rectangular, rhombus, triangle, oval and star shape, but is not limited thereto.
- the fine particles moved in a specific direction is maintained by the laminar flow of the fluid (Laminar Flow), so that even in the absence of a certain pattern to maintain the position in the vertical direction of the passage portion 120, the fine located at the end Through the particle acquisition unit 130 it is possible to obtain a fluid having a high concentration of fine particles.
- the configuration of the pattern of the passage portion 120 and the flow of the fluid thereby the embodiment will be described in detail below with reference to FIGS. 3, 4A, and 4B.
- the microparticle acquisition unit 130 may obtain the separated microparticles. More specifically, the passage part 120, the fine particles can be concentrated and flow in a predetermined direction intensively, install the fine particle acquisition unit 130 at the end of the predetermined direction, separated The microparticles can be obtained.
- leukocyte separation using whole blood may be performed.
- microparticle acquisition unit 130b In the microparticle acquisition unit 130b, a relatively high ratio of red blood cells can be obtained.
- the microparticle separation and alignment device is a polymer (PS (polystyrene),
- PC polycarbonate
- PMMA polymethylmethacrylate
- PDMS polydimethylsiloxane
- FIG. 2 is a flow chart illustrating a method for separating and aligning microparticles according to one embodiment of the present invention.
- step S210 the fluid containing the fine particles may be injected.
- the fine particles in the flow of the injected fluid, may be concentrated and flow in a predetermined direction ⁇ the flow concentrated in the predetermined direction is a predetermined angle with respect to the direction perpendicular to the main direction of movement of the fluid With an inclination of, the pattern may be formed through the passage portion formed.
- the predetermined pattern may include a groove shape formed at a predetermined interval.
- step S230 it is possible to obtain the fine particles concentrated in a certain direction.
- microparticle injection, separation and acquisition process as described above may be made through the microparticle separation and alignment device 100.
- Figure 3 is a view showing a microparticle separation and alignment apparatus according to an embodiment of the present invention
- Figure 4 is a microparticle separation and alignment apparatus according to an embodiment of the present invention It is a figure which shows the passage part in detail.
- the apparatus for separating and aligning microparticles according to an embodiment of the present invention may include an injection unit 1 10, a passage unit 120, and a microparticle acquisition unit 130.
- the micro-injector separation and alignment device 100 when the fluid containing the microparticles are injected into the injection unit 1 10, the fluid passes through the passage portion 120 and the microparticles are separated in a predetermined direction In order to flow, the separated fine particles can be concentrated in the fine particle acquisition unit 130.
- the separation may be made through a pattern of a predetermined shape formed in the passage portion 120, the pattern of the predetermined shape may be determined according to the size and direction of the fine particles to be separated.
- the pattern may be inclined at a predetermined angle ( ⁇ ) with respect to the direction perpendicular to the main flow direction of the fluid, the predetermined angle may include within 45 degrees.
- 3 is for separating leukocytes from whole blood components, and as shown, by inclining the pattern by the predetermined angle ⁇ based on the dotted line (the line perpendicular to the main flow direction of the fluid), thereby the whole blood Is flowing and the white blood cells are said to .
- the particles may be concentrated and separated in the direction of obtaining the fine particles 130.
- a pattern of a predetermined shape formed in the passage part 120 may be inclined at an angle ⁇ with respect to a main flow direction of the fluid, and the predetermined shape may include a groove shape. .
- At least one of the height (Hg) of the groove, the width (Wg) of the groove, the length (Lg) of the groove and the height (He) of the passage portion may be adjusted according to the size of the fine particles to be separated, Based on the diameter of the microparticles to be separated, the height (Hg) and the width (Wg) of the groove is within 0.5 to 2 times the diameter of the microparticle, the length (Lg) of the groove is 3 of the microparticle diameter Fold to within 5 times, the height (He) of the passage portion may be within 1.5 times to 2 times the diameter of the fine particles.
- the diameter is the
- FIG. 5A to 5C illustrate examples of use of the microparticle separation and alignment device according to an embodiment of the present invention. Specifically, white microparticles represent white blood cells, and red microparticles represent red blood cells. An embodiment of obtaining leukocytes from whole blood using a separation and alignment device is shown.
- white blood cells have an average diameter of 12 um (micrometer) to 15 um and red blood cells have an average diameter of 7 um to 8 um. According to the size difference, through the configuration of the passage portion 120 pattern of the microparticle separation and alignment device 100, it is possible to implement the intensive acquisition of the white blood cells or red blood cells.
- the white blood cells in the whole blood can be concentrated and flow in the direction of the arrow, as shown in Figure 5b, red blood cells in the whole blood and leukocytes Otherwise it can flow without a specific orientation.
- white blood cells can be concentrated in the microparticle acquisition unit a (130a), red blood cells to the microparticle acquisition unit b (130b).
- the height of the passage portion 120, the height of the pattern groove in the passage portion 120 by adjusting the width, width, shape, etc. to a predetermined size or shape, the white blood cells are concentrated in a predetermined direction to flow can do.
- the height of the passage portion 120 is within three times the average diameter of the white blood cells, the height and width of the grooves are less than 5 times to 2 times the average diameter of the white blood cells, the length of the grooves of the average diameter of the white blood cells If formed within 3 to 5 times, higher leukocyte acquisition rate can be seen.
- the pattern shape has a predetermined interval, it is preferable to leave a space of 50um between the pattern grooves so that the white blood cells are concentrated in a certain direction and flow.
- the passage portion 120 is to have a length of at least 500um, it is advantageous to allow the white blood cells to flow in a certain direction.
- Figure 5d is a graph showing the microparticle separation according to the use example of the microparticle separation and alignment apparatus according to an embodiment of the present invention.
- the graph the height of the passage portion 120 (height of the channel portion: he) is 25um, the height (hr) of the groove is 25um, the length (lr) of the groove is OOum, the interval of the pattern groove (lr ') is 20um, with a dilution
- the height of the passage portion 120 is preferably within 1.5 times to 2 times the diameter of the fine particles to be separated.
- the injected whole blood can be obtained by separating and sorting the white blood cells and the red blood cells at a high ratio.
- separation through a yeongyeong separator it can be separated through a much simpler and cheaper structure.
- 6a to 6b is a view showing an example of the use of the microparticle separation and alignment apparatus according to another embodiment of the present invention. As shown, different types of microparticles may be concentrated and separated in one direction through the microparticle separation and alignment apparatus according to another embodiment of the present invention.
- the microparticles to be obtained are concentrated flow in a predetermined direction.
- FIGS. 7A to 7B are views illustrating a device for separating and aligning microparticles and a passage thereof according to another embodiment of the present invention, and FIGS. 7C to 7D. Is a view showing an example of the use of the microparticle separation and alignment apparatus according to another embodiment of the present invention.
- the fine particle separation and alignment apparatus according to another embodiment of the present invention, by adjusting the shape of the pattern, in particular the inclination of the pattern in a certain direction, for example in the center portion of the passage, etc. Fine particles can be concentrated.
- the two patterns having different inclinations may form angles symmetric with each other with respect to a specific direction (for example, the central axis of the passage part).
- the flow rate of the fluid does not need to consider significantly, but if the cross-sectional area of the passage portion of 700um * 25um, it is more preferable to maintain the flow rate of 150um / s, By appropriately adjusting the flow rate according to the height and width of the passage portion, it is possible to maximize the separation effect.
- Example of practical use Example of actual use of the microparticle separation and alignment apparatus according to an embodiment of the present invention
- FIG. 8A illustrates a yarn use example of the microparticle separation and alignment device according to an embodiment of the present invention
- FIG. 8B illustrates a yarn use example of the microparticle separation and alignment device according to another embodiment of the present invention.
- the figure shows a microparticle separation and alignment device for centrally separating leukocytes in whole blood.
- the passage portion may be a pattern of a predetermined shape having a predetermined inclination, as shown enlarged in FIG. 8B.
- the microparticle separation and alignment device may include an injection portion, a passage portion and a microparticle acquisition portion, the specific form of the component, the scope of the present invention It can be modified and applied in various ways within.
- the microparticle separation and alignment device according to an embodiment of the present invention based on the pattern formed in the passage portion, by causing the specific microparticles to concentrate and flow in a predetermined direction, the specific microparticles of high concentration To obtain a fluid comprising a.
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Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
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CN201680082906.XA CN108698045A (zh) | 2015-12-31 | 2016-12-30 | 用于分离或对齐细颗粒的装置以及使用其用于分离或对齐细颗粒的方法 |
JP2018554297A JP6757419B2 (ja) | 2015-12-31 | 2016-12-30 | 微細粒子分離または整列装置およびこれを用いた微細粒子分離または整列方法 |
US16/066,090 US11219897B2 (en) | 2015-12-31 | 2016-12-30 | Device for separating or aligning fine particles, and method for separating or aligning fine particles using same |
CN202410877499.8A CN118634875A (zh) | 2015-12-31 | 2016-12-30 | 用于分离或对齐细颗粒的装置以及使用其用于分离或对齐细颗粒的方法 |
EP16882166.8A EP3398680A4 (en) | 2015-12-31 | 2016-12-30 | DEVICE FOR SEPARATING OR ALIGNING PARTICULAR PARTICLES AND METHOD FOR SEPARATING OR ALIGNING FINE PARTICLES WITH USE THEREOF |
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KR10-2015-0191430 | 2015-12-31 | ||
KR1020150191430A KR101791671B1 (ko) | 2015-12-31 | 2015-12-31 | 미세입자 분리 및 정렬 장치, 및 그 방법 |
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WO2017116214A1 true WO2017116214A1 (ko) | 2017-07-06 |
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US (1) | US11219897B2 (ko) |
EP (1) | EP3398680A4 (ko) |
JP (1) | JP6757419B2 (ko) |
KR (1) | KR101791671B1 (ko) |
CN (2) | CN118634875A (ko) |
WO (1) | WO2017116214A1 (ko) |
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KR102083845B1 (ko) * | 2018-07-31 | 2020-03-03 | 광주과학기술원 | 혈액 진단 소자 |
KR102425055B1 (ko) * | 2020-08-03 | 2022-07-26 | 고려대학교 산학협력단 | 나노입자 분리소자 및 이를 이용한 나노입자 분리방법 |
WO2023210966A1 (ko) * | 2022-04-28 | 2023-11-02 | 주식회사 큐리오시스 | 타겟 대상물 분리 장치 및 방법 |
KR102574200B1 (ko) * | 2022-04-28 | 2023-09-04 | 주식회사 큐리오시스 | 타겟 대상물 분리 장치 및 방법 |
JPWO2023243448A1 (ko) * | 2022-06-13 | 2023-12-21 | ||
CN115138410B (zh) * | 2022-07-12 | 2024-01-30 | 珠海大略科技有限公司 | 储液件及输送装置 |
WO2024077016A2 (en) * | 2022-10-03 | 2024-04-11 | West Pharmaceutical Services, Inc. | Microfluidic mixing and/or separater |
KR102626810B1 (ko) * | 2023-05-09 | 2024-01-18 | 주식회사 큐리오시스 | 품질 관리가 개선된 타겟 대상물 분리 장치 및 이의 제조 방법 |
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US11219897B2 (en) | 2022-01-11 |
US20200269242A1 (en) | 2020-08-27 |
EP3398680A1 (en) | 2018-11-07 |
CN108698045A (zh) | 2018-10-23 |
KR101791671B1 (ko) | 2017-11-20 |
EP3398680A4 (en) | 2019-05-22 |
JP6757419B2 (ja) | 2020-09-16 |
JP2019502936A (ja) | 2019-01-31 |
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CN118634875A (zh) | 2024-09-13 |
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