Particle separation device and particle separation method

Abstract

A particle separation device according to an embodiment comprises a storage unit, a filter, and a microchannel. The storage part stores a suspension containing target particles and non-target particles smaller than the target particles. The filter captures the target particles from the suspension and allows the non-target particles to pass. The microchannel separates the target particles from the suspension. The particle separation device sends the suspension stored in the storage unit to the filter and sends the suspension containing the target particles captured by the filter to the microchannel.

Description

Particle separation device and particle separation method

[0001] SUMMARY OF THE INVENTION The embodiments disclosed herein and in the drawings relate to particle separation devices and methods.

[0002] White blood cells are required for the production of iPS (induced pluripotent stem) cells. To separate white blood cells (an example of target particles) from whole blood, it is necessary to remove red blood cells (an example of non-target particles), which make up the majority of whole blood.

[0003] For example, there is a method in which whole blood is diluted with physiological saline (PBS) and then leukocytes are separated from the treated whole blood. However, the dilution process increases the volume of the whole blood, which increases the processing time required for leukocyte separation.

[0004] Japan Special Table No. 2015-535728

[0005] One of the problems to be solved by the embodiments disclosed in this specification and the drawings is to efficiently separate target particles. However, the problems to be solved by the embodiments disclosed in this specification and the drawings are not limited to the above problem. Problems corresponding to the effects of each configuration shown in the embodiments described below can also be positioned as other problems.

[0006] A particle separation device according to an embodiment includes a reservoir, a filter, and a microchannel. The reservoir stores a suspension containing target particles and non-target particles smaller than the target particles. The filter captures the target particles from the suspension and allows the non-target particles to pass through. The microchannel separates the target particles from the suspension. The particle separation device delivers the suspension stored in the reservoir to the filter and delivers the suspension containing the target particles captured by the filter to the microchannel.

[0007] According to the present invention, target particles can be separated efficiently.

[0008] FIG. 1 is a schematic diagram showing an example of the configuration of a particle separation device according to the present embodiment; FIG. 2 is a schematic diagram showing the appearance of a spiral channel according to the present embodiment; FIG. 3 is a flowchart showing an example of the operation of a particle separation device according to the present embodiment; FIG. 4 is a schematic diagram showing blood suction according to the present embodiment; FIG. 5 is a schematic diagram showing blood filtering according to the present embodiment; FIG. 6 is a schematic diagram showing primary PBS suction according to the present embodiment; FIG. 7 is a schematic diagram showing PBS rinsing according to the present embodiment; FIG. 8 is a schematic diagram showing secondary PBS suction according to the present embodiment; FIG. 9 is a schematic diagram showing cell recovery according to the present embodiment; FIG. 10 is a schematic diagram showing primary classification according to the present embodiment; FIG. 11 is a schematic diagram showing secondary classification according to the present embodiment.

[0009] The present embodiment will be described below with reference to the drawings. In the present embodiment, parts with the same reference numerals are considered to perform the same operations, and redundant description will be omitted as appropriate.

[0010] 1 is a schematic diagram showing an example of the configuration of a particle separator 1 according to this embodiment. This diagram shows the particle separator 1 as viewed from a horizontal direction. The particle separator 1 is a device for separating target particles. The particle separator 1 includes a blood bag 21, a reagent bag 22, liquid supply containers 31 and 32, a collection container 33, a filter 4, a spiral flow path 5, a waste liquid container 6, a tapered container 7, a pressure mechanism 8, an adjustment mechanism 91, a vibration mechanism 92, tubes Tu1-Tu19, and valves V1-V13.

[0011] The blood bag 21 is a bag for storing blood (whole blood). The blood bag 21 is connected to the liquid supply container 31 via a tube Tu1. The blood bag 21 is an example of a storage portion (blood storage portion).

[0012] The reagent bag 22 is a bag that stores a reagent (e.g., PBS). The reagent bag 22 is connected to the liquid supply container 32 via a tube Tu2. The reagent bag 22 is an example of a storage section (reagent storage section).

[0013] The liquid supply container 31 (first liquid supply container) is a container that temporarily stores the liquid to be supplied. The liquid supply container 31 temporarily stores blood. The liquid supply container 31 is connected to the filter 4 (particularly the capture surface 4A) by tubes Tu3, Tu8, and Tu12. The liquid supply container 31 is connected to the spiral flow path 5 by tubes Tu3, Tu6, Tu7, Tu10, and Tu13. The liquid supply container 31 is an example of a storage section (blood storage section).

[0014] The liquid supply container 32 (second liquid supply container) is a container that temporarily stores the liquid to be supplied. The liquid supply container 32 temporarily stores a reagent. The liquid supply container 32 is connected to the filter 4 (particularly the capture surface 4A) by tubes Tu4, Tu6, Tu8, and Tu12. The liquid supply container 32 is connected to the filter 4 (particularly the opposite surface 4B) by tubes Tu4, Tu9, and Tu14. The liquid supply container 32 is connected to the spiral flow path 5 by tubes Tu4, Tu7, Tu10, and Tu13. The liquid supply container 32 is an example of a storage section (reagent storage section).

[0015] The collection container 33 is a container that temporarily stores the collected liquid. The collection container 33 stores the suspension containing white blood cells captured by the filter 4 (particularly, the capture surface 4A). The collection container 33 is connected to the filter 4 (particularly, the capture surface 4A) by tubes Tu5, Tu10, Tu11, and Tu12. The collection container 33 is connected to the spiral flow path 5 (particularly, the inlet N1) by tubes Tu5, Tu10, and Tu13. The collection container 33 is an example of a storage section (suspension storage section).

[0016] The filter 4 captures target particles from the suspension and allows non-target particles smaller than the target particles to pass through. The filter 4 captures white blood cells from blood containing white blood cells, red blood cells, platelets, etc., and allows red blood cells, platelets, etc., smaller than white blood cells, to pass through. The filter 4 has a large number of pores. Preferably, the pore size is smaller than the particle diameter of the target particles and larger than the particle diameter of the non-target particles. The filter 4 may be formed of a nonwoven fabric. Examples of the filter 4 that can be used include leukocyte removal filters such as the Acrodisc WBC Syringe Filter (AP-4951) manufactured by PALL Corporation and the Sepacel RZ (RZ-1000N, RZ-2000N) manufactured by Asahi Kasei Medical Corporation. The filter 4 is connected to the adjustment mechanism 91. The filter 4 has a capture surface 4A and an opposite surface 4B. The filter 4 is an example of a capture unit.

[0017] The target particles may have a particle diameter of 7 μm or more and 30 μm or less. The non-target particles may have a particle diameter of less than 7 μm. The target particles may be white blood cells. The non-target particles may be red blood cells, platelets, etc. In particular, when the target particles and non-target particles each have the above particle diameters, the pore size of the filter 4 may be 6 μm or more and 7 μm or less.

[0018] The capture surface 4A of the filter 4 is the surface that captures target particles. A liquid (e.g., blood, reagent, suspension) is delivered to the capture surface 4A. The opposite surface 4B of the filter 4 is located opposite the capture surface 4A. The liquid that has passed through the capture surface 4A is delivered from the opposite surface 4B. The opposite surface 4B is connected to the waste liquid container 6 by tubes Tu14 and Tu17.

[0019] The spiral channel 5 is a spiral-shaped microchannel (see FIG. 2). The spiral channel 5 separates target particles from a suspension. The spiral channel 5 separates white blood cells from blood containing white blood cells, red blood cells, platelets, etc. The spiral channel 5 has one inlet N1 and two outlets U1 and U2. The outlet U1 corresponds to the outer outlet of the microchannel. Particles with a relatively small particle diameter are discharged from the outlet U1. The outlet U2 corresponds to the inner outlet of the microchannel. Particles with a relatively large particle diameter are discharged from the outlet U2. The spiral channel 5 is an example of a separation section.

[0020] A liquid (e.g., blood, reagent, suspension) is delivered to the inlet N1 of the spiral channel 5. A suspension mainly containing non-target particles (e.g., red blood cells, platelets) separated by the spiral channel 5 is delivered from the outlet U1 of the spiral channel 5. The outlet U1 is connected to the waste liquid container 6 by a tube Tu15. A suspension mainly containing target particles (e.g., white blood cells) separated by the spiral channel 5 is delivered from the outlet U2 of the spiral channel 5. The outlet U2 is connected to the waste liquid container 6 by tubes Tu16 and Tu18. The outlet U2 is connected to the tapered container 7 by tubes Tu16 and Tu19.

[0021] The waste liquid container 6 is a container that stores used liquid (waste liquid). The waste liquid container 6 stores the suspension containing non-target particles that has passed through the filter 4. The waste liquid container 6 stores the suspension containing non-target particles that has been separated by the spiral flow path 5. The waste liquid container 6 is an example of a storage section (waste liquid storage section).

[0022] According to this embodiment, one waste liquid container 6 stores the suspension from the filter 4 and stores the suspension from the spiral channel 5. Alternatively, one waste liquid container 6 may store the suspension from the filter 4, and another waste liquid container 6 may store the suspension from the spiral channel 5. Because the particle separator 1 according to this embodiment uses one waste liquid container 6 instead of two waste liquid containers 6, the overall configuration of the particle separator 1 can be simplified.

[0023] The tapered container 7 is a container having a tapered shape. The tapered container 7 has a shape in which the diameter gradually narrows from the top to the bottom. The tapered container 7 stores a suspension that mainly contains target particles separated by the spiral flow path 5. The tapered container 7 is an example of a storage section (suspension storage section, separated liquid storage section).

[0024] The pressure mechanism 8 is a mechanism for pressurizing or depressurizing the containers (liquid supply containers 31 and 32, recovery container 33). The pressure mechanism 8 pressurizes the container by sending air into the container. By pressurizing the container, the liquid stored in the container is sent toward a point where the pressure is lower. The pressure mechanism 8 depressurizes the container by sucking air from the inside of the container. By depressurizing the container, the liquid is sucked toward the container from a point where the pressure is higher. In other words, the pressure mechanism 8 realizes the sending of the liquid stored in the container and the sucking of the liquid into the container. The number of pressure mechanisms 8 is not limited to one, and multiple pressure mechanisms may be used depending on the application. For example, a pressure mechanism that sends the suspension stored in the storage section to the filter 4 and a pressure mechanism that sends the suspension containing the target particles captured in the filter 4 to the microchannel may be provided independently. The pressure mechanism 8 is an example of a pressure unit, a sending unit, or a suction unit.

[0025] The adjustment mechanism 91 is a mechanism that adjusts the attitude (angle) at which the filter 4 is installed. The adjustment mechanism 91 may adjust the attitude of the filter 4 to be horizontal. The adjustment mechanism 91 may have a stage that holds the filter 4 and a drive mechanism that adjusts the attitude of the stage. In this case, the adjustment mechanism 91 controls the drive mechanism to adjust the attitude of the stage, thereby adjusting the attitude of the filter 4 held on the stage. The adjustment mechanism 91 is an example of an adjustment unit.

[0026] According to this embodiment, the pressure mechanism 8 delivers the suspension vertically downward to the filter 4 (particularly the capture surface 4A) that has been adjusted horizontally by the adjustment mechanism 91. At this time, the delivered suspension passes uniformly through the capture surface 4A of the filter 4. Therefore, the filter 4 can efficiently capture target particles from the delivered suspension and efficiently remove non-target particles.

[0027] The vibration mechanism 92 is a mechanism that vibrates the collection container 33. The vibration mechanism 92 may vibrate the suspension contained in the collection container 33. The vibration mechanism 92 may have a base on which the collection container 33 is placed and a vibrator that vibrates the base. In this case, the vibration mechanism 92 controls the vibrator to vibrate the base, thereby vibrating the collection container 33 placed on the base. The vibration mechanism 92 is an example of a vibration unit.

[0028] According to this embodiment, the pressure mechanism 8 sends the suspension vibrated by the vibration mechanism 92 to the spiral channel 5. The vibration mechanism 92 vibrates the suspension to break up or prevent aggregation of particles in the suspension. Therefore, the spiral channel 5 can effectively separate the target particles and non-target particles from the vibrated suspension.

[0029] The tubes Tu1-Tu19 are tubes through which liquid flows. The tubes Tu1-Tu19 are made of silicone rubber, polyethylene, metal, or the like. One tube and another tube may be connected to each other by a branch pipe (e.g., a Y-shaped pipe, a T-shaped pipe, or a cross pipe). The tubes Tu1-Tu19 are an example of a connecting portion.

[0030] The valves V1-V13 are valves that form a flow path for the liquid flowing through the tubes Tu1-Tu19. The valves V1-V13 are valves that allow the liquid to flow in both directions (two-way valves). Each valve is set to an "open state" or a "closed state" manually or automatically. The valves V1-V13 are an example of a flow path forming unit.

[0031] Valves V1-V13 are arranged midway through tubes Tu1-Tu19. Below, each valve and the tube in which it is arranged will be represented as (valve name, tube name). According to this representation, the following combinations are obtained: (V1, Tu1), (V2, Tu2), (V3, Tu3), (V4, Tu5), (V5, Tu6), (V6, Tu7), (V7, Tu8), (V8, Tu11), (V9, Tu13), (V10, Tu9), (V11, Tu17), (V12, Tu18), (V13, Tu19).

[0032] 3 is a flowchart showing an example of the operation of the particle separation device 1 according to this embodiment. The particle separation device 1 controls the pressure mechanism 8 and the valves V1-V13 to circulate a liquid (e.g., blood, a reagent, or a suspension) through the tubes Tu1-Tu19.

[0033] (Step S1) First, the particle separator 1 performs blood suction (see FIG. 4). Specifically, the particle separator 1 sets the valve V1 to the "open state" and the valves V2-V13 to the "closed state." The particle separator 1 controls the pressure mechanism 8 to reduce the pressure in the liquid supply container 31. As a result, the blood stored in the blood bag 21 is sent to the liquid supply container 31 through the tube Tu1.

[0034] (Step S2) Next, the particle separator 1 performs blood filtering (see FIG. 5). Specifically, the particle separator 1 sets valves V3, V7, and V11 to the "open state" and valves V1-V2, V4-V6, V8-V10, and V12-V13 to the "closed state." The particle separator 1 controls the pressure mechanism 8 to pressurize the liquid supply container 31. As a result, blood stored in the liquid supply container 31 is sent to the capture surface 4A of the filter 4 through tubes Tu3, Tu8, and Tu12. The filter 4 captures white blood cells in the blood using the capture surface 4A and allows red blood cells, platelets, etc. to pass through. The blood that has passed through the capture surface 4A is sent from the opposite surface 4B of the filter 4 and sent to the waste liquid container 6 through tubes Tu14 and Tu17.

[0035] The particle separation device 1 may send blood to the filter 4 at a first flow rate for a predetermined time from the start of blood delivery, and then send the blood to the filter 4 at a second flow rate that is smaller than the first flow rate. For example, the particle separation device 1 may send blood to the filter 4 at 10 mL / min for 10 seconds from the start of blood delivery, and then send blood to the filter 4 at 5 mL / min. This allows the filter 4 to effectively capture white blood cells. In other words, the particle separation device 1 can suppress the loss of necessary cells.

[0036] (Step S3) Next, the particle separator 1 performs primary PBS suction (see FIG. 6). Specifically, the particle separator 1 sets valve V2 to the "open state" and valves V1 and V3-V13 to the "closed state." The particle separator 1 controls the pressure mechanism 8 to reduce the pressure in the liquid supply container 32. As a result, the PBS stored in the reagent bag 22 is sent to the liquid supply container 32 through the tube Tu2.

[0037] (Step S4) Next, the particle separator 1 performs a PBS rinse (see FIG. 7). Specifically, the particle separator 1 sets valves V5, V7, and V11 to the "open state" and valves V1-V4, V6, V8-V10, and V12-V13 to the "closed state." The particle separator 1 controls the pressure mechanism 8 to pressurize the liquid supply container 32. As a result, the PBS stored in the liquid supply container 32 is sent to the capture surface 4A of the filter 4 through tubes Tu4, Tu6, Tu8, and Tu12. The sent PBS washes away red blood cells, platelets, and the like remaining on the capture surface 4A. The PBS that has passed through the capture surface 4A is sent out from the opposite surface 4B of the filter 4 and sent to the waste liquid container 6 through tubes Tu14 and Tu17.

[0038] The particle separator 1 may rinse the filter 4 at a first flow rate for a predetermined time from the start of PBS delivery, and then rinse the filter 4 at a second flow rate that is smaller than the first flow rate. This allows the particle separator 1 to effectively flush out red blood cells, platelets, and the like remaining in the filter 4.

[0039] (Step S5) Subsequently, the particle separator 1 performs a secondary PBS suction (see FIG. 8). Specifically, the particle separator 1 sets the valve V2 to the "open state" and the valves V1 and V3-V13 to the "closed state." The particle separator 1 controls the pressure mechanism 8 to reduce the pressure in the liquid supply container 32. As a result, the PBS stored in the reagent bag 22 is sent to the liquid supply container 32 through the tube Tu2. Step S5 is similar to step S3.

[0040] (Step S6) Next, the particle separator 1 performs cell recovery (see FIG. 9 ). Specifically, the particle separator 1 sets valves V4, V8, and V10 to the "open state" and valves V1-V3, V5-V7, V9, and V11-V13 to the "closed state." The particle separator 1 controls the pressure mechanism 8 to pressurize the liquid supply container 32. As a result, the PBS stored in the liquid supply container 32 is sent to the opposite surface 4B of the filter 4 through tubes Tu4, Tu9, and Tu14. The sent PBS recovers the suspension containing white blood cells captured on the capture surface 4A from the direction opposite to the capture surface 4A. The recovered suspension is sent to the recovery container 33 through tubes Tu12, Tu11, Tu10, and Tu5.

[0041] Prior to collecting the suspension, an air vent (not shown) provided in the collection container 33 may be opened. Opening the air vent reduces the pressure in the collection container 33. Therefore, the suspension collected from the filter 4 is efficiently collected in the collection container 33 against gravity.

[0042] (Step S7) Next, the particle separator 1 performs primary classification (see FIG. 10). Specifically, the particle separator 1 sets valves V4, V9, and V12 to the "open state," and valves V1-V3, V5-V8, V10-V11, and V13 to the "closed state." The particle separator 1 controls the pressure mechanism 8 to pressurize the collection container 33. As a result, the suspension collected in the collection container 33 is sent to the inlet N1 of the spiral channel 5 through tubes Tu5, Tu10, and Tu13. A suspension mainly containing red blood cells, platelets, etc. is sent from the outlet U1 of the spiral channel 5. The sent suspension is sent to the waste container 6 through tube Tu15. A suspension mainly containing white blood cells is sent from the outlet U2 of the spiral channel 5. The sent suspension is sent to the waste container 6 through tubes Tu16 and Tu18.

[0043] The particle separator 1 may perform primary classification until the flow rate of the suspension delivered to the inlet N1 of the spiral channel 5 reaches a predetermined value. After the flow rate reaches the predetermined value, the particle separator 1 performs secondary classification.

[0044] (Step S8) Finally, the particle separator 1 performs secondary classification (see FIG. 11). Specifically, the particle separator 1 sets valves V4, V9, and V13 to the "open state" and valves V1-V3, V5-V8, and V10-V12 to the "closed state." The particle separator 1 controls the pressure mechanism 8 to pressurize the collection container 33. As a result, the suspension collected in the collection container 33 is sent to the inlet N1 of the spiral channel 5 through the tubes Tu5, Tu10, and Tu13. A suspension containing mainly red blood cells, platelets, etc. is sent from the outlet U1 of the spiral channel 5. The sent suspension is sent to the waste container 6 through the tube Tu15. A suspension containing mainly white blood cells is sent from the outlet U2 of the spiral channel 5. The sent suspension is sent to the tapered container 7 through the tubes Tu16 and Tu19.

[0045] According to the present embodiment described above, the particle separator 1 roughly removes red blood cells, platelets, and the like from the blood by sending the blood to the filter 4. The particle separator 1 sends PBS to the filter 4, and collects a suspension mainly containing white blood cells captured by the filter 4 in the collection container 33. The particle separator 1 further removes red blood cells, platelets, and the like from the suspension by sending the suspension collected in the collection container 33 to the spiral channel 5, and separates the white blood cells. According to experiments conducted by the present inventors, when the cell suspension after separation was analyzed with a flow cytometer, it was confirmed that approximately 90% or more of the obtained cells were composed of white blood cells.

[0046] Particle separator 1 does not, for example, dilute blood. By passing blood through filter 4, particle separator 1 can adjust the cell count of the suspension sent to spiral channel 5 in a short time to a cell count suitable for spiral channel 5. Therefore, particle separator 1 can efficiently separate white blood cells from a large amount of blood (e.g., 10 mL). Furthermore, by passing blood through filter 4, particle separator 1 can adjust the cell count without using chemicals that may damage cells or pose a risk.

[0047] The suspension stored in the blood bag 21 or the fluid supply container 31 may be referred to as a first suspension. The suspension delivered to the spiral channel 5 may be referred to as a second suspension. The ratio between the number of non-target particles in the first suspension and the number of non-target particles in the second suspension may be 1000 to 1. In this case, the spiral channel 5 can more effectively remove non-target particles from the suspension.

[0048] It should be noted that a microchannel of any shape (e.g., linear, bellows-like, curved) may be used instead of the spiral channel 5. In the above-described embodiment, the step of sending the suspension containing the target particles and non-target particles smaller than the target particles to the filter 4 was performed via the pressure mechanism 8, but this is not necessarily required. In the above-described embodiment, the step of sending the suspension containing the target particles captured by the filter 4 to the microchannel was performed via the pressure mechanism 8, but this is not necessarily required.

[0049] At least one of the embodiments described above allows for efficient separation of target particles.

[0050] Although several embodiments have been described, these embodiments are presented as examples and are not intended to limit the scope of the invention. These embodiments can be implemented in various other forms, and various omissions, substitutions, modifications, and combinations of embodiments can be made without departing from the spirit of the invention. These embodiments and their modifications are included within the scope and spirit of the invention, as well as within the scope of the invention and its equivalents as defined in the claims.

[0051] With respect to the above embodiment, the following supplementary notes are disclosed as one aspect and optional features of the invention.

[0052] (Supplementary Note 1) A particle separation device comprising: a storage section that stores a suspension containing target particles and non-target particles smaller than the target particles; a filter that captures the target particles from the suspension and allows the non-target particles to pass through; and a microchannel that separates the target particles from the suspension, wherein the suspension stored in the storage section is delivered to the filter, and the suspension containing the target particles captured by the filter is delivered to the microchannel.

[0053] (Supplementary Note 2) The filter may have a capture surface that captures the target particles. The particle separation device may recover the suspension containing the target particles captured on the capture surface by sending a liquid to the capture surface from a direction opposite to the capture surface.

[0054] (Supplementary Note 3) The particle separation device may include a first tube connecting the storage section and the capture surface. The particle separation device may include a second tube connecting the capture surface and the microchannel. The particle separation device may deliver the suspension to the capture surface through the first tube. The particle separation device may deliver the suspension to the microchannel through the second tube.

[0055] (Supplementary Note 4) The particle separation device may deliver the suspension to the filter at a first flow rate for a predetermined time from the start of delivery of the suspension, and then deliver the suspension to the filter at a second flow rate that is smaller than the first flow rate.

[0056] (Supplementary Note 5) The particle separation device may rinse the filter with a liquid, and may deliver the suspension containing the target particles captured on the rinsed filter to the microchannel.

[0057] (Supplementary Note 6) The particle separator may rinse the filter at a first flow rate for a predetermined time from the start of delivery of the liquid, and then rinse the filter at a second flow rate that is smaller than the first flow rate.

[0058] (Supplementary Note 7) The particle separation device may include a collection container that stores the suspension containing the target particles captured by the filter. The particle separation device may deliver the suspension stored in the collection container to the microchannel.

[0059] (Supplementary Note 8) The particle separation device may include a vibration mechanism that vibrates the collection container. The vibration mechanism may vibrate the suspension stored in the collection container. The particle separation device may send the vibrated suspension to the microchannel.

[0060] (Supplementary Note 9) The waste liquid container may store the suspension containing the non-target particles that has passed through the filter. The waste liquid container may store the suspension containing the non-target particles that has been separated by the microchannel.

[0061] (Supplementary Note 10) The particle separation device may include an adjustment mechanism that adjusts the orientation of the filter. The adjustment mechanism may adjust the orientation to horizontal. The particle separation device may deliver the suspension vertically downward to the filter that has been adjusted to the horizontal position.

[0062] (Supplementary Note 11) The target particles may have a particle diameter of 7 μm or more and 30 μm or less, and the non-target particles may have a particle diameter of less than 7 μm.

[0063] (Supplementary Note 12) The target particle may be a white blood cell.

[0064] (Supplementary Note 13) The suspension stored in the reservoir may be a first suspension. The suspension delivered to the microchannel may be a second suspension. The ratio between the number of the non-target particles in the first suspension and the number of the non-target particles in the second suspension may be 1000:1.

[0065] (Supplementary Note 14) The microchannel may be a spiral microchannel.

[0066] (Supplementary Note 15) A particle separation method comprising: sending a suspension containing target particles and non-target particles smaller than the target particles to a filter; the filter capturing the target particles from the suspension and allowing the non-target particles to pass; sending the suspension containing the target particles captured by the filter to a microchannel; and the microchannel separating the target particles from the suspension.

[0067] (Supplementary Note 16) The filter may have a capture surface that captures the target particles. The particle separation method may include a step of recovering the suspension containing the target particles captured on the capture surface by sending a liquid to the capture surface from a direction opposite to the capture surface.

[0068] (Supplementary Note 17) The particle separation method may include a step of delivering the suspension to the filter at a first flow rate for a predetermined time from the start of delivery of the suspension, and then delivering the suspension to the filter at a second flow rate that is smaller than the first flow rate.

[0069] (Supplementary Note 18) The particle separation method may include a step of rinsing the filter with a liquid, and a step of sending the suspension containing the target particles captured on the rinsed filter to the microchannel.

[0070] (Supplementary Note 19) The particle separation method may include a step of rinsing the filter at a first flow rate for a predetermined time from the start of delivery of the liquid, followed by a step of rinsing the filter at a second flow rate lower than the first flow rate.

[0071] (Supplementary Note 20) The particle separation method may include a step of adjusting an installation orientation of the filter to be horizontal. The particle separation method may also include a step of feeding the suspension vertically downward to the filter adjusted to the horizontal orientation.

[0072] 1...particle separator, 4...filter, 4A...capturing surface, 4B...opposite surface, 5...swirl channel, 6...waste container, 7...tapered container, 8...pressure mechanism, 21...blood bag, 22...reagent bag, 31, 32...liquid supply container, 33...collection container, 91...adjustment mechanism, 92...vibration mechanism, Tu1-Tu19...tubes, V1-V13...valves, N1...inlet, U1, U2...outlets

Claims

1. A particle separation device comprising: a storage section for storing a suspension containing target particles and non-target particles smaller than the target particles; a filter for capturing the target particles from the suspension and allowing the non-target particles to pass through; and a microflow channel for separating the target particles from the suspension, wherein the suspension stored in the storage section is delivered to the filter, and the suspension containing the target particles captured by the filter is delivered to the microflow channel.

2. The particle separation device described in claim 1, wherein the filter has a capture surface that captures the target particles, and the suspension containing the target particles captured on the capture surface is recovered by sending liquid to the capture surface from a direction opposite to the capture surface.

3. The particle separation device of claim 2, further comprising: a first tube connecting the storage section and the capture surface; and a second tube connecting the capture surface and the microchannel, wherein the suspension is delivered to the capture surface through the first tube and the suspension is delivered to the microchannel through the second tube.

4. A particle separation device as described in any one of claims 1 to 3, wherein the suspension is delivered to the filter at a first flow rate for a predetermined time from the start of delivery of the suspension, and then the suspension is delivered to the filter at a second flow rate smaller than the first flow rate.

5. The particle separation device according to any one of claims 1 to 4, further comprising rinsing the filter with a liquid and sending the suspension containing the target particles captured on the rinsed filter to the microchannel.

6. The particle separator according to claim 5, wherein after rinsing the filter at a first flow rate for a predetermined time from the start of delivery of the liquid, the filter is rinsed at a second flow rate lower than the first flow rate.

7. A particle separation device as described in any one of claims 1 to 6, further comprising a collection container for storing the suspension containing the target particles captured by the filter, and the suspension stored in the collection container is delivered to the microchannel.

8. The particle separation device according to claim 7, further comprising a vibration mechanism for vibrating the collection container, wherein the vibration mechanism vibrates the suspension stored in the collection container and sends the vibrated suspension to the microchannel.

9. A particle separation device as described in any one of claims 1 to 8, further comprising: a waste liquid container for storing the suspension containing the non-target particles that have passed through the filter and for storing the suspension containing the non-target particles separated by the microchannel.

10. A particle separation device as described in any one of claims 1 to 9, further comprising an adjustment mechanism for adjusting the attitude at which the filter is installed, the adjustment mechanism adjusting the attitude to be horizontal and delivering the suspension vertically downward to the filter adjusted to be horizontal.

11. A particle separation device according to any one of claims 1 to 10, wherein the target particles have a particle diameter of 7 μm or more and 30 μm or less, and the non-target particles have a particle diameter of less than 7 μm.

12. A particle separation device according to any one of claims 1 to 11, wherein the target particles are white blood cells.

13. A particle separation device as described in any one of claims 1 to 12, wherein the suspension stored in the storage section is a first suspension, the suspension sent to the microchannel is a second suspension, and a ratio between the number of the non-target particles in the first suspension and the number of the non-target particles in the second suspension is 1000:

1.

14. The particle separation device according to any one of claims 1 to 13, wherein the microchannel is a spiral microchannel.

15. A particle separation method comprising the steps of: sending a suspension containing target particles and non-target particles smaller than the target particles to a filter; the filter capturing the target particles from the suspension and allowing the non-target particles to pass through; sending the suspension containing the target particles captured by the filter to a microchannel; and the microchannel separating the target particles from the suspension.

16. The particle separation method described in claim 15, further comprising: a step of recovering the suspension containing the target particles captured on the capture surface by sending liquid to the capture surface from a direction opposite to the capture surface, wherein the filter has a capture surface that captures the target particles.

17. The particle separation method according to claim 15 or 16, further comprising the step of: after a step of delivering the suspension to the filter at a first flow rate for a predetermined time from the start of delivery of the suspension, delivering the suspension to the filter at a second flow rate smaller than the first flow rate.

18. A particle separation method described in any one of claims 15 to 17, further comprising the steps of: rinsing the filter with a liquid; and sending the suspension containing the target particles captured on the rinsed filter to the microchannel.

19. The method of claim 18, further comprising the step of rinsing the filter at a second flow rate less than the first flow rate after the step of rinsing the filter at a first flow rate for a predetermined time from the start of the liquid delivery.

20. A particle separation method according to any one of claims 15 to 19, further comprising the steps of: adjusting the orientation of the filter to be installed horizontally; and sending the suspension vertically downward toward the filter adjusted to the horizontal position.

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