Particle separation system

Abstract

To provide a particle separation system excellent in a suspension characteristic of particles in a suspension.SOLUTION: A particle separation system 1 has a plurality of micro fluid devices 10 to separate a suspension into concentrated liquid and clarified liquid. Each of the plurality of micro fluid devices 10 is connected with a concentrated liquid derivation port 17 and an introduction port 16 and arranged in series. The plurality of micro fluid devices 10 includes a first micro fluid device 11 and a second micro fluid device 12. The concentrated liquid is diluted and supplied to the introduction port 16 of the second micro fluid device 12.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] This disclosure relates to a particle separation system. [Background technology]

[0002] There are processes for selectively recovering a target component dissolved in a liquid after removing particles from a suspension containing particles. For example, such a process involves dispersing particulate catalysts in a liquid phase, carrying out a chemical reaction, and recovering the target substance generated in the liquid phase.

[0003] Conventionally, membrane separation and centrifugation have been known as methods for removing particles from suspensions. However, when particles are separated from a suspension by membrane separation, the particles may clog the pores of the membrane, potentially causing clogging. Furthermore, with centrifugation, if the volume proportion of particles in the suspension is high, separation may be difficult unless the solid portion after centrifugation hardens. On the other hand, microfluidic devices separate particles in a suspension by vortex flow generated by the flow through the channel, thus minimizing these problems.

[0004] Patent Document 1 discloses a hydrodynamic separation device as a microfluidic device. The hydrodynamic separation device comprises an inlet for a fluid containing particles, a curved channel for receiving the fluid, and an outlet configured such that a concentrated stream exits the channel through a first path and the remaining fluid exits the channel through a second path. [Prior art documents] [Patent Documents]

[0005] [Patent Document 1] Special Publication No. 2016-526479 [Overview of the project] [Problems that the invention aims to solve]

[0006] Microfluidic devices separate particles from liquid in a suspension by creating vortices as the fluid flows through the channel. However, this process removes some of the liquid along with the particles. Therefore, it is conceivable to improve particle separation accuracy by arranging multiple microfluidic devices in series. The concentrated liquid with a high particle concentration, separated by the first microfluidic device, is then separated again by the second microfluidic device. However, simply arranging microfluidic devices in series may not yield sufficient separation accuracy.

[0007] Therefore, the present disclosure aims to provide a particle separation system that exhibits excellent particle separation characteristics in a suspension. [Means for solving the problem]

[0008] The particle separation system according to this disclosure includes a liquid channel having an inlet into which a suspension containing particles is introduced, a concentrated liquid outlet from which a concentrated liquid containing the particles in the suspension is discharged, and a clarified liquid outlet from which a clarified liquid obtained by removing the concentrated liquid from the suspension is discharged, and comprises a plurality of microfluidic devices that separate the suspension into a concentrated liquid and a clarified liquid by vortex flow generated as the suspension flows through the liquid channel having a rectangular cross-section. Each of the plurality of microfluidic devices is arranged in series with its concentrated liquid outlet and inlet connected. The plurality of microfluidic devices include a first microfluidic device located furthest upstream and a second microfluidic device located downstream of the first microfluidic device. Diluted concentrated liquid is supplied to the inlet of the second microfluidic device.

[0009] The particle separation system may include reflux channels and dilution channels. Multiple microfluidic devices may include a third microfluidic device located downstream of the concentrate outlet of a second microfluidic device. The clarification outlet of the third microfluidic device may be connected to the inlet of the second microfluidic device via a reflux channel. The inlet of the third microfluidic device may be connected via a dilution channel that supplies a diluent to the concentrate.

[0010] The concentrated liquid outlet of the third microfluidic device may be arranged most downstream among the concentrated liquid outlets of the plurality of microfluidic devices.

[0011] The concentrated liquid derived from the concentrated liquid outlet of the second microfluidic device may be introduced into the inlet of the third microfluidic device.

[0012] The microfluidic device arranged immediately after the first microfluidic device among the plurality of microfluidic devices may discharge the clarified liquid from the clarified liquid outlet to the outside of the plurality of microfluidic devices.

[0013] The particles may contain cells. The particle separation system may further include a culture device for culturing cells. The culture device may be connected to the inlet of the first microfluidic device.

[0014] The liquid flow path may have a linear flow path. Each of the microfluidic devices may include a secondary flow generation mechanism that generates a secondary flow in the cross-sectional direction in the suspension flowing upstream of the linear flow path. The linear flow path may have a rectangular cross-section defined by a flow path width and a flow path height perpendicular to the flow path width. In the cross-section at least downstream of the secondary flow generation mechanism in the linear flow path, the aspect ratio represented by the ratio of the flow path width to the flow path height may be in the range from 10 to 100. The secondary flow generation mechanism may protrude in the flow path height direction from the side wall having the flow path width, be parallel to the side wall, and extend inclined with respect to the direction perpendicular to the cross-section.

Advantages of the Invention

[0015] According to the present disclosure, a particle separation system excellent in the separation characteristics of particles in a suspension can be provided.

Brief Description of the Drawings

[0016] [Figure 1] It is a schematic diagram showing a particle separation system according to an embodiment. [Figure 2]This is a schematic diagram showing a microfluidic device according to one embodiment. [Figure 3] This is a cross-sectional view of a portion of the flow path, corresponding to the III-III section in Figure 2. [Figure 4] This is a schematic diagram illustrating the shape and arrangement of the baffles. [Figure 5] This is a fluid image showing the behavior of particles in a fluid after passing through multiple baffles. [Figure 6] This is a schematic diagram showing a particle separation system according to one embodiment. [Figure 7] This is a schematic diagram showing a particle separation system according to one embodiment. [Figure 8] This is a schematic diagram showing a particle separation system according to one embodiment. [Figure 9] This is a schematic diagram showing a particle separation system according to one embodiment. [Figure 10] This is a schematic diagram showing the particle separation system according to Example 1. [Figure 11] This is a schematic diagram showing the particle separation system according to Example 2. [Figure 12] This is a schematic diagram showing the particle separation system according to Comparative Example 1. [Modes for carrying out the invention]

[0017] Several exemplary embodiments will be described below with reference to the drawings. Note that the dimensional ratios in the drawings are exaggerated for illustrative purposes and may differ from the actual ratios.

[0018] <First Embodiment> First, the particle separation system 1 according to the first embodiment will be described with reference to Figure 1. As shown in Figure 1, the particle separation system 1 comprises a plurality of microfluidic devices 10, a connecting channel 19, and a dilution channel 20.

[0019] The multiple microfluidic devices 10 include a first microfluidic device 11 and a second microfluidic device 12. Each of the multiple microfluidic devices 10 is arranged in series. The first microfluidic device 11 and the second microfluidic device 12 are arranged sequentially from upstream to downstream. That is, the first microfluidic device 11 is located at the upstream end of the multiple microfluidic devices 10. The second microfluidic device 12 is located downstream of the first microfluidic device 11. Since the first microfluidic device 11 and the second microfluidic device 12 have the same configuration in this embodiment, they will be described below as microfluidic device 10.

[0020] The microfluidic device 10 includes a liquid channel 15. The liquid channel 15 has an inlet 16, a concentrated liquid outlet 17, and a clarified liquid outlet 18. An inlet 16 is provided at one end of the liquid channel 15, and a concentrated liquid outlet 17 and a clarified liquid outlet 18 are provided at the end of the channel opposite to the inlet 16. Each of the multiple microfluidic devices 10 is arranged in series with the concentrated liquid outlet 17 and the inlet 16 connected. Each of the multiple microfluidic devices 10 is connected to the concentrated liquid outlet 17 and the inlet 16 by a connecting channel 19.

[0021] A suspension containing particles is introduced into the inlet 16. A concentrated liquid, in which the particles in the suspension are concentrated, is discharged from the concentrated liquid outlet 17. A clarified liquid, in which the concentrated liquid has been removed from the suspension, is discharged from the clarified liquid outlet 18. The number concentration of particles in the concentrated liquid is greater than the number concentration of particles in the clarified liquid. As will be described later, the liquid channel 15 has a rectangular cross-section. The microfluidic device 10 separates the suspension into a concentrated liquid and a clarified liquid by the vortex flow generated as the suspension flows through the liquid channel 15.

[0022] The suspension comprises a liquid medium and particles dispersed in the liquid medium. The particles are the substances to be separated in the microfluidic device 10. The particles may be solid particles such as catalysts, cells, metal particles, resin particles, inorganic particles, and ceramic particles. The liquid medium may contain the target substance to be recovered. If the particles are catalysts, the target substance may be the product obtained in the liquid medium by chemically reacting with the catalyst dispersed in the liquid phase. If the particles are cells, the target substance may be useful substances such as proteins produced by the cells.

[0023] A suspension is introduced into the inlet 16 of the first microfluidic device 11. The concentrated liquid outlet 17 of the first microfluidic device 11 is connected to the inlet 16 of the second microfluidic device 12. The clarified liquid outlet 18 of the first microfluidic device 11 is connected to the outside of the multiple microfluidic devices 10. The outside of the multiple microfluidic devices 10 may be, for example, a recovery container. The first microfluidic device 11 discharges the clarified liquid from the clarified liquid outlet 18 to the outside of the multiple microfluidic devices 10.

[0024] The dilution channel 20 is connected to the connecting channel 19. The dilution channel 20 is configured to supply a diluent for diluting the concentrated liquid. That is, the concentrated liquid is supplied diluted to the inlet 16 of the second microfluidic device 12. The diluent may be a liquid component contained in the suspension, or it may be water.

[0025] The concentrated liquid outlet 17 of the second microfluidic device 12 is connected to the outside of the multiple microfluidic devices 10. The clarified liquid outlet 18 of the second microfluidic device 12 is connected to the outside of the multiple microfluidic devices 10. The outside of the multiple microfluidic devices 10 may be, for example, a collection container. The second microfluidic device 12, which is positioned immediately after the first microfluidic device 11 among the multiple microfluidic devices 10, discharges the clarified liquid to the outside of the multiple microfluidic devices 10 from its clarified liquid outlet 18.

[0026] Figure 2 is a schematic diagram showing the configuration of the microfluidic device 10 according to this embodiment. In the microfluidic device 10, the liquid flow path 15 has a linear flow path 31. Each of the microfluidic devices 10 is equipped with a secondary flow generation mechanism that generates a secondary flow in the transverse direction in the suspension flowing upstream of the linear flow path 31.

[0027] The channel 31 may be formed by overlapping two flat plates, a first plate 33 and a second plate 34, in the Z direction. In this case, a groove corresponding to the channel 31 is formed on the upper surface of the lower second plate 34. In contrast, the upper first plate 33 is a so-called lid and is joined to the second plate 34 so as to cover the channel 31 on its lower surface. In Figure 2, the first plate 33 is drawn with a dashed line to clearly show the overall shape of the channel 31. The groove of the second plate 34 forms the first side wall 34a, the second side wall 34b, and the third side wall 34c of the channel 31. A part of the lower surface of the first plate 33 forms the fourth side wall 33a of the channel 31. The fourth side wall 33a and the third side wall 34c face each other and are side walls corresponding to the long sides of their respective cross-sections. Furthermore, the first side wall 34a and the second side wall 34b face each other and are side walls corresponding to the shorter sides of the cross-section.

[0028] If the extension direction of the linear channel 31 is along the X direction, then the cross-section of the channel 31 defined by these side walls is a YZ cross-section. In this case, the longer side of the cross-section of the channel 31 is along the Y direction and will be defined below as the channel width w. On the other hand, the shorter side of the cross-section of the channel 31 is along the Z direction and will be defined below as the channel height h. In other words, the channel height h is perpendicular to the channel width w on the cross-section. Hereafter, the Y direction may be referred to as the channel width direction and the Z direction as the channel height direction.

[0029] The linear flow channel 31 has a rectangular cross-section defined by the flow channel width w and the flow channel height h perpendicular to the flow channel width w. In the cross-section of the linear flow channel 31, at least downstream of the secondary flow generation mechanism, the aspect ratio A, which is expressed as the ratio of the flow channel width w to the flow channel height h, RIt falls within the range of 10 to 100.

[0030] First, the cross-section of the channel 31 has an aspect ratio of A R Since the parameters are set to be within the above range, the main flow of the suspension, which is the fluid flowing through the channel 31, induces lift, and the particles dispersed in the fluid receive the lift induced by the main flow. As a result, the particles can be trapped near the first side wall 34a and the second side wall 34b, which are the side walls on the short side of the channel 31.

[0031] Furthermore, the secondary flow generation mechanism generates a secondary flow in the transverse direction in the fluid flowing upstream of the channel 31, so that the particles dispersed in the fluid are subjected to a drag force induced by the secondary flow. As a result, in the channel 31 downstream of the part where the secondary flow generation mechanism is installed or formed, particles can be transported toward the first side wall 34a and the second side wall 34b, which are the side walls on the shorter side. Therefore, the microfluidic device 10 can improve separation efficiency compared to, for example, simply separating particles using only the lift force induced by the main fluid flow.

[0032] In the microfluidic device 10, the particle size D p If the particle size is in the range of 1 μm to 1 mm, the channel height h is the particle size D of the particles to be separated. p The dimensions may be set to be more than 10 times and less than 100 times the original dimensions. This microfluidic device 10 makes it possible to further improve the separation effect between the lift induced by the main fluid flow and the drag induced by the secondary fluid flow.

[0033] Furthermore, in the microfluidic device 10, the length L in the extension direction downstream of the secondary flow generation mechanism in the flow path 31 may be set to a dimension of 100 times or more and 10,000 times or less the flow path width w. This microfluidic device 10 makes it possible to further improve the separation effect between the lift force induced by the main fluid flow and the drag force induced by the secondary fluid flow.

[0034] The secondary flow generation mechanism may protrude in the direction of the flow path height Z from the side walls (third side wall 34c, fourth side wall 33a) having a flow path width w, and may extend parallel to the side walls and inclined with respect to the direction X perpendicular to the cross-section. In the microfluidic device 10 according to this embodiment, the flow path shape changing parts constituting the secondary flow generation mechanism are a plurality of baffles 35. For example, the baffle 35 in this embodiment is a protruding part of the second flat plate 34 that protrudes from the third side wall 34c toward the fourth side wall 33a. The upper surface of the baffle 35 does not come into contact with the first flat plate 33. The plurality of baffles 35 are all the same shape and are arranged in the flow path 31 with a certain regularity as will be described in detail below. Figure 2 illustrates five baffles 35 represented by the first plate 35a, the second plate 35b, the third plate 35c, the fourth plate 35d, and the fifth plate 35e. In Figure 2, the baffle plate 35 that intersects with the inlet or outlet of the secondary flow generation mechanism is depicted as having a shape where a portion extending outward from the intersection point or its vicinity is absent, as an illustrative example.

[0035] Figure 3 corresponds to the III-III section in Figure 2 and is a cross-sectional view obtained by cutting a portion of the flow path 31 with a plane perpendicular to the X direction. In Figure 3, the flow of the fluid circulating in the flow path 31 at this cross-section is illustrated with vectors. Figure 4 is a schematic plan view of the baffles 35 viewed along the Z direction, illustrating the shape of the baffles 35 and the arrangement of the baffles 35.

[0036] The baffle plate 35 is rod-shaped, parallel to the third side wall 34c along the XY plane, and extending in a direction inclined at an angle θ with respect to the X direction. However, both ends of each baffle plate 35 may be cut out along the XZ plane. The length of the baffle plate 35 in the extension direction is defined as the baffle plate length L. P Therefore, the length component L of the baffle plate 35 in the Y direction, which is the flow path width direction. Y L P It is expressed as sinθ and is shorter than the flow path width w. Also, the baffle plate 35 does not come into contact with either the first side wall 34a or the second side wall 34b. In the flow path 31, n baffle plates 35 having this shape are arranged at a pitch P i They are arranged at equal intervals along the X direction.

[0037] The shape of a cross-section perpendicular to the extending direction of the baffle plate 35 is approximately rectangular. Hereinafter, regarding the cross-section of the baffle plate 35, the height will be denoted as the baffle plate height h P and the width will be denoted as the baffle plate width w p respectively.

[0038] The baffle plate height h P is set as follows, for example, based on the channel height h of the flow channel 31. First, the flow velocity of the fluid flowing through the flow channel 31 is defined as follows. V0 is the mainstream flow velocity of the fluid introduced into the flow channel 31 along the X direction, which is the extending direction of the flow channel 31. V1 is the first flow velocity in the direction along the extending direction of the baffle plate 35. V2 is the second flow velocity in the Y direction, which is the flow channel width direction, and is expressed by Equation (1) using the mainstream velocity V0.

[0039]

Number

[0040] Also, the time t for the mainstream of the fluid to pass through the section where a plurality of baffle plates 35 are provided is expressed by Equation (2).

[0041]

Number

[0042] Furthermore, in order to capture the particles dispersed in the fluid near the first side wall 34a or the second side wall 34b, it is necessary for the flow in the flow channel width direction to circulate at least once through the cross-section of the flow channel 31 while the mainstream of the fluid passes through the section where a plurality of baffle plates 35 are provided. Therefore, Equation (3) holds.

[0043]

Number

[0044] Here, first, the baffle plate height h PHowever, when the baffle plates 35 are half the height of the flow path height h, i.e., 0.5h, they can generate secondary flow most efficiently.

[0045] Secondly, the height of the baffle board h P When the baffle height h is lower than 0.5h, the flow rate of the secondary flow decreases. Therefore, the baffle height h P Assuming that the flow rate of the secondary flow decreases proportionally as the temperature decreases, the above condition that the flow in the width direction of the flow path completes at least one circuit around the cross-section of the flow path 31 is at least (0.5 h / h P The condition may be changed to ) circumferential. In this case, equation (3) is modified to equation (4).

[0046]

number

[0047] Substituting equations (1) and (2) into equation (4) and rearranging, we obtain equation (5).

[0048]

number

[0049] Therefore, baffle height h P When is lower than 0.5h, for a flow path 31 having any flow path width w and flow path height h, the pitch P of the arrangement of baffles 35 is set such that the condition of equation (5) is satisfied. i , the number of baffle boards 35 installed n and the height of the baffle boards h P It should be set as follows.

[0050] Thirdly, the height of the baffle board h P When the baffle height h is higher than 0.5h, the flow rate of the secondary flow also decreases. Therefore, the baffle height h P Assuming that the flow rate of the secondary flow decreases proportionally as the value increases, the above condition that the flow in the width direction of the flow path makes at least one circuit around the cross-section of the flow path 31 is at least (0.5h / (hh PThe condition may be changed to ))circle. In this case, equation (3) is modified to equation (6).

[0051]

number

[0052] Substituting equations (1) and (2) into equation (6) and rearranging, we obtain equation (7).

[0053]

number

[0054] Therefore, baffle height h P When is greater than 0.5h, the pitch P of the arrangement of baffles 35 is set such that the conditions of equation (7) are satisfied for a channel 31 having any channel width w and channel height h. i , the number of baffle boards 35 installed n and the height of the baffle boards h P It should be set as follows.

[0055] In other words, when multiple baffles 35 are used as a secondary flow generation mechanism, the baffle height h P The upper limit is determined based on equation (7), where h is the baffle height. P The lower limit can be determined based on equation (5).

[0056] Also, the width of the baffle board lol p For example, in order to reduce pressure loss within the flow path 31, it is desirable to keep the occlusion rate of the cross-section of the flow path 31 to 0.5 or less, and this is set as follows. The cross-section of the flow path 31 when no baffles 35 are present is represented by (flow path width w × flow path height h). Therefore, if the number of baffles 35 in a certain cross-section is m, then in order to satisfy the condition that the occlusion rate is 0.5 or less, the baffle width w p The upper limit of should be set to satisfy equation (8). On the other hand, the baffle width w p The lower limit should ideally be set as small as possible.

[0057]

number

[0058] Furthermore, the inclination angle θ of the baffle plate 35 may be determined by defining an upper and lower limit based on equations (5) and (7), and set to a value that falls within that range. However, if the inclination angle θ is too large, flow separation may occur, and the secondary flow may be unintended. Therefore, it is desirable that the inclination angle θ be 45° or less, and even more desirable that it be 30° or less.

[0059] In the microfluidic device 10, by employing multiple baffles 35 as flow path shape changing sections, it is clear from the direction of the vectors at each position within the flow path 31 shown in Figure 3 that secondary flow occurs in the transverse direction of the fluid flowing through the flow path 31. Furthermore, employing multiple baffles 35 as flow path shape changing sections has the advantage that the secondary flow is less likely to be attenuated.

[0060] Figure 5 is a fluid image showing the behavior of particles p in a fluid that has passed through a secondary flow generation mechanism. This fluid image was obtained by photographing the fluid flowing through a portion of the channel 31 along the Z direction. Here, the secondary flow generation mechanism, which consists of multiple baffles 35, is located upstream of the channel 31 along the X direction. In Figure 5, to illustrate the position of the secondary flow generation mechanism relative to the position in the channel 31 where the fluid image was acquired, the part corresponding to the secondary flow generation mechanism is shown with a dashed line adjacent to the fluid image.

[0061] As shown in Figure 5, in the microfluidic device 10, as the fluid in which the particles p are dispersed flows through the channel 31, the particles p are captured at least near the first side wall 34a or the second side wall 34b. As an example, when the fluid image shown in Figure 5 is obtained, the inlet region R of the channel 31 IN The particle concentration was 0.55 vol%. In contrast, at the outlet side of channel 31, a high-concentration region R where particles p had accumulated was observed. HThe particle concentration was 1.33 vol%. On the other hand, at the outlet side of the flow path 31, there was a low-concentration region R with fewer particles. L The particle concentration was 0.11 vol%.

[0062] Furthermore, by employing multiple baffles 35 as a secondary flow generation mechanism, the microfluidic device 10 may be able to capture particles p not only in the vicinity of the first side wall 34a or the second side wall 34b, but also in the central region in the width direction of the flow channel 31, as shown in Figure 5.

[0063] In the example of the microfluidic device 10 described above, the baffles 35 are provided on the third side wall 34c of the second flat plate 34, which is on the flow path floor side, and protrude from the third side wall 34c toward the fourth side wall 33a. Alternatively, the baffles 35 may be provided on the first flat plate 33, which is on the ceiling side, and protrude from the fourth side wall 33a toward the third side wall 34c. Or, the baffles 35 may be provided on both the third side wall 34c of the second flat plate 34, which is on the flow path floor side, and the fourth side wall 33a of the first flat plate 33, which is on the ceiling side.

[0064] Furthermore, in the example of the microfluidic device 10 described above, the entire secondary flow generation mechanism has multiple baffles 35 with a pitch P of a single value. i They are arranged in this manner. In contrast, the multiple baffles 35 have multiple pitch values ​​P in the entire secondary flow generation mechanism. i They are arranged in such a way that, in the middle, the pitch P i The values ​​of may be changed and then added to the array. However, the pitch P i If the value of is too small, the viscous resistance will increase, so pitch P i It is desirable to set the value of to be greater than the flow path height h.

[0065] Furthermore, in the example of the microfluidic device 10 described above, multiple baffles 35 are provided in the center of the flow path width w of the flow path 31. That is, in the flow path width direction, the distance from the baffle 35 to the first side wall 34a is the same as the distance from the baffle 35 to the second side wall 34b. In contrast, the multiple baffles 35 may be provided so as to be closer to the first side wall 34a than to the second side wall 34b in the flow path width direction, or conversely, closer to the second side wall 34b than to the first side wall 34a.

[0066] The secondary flow generation mechanism may be a flow path shape changing section that changes the shape of at least a portion of the cross-section as the flow path 31 extends in the direction of extension. The flow path shape changing section may be a Venturi structure that generates a Venturi effect by providing multiple support columns instead of multiple baffles 35, or by providing a region in a part of the flow path 31 in which the cross-section is reduced. Even with such a structure, secondary flow can be generated in the fluid. Alternatively, the secondary flow generation mechanism may be an ultrasonic transducer that emits ultrasonic waves from the side wall on the long side of the flow path 31 toward the interior of the flow path 31. Using the spatial gradient of sound pressure due to the viscous attenuation of the traveling ultrasonic wave as a driving force, a vortex acoustic flow is generated in the fluid within the flow path 31 as a secondary flow in the direction of the cross-section. Furthermore, in the microfluidic device 10 shown in Figure 2, the case in which the flow path 31 is composed of a combination of two flat plates is illustrated. In contrast, the flow path 31 may be formed by, for example, using three-dimensional metal additive manufacturing technology. Furthermore, although a configuration in which the liquid channel 15 has a straight channel 31 has been described, the liquid channel 15 may also have a substantially circular, substantially arc-shaped, or vortex-shaped channel. The suspension can be separated into a concentrated liquid and a clarified liquid by the vortex flow generated when the suspension flows through a curved channel having a rectangular cross-section.

[0067] In this embodiment, an example is described in which the particle separation system 1 comprises two microfluidic devices 10. However, the particle separation system 1 may have three or more microfluidic devices 10 arranged in series. In this case, diluted concentrate may be supplied to all inlets 16 except for the first microfluidic device 11. Alternatively, diluted concentrate may be supplied to one of the inlets 16 of these microfluidic devices 10, and undiluted concentrate may be supplied to the inlets 16 of the remaining microfluidic devices 10.

[0068] The particle separation system 1 comprises a plurality of microfluidic devices 10 that separate a suspension into a concentrated liquid and a clarified liquid by vortex flow generated when the suspension flows through a liquid channel 15 having a rectangular cross-section. The microfluidic device 10 includes a liquid channel 15 having an inlet 16 into which a suspension containing particles is introduced, a concentrated liquid outlet 17 from which the concentrated liquid containing the particles in the suspension is discharged, and a clarified liquid outlet 18 from which the clarified liquid, from which the concentrated liquid has been removed from the suspension, is discharged. Each of the plurality of microfluidic devices 10 is arranged in series with its concentrated liquid outlet 17 and inlet 16 connected. The plurality of microfluidic devices 10 include a first microfluidic device 11 located furthest upstream and a second microfluidic device 12 located downstream of the first microfluidic device 11. The concentrated liquid is supplied diluted to the inlet 16 of the second microfluidic device 12.

[0069] In the particle separation system 1 according to this embodiment, a plurality of microfluidic devices 10 are arranged in series. However, if the concentrated liquid discharged from the first microfluidic device 11 is directly introduced into the second microfluidic device 12, there is a risk that the second microfluidic device 12 may not be able to sufficiently separate the particles from the suspension. On the other hand, in the particle separation system 1 according to this embodiment, the concentrated liquid is supplied to the second microfluidic device 12 in a diluted state. Therefore, the particle separation system 1 according to this embodiment has excellent particle separation characteristics in a suspension.

[0070] Furthermore, the liquid channel 15 may have a linear channel 31. Also, each of the microfluidic devices 10 may include a secondary flow generation mechanism that generates a secondary flow in the transverse direction in the suspension flowing upstream of the linear channel 31. The linear channel 31 may have a rectangular cross-section defined by a channel width w and a channel height h perpendicular to the channel width w. In the cross-section of the linear channel 31 at least downstream of the secondary flow generation mechanism, the aspect ratio A, expressed as the ratio of the channel width w to the channel height h, R This can be in the range of 10 to 100. Such a microfluidic device 10 can improve separation efficiency compared to, for example, simply separating particles using only the lift induced by the main fluid flow.

[0071] Furthermore, the secondary flow generation mechanism may protrude in the direction of the flow path height Z from the side walls (third side wall 34c, fourth side wall 33a) having a flow path width w, and extend parallel to the side walls and inclined with respect to the direction X perpendicular to the cross-section. For example, such a structure can generate a secondary flow in the fluid.

[0072] <Second Embodiment> Next, the particle separation system 1 according to the second embodiment will be described with reference to Figure 6. As shown in Figure 6, the particle separation system 1 according to the second embodiment further comprises a first reflux channel 21 and a dilution channel 20. In addition, the plurality of microfluidic devices 10 include a third microfluidic device 13. Unless otherwise specified, the other aspects are the same as the particle separation system 1 according to the first embodiment, and therefore will not be described further.

[0073] The multiple microfluidic devices 10 include a first microfluidic device 11, a second microfluidic device 12, and a third microfluidic device 13. Each of the multiple microfluidic devices 10 is arranged in series. The first microfluidic device 11, the second microfluidic device 12, and the third microfluidic device 13 are arranged sequentially from upstream to downstream. That is, the first microfluidic device 11 is located furthest upstream of the multiple microfluidic devices 10. The second microfluidic device 12 is located downstream of the first microfluidic device 11. The third microfluidic device 13 is located downstream of the concentrated liquid outlet 17 of the second microfluidic device 12. The concentrated liquid outlet 17 of the third microfluidic device 13 is located furthest downstream of the concentrated liquid outlets of the multiple microfluidic devices 10. The third microfluidic device 13 may have the same configuration as the first microfluidic device 11 and the second microfluidic device 12.

[0074] A suspension is introduced into the inlet 16 of the first microfluidic device 11. The concentrated liquid outlet 17 of the first microfluidic device 11 is connected to the inlet 16 of the second microfluidic device 12. The clarified liquid outlet 18 of the first microfluidic device 11 is connected to the outside of the multiple microfluidic devices 10. The first microfluidic device 11 discharges the clarified liquid from the clarified liquid outlet 18 to the outside of the multiple microfluidic devices 10.

[0075] The inlet 16 of the second microfluidic device 12 is connected via the first reflux channel 21. Therefore, the concentrated liquid is supplied to the inlet 16 of the second microfluidic device 12 in a diluted state. The concentrated liquid outlet 17 of the second microfluidic device 12 is connected to the inlet 16 of the third microfluidic device 13. The concentrated liquid discharged from the concentrated liquid outlet 17 of the second microfluidic device 12 is introduced into the inlet 16 of the third microfluidic device 13. The clarified liquid outlet 18 of the second microfluidic device 12 is connected to the outside of the multiple microfluidic devices 10. The outside of the multiple microfluidic devices 10 may be, for example, a recovery container.

[0076] The inlet 16 of the third microfluidic device 13 is connected via a dilution channel 20 that supplies a diluent to the concentrated liquid. The clarified liquid outlet 18 of the third microfluidic device 13 is connected to the inlet 16 of the second microfluidic device 12 via a first reflux channel 21 (reflux channel).

[0077] Diluent is added to the concentrated liquid discharged from the concentrated liquid outlet 17 of the second microfluidic device 12 via the dilution channel 20, and the diluted suspension is introduced into the third microfluidic device 13. The clarified liquid discharged from the concentrated liquid outlet 17 of the first microfluidic device 11 is added to the clarified liquid discharged from the clarified liquid outlet of the third microfluidic device 13. Therefore, the diluted suspension is introduced into the second microfluidic device 12. The second microfluidic device 12, which is positioned immediately after the first microfluidic device 11 among the multiple microfluidic devices 10, discharges the clarified liquid to the outside of the multiple microfluidic devices 10 from the clarified liquid outlet 18.

[0078] As described above, the particle separation system 1 according to this embodiment includes a first reflux channel 21 (reflux channel) and a dilution channel 20. The plurality of microfluidic devices 10 include a third microfluidic device 13 located downstream of the concentrate outlet 17 of the second microfluidic device 12. The clarification outlet 18 of the third microfluidic device 13 is connected to the inlet 16 of the second microfluidic device 12 via the first reflux channel 21. The inlet 16 of the third microfluidic device 13 is connected via a dilution channel 20 that supplies a diluent to the concentrate.

[0079] The concentrated liquids separated by the first microfluidic device 11 and the second microfluidic device 12 are diluted before being introduced into the third microfluidic device 13. As a result, the diluted concentrated liquid is separated in the third microfluidic device 13, which reduces the amount of particles contained in the clarified liquid compared to when the concentrated liquid is separated as is. Therefore, the particle separation system 1 according to this embodiment has excellent particle separation characteristics in suspensions.

[0080] Furthermore, the clarified liquid from the third microfluidic device 13 is introduced into the second microfluidic device 12. As a result, the concentrated liquid introduced from the first microfluidic device 11 to the second microfluidic device 12 is diluted. This causes the diluted suspension to be separated in the second microfluidic device 12, thus reducing the amount of particles in the clarified liquid compared to when the concentrated liquid is separated. In addition, since the concentrated liquid introduced into the second microfluidic device 12 is diluted with the clarified liquid from the third microfluidic device 13, the amount of diluent used can be reduced.

[0081] The concentrated liquid outlet 17 of the third microfluidic device 13 may be located as the downstreammost of the concentrated liquid outlets of the multiple microfluidic devices 10.

[0082] This introduces the diluted suspension into the microfluidic device 10 located furthest downstream. Therefore, the amount of particles in the clarified liquid can be reduced compared to when the concentrated liquid is separated directly. In addition, since the clarified liquid from the microfluidic device 10 located furthest downstream is refluxed, the amount of diluent used can be reduced.

[0083] The concentrated liquid discharged from the concentrated liquid outlet 17 of the second microfluidic device 12 may be introduced into the inlet 16 of the third microfluidic device 13.

[0084] This allows the clarified liquid separated in the third microfluidic device 13 to dilute the concentrated liquid introduced directly into the second microfluidic device 12. Therefore, the configuration of the first reflux channel 21 can be simplified.

[0085] <Third Embodiment> Next, the particle separation system 1 according to the third embodiment will be described with reference to Figure 7. As shown in Figure 7, the particle separation system 1 according to the third embodiment further comprises a fourth microfluidic device 14 compared to the particle separation system 1 according to the second embodiment. Unless otherwise specified, the other aspects are the same as the particle separation system 1 according to the above embodiment, and therefore will not be described further.

[0086] The multiple microfluidic devices 10 include a first microfluidic device 11, a second microfluidic device 12, a third microfluidic device 13, and a fourth microfluidic device 14. Each of the multiple microfluidic devices 10 is arranged in series. The fourth microfluidic device 14 is located downstream of the concentrated liquid outlet 17 of the first microfluidic device 11 and upstream of the inlet 16 of the second microfluidic device 12. That is, they are arranged in the order of first microfluidic device 11, fourth microfluidic device 14, second microfluidic device 12, and third microfluidic device 13 from upstream to downstream.

[0087] The inlet 16 of the fourth microfluidic device 14 is connected to the concentrated liquid outlet 17 of the first microfluidic device 11. Furthermore, the inlet 16 of the fourth microfluidic device 14 is connected to the clarified liquid outlet 18 of a microfluidic device 10 located downstream of the fourth microfluidic device 14 via a second reflux channel 22 (reflux channel). Specifically, the inlet 16 of the fourth microfluidic device 14 is connected to the clarified liquid outlet 18 of the second microfluidic device 12 via a second reflux channel 22. The concentrated liquid outlet 17 of the fourth microfluidic device 14 is connected to the inlet 16 of the second microfluidic device 12. The fourth microfluidic device 14, located immediately after the first microfluidic device 11 among the multiple microfluidic devices 10, discharges clarified liquid from its clarified liquid outlet 18 to the outside of the multiple microfluidic devices 10. Specifically, the clarified liquid outlet 18 of the fourth microfluidic device 14 is connected to the outside of the multiple microfluidic devices 10. The exterior of the multiple microfluidic devices 10 may be, for example, a collection container.

[0088] As described above, the multiple microfluidic devices 10 may include at least one microfluidic device 10 positioned between the first microfluidic device 11 and the third microfluidic device 13. The concentrated liquid outlet 17 of at least one microfluidic device 10 may be connected to the inlet 16 of the microfluidic device 10 positioned immediately before it via a reflux channel.

[0089] Specifically, the multiple microfluidic devices 10 may include a fourth microfluidic device 14 located downstream of the first microfluidic device 11 and upstream of the second microfluidic device 12. The inlet 16 of the fourth microfluidic device 14 may be connected to the concentrated liquid outlet 17 of the first microfluidic device 11. Alternatively, the inlet 16 of the fourth microfluidic device 14 may be connected via a reflux channel to the clarified liquid outlet 18 of a microfluidic device 10 located downstream of the fourth microfluidic device 14. The fourth microfluidic device 14 may discharge the clarified liquid from the clarified liquid outlet 18 to the outside of the multiple microfluidic devices 10.

[0090] According to the particle separation system 1 of this embodiment, the fourth microfluidic device 14 can further improve the separation accuracy.

[0091] Among the multiple microfluidic devices 10, the microfluidic device 10 positioned immediately after the first microfluidic device 11 may discharge the clarified liquid to the outside of the multiple microfluidic devices 10 from the clarified liquid outlet 18.

[0092] This allows a suspension diluted with the clarified liquid of the downstream microfluidic device 10 to be separated by the upstream microfluidic device 10 using a simple configuration.

[0093] In the particle separation system 1 according to the first to third embodiments, an example was described in which each of the multiple microfluidic devices 10 is directly connected by a connecting channel 19. However, as shown in Figure 8, for example, a buffer tank 23 may be provided in the connecting channel 19. The buffer tank 23 is provided downstream of the connection between the dilution channel 20 and the connecting channel 19. The buffer tank 23 can contain a mixture of the concentrated liquid discharged from the concentrated liquid outlet 17 and the diluent supplied via the dilution channel 20. Therefore, it is possible to suppress overflow of the concentrated liquid and the diluent. Although not shown, the buffer tank may be provided downstream of the connection between the reflux channel and the connecting channel in the connecting channel.

[0094] <Fourth Embodiment> Next, the particle separation system 1 according to the fourth embodiment will be described with reference to Figure 9. As shown in Figure 9, the particle separation system 1 further includes a culture device 40. In addition, in the particle separation system 1 according to the fourth embodiment, the particles contained in the suspension are cells. Unless otherwise specified, the other aspects are the same as the particle separation system 1 according to the above embodiment, and therefore the explanation will be omitted.

[0095] The culture apparatus 40 cultures cells. The culture apparatus 40 includes a culture tank 41. The culture tank 41 contains a suspension containing cells and liquid culture medium, and the cells are cultured in the culture tank 41.

[0096] The culture apparatus 40 is connected to the inlet 16 of the first microfluidic device 11. The suspension is then introduced into the first microfluidic device 11 from the culture apparatus 40. The inlet 16 of the first microfluidic device 11 is not connected to a dilution channel 20 or a reflux channel. Therefore, the suspension from the culture apparatus 40, without any diluent, is introduced directly into the inlet 16 of the first microfluidic device 11.

[0097] In this embodiment, the particles contained in the suspension contain cells. The cells may include eukaryotic cells or prokaryotic cells. Eukaryotic cells may include animal cells or yeast cells. Prokaryotic cells may include cells of Escherichia coli. Animal cells may include at least one of vertebrate cells and invertebrate cells. Animal cells may include at least one selected from the group consisting of mammalian cells, avian cells, reptile cells, amphibian cells and fish cells. Mammalian cells may include at least one selected from the group consisting of human cells, mouse cells, hamster cells, monkey cells, rat cells, pig cells, sheep cells, horse cells and rabbit cells. Specifically, animal cells may include at least one selected from the group consisting of CHO cells (Chinese hamster ovary cells), BHK cells (baby hamster kidney cells), HEK cells (human fetal kidney cells), PER.C.6 cells, COS-1 cells, COS-7 cells, NS0 cells, SP2 / 0 cells, myeloma cells and HeLa cells. The cells may be of only one type or a mixture of multiple types. The particles in the suspension may be cell clumps. The cells may be suspended cells.

[0098] The suspension may contain a liquid medium. The liquid medium may include a liquid culture medium used for cell culture. This allows cells cultured in the liquid medium to be directly introduced into the microfluidic device 10. The liquid medium can be appropriately selected and used to suit the cells to be cultured. The liquid medium may be a synthetic medium, a semi-synthetic medium, or a natural medium. The liquid medium may be appropriately selected from commercially available liquid media and may contain nutrients and purified water.

[0099] The culture apparatus 40 may include a stirring unit 42 located inside the culture tank 41 to homogenize the cells in the suspension. The stirring unit 42 includes a motor (not shown), a shaft 43 connected to the motor, and a stirring blade 44 connected to the shaft 43. By operating the motor, the stirring blade 44 is rotated, and the suspension is stirred. The stirring unit 42 may also include a magnetic stirrer instead of a structure including a motor, shaft 43, and stirring blade 44.

[0100] The culture apparatus 40 may include a temperature control unit (not shown) for adjusting the temperature of the suspension in the culture vessel 41. The temperature control unit can maintain the temperature of the suspension in the culture vessel 41 at a temperature suitable for cell culture or storage. An example of a temperature control unit is a thermostat.

[0101] The culture apparatus 40 may include a replenishment unit 45 for replenishing materials such as nutrients contained in the liquid culture medium. Such a replenishment unit 45 makes it possible to maintain a uniform composition of liquid components in the suspension during the cell culture period.

[0102] The culture apparatus 40 may be equipped with functions to adjust gas components such as oxygen, carbon dioxide, and air, pH, conductivity, and light intensity as needed, in order to maintain an environment suitable for cells. The culture apparatus 40 may also be equipped with a concentration measuring unit for measuring the gas concentration in the culture tank 41, and a pH measuring unit for the suspension.

[0103] The concentrated liquid discharged from the multiple microfluidic devices 10 may be refluxed to the culture device 40. This allows the cell culture to continue in the culture device 40.

[0104] By separating and generating clarified liquids from multiple microfluidic devices 10, useful substances such as proteins produced by cells can be recovered from the clarified liquids. Separation methods include centrifugation and membrane separation. Purification methods include ultrafiltration, microfiltration, and chromatography.

[0105] Examples of proteins produced by cells include antibodies, hormones, cytokines, enzymes, and vaccines. Antibodies may be monoclonal antibodies. Examples of monoclonal antibodies include infliximab, adalimumab, trastuzumab, bevacizumab, cetuximab, rituximab, pembrolizumab, nivolumab, daratumumab, denosumab, ocrelizumab, dupilumab, pertuzumab, vedolizumab, atezolizumab, ranibizumab, golimumab, tocilizumab, omalizumab, emicizumab, risankizumab, ipilimumab, natalizumab, guselkumab, mepolizumab, teprotumumab, benralizumab, evolocumab, and belimumab.

[0106] As described above, in the particle separation system 1 according to this embodiment, the particles include cells. The particle separation system 1 further comprises a culture device 40 for culturing cells. The culture device 40 is connected to the inlet 16 of the first microfluidic device 11.

[0107] According to the particle separation system 1 of this embodiment, cultured cells can be directly separated by multiple microfluidic devices 10.

[0108] In this embodiment of the particle separation system 1, the culture device 40 is connected to the particle separation system 1 according to the first embodiment, but the culture device 40 may also be connected to the particle separation system 1 according to the second to third embodiments. [Examples]

[0109] The embodiment will be described in more detail below with reference to the following examples and comparative examples, but the embodiment is not limited to these examples.

[0110] (Example 1) The separation of a suspension using the particle separation system shown in Figure 10 was evaluated by simulation. In the particle separation system, the concentrated liquid outlet and inlet of each microfluidic device 10 were connected, and five microfluidic devices 10 were connected in series. The first microfluidic device from the front contained a concentration of particles of 10 6 1000 L of stock solution with a concentration of 1000 g / mL was introduced. Immediately before the 3rd to 5th stage microfluidic devices from the front, 75 L each of diluent was introduced in addition to the concentrated solution discharged from the previous microfluidic device 10. Clarified solutions were collected from the 1st to 5th stage microfluidic devices from the front, and concentrated solutions were collected from the 5th stage microfluidic device from the front.

[0111] (Example 2) The separation of a suspension using the particle separation system shown in Figure 11 was evaluated by simulation. In the particle separation system, the concentrated liquid outlet and inlet of each microfluidic device 10 were connected, and five microfluidic devices 10 were connected in series. The first microfluidic device from the front contained a concentration of particles of 10 6 1000 L of stock solution containing 10 cells / mL was introduced. 250 L of clarified solution from the fourth-stage microfluidic device was refluxed into the third-stage microfluidic device from the front, in addition to the concentrated solution discharged from the second-stage microfluidic device 10. 250 L of clarified solution from the fifth-stage microfluidic device was refluxed into the fourth-stage microfluidic device from the front, in addition to the concentrated solution discharged from the third-stage microfluidic device 10. 250 L of diluent was introduced into the fifth-stage microfluidic device from the front, in addition to the concentrated solution discharged from the fourth-stage microfluidic device 10. Clarified solutions were collected from the first to third-stage microfluidic devices from the front, and concentrated solutions were collected from the fifth-stage microfluidic device from the front.

[0112] (Comparative Example 1) The separation of the suspension using the particle separation system shown in Figure 12 was evaluated by simulation. In the particle separation system, the concentrated liquid outlet and inlet of each microfluidic device 10 were connected, and five microfluidic devices 10 were connected in series. The clarified liquid was recovered from the first to fifth microfluidic devices from the front, and the concentrated liquid was recovered from the fifth microfluidic device from the front.

[0113] [Table 1]

[0114] In the particle separation system of Example 1, the average particle concentration of the resulting clarified liquid was 0.26 × 10⁶. 6 The particle concentration was 0.27 × 10¹⁶ particles / mL. In the particle separation system of Example 2, the average particle concentration of the resulting clarified liquid was 0.27 × 10¹⁶ particles / mL. 6 The particle count was 1 × 10¹⁶ particles / mL. 6 Comparing the particles / mL and the total volume of the clarified liquid with the average particle concentration of the clarified liquid, it can be seen that the particle separation systems of Examples 1 and 2 were able to sufficiently remove particles from the stock solution. On the other hand, in the particle separation system of Comparative Example 1, five stages were separated in series to achieve a recovery rate of 95% of the target substance in the liquid phase, but the average particle concentration of the resulting clarified liquid was 0.7 × 10⁻⁶. 6 The particle count was 1 × 10¹⁶ particles / mL. 6 Comparing the particle count per mL and the total volume of the clarified liquid with the average particle concentration of the clarified liquid, the particle removal rate by the particle separation system was only about 30%.

[0115] These results indicate that the separation efficiency of the microfluidic devices can be maintained by diluting the suspension after separation using one microfluidic device and before separation using the next. Furthermore, the target substance is a component that dissolves in the liquid phase of the stock solution, and the recovery rate of the target substance did not decrease with dilution, remaining at approximately 95% in all cases.

[0116] Furthermore, in the particle separation system of Example 2, the clarified liquid generated in the subsequent separation is refluxed and used as a diluent. Therefore, the total amount of clarified liquid obtained can be reduced, and the processing load for the separation and purification of the target substance can be reduced. Specifically, the total amount of clarified liquid obtained in the particle separation system of Example 1 was 1130 L, while the total amount of clarified liquid obtained in the particle separation system of Example 2 was 1000 L. The total amount of clarified liquid obtained in the particle separation system of Example 2 was about the same as the total amount of clarified liquid obtained in the particle separation system of Comparative Example 1, where no diluent was added.

[0117] Although several embodiments have been described, it is possible to modify or transform the embodiments based on the above disclosure. All components of the above embodiments, and all features described in the claims, may be taken individually and combined, provided that they do not conflict with each other. [Explanation of symbols]

[0118] 1. Particle separation system 10 Microfluidic Devices 11. First Microfluidic Devices 12. Second Microfluidic Device 13. Third Microfluidic Devices 15 Liquid flow path 16 Inlet 17 Concentrate outlet 18. Clarification liquid outlet 20 Dilution channel 21 1st reflux channel (reflux channel) 31. Straight channel 33a 4th side wall (side wall) 34c 3rd side wall (side wall) 40 Culture device w channel width h channel height

Claims

1. The device includes a liquid channel having an inlet into which a suspension containing particles is introduced, a concentrated liquid outlet from which a concentrated liquid containing the particles in the suspension is discharged, and a clarified liquid outlet from which a clarified liquid obtained by removing the concentrated liquid from the suspension is discharged, and comprises a plurality of microfluidic devices that separate the suspension into the concentrated liquid and the clarified liquid by a vortex flow generated as the suspension flows through the liquid channel having a rectangular cross-section. Each of the aforementioned plurality of microfluidic devices is arranged in series with the concentrated liquid outlet and the inlet connected. The plurality of microfluidic devices include a first microfluidic device located furthest upstream and a second microfluidic device located downstream of the first microfluidic device. A particle separation system in which the concentrated liquid is supplied diluted to the inlet of the second microfluidic device.

2. The particle separation system comprises a reflux channel and a dilution channel, The plurality of microfluidic devices include a third microfluidic device located downstream of the concentrate outlet of the second microfluidic device. The clarification liquid outlet of the third microfluidic device is connected to the inlet of the second microfluidic device via the reflux channel. The particle separation system according to claim 1, wherein the inlet of the third microfluidic device is connected to the dilution channel that supplies the diluent to the concentrate.

3. The particle separation system according to claim 2, wherein the concentrated liquid outlet of the third microfluidic device is located at the downstream end among the multiple concentrated liquid outlets of the microfluidic devices.

4. The particle separation system according to claim 2 or 3, wherein the concentrated liquid discharged from the concentrated liquid outlet of the second microfluidic device is introduced into the inlet of the third microfluidic device.

5. The particle separation system according to claim 2 or 3, wherein the microfluidic device among the plurality of microfluidic devices, which is positioned immediately after the first microfluidic device, discharges the clarified liquid to the outside of the plurality of microfluidic devices from the clarified liquid outlet.

6. The aforementioned particles contain cells, The particle separation system further comprises a culture device for culturing the cells, The particle separation system according to any one of claims 1 to 3, wherein the culture apparatus is connected to the inlet of the first microfluidic device.

7. The liquid flow path has a straight flow path, Each of the microfluidic devices includes a secondary flow generation mechanism that generates a secondary flow in the transverse direction in the suspension flowing upstream of the linear channel, The aforementioned straight channel has a rectangular cross-section defined by the channel width and the channel height perpendicular to the channel width. In the linear flow path, at least in the cross-section downstream of the secondary flow generation mechanism, the aspect ratio, expressed as the ratio of the flow path width to the flow path height, is in the range of 10 to 100. The particle separation system according to any one of claims 1 to 3, wherein the secondary flow generation mechanism protrudes from the side wall having the flow path width in the direction of the flow path height, extends parallel to the side wall and inclined with respect to a direction perpendicular to the cross-section.

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