JP7008921B2 - filter - Google Patents

Description

The present invention relates to filters that separate nanometer-order exosomes in body fluids, in particular.

A method for manufacturing a filter for filtration is disclosed (see Patent Document 1). This involves forming a flow path forming film on the substrate, forming a plurality of grooves along the surface of the substrate on the flow path forming film by etching, filling each groove with a sacrificial film, and polishing the sacrificial film to form a flow path. The surface of the forming film and the surface of the sacrificial film are flattened, a flow path encapsulating film is formed on the flattened flow path forming film and the sacrificial film, and etching is performed on each part of the substrate and the sacrificial film. The inflow hole and the outflow hole are formed, a part of the sacrificial membrane is exposed to the inflow hole and the outflow hole, the sacrificial membrane is removed through the inflow hole and the outflow hole, and each filtration flow path is formed in each groove. It is a method of manufacturing a filter for filtration.

Japanese Unexamined Patent Publication No. 2014-57934

In the above-mentioned conventional example, the flow path forming film is formed on the substrate by CVD, PVD or ALD, and the groove (filtration flow path) of the filter is formed by etching the flow path forming film. Since a part of the flow path forming film is removed by etching to form a groove, the thickness of the flow path forming film corresponds to the depth of the groove (filtration flow path). However, it is considered difficult to control the thickness (groove depth) of the flow path forming film by the above CVD or the like, especially on the order of nanometers.

Further, in this filter, since there is one inflow hole and one outflow hole, it is considered difficult to improve the filtration efficiency.

The present invention is particularly suitable for separating nanometer-order exosomes (30 nm to 100 nm in size) released via intracellular polytopes (polytope) from fluids that are body fluids. It is an object of the present invention to provide a filter having high separation efficiency.

The filter according to the first aspect is superposed on a plurality of grooves, one plate-shaped plate in which a plurality of first entrances and exits through which fluid enters and exits are formed in the openings at both ends of the grooves, and the one plate. It has a plate-like other plate in which a plurality of second entrances / exits through which the fluid enters / exits are formed at positions that are joined together and do not overlap with the plurality of first entrances / exits in the thickness direction of the one plate. , The space formed by the groove of the one plate and the other plate is used as the separation flow path of the fluid.

In this filter, the fluid that is the body fluid to be separated is flowed from the second inlet / outlet to the first inlet / outlet, or from the first inlet / outlet to the second inlet / outlet, and the cells are separated from the fluid that is the body fluid in the separation flow path. At this time, since a plurality of first doorways and second doorways are provided, the separation efficiency can be improved.

The second aspect is that the depth of the groove is on the order of nanometers. Therefore, cells, erythrocytes, etc. larger than the height of the separation channel are captured by the separation channel of the fluid having a height on the order of nanometers. As a result, nanometer-order (30 nm to 100 nm in size) exosomes smaller than the height of the separation channel are discharged, and separation can be performed based on the nanometer-order size.

A third aspect is that in the filter according to the first aspect, the groove is continuous from one of the first entrance / exit sides adjacent to the second entrance / exit in the extending direction of the groove to the other first entrance / exit side. Is formed.

In this filter, when a fluid is introduced from the second inlet / outlet, the fluid immediately enters the groove and branches along the groove into one first inlet / outlet side and the other first inlet / outlet side, corresponding to each groove. It passes through the separated flow path and flows out from one of the first entrances and exits and the other of the first entrances and exits, respectively.

Further, when a fluid is introduced from the first inlet / outlet, it branches into one second inlet / outlet side and the other second inlet / outlet side adjacent to the first inlet / outlet in the extending direction of the groove, and is separated corresponding to each groove. It passes through the flow path and flows out from one second entrance and the other second entrance, respectively. In this way, since the fluid is branched and flows, the separation efficiency can be further improved.

A fourth aspect is that in the filter according to the first aspect, the groove is independently formed on the first entrance / exit side adjacent to the second entrance / exit in the extending direction of the groove, and the groove is formed. They are connected to each other via a flat surface at the same height as the depth of .

In this filter, when a fluid is introduced from the second inlet / outlet, the fluid enters the flat surface between the groove on one first inlet / outlet side and the groove on the other first inlet / outlet side, and then corresponds to each groove. It branches into the separation flow path, passes through the separation flow path, and flows out from one first entrance / exit and the other first entrance / exit, respectively. Since the groove is formed independently on one of the first entrance / exit sides adjacent to the second entrance / exit and on the other first entrance / exit side, the efficiency of discharging exosomes and the like in the groove is improved, and the inflowing fluid The pressure loss can be reduced.

Further, when a fluid is introduced from the first inlet / outlet, the fluid enters the flat surface portion between the groove on one second inlet / outlet side and the groove on the other second inlet / outlet side, and then separates corresponding to each groove. It branches into a flow path, passes through the separation flow path, and flows out from one second inlet / outlet and the other second inlet / outlet, respectively. In this way, since the fluid is branched and flows, the separation efficiency can be further improved.

A fifth aspect is that in the filter according to any one of the first to fourth aspects, the second entrance / exit is on the upstream side, the first entrance / exit is on the downstream side, and the width of the groove is from the upstream side. It is expanding toward the downstream side.

In this filter, the width of the groove expands from the second inlet / outlet on the upstream side toward the first inlet / outlet on the downstream side. Can be flushed to. Therefore, clogging in the separation flow path is suppressed.

According to the present invention, it is possible to improve the reliability and separation efficiency of separating exosomes on the order of nanometers from a fluid which is a body fluid.

It is an exploded perspective view which shows the rectangular filter which concerns on 1st Embodiment. It is a perspective view which shows the rectangular filter. (A) is a cross-sectional view taken along the line 3A-3A in FIG. (B) is a cross-sectional view taken along the line 3B-3B in FIG. (C) is a cross-sectional view taken along the line 3C-3C in FIG. (D) is a cross-sectional view taken along the line 3D-3D in FIG. It is a perspective view which shows the flow of the fluid at the time of separation in a rectangular filter. It is an exploded perspective view which shows the modification 1 of the rectangular filter in 1st Embodiment. It is a perspective view which shows the modification 1 of the rectangular filter. It is a perspective view which shows the flow of the fluid at the time of separation in the modification 1 of a rectangular filter. It is an exploded perspective view which shows the modification 2 of the rectangular filter in 1st Embodiment. It is a perspective view which shows the modification 2 of the rectangular filter. (A) is a perspective view showing the flow of fluid at the time of separation in the modified example 2 of the rectangular filter. (B) is an enlarged plan view showing cells passing through the groove. It is an exploded perspective view which shows the disk-shaped filter which concerns on 2nd Embodiment. It is a perspective view which shows the disk-shaped filter. It is a top view which shows one plate and the other plate in the disk-shaped filter which concerns on 3rd Embodiment. It is a top view which shows the disk-shaped filter. FIG. 14 is an enlarged cross-sectional view taken along the line 15-15 in FIG. It is a partially enlarged plan view which shows one plate. It is sectional drawing which shows the modification of the disk-shaped filter. In the modified example of the disk-shaped filter, it is a partially enlarged perspective view corresponding to FIG. 15 showing one plate.

Hereinafter, as a mode for carrying out the present invention, a filter for separating exosomes in a fluid (body fluid) will be described with reference to the drawings.

[First Embodiment]
1 to 10, the filter 10 according to the present embodiment has one plate 14 and the other plate 12, and the space formed by the groove of one plate 14 and the other plate 12 is formed. For example, it is a separation flow path 16 (FIG. 3 (C)) having a height h on the order of nanometers. 1 to 10 show a rectangular filter 10. In these figures, one plate 14 is located on the lower side and the other plate 12 is located on the upper side.

One plate 14 is formed in a plate shape, and for example, a groove 22 having a depth on the order of nanometers is intermittently formed by using electroformed metal. The material of the electrocast metal is, for example, nickel, nickel alloy, copper, gold, platinum, and palladium.

At the end of the groove 22 in one plate 14, a plurality of first entrances / exits, for example, two first entrances / exits 14A and 14B, which penetrate in the thickness direction of the one plate 14 and allow fluid to enter and exit, are formed. There is. The groove 22 can be made, for example, by using LIGA (Lithogaphie Galvanoformung Abfomung) technology (Tadashi Hattori, Surface Technology, Vol. 62, No. 12, 619-624, 2011; W. Elufeld and H. Lhe. , Radiat. Phys. Chem., 45 (3): 340-365, 1995).

As the groove 22, for example, a groove 22A on one end side, a groove 22B in the center, and a groove 22C on the other end side are formed. The groove 22 is formed in a rectangular cross section. The depth and width of the groove 22 are, for example, constant. The first entrance / exit 14A is formed between the groove 22A on one end side and the groove 22B in the center. Further, the first entrance / exit 14B is formed between the central groove 22B and the groove 22C on the other end side.

One plate 14 has a land portion 24A partitioned by a groove 22A, a land portion 24B partitioned by a groove 22B, a land portion 24C partitioned by a groove 22C, and both sides of one plate 14 in the width direction. Each of the formed land portions 26 is formed. The land portion 26 extends continuously over the entire length in the longitudinal direction. The first entrances 14A and 14B are formed inside the plate 14 in the width direction from the land portions 26 on both sides. The groove 22 is also formed between the land portions 24A to 24C and the land portion 26. The upper surfaces of the land portions 24A to 24C and 26 are formed in a plane shape located on the same plane.

The entire plate 14 may be manufactured by the LIGA technique, or the groove 22 may be manufactured by the LIGA technique. In the latter case, the groove 22 can be formed by laminating an electroformed metal other than the portion corresponding to the groove 22 on the substrate (not shown) on which the first entrances 14A and 14B are formed. The material of this substrate may be any conductive metal and is not limited to electroformed metal. For example, a silicon resin or a PMMA acrylic resin produced by MEMS technology may be used.

As shown in FIGS. 1 to 3, the other plate 12 is superimposed and coupled to the one plate 14. Specifically, the planar external dimensions of the other plate 12 are, for example, the same as those of the one plate 14. The other plate 12 is bonded to the upper surfaces of the land portions 24A to 24C, 26 of the one plate 14 by adhesion or the like. In the other plate 12, a plurality of second plates penetrating in the thickness direction and entering / exiting the fluid at positions not overlapping with the first inlet / outlet 14A, 14B of the one plate 14 in the thickness direction of the one plate 14. Doorways, for example, three second doorways 12A to 12C are formed. In the longitudinal direction of the other plate 12, between the second entrances 12A and 12B and between the second entrances 12B and 12C are non-penetrating portions 12D and 12E, respectively. As shown in FIGS. 3A and 3B, the non-penetrating portion 12D covers the first entrance / exit 14A, and the non-penetrating portion 12E covers the first entrance / exit 14B. The non-penetrating portion 12D overlaps the end portion of the land portion 24A on the first entrance / exit 14A side and the end portion of the land portion 24B on the first entrance / exit 14A side. The non-penetrating portion 12E overlaps the end portion of the land portion 24B on the first entrance / exit 14B side and the end portion of the land portion 24C on the first entrance / exit 14B side. A separation flow path 16 is formed in this overlapping portion.

The material of the other plate 12 may be metal or resin. In the case of metal, it may be electroformed metal or may not be electroformed metal. In the case of the resin, a silicon resin or a PMMA acrylic resin produced by MEMS technology is preferable.

The first entrance / exit 14A, 14B and the second entrance / exit 12A, 12B, 12C are each formed in a rectangular shape, for example, and are arranged in a row in the longitudinal direction of the filter 10. The shapes and opening areas of the first entrances 14A and 14B are, for example, the same as each other. Further, the shapes and opening areas of the second entrances 12A, 12B, and 12C are also the same, for example.

The groove 22 is continuously formed in the extending direction of the groove 22, for example, between one first entrance / exit 14A side adjacent to the central second entrance / exit 12B and the other first entrance / exit 14B side. Since the first inlet / outlet does not exist on the end side in the longitudinal direction with respect to the second inlet / outlet 12A and 12C, the fluid can flow out from the end portion of the groove 22 (separation flow path 16). The separation flow path 16 may be blocked at both ends of the filter 10 in the longitudinal direction in order to prevent the fluid from flowing out from this end.

(Action)
This embodiment is configured as described above, and its operation will be described below. In FIG. 4, in the nanofilter 10 according to the present embodiment, the fluid which is the body fluid to be separated is transferred from the second inlet / outlet 12A, 12B, 12C to the first inlet / outlet 14A, 14B, or from the first inlet / outlet 14A, 14B to the second. It is flushed to the doorways 12A, 12B, 12C. At this time, due to the separation channel 16 having a height on the order of nanometers, peripheral circulating tumor cells having a height on the order of micrometer (about 8 μm in size) larger than the height h (FIG. 3C) of the separation channel 16 Alternatively, rare cells, erythrocytes, etc. (not shown) are captured. As a result, exosomes on the order of nanometers (size 30 nm to 100 nm) can be separated from body fluids that are fluids, and the reliability of separation on the order of nanometers can be enhanced. Further, since a plurality of second entrances 12A, 12B, 12C and a plurality of first entrances 14A, 14B are provided, the separation efficiency can be improved.

Specifically, when a fluid is introduced from the central second entrance / exit 12B, the fluid immediately enters the central groove 22B, and one side of the first entrance / exit 14A and the other side of the first entrance / exit 14B along the groove 22B. It branches to and flows out through the separation flow path 16 corresponding to each groove 22B, and flows out from one first entrance / exit 14A and the other first entrance / exit 14B (arrow FB1 direction and arrow FB2 direction), respectively.

When a fluid is introduced from the second inlet / outlet 12A, the fluid immediately enters the groove 22A on one end side, passes through the separation flow path 16 corresponding to the groove 22A, and flows out from the first inlet / outlet 14A (arrow FA direction). At this time, since the separation flow path 16 is also formed on the side opposite to the first entrance / exit 14A side with respect to the second entrance / exit 12A, the fluid may flow out from the separation flow path 16. When the separation flow path 16 at the end is blocked, the fluid introduced from the second inlet / outlet 12A flows out from the first inlet / outlet 14A.

When a fluid is introduced from the second inlet / outlet 12C, the fluid immediately enters the groove 22C on the other end side, passes through the separation flow path 16 corresponding to the groove 22C, and flows out from the first inlet / outlet 14B (arrow FC direction). At this time, since the separation flow path 16 is also formed on the side opposite to the first entrance / exit 14B side with respect to the second entrance / exit 12C, the fluid may flow out from the separation flow path 16. When the separation flow path 16 at the end is blocked, the fluid introduced from the second inlet / outlet 12C flows out from the first inlet / outlet 14B.

On the contrary, when the fluid is introduced from the first entrance / exit 14A, it branches into one second entrance / exit 12A side and the other second entrance / exit 12B side adjacent to the first entrance / exit 14A in the extending direction of the groove 22, respectively. It passes through the separation flow path 16 corresponding to the grooves 22A and 22B, and flows out from one second entrance / exit 12A and the other second entrance / exit 12B, respectively (arrow RA direction and arrow RB1 direction).

When fluid is introduced from the first inlet / outlet 14B, it branches into one second inlet / outlet 12B side and the other second inlet / outlet 12C side adjacent to the first inlet / outlet 14B in the extending direction of the groove 22, and each groove 22B. , 22C, and flows out from one second inlet / outlet 12B and the other second inlet / outlet 12C, respectively (arrow RB2 direction and arrow RC direction). At the second entrance / exit 12B, the fluid flowing from the first entrance / exit 14A and the fluid flowing from the first entrance / exit 14B merge (arrow RB1 direction and arrow RB2 direction).

In the present embodiment, since the fluid flows while branching or merging in this way, the separation efficiency can be further improved. Further, the filter 10 has no front and back sides in use, and it is possible to flow a fluid from either side to perform separation.

(Modification 1)
5 to 7, in the filter 10 according to the first modification, the central groove 22B corresponding to the second entrance / exit 12B is one of the first entrance / exit 14A adjacent to the second entrance / exit 12B in the extending direction of the groove 22B. It is formed independently on the side and the other first entrance / exit 14B side. Specifically, the land portion 24B is divided into a first entrance / exit 14A side and the other first entrance / exit 14B side, and a groove 22B is not formed in the region between both land portions 24B. In this region, a plane 28B at the same height as the depth of the groove 22B is formed. In other words, the bottom of the groove 22B and the plane 28B are continuous with each other.

The groove 22A on one end side corresponding to the second entrance / exit 12A is formed independently on the first entrance / exit 14A side adjacent to the second entrance / exit 12A in the extending direction of the groove 22A and on the opposite side thereof. Specifically, the land portion 24A is divided into the first entrance / exit 14A side and the opposite side thereof, and the groove 22A is not formed in the region between both land portions 24A. In this region, a plane 28A at the same height as the depth of the groove 22A is formed. In other words, the bottom of the groove 22A and the plane 28A are continuous with each other.

The groove 22C on the other end side corresponding to the second entrance / exit 12C is formed independently on the first entrance / exit 14B side adjacent to the second entrance / exit 12C in the extending direction of the groove 22C and on the opposite side thereof. Specifically, the land portion 24C is divided into the first entrance / exit 14B side and the opposite side thereof, and a groove 22C is not formed between both land portions 24C. In the region between both land portions 24C, a plane 28C at the same height as the depth of the groove 22C is formed. In other words, the bottom of the groove 22C and the plane 28C are continuous with each other.

In FIG. 7, in the filter 10 according to the first modification, when a fluid is introduced from the central second inlet / outlet 12B, the fluid is located in the groove 22B on one first inlet / outlet 14A side and on the other first inlet / outlet 14B side. After entering the region (plane 28B) between the grooves 22B, it branches into the separation flow path 16 corresponding to each groove 22B, passes through the separation flow path 16, and passes through the separation flow path 16 to one first inlet / outlet 14A and the other. Outflow from the first entrance / exit 14B of the above (arrow FB1 direction and arrow FB2 direction), respectively. Since the groove 22B is independently formed on one of the first entrance / exit 14A side adjacent to the second entrance / exit 12B and on the other side of the first entrance / exit 14B, the exosome discharge efficiency in the groove is enhanced and the inflow is increased. The pressure loss of the fluid can be reduced.

When a fluid is introduced from the second inlet / outlet 12A, the fluid enters the central groove 22A from the plane 28B, passes through the separation flow path 16 corresponding to the groove 22A, and flows out from the first inlet / outlet 14A (arrow FA direction). At this time, since the separation flow path 16 is also formed on the side opposite to the first entrance / exit 14A side with respect to the second entrance / exit 12A, the fluid may flow out from the separation flow path 16. When the separation flow path 16 at the end is blocked, the fluid introduced from the second inlet / outlet 12A flows out from the first inlet / outlet 14A.

When a fluid is introduced from the second inlet / outlet 12C, the fluid enters the groove 22C on one end side from the flat surface 28C, passes through the separation flow path 16 corresponding to the groove 22C, and flows out from the first inlet / outlet 14B (arrow FC direction). .. At this time, since the separation flow path 16 is also formed on the side opposite to the first entrance / exit 14B side with respect to the second entrance / exit 12C, the fluid may flow out from the flow separation passage 16. When the separation flow path 16 at the end is blocked, the fluid introduced from the second inlet / outlet 12C flows out from the first inlet / outlet 14B.

On the contrary, when the fluid is introduced from the first entrance / exit 14A, it branches into one second entrance / exit 12A side and the other second entrance / exit 12B side adjacent to the first entrance / exit 14A in the extending direction of the groove 22, respectively. It passes through the separation flow path 16 corresponding to the grooves 22A and 22B, and flows out from one second entrance / exit 12A and the other second entrance / exit 12B, respectively (arrow RA direction and arrow RB1 direction).

When fluid is introduced from the first inlet / outlet 14B, it branches into one second inlet / outlet 12B side and the other second inlet / outlet 12C side adjacent to the first inlet / outlet 14B in the extending direction of the groove 22, and each groove 22B. , 22C, and flows out from one second inlet / outlet 12B and the other second inlet / outlet 12C, respectively (arrow RB2 direction and arrow RC direction). At the second entrance / exit 12B, the fluid flowing from the first entrance / exit 14A and the fluid flowing from the first entrance / exit 14B merge (arrow RB1 direction and arrow RB2 direction).

(Modification 2)
8 to 10, in the filter 10 according to the modification 2, the width of the central groove 22B in the filter 10 according to the modification 1 is from the upstream side to the downstream side, specifically, from the second entrance / exit 12B side to the second. 1 It expands toward the entrances 14A and 14B, respectively. In this modification, the second entrances 12A, 12B, 12C are on the upstream side, and the first entrances 14A, 14B are on the downstream side. The width of the groove 22B on the first entrance / exit 14A side of the plane 28B gradually increases from the plane 28B side toward the first entrance / exit 14A side. Further, the width of the groove 22B on the first entrance / exit 14B side of the plane 28B gradually increases from the plane 28B side toward the first entrance / exit 14B. The groove walls of the grooves 22A, 22B, and 22C are not limited to a straight line, but may be a curved line.

Similarly, the width of the groove 22A also expands from the second entrance / exit 12A side toward the first entrance / exit 14A side and the opposite side thereof, respectively. The width of the groove 22C also expands from the second entrance / exit 12C side toward the first entrance / exit 14B side and the opposite side, respectively.

In this modification, the width of the groove 22 expands from the upstream side to the downstream side. Therefore, taking the central groove 22B as an example in FIG. 10B, the width of the groove 22B in the separation flow path 16 is Exosomes 18 that have passed through the narrowest portion can then be smoothly flowed. By expanding the width of the groove 22B, the contact between the exosome 18 and the groove wall of the groove 22B is suppressed, so that friction is reduced. Therefore, clogging in the separation flow path 16 is suppressed.

The minimum width of the groove 22 and the depth of the groove 22 may be set to be the same.

[Second Embodiment]
In FIGS. 11 and 12, the filter 20 according to the present embodiment is formed in a disk shape. The filter 20 is configured by superimposing the other plate 32 on one plate 34 and joining them together. The other plate 32 and the other plate 34 are formed in a disk shape having the same outer diameter as each other, for example. The second entrance / exit 32A is arranged in a matrix on the other plate 32. The second entrance / exit 32A corresponds to a further arrangement of the second entrance / exit 12A, 12B, 12C of the first embodiment. Further, on one of the plates 34, the first entrance / exit 34A are arranged in a matrix. The first doorway 34A corresponds to a further arrangement of the first doorways 14A and 14B of the first embodiment. On one of the plates 34, as in the first embodiment, the groove 22 is formed linearly in the width direction of the first entrance / exit 34A.

In this filter 20, since the first entrance / exit 34A and the second entrance / exit 32A can be arranged at high density, the separation efficiency can be further improved.

Since the other parts are the same as those in the first embodiment, the same parts are designated by the same reference numerals and the description thereof will be omitted.

[Third Embodiment]
In FIGS. 13 and 14, the filter 30 according to the present embodiment is formed in a disk shape. The filter 30 is configured by superimposing the other plate 42 on one plate 44 and joining them together. The other plate 42 and the one plate 44 are formed in a disk shape having the same outer diameter as each other, for example.

On the other plate 42, the second entrance / exit 42A is arranged in a substantially concentric arc shape. For example, two crosspieces 42B are integrally formed on the other plate 42. The two crosspieces 42B are orthogonal to each other at the center of the other plate 42. The second entrance / exit 42A having the same radius of curvature is divided at four points in the circumferential direction by the crosspiece 42B. As a result, the second entrances and exits 42A at four locations are intermittently formed in the circumferential direction. The second entrance / exit 42A corresponds to a second entrance / exit 12A, 12B, 12C of the first embodiment arranged in a larger number in the radial direction of the other plate 42.

On one plate 44, the first entrance / exit 44A is arranged in a substantially concentric arc shape. For example, two crosspieces 44B are integrally formed on one plate 44. The two crosspieces 44B are orthogonal to each other at the center of one plate 44. The first entrance / exit 44A having the same radius of curvature is divided at four points in the circumferential direction by the crosspiece 44B. As a result, the first entrances and exits 44A at four locations are intermittently formed in the circumferential direction. The first entrance / exit 44A corresponds to an arrangement of the first entrance / exit 14A, 14B, 14C of the first embodiment in a larger number in the radial direction of one of the plates 44.

On one plate 44, a groove 22 similar to that of the first embodiment is formed linearly in the width direction of the first entrance / exit 44A. In other words, the grooves 22 are formed radially in the radial direction of one of the plates 44.

As shown in FIG. 15, the second entrance / exit 42A is formed at a position that does not overlap with the first entrance / exit 44A. In other words, the second entrance / exit 42A is formed at a position overlapping the groove 22. The non-penetrating portion 42C of the other plate 42 overlaps the first entrance / exit 44A. The non-penetrating portion 42C straddles the land portion 44C on the inner side in the radial direction and the land portion 44C on the outer side in the radial direction of the first entrance / exit 44A.

As shown in FIG. 16, the width W of the groove 22 located between the first entrances and exits 44A adjacent to each other in the radial direction is, for example, constant. Regarding the width of the groove 22, the groove 22 located further radially inside the first inlet / outlet 44A on the innermost radial direction and the groove 22 located further radially outer than the first inlet / outlet 44A on the outermost radial direction are also used. The same is true.

In FIG. 15, when a fluid is introduced from the second inlet / outlet 42A, the fluid immediately enters the groove 22 and branches along the groove 22 into one first inlet / outlet 44A side and the other first inlet / outlet 44A side. It passes through the separation flow path 16 corresponding to each groove 22 and flows out from one first entrance / exit 44A and the other first entrance / exit 44A (in the direction of arrow F).

On the contrary, when a fluid is introduced from the first inlet / outlet 44A, it branches into one second inlet / outlet 42A side and the other second inlet / outlet 42A side adjacent to the first inlet / outlet 44A in the extending direction of the groove 22, respectively. It passes through the separation flow path 16 corresponding to the groove 22 and flows out from one second entrance / exit 42A and the other second entrance / exit 42A (in the direction of arrow R).

Also in this embodiment, since the fluid flows while branching or merging in this way, the separation efficiency can be further improved.

(Modification example)
As shown in FIG. 17, the width of the groove 22 in one of the plates 46 may be expanded toward the outside in the radial direction. The structure of the groove 22 is the same as that of the groove 22 in FIGS. 8 to 10. The minimum width of the groove 22 and the depth of the groove 22 may be set to be the same as each other. The groove 22 and the land portion 48 partitioned by the groove 22 are located radially outward in the region between the two first entrances and exits 46A radially adjacent to each other in one plate 46. A land portion 46B extends in the circumferential direction on the inner side in the radial direction of the region. In the region between the land portions 46B and 48, a plane 50 at the same height as the depth of the groove 22 is formed. In other words, the bottom of the groove 22 and the plane 50 are continuous with each other.

Since the heights of the land portions 46B and 48 are, for example, the same, both of the land portions 46B and 48 can abut on the lower surface of the other flat plate 42 (FIG. 18). With reference to the non-penetrating portion 42C of the other plate 42, the radial inner end of the non-penetrating portion 42C abuts on the land portion 48 and the radial outer end abuts on the land portion 46B. The configuration of the first entrance / exit 46A is the same as that of the first entrance / exit 42A in FIG.

In FIG. 18, when a fluid is introduced from the second inlet / outlet 42A, the fluid enters the groove 22 on the outer side in the radial direction from the plane 50, passes through the separation flow path 16 corresponding to the groove 22, and flows out from the first inlet / outlet 46A. (Arrow F direction). Since the land portion 46B obstructs the flow of fluid from the plane 50 inward in the radial direction, there is no merging or branching.

In this modified example, as in the modified example 2 of the first embodiment, the contact between the exosome 18 and the groove wall of the groove 22 is suppressed by expanding the width of the groove 22 (see FIG. 10), so that friction Is reduced. Therefore, clogging in the separation flow path 16 is suppressed.

The arrangement of the groove 22 (land portion 48) and the land portion 46B in the radial direction of one of the plates 46 may be reversed from the above. That is, the groove 22 (land portion 48) may be located on the inner side in the radial direction, and the land portion 46B may be located on the outer side in the radial direction. In that case, the width of the groove 22 increases inward in the radial direction.

Since the other parts are the same as those in the first embodiment, the same parts are designated by the same reference numerals and the description thereof will be omitted.

[Other embodiments]
Although an example of the embodiment of the present invention has been described above, the embodiment of the present invention is not limited to the above, and can be variously modified and implemented without departing from the gist thereof. Of course there is.

As described above, the filter of the present invention can separate exosomes from fluids that are body fluids by setting the groove depth (separation flow path height) to the nanometer order (size 30 nm to 100 nm), and thus electrocasting. Even if the technique is used, it is possible to solve the problem that it is difficult to make fine pores on the order of nanometers in the filter, and it is extremely useful for exosome samples in the medical and biotechnology fields.
In addition to exosomes, nanoparticles on the order of nanometers include metal nanoparticles (gold nanoparticles, silver nanoparticles, nickel nanoparticles, magnetic nanoparticles such as iron oxide) and organic nanoparticles (acrylic, styrene) in the industrial field. Systems, etc.), ceramic nanoparticles, etc., and these particles can also be separated by the filter of the present invention, which is extremely useful in the industrial field as well.

10 Filter 12 Another plate 12A 2nd doorway 12B 2nd doorway 12C 2nd doorway 14 One plate 14A 1st doorway 14B 1st doorway 16 Separation flow path 20 Filter 22 Groove 22A One end side groove 22B Central groove 22C The other end Side groove
28B flat surface
30 Filter 32 The other plate 32A Second doorway 34 One plate 34A First doorway 42 The other plate 42A Second doorway 44 One plate 44A First doorway 46 One plate 46A First doorway

Claims (5)

A plurality of grooves, and one plate-shaped plate in which a plurality of first entrances / exits through which fluid enters / exits are formed in the openings at both ends of these grooves.
The other plate-like plate formed by being laminated on one of the plates and having a plurality of second entrances / exits through which the fluid enters / exits at positions that do not overlap with the plurality of first entrances / exits in the thickness direction of the one plate. With the plate
Have,
A filter in which the space formed by the groove of the one plate and the other plate is used as the separation flow path of the fluid. The filter according to claim 1, wherein the groove depth is on the order of nanometers. The filter according to claim 1, wherein the groove is continuously formed from one of the first entrance / exit sides adjacent to the second entrance / exit in the extending direction of the groove to the other first entrance / exit side. The groove is independently formed on one of the first entrance / exit sides and the other of the first entrance / exit sides adjacent to the second entrance / exit in the extending direction of the groove, and is at the same height as the depth of the groove. The filter according to claim 1, which is connected to each other via a flat surface portion in the vertical position . The second entrance / exit is on the upstream side, and the first entrance / exit is on the downstream side.
The filter according to any one of claims 1 to 4, wherein the width of the groove expands from the upstream side to the downstream side.

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