WO2017199993A1

WO2017199993A1 - Separation device

Info

Publication number: WO2017199993A1
Application number: PCT/JP2017/018486
Authority: WO
Inventors: 悠司豊田; 山本　元; 片山　博之
Original assignee: 日東電工株式会社
Priority date: 2016-05-17
Filing date: 2017-05-17
Publication date: 2017-11-23
Also published as: JP2017205759A

Abstract

The present invention relates to a separation device provided with: a structure which has a first surface and a second surface that faces the first surface and also has through-holes that penetrate between the first surface and the second surface; and a porous separation layer which has a third surface and a fourth surface that faces the third surface, wherein the structure and the separation layer are laminated on each other in such a manner that the second surface side of the structure and the third surface side of the separation layer face each other, and the pore size of each of micropores in the third surface of the separation layer is smaller than the pore size of each of the through-holes in the second surface of the structure. According to this separation device, the separation of a substance to be separated from a substance to be held is ensured with superior separation efficiency.

Description

Separation device

The present invention relates to a separation device.

In recent years, when platelets are produced from megakaryocytes derived from iPS cells (induced Pluripotent Stem cells), platelets are separated from megakaryocytes, which are nucleated cells remaining without producing platelets after platelet production. For this reason, a porous material is used.

For example, Patent Document 1 discloses a platelet production apparatus, and a megakaryocyte is held on a holding member by a holding member in which an opening such as a hole having a diameter that allows passage of platelets is formed. It is disclosed that platelets already produced from megakaryocytes and platelets produced from megakaryocytes are separated by passing through an opening.

Japanese Unexamined Patent Publication No. 2015-181405

By the way, in such a platelet production apparatus, it is important to hold megakaryocytes that produce platelets in the vicinity of the opening of the holding member from the viewpoint of separation efficiency. However, in the platelet production apparatus as described in Patent Document 1, since the vicinity of the opening of the holding member is a flat portion, the megakaryocytes are easily separated or moved due to pressure fluctuations or the like, and platelets The separation efficiency was not sufficient. Further, such a problem is not limited to a platelet production apparatus, but is a separation target of cells as a retention target, cells differentiated from cells as a retention target, and metabolites metabolized from cells as a retention target. This is a common problem when separating objects.
Further, in the holding member as described in Patent Document 1, the risk that the holding object passes through the opening due to deformation of the holding member due to suction force or a processing error when forming the opening, or the separation object There was a problem of being stuck.

Therefore, an object of the present invention is to provide a separation device that can reliably separate a holding object and a separation object with excellent separation efficiency.

As a result of intensive studies in view of the above problems, the present inventors have found that the above problems can be solved by a separation device having the following configuration, and have completed the present invention.

That is, the present invention has a first surface and a second surface facing the first surface, and a structure including a through-hole penetrating between the first surface and the second surface;
A separation device comprising a third surface and a porous separation layer having a fourth surface facing the third surface,
The structure and the separation layer are laminated so that the second surface side of the structure and the third surface side of the separation layer face each other.
The hole diameter of the micropore in the said 3rd surface of the said separation layer is related with the separation device smaller than the hole diameter of the said through-hole in the said 2nd surface of the said structure.

In the separation device according to an embodiment of the present invention, the entire separation layer may be porous.

In the separation device according to an embodiment of the present invention, the plurality of micro holes in the third surface of the separation layer may be connected to the through hole in the second surface of the structure.

In the separation device of one embodiment of the present invention, the structure and the separation layer may be directly laminated.

In the separation device according to an embodiment of the present invention, at least one of the structure and the separation layer may be formed of a polymer material.

In the separation device according to an embodiment of the present invention, the separation layer may include a plurality of micropores penetrating between the third surface and the fourth surface.

In the separation device according to the embodiment of the present invention, the diameter of the through hole on the first surface side may be larger than the diameter of the through hole on the second surface side.
In the separation device according to the embodiment of the present invention, the diameter of the through hole on the first surface side may be smaller than the diameter of the through hole on the second surface side.

A separation device according to an embodiment of the present invention is a separation device that separates a holding object and a separation object, and the micropores do not pass the holding object and the separation object passes. It may have a possible pore size.

In the separation device according to an embodiment of the present invention, the holding object may be held by the through hole.

According to the present invention, a separation device capable of reliably separating a holding object and a separation object with excellent separation efficiency is provided.

1 (a) to 1 (c) are schematic cross-sectional views showing several embodiments of the separation device of the present invention. FIG. 2 shows the amount of particles remaining after dripping and washing (unit: mg) when the aqueous dispersion containing polystyrene particles 1 was dripped and washed using the separation devices (filters) of each Example and Comparative Example. It is a graph showing the ratio (weight%) with respect to the particle amount (5 mg) before a process. FIG. 3 shows the amount of particles remaining after dripping and washing (unit: mg) when the aqueous dispersion containing polystyrene particles 2 was dripped and washed using the separation devices (filters) of each Example and Comparative Example. It is a graph showing the ratio (weight%) with respect to the particle amount (5 mg) before a process. FIG. 4 shows the amount of particles remaining after dropping and washing (unit: mg) when the aqueous dispersion containing polystyrene particles 3 was dropped and washed using the separation devices (filters) of each Example and Comparative Example. It is a graph showing the ratio (weight%) with respect to the particle amount (5 mg) before a process.

Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings as appropriate. In the following, the description will focus on a separation device that separates a holding object and a separation object that is mixed with and / or separated from the holding object. Here, the retention target is not particularly limited, but a cell is exemplified, and the separation target is not particularly limited, but from a cell differentiated from a cell as a retention target or a cell as a retention target. Examples include metabolized metabolites and the like. Moreover, as an example of a more specific application of the separation device of the present embodiment, from a culture solution containing megakaryocytes and platelets already produced from megakaryocytes, produced from platelets and megakaryocytes already produced from megakaryocytes Use as a separation device for regenerative medicine, such as separating platelets to be used.

1 (a) to 1 (c) show schematic cross-sectional views of several embodiments of the separation device of the present invention. The separation device 1 of the embodiment shown in FIGS. 1A to 1C has a first surface 101 and a second surface 102 facing the first surface 101, and the first surface 101 and the second surface And a porous separation layer 21 having a structure 11 having a through-hole 111 penetrating between them and a third surface 203 and a fourth surface 204 facing the third surface 203. Here, the structure 11 and the separation layer 21 are laminated so that the second surface 102 side of the structure 11 and the third surface 203 side of the separation layer 21 face each other. In addition, the hole diameter of the minute hole 211 on the third surface 203 of the separation layer 21 is smaller than the hole diameter of the through hole 111 on the second surface 102 of the structure 11.

The separation device 1 of the present embodiment, for example, reduces the pressure on the fourth surface 204 side than the first surface 101 side, so that the holding object and the holding object are mixed and / or separated from the holding object. By sucking the medium containing the separated object from the fourth surface 204 side, the object to be held is mixed with the object to be held while being held by the through hole 111 without passing through the micro holes 211 and / or The separation object separated from the holding object is used so as to be separated by passing through the micro holes 211. The medium is appropriately selected according to the type and properties of the holding object and the separation object, but is typically liquid or gas. For example, when separating platelets already produced from megakaryocytes and platelets produced from megakaryocytes from a culture solution containing megakaryocytes and platelets already produced from megakaryocytes, the culture solution is the medium.

In the separation device 1 of the present embodiment, the structure 11 has a first surface 101 and a second surface 102 that faces the first surface 101, and penetrates between the first surface 101 and the second surface 102. A through-hole 111 is provided. Here, the through hole 111 of the structure 11 plays a role of holding the object to be held in the vicinity of the minute hole 211 of the separation layer 21. From the viewpoint of separation efficiency, the structure 11 preferably has a plurality of through holes 111.

The cross-sectional shape of the through-hole 111 in the thickness direction of the structure 11 (hereinafter, also simply referred to as a cross-sectional shape) is a through-hole penetrating between the first surface 101 and the second surface 102 of the structure 11. There is no particular limitation. For example, as shown in FIG. 1A, in the cross section in the thickness direction of the structure 11, a shape (hereinafter referred to as a straight hole) in which the diameter of the through hole 111 is the same from the first surface 101 side to the second surface 102 side. (Also referred to as a shape). In addition, as shown in FIG. 1B, in the cross section in the thickness direction of the structure 11, a shape in which the hole diameter of the through hole 111 decreases from the first surface 101 side to the second surface 102 side (hereinafter also referred to as a taper shape). Or the diameter of the through-hole 111 increases from the first surface 101 side to the second surface 102 side in the cross section in the thickness direction of the structure 11 as shown in FIG. It may be a shape (hereinafter also referred to as a reverse taper shape). Furthermore, part of the cross-sectional shape includes a reverse taper shape, such as a combination of a straight shape and a taper shape. It may have a shape such as a partially reverse tapered shape. When the structure 11 has a plurality of through-holes 111, the cross-sectional shapes and hole diameters of the plurality of through-holes 111 may be the same or different.

Here, from the viewpoint of improving the separation efficiency, the cross-sectional shape of the through-hole 111 of the structure 11 is that the object to be held that has once entered the through-hole 111 is easily held in the through-hole 111. A shape in which the hole diameter of the through hole 111 in the first surface 101 is smaller than the hole diameter of the through hole 111 in the second surface 102 is preferable, such as a tapered shape or a partially reverse tapered shape.

Further, when a holding object larger than the through hole 111 is used, the hole diameter of the through hole 111 on the first surface is larger than the hole diameter of the through hole 111 on the second surface 102 such as a tapered shape or a partially tapered shape. Shape is also preferred.

The hole diameter of the through hole 111 is not particularly limited as long as it is a hole diameter capable of holding the holding object in the through hole 111, and is appropriately determined in consideration of the shape of the through hole 111, the size of the holding object, and the like. Just choose.
Here, for example, when separating megakaryocytes and platelets, considering that the size of megakaryocytes, which are objects to be retained, is usually about 20 to 150 μm, the hole diameter of the through-hole 111 is, for example, FIG. ) Is preferably 20 to 500 μm, more preferably 50 to 200 μm.
In the case of the tapered shape shown in FIG. 1B, the hole diameter of the through hole 111 on the first surface 101 side is preferably 50 to 1000 μm, and more preferably 100 to 500 μm. The diameter of the through hole 111 on the second surface 102 side is preferably 10 to 500 μm, more preferably 20 to 250 μm.
In the case of the reverse tapered shape shown in FIG. 1C, the hole diameter of the through hole 111 on the first surface 101 side is preferably 20 to 1000 μm, and more preferably 50 to 500 μm. Further, the hole diameter of the through hole 111 on the second surface 102 side is preferably 50 to 5000 μm, and more preferably 100 to 1000 μm.
In addition, the hole diameter of the through-hole 111 can be measured with SEM, an optical microscope, etc.

Further, the planar shape of the through hole 111 on the first surface 101 side and the second surface 102 side is not particularly limited, and various shapes such as an ellipse, a triangle, a polygon such as a quadrangle, and the like can be used. Possible. Note that the planar shapes of the plurality of through holes 111 may be the same or different. Moreover, the planar shape of the first surface 101 side and the second surface 102 side of a certain through-hole 111 may be the same or different.
In addition, when the planar shape of the through hole 111 is a shape other than a circle, the hole area is obtained, and the hole diameter (equivalent circle diameter) in a circle having the same hole area is regarded as the hole diameter of the through hole 111. To do.
In addition, the “tapered shape” in the present specification is not limited to the case where the planar shape of the through hole 111 is circular, and the thickness direction of the structure 11 even when the planar shape of the through hole 111 is other than circular. In this cross section, any shape in which the hole diameter decreases from the first surface 101 side to the second surface 102 side is included in this. The “reverse taper shape” is also interpreted in the same manner.

When the structure 11 includes a plurality of through holes 111, the hole density on the surface (the first surface 101 and the second surface 102) of the structure 11 is not particularly limited, but the hole density of the through holes 111 in the structure 11 is not limited. If it is 100 pieces / cm ² or more, separation efficiency is improved by parallel processing, which is preferable. More preferably, it is 1000 pieces / cm < ² > or more, More preferably, it is 10,000 pieces / cm < ² > or more. On the other hand, it is preferable that the pore density is 100000 pieces / cm ² or less because the porosity is not excessively increased and a decrease in strength can be prevented. More preferably, it is 50000 piece / cm < ² > or less, More preferably, it is 10,000 piece / cm < ² > or less.

The thickness of the structure 11 is not particularly limited as long as the object to be held is held in the through-hole 111, and may be appropriately selected in consideration of the size of the object to be held. For example, when separating megakaryocytes and platelets, the thickness is preferably 10 to 1000 μm, more preferably 50 to 300 μm.

As a material constituting the structure 11, an organic material such as a polymer material or an inorganic material such as silicon or metal can be used. Here, in order to use it as a separation device for regenerative medicine, such as when separating megakaryocytes and platelets, non-reactive polymer materials and biocompatible metal materials are used because they do not exhibit cytotoxicity. Etc. are preferred.

In the separation device 1 of the present embodiment, the second surface 102 side of the structure 11 is laminated so that the third surface 203 side of the porous separation layer 21 having a plurality of micropores 211 faces each other. Here, in the separation device 1 of the present embodiment, the hole diameter of the micro hole 211 in the third surface 203 of the separation layer 21 is smaller than the hole diameter of the through hole 111 in the second surface 102 of the structure 11.

According to the separation device 1 of the present embodiment, the object to be held is held in the vicinity of the minute hole 211 of the separation layer 21 by the through hole 111 of the structure 11 without passing through the minute hole 211 of the separation layer 21. The In addition, the separation object mixed with and / or separated from the retention object passes through the micro holes 211 from the third surface 203 side of the separation layer 21 to the fourth surface 204 side of the separation layer 21. Separated.
As described above, in the separation device 1 of the present embodiment, the through hole 111 of the structure 11 is surely provided in the vicinity of the micro hole 211 of the separation layer 21 without passing the object to be held through the micro hole 211 of the separation layer 21. The separation target mixed with the separation target and / or separated from the retention target can be efficiently separated through the micro holes 211 of the separation layer 21. Therefore, for example, when separating a cell as a retention target from a separation target such as a cell differentiated from a cell as a retention target or a metabolite metabolized from a cell as a retention target, it is excellent. Separation can be reliably performed with separation efficiency.
Further, since the structure 11 and the separation layer 21 have a laminated structure, the separation device can be used even when many through holes 111 are provided in the structure 11 in order to efficiently hold the object to be held. The necessary strength can be secured.

The hole diameter of the minute hole 211 of the separation layer 21 is not particularly limited as long as it is smaller than the hole diameter of the through hole 111 in the second surface 102 of the structure 11, and the size of the holding object, the size of the separation object, and the like. It may be selected as appropriate in consideration, but in order to perform reliable separation, it is preferable that the hole diameter is such that the object to be held is not allowed to pass through and the object to be separated can pass. According to this viewpoint, it is preferable that the hole diameter of the micropore is smaller than the size of the holding object and larger than the size of the separation object.
For example, when separating megakaryocytes and platelets, the size of the megakaryocytes that are the retention target is usually about 20 to 150 μm, and the size of the platelets that are the separation target is about 2 to 5 μm. The pore diameter is preferably 2 to 15 μm, more preferably 3 to 6 μm. In addition, the hole diameter of a micropore can be measured with SEM, an optical microscope, etc.

Further, only one of the micro holes 211 in the third surface 203 of the separation layer 21 may be connected to one through hole 111 in the second surface 102 of the structure 11, but the separation efficiency is further improved. In order to increase, it is preferable that a plurality of micro holes 211 in the third surface 203 of the separation layer 21 are connected to one through hole 111 in the second surface 102 of the structure 11. Further, in the separation device 1 having such a configuration, even if a part of the plurality of micro holes 211 connected to the through hole 111 is clogged, the micro hole that is not clogged is formed. This is also preferable because the separation function can be ensured by 211.
When a plurality of micro holes 211 in the third surface 203 of the separation layer 21 are connected to one through hole 111 in the second surface 102 of the structure 11, the connection is made to one through hole 111. The number of micropores 211 to be formed is preferably as many as possible, but is not particularly limited, and is, for example, 2 to 1 million, and preferably 3 to 1 million.

The average pore diameter of the plurality of micropores 211 may be appropriately selected in consideration of the size of the object to be held, the size of the object to be separated, and the like. For example, when separating megakaryocytes and platelets, the average pore diameter is 2 to 15 μm. Preferably, it is 3 to 6 μm. Further, when separating platelets and proteins such as growth factors, the thickness is preferably 0.1 to 2.0 μm, more preferably 0.2 to 1.0 μm.

The cross-sectional shape of the micropores 211 in the porous separation layer 21 in the thickness direction of the separation layer 21 (hereinafter also simply referred to as the cross-sectional shape) allows the separation target to pass from the third surface 203 side to the fourth surface 204 side. The shape is not particularly limited, but may be a plurality of micro holes penetrating the separation layer 21, for example, a straight hole shape as shown in FIGS. 1 (a) to 1 (c). It may have a shape, or a shape such as a partially tapered shape or a partially inverted tapered shape. Or the random hole which a nonwoven fabric, Nitto Denko Co., Ltd. TEMISH (trademark), etc. have may be sufficient. In addition, the cross-sectional shape and hole diameter of the plurality of micro holes 211 may be the same or different.

Here, when the separation target is a cell, stress (damage) to the cell that is the separation target can be reduced. Therefore, the shape of the micropore 211 in the separation layer 21 is a cross-section in the thickness direction of the separation layer 21. In this case, it is preferable that the hole diameter of the minute hole 211 decreases from the third surface 203 side to the fourth surface 204 side (taper shape). For example, when separating platelets from megakaryocytes, the pore diameter of the micropores 211 on the third surface 203 side is preferably 10 μm or more, more preferably 20 μm or more, and the micropores on the fourth surface 204 side. The hole diameter of the hole 211 is preferably 10 μm or less, and more preferably 5 μm or less.

Pore density in the surface of the porous separation layer 21 having a plurality of micropores 211 (third surface 203 and a fourth surface 204) is not particularly limited, 10 ⁴ pore density of micropores 211 in the separation layer 21 is / Cm ² or more is preferable because separation efficiency is improved by parallel processing. More preferably, it is 10 ⁵ pieces / cm ² or more, and further preferably 10 ⁶ pieces / cm ² or more. On the other hand, it is preferable that the pore density is 10 ⁸ pieces / cm ² or less because the porosity is not excessively increased and strength reduction can be prevented. More preferably, it is 10 ⁷ pieces / cm ² or less, and still more preferably 10 ⁶ pieces / cm ² .

The thickness of the separation layer 21 is not particularly limited, and may be appropriately selected in consideration of the size of the separation object. For example, when separating megakaryocytes and platelets, the thickness is preferably 5 to 100 μm and more preferably 10 to 50 μm from the viewpoint of prevention of clogging and sheet strength.

As a material constituting the separation layer 21, an organic material such as a polymer material or an inorganic material such as silicon or metal can be used. Moreover, you may use a nonwoven material and porous materials, such as Nitto Denko Corporation TEMISH (trademark). Here, in order to use it as a separation device for regenerative medicine, such as when separating megakaryocytes and platelets, non-reactive polymer materials and biocompatible metal materials are used because they do not exhibit cytotoxicity. Etc. are preferred.

In the separation device 1 of this embodiment, the structure 11 and the separation layer 21 may be directly laminated, or may be indirectly laminated using an adhesive or the like. Note that the state in which the structure 11 and the separation layer 21 are directly stacked means that no other layer is interposed between the structure 11 and the separation layer 21, and the second surface 102 of the structure 11 and the separation layer 21 are not present. This shows that the third surface 203 is in direct contact.

When the structure 11 and the separation layer 21 are directly laminated, at least one of the structure 11 and the separation layer 21 is preferably formed of a flexible material such as a polymer material. If at least one of the structure 11 and the separation layer 21 is formed of a flexible material such as a polymer material, the adsorbing effect using the suction force from the micropores 211 can be used without using an adhesive or the like. The structure 11 and the separation layer 21 can be directly adhered with high adhesion. In addition, a gel material such as silicone resin or gelatin is particularly preferable because it has excellent wettability and can further enhance the adsorption effect.

The micro holes 211 in the separation layer 21 are formed at positions where the micro holes 211 in the third surface 203 of the separation layer 21 are connected to at least the through holes 111 in the second surface 102 of the structure 11. However, the micropores 211 are preferably formed on the entire surface of the separation layer 21. That is, the entire separation layer 21 is preferably porous. In the separation device 1 having such a configuration, even when a deviation occurs between the structure 11 and the separation layer 21 during use, the state in which the micro holes 211 are connected to each through-hole 111 is obtained. Since it can ensure, the separation function of the separation device 1 can be continuously secured. Such a configuration is particularly useful when the structure 11 and the separation layer 21 are directly laminated. Further, the separation layer 21 which is entirely porous is advantageous in terms of productivity.

Further, from the viewpoint of easy processing into a desired shape such as a cylindrical shape or a curved surface shape, it is preferable that both the structure 11 and the separation layer 21 are formed of a polymer material.

In addition, the separation device 1 of the present embodiment only needs to include at least the structure 11 and the separation layer 21, but may further include other layers such as a surface coating agent layer according to desired characteristics. Good. Further, the separation device 1 of the present embodiment may include a plurality of at least one of the structure 11 and the separation layer 21.

Next, each manufacturing process of the separation device 1 of the present embodiment will be described.

First, the manufacturing process of the structure 11 which comprises the separation device 1 of this invention is demonstrated.
In the case of manufacturing the structure 11 using a polymer material, for example, known molding methods such as compression molding, injection molding, and hot roll transfer can be appropriately applied. In addition, a semi-cured polymer material is molded by pressure using a mold corresponding to the shape of the through-hole of the target structure, and heated to allow the curing to proceed completely. It is also possible to manufacture the structure 11 having the through hole 111 having a shape to be formed. Or the structure 11 which has the through-hole 111 of the target shape can also be manufactured by laser drilling to a polymeric material.
Moreover, also when manufacturing the structure 11 using inorganic materials, such as a ceramic and a metal, a well-known shaping | molding method and manufacturing method can be applied suitably.

Moreover, as a manufacturing method of the porous separation layer 21, a well-known manufacturing method is suitably applied as a manufacturing method of a porous material according to the kind of material which comprises the separation layer 21, and the hole diameter of the micropore 211. it can.
For example, in order to form the separation layer 21 having a plurality of micropores 211 having a straight hole shape using a polymer material, a resin film having a plurality of through-holes described in JP-A-2015-164728 is produced. A method or the like can be appropriately employed.
As the porous separation layer 21, a commercially available nonwoven fabric or TEMISH (registered trademark) manufactured by Nitto Denko Corporation can also be used.

The separation device 1 of this embodiment can be manufactured by laminating the structure 11 and the separation layer 21 thus obtained directly or indirectly via an adhesive or the like.

Hereinafter, the present invention will be described in detail with reference to examples. However, the present invention is not limited to these examples.

(Comparative Example 1)
Filter paper for Kiriyama funnel with a reserved particle diameter of 4 μm No. 5A (manufactured by Kiriyama Seisakusho Co., Ltd.) was used as the separation device (filter) of Comparative Example 1.

(Comparative Example 2)
A separation layer A (Osydisk manufactured by Oxyphen) having a thickness of 3.0 μm formed with a pore having a diameter of 3.0 μm formed on a non-porous base sheet made of PET by ion beam irradiation and etching was separated into a separation layer. Only as a separation device (filter) of Comparative Example 2.

A microphotograph of one surface of the separation membrane A was taken, and the number of holes per fixed area was counted to measure the micropore density of the separation membrane A at 10 locations. As a result, the density of the through holes was 3.0 × 10 ³ to It was 5.0 × 10 ³ pieces / mm ² .

Example 1
The separation membrane A used in Comparative Example 2 was used as the separation layer 21.

A taper-shaped through-hole sheet B having a 25 mm square and a thickness of 400 μm was produced by heat press molding using a semi-cured silicone resin sheet as the structure 11 and a mold having a plurality of convex shapes.
The semi-cured silicone resin sheet was prepared by mixing 99.0 wt% of methylated silicone (manufactured by Nitto Denko, KL-100) with 1.0 wt% of dimethylsilylated silica (manufactured by Nippon Aerosil Co., Ltd., AEROSIL R976S). It was obtained by coating to a thickness of 300 μm using a coating apparatus (PI-1210, manufactured by Tester Sangyo) and heating at 130 ° C. for 10 minutes with a dryer.

The tapered through-hole sheet B has a tapered shape in which one side of the through-hole is 500 μm square (equivalent circle diameter: about 564 μm) and the other side is 250 μm square (equivalent circle diameter: about 282 μm). Through holes of 50 × 50 = 2500 holes are formed.

As shown in FIG. 1B, the tapered through-hole sheet B is installed so that the surface side of the through-hole having a 250 μm square is laminated on the separation membrane A, and a laminated body is produced. Used as a separation device (filter). Here, about 200,000 fine holes of the separation membrane A are connected to one 250 μm square through hole of the tapered through hole sheet B.

(Example 2)
As shown in FIG. 1C, a laminated body was produced in the same manner as in Example 1 except that the tapered through-hole sheet B was placed so that the surface side with the through-hole of 500 μm square was laminated on the separation membrane A. This was used as the separation device (filter) of Example 2. Here, about 750,000 micropores of the separation membrane A are connected to one 500 μm square through hole of the tapered through hole sheet B.

(Example 3)
As a separation membrane A, a separation device was produced by performing the same operation as in Example 1 except that a separation membrane having a diameter of through-holes of 1.0 μm was used.

Example 4
As a separation membrane A, a separation device was manufactured by performing the same operation as in Example 1 except that a separation membrane having a diameter of through-holes of 0.5 μm was used.

(Test 1)
Polystyrene particles 1 having an average particle size of 2.0 μm (CV value 5%, 2.5 wt%) (Polybeads manufactured by Polysciences), polystyrene having an average particle size of 6.0 μm (CV value 10%, 2.5 wt%) Particles 2 (manufactured by Polysciences, polybead), and polystyrene particles 3 in which polystyrene particles 1 and polystyrene particles 2 are mixed at a weight ratio of 1: 1, each diluted 10 times with ion-exchanged water, are used. The particle passage ability and retention ability of the filter were evaluated.

Each filter is set on a Kiriyama funnel, and 2 ml of polystyrene particle aqueous dispersion (0.25 wt%, particle amount 5 mg) is dropped while sucking from below, and particles remaining on and in the filter due to weight increase after dropping. The particle passing ability was confirmed by measuring the amount. The filters of Examples 1 and 2 were set on the Kiriyama funnel so that the tapered through-hole sheet B was on the upper side and the separation membrane A was on the lower side (Kiriyama funnel side).
Moreover, each filter carrying the remaining particles was set on a Kiriyama funnel, washed with 100 ml of ion-exchanged water while being sucked from below, and the particle retention ability was measured from the change in weight after washing.
These results are shown in Tables 1 and 2. Table 1 shows the results of evaluating the particle passage ability and retention ability for each of the polystyrene particles 1 to 3 for the filters of Examples and Comparative Examples in terms of the amount of remaining particles (unit: mg). These are the results of evaluating these by the ratio (% by weight) to the amount of particles (5 mg) before treatment. The results in Table 2 are summarized in the graphs of FIGS.
In Tables 1 and 2 and FIGS. 2 to 4, the column “2 μm” is the evaluation result when polystyrene particles 1 are used, and the column “6 μm” is the evaluation result when polystyrene particles 2 are used. The column of “2 + 6 μm” is an evaluation result when polystyrene particles 3 are used.

As shown in Tables 1 and 2 and FIGS. 2 to 4, the separation devices (filters) of Example 1 and Example 2 having both the separation membrane A and the tapered through-hole sheet B are based on the separation membrane A having micropores. The tapered through-hole sheet B having a high separation performance and having a through-hole laminated on the upper part of the separation membrane A can keep many particles after washing.

(Test 2)
Polystyrene particles 4 having an average particle size of 1.0 μm (CV value 5%, 2.5 wt%) (Polybeads manufactured by Polysciences), polystyrene having an average particle size of 0.5 μm (CV value 5%, 2.5 wt%) Particles 5 (manufactured by Polysciences, polybead) and polystyrene particles 6 having an average particle diameter of 0.2 μm (CV value 5%, 2.5 wt%) (polysciences, polybead) were each 10 in ion-exchanged water. Using the one diluted twice, the particle passing ability of each filter was evaluated.

Each filter is set on a Kiriyama funnel, and 2 ml of polystyrene particle aqueous dispersion (0.25 wt%, particle amount 5 mg) is dropped while sucking from below, and particles remaining on and in the filter due to weight increase after dropping. The particle passing ability was confirmed by measuring the amount. The filters of Examples 3 and 4 were set on the Kiriyama funnel so that the tapered through-hole sheet B was on the upper side and the separation membrane A was on the lower side (Kiriyama funnel side).
The results are shown in Table 3. As shown in Table 3, the separation devices (filters) of Example 3 and Example 4 having both the separation membrane A and the tapered through-hole sheet B have high separation performance due to the separation membrane A having micropores. all right.

The preferred embodiments of the present invention have been described above. However, the present invention is not limited to the above-described embodiments, and various modifications may be made to the above-described embodiments without departing from the scope of the present invention. And substitutions can be added.

Although the invention has been described in detail with reference to specific embodiments, it will be apparent to those skilled in the art that various changes and modifications can be made without departing from the spirit and scope of the invention.
This application is based on a Japanese patent application (Japanese Patent Application No. 2016-098854) filed on May 17, 2016, and is incorporated by reference in its entirety.

DESCRIPTION OF SYMBOLS 1 Separation device 11 Structure 21 Separation layer 101 1st surface 102 2nd surface 111 Through-hole 203 3rd surface 204 4th surface 211 Micro hole

Claims

A structure having a first surface and a second surface facing the first surface, and having a through-hole penetrating between the first surface and the second surface;
A separation device comprising a third surface and a porous separation layer having a fourth surface facing the third surface,
The structure and the separation layer are laminated so that the second surface side of the structure and the third surface side of the separation layer face each other.
A separation device in which a pore diameter of the micro hole in the third surface of the separation layer is smaller than a diameter of the through hole in the second surface of the structure.
The separation device according to claim 1, wherein the entire separation layer is porous.
The separation device according to claim 1 or 2, wherein a plurality of the micropores in the third surface of the separation layer are connected to the through-hole in the second surface of the structure.
The separation device according to any one of claims 1 to 3, wherein the structure and the separation layer are directly laminated.
The separation device according to any one of claims 1 to 4, wherein at least one of the structure and the separation layer is formed of a polymer material.
The separation device according to any one of claims 1 to 5, wherein the separation layer includes a plurality of micropores penetrating between the third surface and the fourth surface.
The separation device according to any one of claims 1 to 6, wherein a diameter of the through hole on the first surface side is larger than a diameter of the through hole on the second surface side.
The separation device according to any one of claims 1 to 6, wherein a hole diameter of the through hole on the first surface side is smaller than a hole diameter of the through hole on the second surface side.
A separation device for separating a holding object and a separation object,
The separation device according to any one of claims 1 to 8, wherein the micropore has a hole diameter that does not allow the holding object to pass therethrough and allows the separation object to pass therethrough.
The separation device according to claim 9, wherein the object to be held is held by the through hole.