JP2019162624A - Filtration device and filtration method - Google Patents

Abstract

To provide a filtration device and a filtration method which suppresses clogging due to a substance originated from organism and can separate the substance originated from organism from liquid.SOLUTION: A filtration device 100A includes a container part 10 having an introduction port 11 for introducing liquid 60 which contains a substance 61 originated from organism and a discharge port 12 for discharging liquid, and a membrane part 20 which is provided between the introduction port and the discharge port of the container part and has a plurality of through-holes 21. Therein, the membrane part has a first principal plane VS1 and a second principal plane VS2 located on the upper side than the first principal plane, liquid is caused to pass through from the first principal plane to the second principal plane of the membrane part and, thereby, the substance originated from organism is separated from liquid.SELECTED DRAWING: Figure 1

Description

  The present invention relates to a filtration apparatus and a filtration method for filtering a biological material in a liquid.

  In recent years, a cell trapping system that filters biological substances in a liquid has been disclosed (for example, see Patent Document 1). The cell capture system disclosed in Patent Document 1 captures cells by passing a liquid containing cells as a biological substance from the upper side to the lower side in the vertical direction of the filter.

International Publication No. 2015/019889

  The cell capture system of Patent Document 1 has a problem that clogging occurs due to the deposition of biological material on the filter, making it impossible to separate the biological material from the liquid.

  The present invention solves the above-described problems, and an object of the present invention is to provide a filtration device and a filtration method capable of suppressing clogging caused by a biological substance and separating the biological substance from a liquid.

The filtration device according to one embodiment of the present invention includes:
A container having an inlet for introducing a liquid containing a biological substance and an outlet for discharging the liquid;
A membrane part provided between the inlet and the outlet of the container part and having a plurality of through holes;
With
The film portion has a first main surface and a second main surface located above the first main surface,
The biological substance is separated from the liquid by allowing the liquid to pass from the first main surface to the second main surface of the membrane portion.

The filtration method of one embodiment of the present invention includes:
A method of filtering biological material from a liquid,
A container part having an inlet for introducing a liquid containing a biological substance and an outlet for discharging the liquid, and provided between the inlet and the outlet of the container part, and having a plurality of through holes A step of preparing a filtration device comprising a membrane part,
Separating the biological material from the liquid by allowing the liquid to pass from the first main surface of the membrane portion to a second main surface located above the first main surface;
including.

  ADVANTAGE OF THE INVENTION According to this invention, the filtration apparatus and filtration method which can suppress clogging by a biological material and can isolate | separate a biological material from a liquid can be provided.

1 is a schematic configuration diagram of a filtration device according to a first embodiment of the present invention. Schematic which shows a part of film | membrane part in Embodiment 1 which concerns on this invention. Schematic of a part of the film part of FIG. 2 as seen from the thickness direction The flowchart which shows the filtration method of Embodiment 1 which concerns on this invention. The figure which shows operation | movement of the filtration apparatus of Embodiment 1 which concerns on this invention. The figure which shows operation | movement of the filtration apparatus of Embodiment 1 which concerns on this invention. The figure which shows operation | movement of the filtration apparatus of Embodiment 1 which concerns on this invention. The figure which shows operation | movement of the filtration apparatus of Embodiment 1 which concerns on this invention. The figure which shows the operation of the filtration device of the reference example The figure which shows the operation of the filtration device of the reference example The figure which shows the operation of the filtration device of the reference example The figure which shows the operation of the filtration device of the reference example The figure which shows the measurement result of the biological substance concentration contained in the liquid in the filtration apparatus of Embodiment 1 which concerns on this invention. The figure which shows the measurement result of the biological substance concentration contained in the liquid in the filtration apparatus of a reference example The figure which shows the measurement result of the leak rate of the biological material in the filtration apparatus of Embodiment 1 which concerns on this invention The figure which shows the measurement result of the leak rate of the biological material in the filtration apparatus of a reference example Schematic block diagram of a filtration device of a modification of the first embodiment according to the present invention Schematic configuration diagram of a filtration device according to a second embodiment of the present invention The figure which shows operation | movement of the filtration apparatus of Embodiment 2 which concerns on this invention. The figure which shows operation | movement of the filtration apparatus of Embodiment 2 which concerns on this invention. The figure which shows operation | movement of the filtration apparatus of Embodiment 2 which concerns on this invention. The figure which shows operation | movement of the filtration apparatus of Embodiment 2 which concerns on this invention. Schematic configuration diagram of a filtration device according to a third embodiment of the present invention The figure which shows operation | movement of the filtration apparatus of Embodiment 3 which concerns on this invention. The figure which shows operation | movement of the filtration apparatus of Embodiment 3 which concerns on this invention. Schematic configuration diagram of a filtration device according to a fourth embodiment of the present invention The figure which shows operation | movement of the filtration apparatus of Embodiment 4 which concerns on this invention. The figure which shows operation | movement of the filtration apparatus of Embodiment 4 which concerns on this invention. The figure which shows operation | movement of the filtration apparatus of Embodiment 4 which concerns on this invention. The figure which shows operation | movement of the filtration apparatus of Embodiment 4 which concerns on this invention. The figure which shows operation | movement of the filtration apparatus of Embodiment 4 which concerns on this invention. The figure which shows operation | movement of the filtration apparatus of Embodiment 4 which concerns on this invention.

The filtration device according to one embodiment of the present invention includes:
A container having an inlet for introducing a liquid containing a biological substance and an outlet for discharging the liquid;
A membrane part provided between the inlet and the outlet of the container part and having a plurality of through holes;
With
The film portion has a first main surface and a second main surface located above the first main surface,
The biological material may be separated from the liquid by allowing the liquid to pass from the first main surface to the second main surface of the membrane portion.

  With such a configuration, the clogging of the film portion due to the deposition of the biological material can be suppressed, and the biological material can be separated from the liquid.

  In the filtration device, the film part may be a metal thin film.

  With such a configuration, even when a force is applied to the film part, the film part can be prevented from being deformed.

  In the filtration device, at least a part of the membrane part may be provided obliquely with respect to the vertical direction.

  With such a configuration, the clogging of the film part due to the biological substance can be further suppressed.

  In the said filtration apparatus, you may provide the suction part which attracts | sucks the said liquid from the said inlet of the said container part to the said discharge port.

  With such a configuration, the biological substance can be separated from the liquid by sucking the liquid. Moreover, a biological substance can be separated from the liquid in a short time.

The filtration device includes a liquid container that holds the liquid,
The inlet of the container portion is disposed in the liquid held in the liquid container,
The liquid container may be provided with a vent for releasing pressure applied to the liquid.

  With such a configuration, by releasing the pressure applied to the liquid held in the liquid container from the vent, the pressure applied to the biological substance in the liquid in the liquid container can be reduced, and the biological substance is damaged. Can be reduced. As a result, clogging due to the deformation of the biological substance can be suppressed in the film part.

  In the said filtration apparatus, you may provide the moving part which moves the said film | membrane part below.

  With such a configuration, it is possible to maintain the state in which the film part is arranged near the liquid surface by moving the film part downward as the liquid decreases. Therefore, clogging due to a biological substance in the film part can be further suppressed.

The filtration method of one embodiment of the present invention includes:
A method of filtering biological material from a liquid,
A container part having an inlet for introducing a liquid containing a biological substance and an outlet for discharging the liquid, and provided between the inlet and the outlet of the container part, and having a plurality of through holes A step of preparing a filtration device comprising a membrane part,
Separating the biological material from the liquid by allowing the liquid to pass from the first main surface of the membrane portion to a second main surface located above the first main surface;
May be included.

  With such a configuration, the clogging of the film portion due to the deposition of the biological material can be suppressed, and the biological material can be separated from the liquid.

  In the filtration method, in the separation step, the liquid may be passed through the film part provided at least partially obliquely with respect to the vertical direction.

  With such a configuration, the clogging of the film part due to the biological substance can be further suppressed.

  In the filtration method, the separating step may include a step of sucking the liquid from the introduction port of the container part to the discharge port.

  With such a configuration, the biological substance can be separated from the liquid by sucking the liquid. Moreover, a biological substance can be separated from the liquid in a short time.

  In the filtration method, the separating step may include a step of releasing pressure applied to the liquid.

  With such a configuration, the pressure applied to the liquid can be released. Therefore, the clogging due to the deformation of the biological substance can be suppressed in the film part. In addition, damage to biological materials can be reduced.

  In the filtration method, the separating step may include a step of moving the membrane portion downward.

  With such a configuration, it is possible to maintain the state in which the film portion is disposed near the liquid surface by moving the film portion downward as the liquid decreases. Therefore, clogging due to a biological substance in the film part can be further suppressed.

  Hereinafter, embodiments according to the present invention will be described with reference to the accompanying drawings. In each drawing, each element is exaggerated for easy explanation.

(Embodiment 1)
[overall structure]
FIG. 1 is a schematic diagram of a filtration device 100A according to Embodiment 1 of the present invention. As shown in FIG. 1, the filtration device 100 </ b> A includes a container unit 10 that introduces a liquid 60 containing a biological substance 61, a membrane unit 20 that separates the biological substance 61 from the liquid 60, and a liquid container that holds the liquid 60. 30, a suction unit 40 that sucks the liquid 60, and a moving unit 50 that moves the film unit 20.

  In the present specification, the “biological substance” means a substance derived from a living organism such as a cell (eukaryotic organism), a bacterium (eubacteria), or a virus. Examples of cells (eukaryotes) include eggs, sperm, induced pluripotent stem cells (iPS cells), ES cells, stem cells, mesenchymal stem cells, mononuclear cells, single cells, cell masses, suspension cells, and adhesions. Includes sex cells, nerve cells, leukocytes, lymphocytes, cells for regenerative medicine, autologous cells, cancer cells, circulating cancer cells (CTC), HL-60, HELA, and fungi. Examples of bacteria (true bacteria) include gram positive bacteria, gram negative bacteria, Escherichia coli, and tuberculosis bacteria. Examples of the virus include DNA virus, RNA virus, rotavirus, (bird) influenza virus, yellow fever virus, dengue fever virus, encephalitis virus, hemorrhagic fever virus, and immunodeficiency virus. In Embodiment 1, filtration device 100A is particularly excellent in separating artificial pluripotent stem cells (iPS cells), ES cells, stem cells, and circulating cancer cells (CTC) in blood. In addition, the biological substance may be a tissue in which cells are collected or an aggregated cell.

<Container part>
The container unit 10 has a cylindrical shape, and includes an introduction port 11 for introducing the liquid 60 at one end and a discharge port 12 for discharging the liquid 60 at the other end. As shown in FIG. 1, in Embodiment 1, the container part 10 is arrange | positioned so that the axial direction of the container part 10 may turn into the same direction as a perpendicular direction. The introduction port 11 of the container part 10 is located vertically below the discharge port 12. A film part 20 is provided at the inlet 11 of the container part 10. Further, the inlet 11 of the container unit 10 is disposed in the liquid 60 held in the liquid container 30. The discharge port 12 of the container unit 10 is connected to the suction unit 40 via the tube 41. A moving part 50 is attached to the outer wall of the container part 10.

  The container portion 10 is formed of a resin such as acrylic, epoxy, polystyrene, or polycarbonate, glass mainly composed of silicon oxide, or the like. The container portion 10 may be formed of a thermoplastic resin such as polypropylene, polystyrene, or polycarbonate resin. The material of the container part 10 is preferably a material capable of various sterilizations such as gamma ray irradiation, autoclave, ethylene oxide gas, and the like. The container portion 10 has, for example, an outer diameter of 1 mm to 60 mm, an inner diameter of 0.5 mm to 50 mm, and a height of 5 mm to 300 mm within a range smaller than the outer shape.

<Membrane part>
The membrane unit 20 is a porous membrane that separates the biological material 61 from the liquid 60. Specifically, the film part 20 is a metal thin film having a plurality of through holes 21. In the first embodiment, the film unit 20 is a circular metal mesh, and has a pair of main surfaces facing each other, and a structure having a plurality of through holes 21 penetrating both main surfaces.

  In the first embodiment, as shown in FIG. 1, the main surface on the lower side in the vertical direction is the first main surface VS1, and the main surface located on the upper side in the vertical direction from the first main surface VS1 is the second main surface VS2. It is defined as In the present specification, the upward direction in the vertical direction is defined as the upper side, and the downward direction in the vertical direction is defined as the lower side. In the film part 20, the second main surface VS2 side is defined as the upper side and the first main surface VS1 side is defined as the lower side when viewed from the thickness direction of the film part 20. The film part 20 is provided in the introduction port 11 of the container part 10. In the first embodiment, the film unit 20 is disposed such that the first main surface VS1 and the second main surface VS2 are perpendicular to the inner wall of the container unit 10. That is, the first main surface VS1 and the second main surface VS2 of the film unit 20 are perpendicular to the direction in which the liquid 60 flows from the introduction port 11 to the discharge port 12 of the container unit 10 (arrow 80 shown in FIG. 1). Are arranged as follows.

  The plurality of through holes 21 are periodically arranged over the first main surface VS1 and the second main surface VS2 of the film unit 20. The film part 20 is made of nickel, for example. The dimensions of the film part 20 are, for example, a diameter of 6 mm and a thickness of 1.2 μm. The material of the film part 20 may be gold, silver, copper, platinum, iron, nickel, chromium, stainless steel, palladium, titanium, cobalt, and oxides or alloys thereof. In particular, as the material of the film part 20, when the biological substance 61 is captured, gold, nickel, stainless steel, and titanium are preferable. When the material of the film part 20 is nickel, the nickel surface may be plated with gold. Moreover, it is preferable that the material of the film | membrane part 20 is a material which can perform various sterilizations, such as gamma ray irradiation, an autoclave, and ethylene oxide gas.

  FIG. 2 is a schematic configuration diagram of a part of the film unit 20 that is a two-dimensional periodic structure. The X, Y, and Z directions in FIG. 2 indicate the vertical direction, horizontal direction, and thickness direction of the structure, respectively. FIG. 3 shows a view of a part of the film part 20 of FIG. 2 as viewed from the Z direction. As shown in FIGS. 2 and 3, the film part 20 may be a plate-like structure (lattice-like structure) in which a plurality of through holes 21 are arranged in a matrix at regular intervals. The film part 20 is a plate-like structure provided with a plurality of square through holes 21 when viewed from the Z direction which is the main surface side. The plurality of through holes 21 are provided at equal intervals in two arrangement directions parallel to each side of the square, that is, in the X direction and the Y direction in FIG. In addition, the through-hole 21 is not limited to a square, For example, a rectangle, a circle | round | yen, an ellipse etc. may be sufficient. Further, the arrangement of the holes is not limited to the square lattice arrangement, and for example, if the arrangement is a square arrangement, a rectangular arrangement in which the intervals in the two arrangement directions are not equal may be used, and a triangular lattice arrangement or a quasi-periodic arrangement may be used. The through hole 21 may be provided with a taper.

  The shape and size of the through-hole 21 of the membrane part 20 are appropriately designed according to the size and shape of the biological substance 61 to be filtered.

<Liquid container>
The liquid container 30 is a container that holds the liquid 60 containing the biological substance 61. The liquid container 30 is a container having an opening larger than the diameter of the container unit 10. As shown in FIG. 1, the inlet 11 of the container unit 10 is arranged in the liquid 60 held in the liquid container 30. In the first embodiment, a gap is formed between the outer wall of the container unit 10 and the inner wall of the liquid container 30. This gap functions as a vent 31 for releasing the pressure applied to the liquid 60 held in the liquid container 30. In the first embodiment, since the liquid 60 is sucked by the suction unit 40, the biological substance 61 is pressurized by a negative pressure. In the filtering device 100A, the liquid 60 can be opened to the outside by the vent 31. Therefore, the pressure applied to the biological substance 61 in the liquid 60 can be released to the outside.

<Suction part>
The suction unit 40 sucks the liquid 60 held in the liquid container 30 from the introduction port 11 of the container unit 10 to the discharge port 12. The suction part 40 is connected to the discharge port 12 of the container part 10 via the tube 41. In the first embodiment, the suction unit 40 is a syringe. As shown in FIG. 1, the suction part 40 sucks the liquid 60 held in the liquid container 30 by pulling the plunger of the syringe (arrow 81 shown in FIG. 1). Thereby, the liquid 60 in the liquid container 30 is sucked up by the suction part 40 from the introduction port 11 of the container part 10 to the discharge port 12 (arrow 80 shown in FIG. 1). In other words, the liquid 60 passes from the first main surface VS1 of the film unit 20 to the second main surface VS2 positioned on the upper side in the vertical direction from the first main surface VS1.

<Moving part>
The moving part 50 moves the film part 20 downward. Specifically, the moving unit 50 moves the film unit 20 toward the liquid 60 held in the liquid container 30. As shown in FIG. 1, in the first embodiment, the moving unit 50 is attached to the outer wall of the container unit 10. The moving part 50 moves the container part 10 vertically downward as the liquid 60 in the liquid container 30 is reduced by the suction part 40 (arrow 82 shown in FIG. 1). Thereby, the moving part 50 can maintain the state which has arrange | positioned the inlet 11 of the container part 10 in the liquid 60 by moving the container part 10 toward the direction 82. FIG. In the first embodiment, the film part 20 is arranged near the liquid surface of the liquid 60 held in the liquid container 30. The vicinity of the liquid surface is a portion where the concentration of the biological substance 61 is low in the liquid container 30. In the first embodiment, the first main surface VS1 of the film unit 20 provided at the inlet 11 is at least liquid. It is a position in contact with 60.

[Filtration method]
The filtration method according to Embodiment 1 will be described with reference to FIG.
FIG. 4 is a flowchart of the filtration method according to the first embodiment.

  As shown in FIG. 4, in step ST11, a filtering device 100A is prepared.

  In step ST12, the liquid 60 containing the biological substance 61 is introduced into the liquid container 30.

  In step ST <b> 13, the introduction port 11 of the container unit 10 is disposed in the liquid 60. Specifically, the inlet 11 of the container unit 10 is arranged in the liquid 60 held in the liquid container 30. The arrangement of the container unit 10 may be performed by the moving unit 50. The inlet 11 of the container unit 10 is disposed near the liquid surface of the liquid 60.

  In step ST <b> 14, the biological material 61 is separated from the liquid 60 by allowing the liquid 60 to pass through the membrane unit 20. Step ST14 includes step ST15 in which the liquid 60 in the liquid container 30 is sucked by the suction unit 40. In step ST15, by pulling the plunger of the suction part 40 (arrow 81 shown in FIG. 1), the liquid 60 held in the liquid container 30 is sucked from the inlet 11 of the container 10 to the outlet 12 ( Arrow 80 shown in FIG. By sucking the liquid 60 by the suction unit 40, the liquid 60 passes from the first main surface VS1 of the film unit 20 to the second main surface VS2 positioned on the upper side in the vertical direction from the first main surface VS1. When the liquid 60 passes through the membrane part 20, the biological substance 61 cannot pass through the through hole 21 and remains in the liquid container 30.

  Step ST14 includes step ST16 of releasing the pressure applied to the liquid 60 held in the liquid container 30. When the suction pressure is applied to the liquid 60 in the liquid container 30 by the suction unit 40, the biological material 61 may be deformed. Therefore, the pressure applied to the biological substance 61 in the liquid 60 can be reduced by releasing the pressure applied to the liquid 60 from the vent 31 of the liquid container 30.

  In step ST14, step ST17 for moving the film part 20 downward may be included. By sucking the liquid 60 by the suction unit 40, the liquid 60 held in the liquid container 30 decreases. By moving the container part 10 downward toward the liquid 60 in the liquid container 30 by the moving part 50, it is possible to maintain the state where the inlet 11 of the container part 10 is arranged near the liquid surface of the liquid 60.

  As described above, in the filtration method according to the first embodiment, the biological material 61 is separated from the liquid 60 by steps ST11 to ST16. In the filtration method according to the first embodiment, the liquid 60 that has passed through the membrane unit 20 can also be recovered.

[Operation of filtration device]
Operation | movement of 100 A of filtration apparatuses is demonstrated in detail using FIG. 5A-FIG. 5D.
5A to 5D show the operation of the filtration device 100A. 5A to 5D omit the suction unit 40 and the moving unit 50 in order to simplify the description.

  As shown in FIG. 5A, the inlet 11 of the container unit 10 is disposed in the liquid 60 held in the liquid container 30 before the filtration is started. At this time, the film unit 20 is disposed near the liquid surface of the liquid 60.

  As shown in FIG. 5B, the liquid 60 is sucked from the inlet 11 of the container 10 toward the outlet 12 by the suction part 40 (arrow 80 shown in FIG. 5B). The liquid 60 in the liquid container 30 passes from the first main surface VS1 of the film unit 20 to the second main surface VS2. When the liquid 60 passes through the membrane part 20, the biological substance 61 cannot be passed through the through hole 21 and is captured by the membrane part 20. Therefore, the biological material 61 starts to collect on the first main surface VS1 of the film unit 20.

  As illustrated in FIG. 5C, when the liquid 60 is continuously sucked in the direction 80, the biological substance 61 further gathers on the first main surface VS <b> 1 of the film unit 20 to form the cake layer A <b> 1. As the filtration time increases, the biological material 61 further gathers in the membrane part 20, so that the cake layer A1 becomes thicker.

  As shown in FIG. 5D, when the thickness of the cake layer A1 increases, the biological material 61 repeats the assembly and separation in the lower layer A2 of the cake layer A1. By the collection and separation of the biological material 61, the increase in the thickness of the cake layer A1 is stopped and clogging is suppressed, so that the filtration does not stop. That is, in the filtration device 100A, the cake layer A1 does not become thick enough to stop filtration, so that the separation of the biological material 61 can be continued.

The assembly and withdrawal of the biological material 61 will be described in detail.
When the cake layer A1 is formed on the first main surface VS1 of the film part 20, the through-hole 21 of the film part 20 is blocked by the cake layer A1, so that pressure resistance is generated. In the first embodiment, since the liquid 60 is sucked by the suction part 40, when the pressure resistance increases in the lower layer A2 of the cake layer A1, the suction force by the suction part 40 becomes small. In addition, a force in the direction of gravity due to its own weight is applied to the biological substance 61 in the liquid 60. In the lower layer A2 of the cake layer A1, when the suction force by the suction unit 40 is larger than the force in the direction of gravity, the biological material 61 collects in the cake layer A1. On the other hand, when the suction force by the suction unit 40 is smaller than the force in the direction of gravity, the biological substance 61 is detached from the cake layer A1. As described above, in the filtering device 100A, the collection and separation of the biological material 61 are repeated by the balance between the suction force of the suction unit 40 and the force in the direction of gravity. Moreover, the biological substance 61 can be detached from the cake layer A1 by vibration of the filtration device 100A. For example, the biological material 61 may be separated from the cake layer A1 by vibration generated by shaking the filtering device 100A up and down and / or left and right.

  Next, for comparison, a filtering device of a reference example will be described with reference to FIGS. 6A to 6D.

  The filtration device of the reference example includes a container part 110 having an introduction port 111 for introducing the liquid 60 and a discharge port 112 for discharging the liquid 60, and a membrane part 120 having a plurality of through holes. In the filtering device of the reference example, the introduction port 111 is positioned above the discharge port 112 in the vertical direction, and the film unit 120 is provided in the discharge port 112 of the container unit 110. In the filtering device of the reference example, the liquid 60 is allowed to pass from the second main surface VS12 of the membrane unit 120 to the first main surface VS11 positioned vertically below the second main surface VS12. That is, the filtering device 100A according to the first embodiment allows the liquid 60 to pass through the membrane portion 20 from the lower side in the vertical direction to the upper side, whereas the filtering device in the reference example is from the upper side in the vertical direction toward the lower side. The liquid 60 is passed through the membrane part 120. In the filtration device of the reference example, the liquid 60 is passed through the membrane part 120 by sucking the liquid 60 with a suction pump installed below.

  As shown to FIG. 6A, in the filtration apparatus of a reference example, the liquid 60 containing the biological material 61 flows toward the downward direction. That is, in the filtration device of the reference example, the liquid 60 flows from the inlet 111 of the container 110 toward the outlet 112 (arrow 80r shown in FIG. 6A). For this reason, the liquid 60 flowing in the container part 110 passes from the second principal surface VS12 of the film part 120 to the first principal surface VS11 located on the lower side in the vertical direction than the second principal surface VS12. When the liquid 60 passes through the membrane part 120, the biological substance 61 is captured by the membrane part 120. Therefore, the biological material 61 is deposited on the second main surface VS12 of the film unit 120.

  As shown in FIG. 6B, when the liquid 60 continues to flow in the direction 80r, a cake layer A3 is formed on the second main surface VS12 of the film part 120 due to the deposition of the biological material 61.

  As shown in FIG. 6C, the thickness of the cake layer A3 gradually increases as the capture of the biological substance 61 by the membrane unit 120 increases. At this time, the filtration gradually shifts from the second main surface VS12 of the film part 120 to the upper layer A4 of the cake layer A3. That is, the separation of the biological substance 61 is not performed in the membrane part 120 but in the upper layer A4 of the cake layer A3.

  As shown in FIG. 6D, when the biological substance 61 is further deposited on the second main surface VS12 of the film part 120, the thickness of the cake layer A3 is further increased. In the upper layer A4 of the cake layer A3, clogging due to the deposition of the biological material 61 proceeds. If clogging increases in the upper layer A4 of the cake layer A3, the liquid 60 cannot pass through the upper layer A4 of the cake layer A3.

  Thus, in the filtration device of the reference example, the biological substance 61 captured by the film unit 120 is deposited on the second main surface VS12 of the film unit 120. For this reason, since the cake layer A3 gradually increases as the amount of the biological substance 61 captured by the membrane portion 120 increases, clogging occurs in the upper layer A4 of the cake layer A3. As a result, in the filtering device of the reference example, the filtration is stopped due to clogging due to the deposition of the biological substance 61 captured by the membrane part 120, and the biological substance 61 cannot be separated from the liquid 60.

  On the other hand, in the filtration device 100A of the first embodiment, the collection and separation of the biological material 61 are repeatedly performed in the lower layer A2 of the cake layer A1 formed on the first main surface VS1 of the membrane unit 20. For this reason, in the filtration device 100A, the filtration does not stop due to clogging by the biological material 61. Therefore, the filtering device 100A can continue to separate the biological material 61 from the liquid 60 by suppressing clogging as compared with the filtering device of the reference example.

[effect]
<High concentration liquid filtration>
The filtration of the liquid 60 in the filtration device 100A and the filtration of the liquid 60 in the filtration device of the reference example will be described with reference to FIGS.
FIG. 7 shows the measurement result of the concentration of the biological substance 61 when the liquid 60 is filtered by the filtering device 100A. In FIG. 7, the vertical axis indicates the time (min) required for filtration, and the horizontal axis indicates the concentration (cell / ml) of the biological substance 61. FIG. 8 shows a measurement result of the concentration of the biological substance 61 when the liquid 60 is filtered by the filtration device of the reference example. In FIG. 8, the vertical axis indicates the time (min) required for filtration, and the horizontal axis indicates the concentration (cell / ml) of the biological substance 61. The concentration of the biological substance 61 means the number of biological substances 61 per ml. In addition, HL-60 which is a nucleated cell was used as a biological substance, and physiological saline was used as a solution.

The measurement conditions for filtration in FIGS. 7 and 8 will be described.
In the filtration device 100A and the filtration device of the reference example, after filtering the liquid 60 and extracting and discarding 80% of the liquid amount, the concentration of the liquid 60 containing the biological substance 61 captured by the membrane part was measured. . Further, the time required for filtering the liquid 60 was also measured.

Detailed conditions are shown below.
Diameter of membrane part: φ6mm
Diameter of through hole: 2.5 μm
Hole spacing between through holes: 3.6 μm
Syringe suction speed at the start of suction: 0.2 ml / min
Liquid volume: 1.0ml
Liquid extraction volume: 0.8ml

As shown in FIG. 7, in the filtering device 100A, when the liquid 60 is filtered to extract an amount of 80% and discarded, the upper limit concentration of the biological substance 61 in the liquid 60 is about 1.0 ×. 10 ⁷ cells / ml. Moreover, it took about 13 minutes to filter the liquid 60 and extract the liquid amount of 80%.

As shown in FIG. 8, in the filtration device of the reference example, when the liquid 60 is filtered to extract an amount of 80% and discarded, the upper limit concentration of the biological substance 61 in the liquid 60 is about 2.0. × 10 ⁶ cells / ml. Moreover, the time from filtering the liquid 60 to extracting the 80% liquid volume was about 20 min. In the filtration device of the reference example, an attempt was made to filter the liquid 60 having a biological substance 61 concentration of about 1.0 × 10 ⁷ cells / ml, but the filtration did not proceed even after 1 hour.

  Thus, the filtering device 100A can filter the liquid 60 having a high concentration in a shorter time than the filtering device of the reference example. That is, the filtering device 100A has a higher filtering concentration limit of the biological material 61 than the filtering device of the reference example, and can filter the liquid 60 in a shorter time.

<Leakage rate of biological materials>
The leak rate of the biological substance 61 in the filtration device 100A and the leak rate of the biological substance 61 in the filtration device of the reference example will be described with reference to FIGS.
FIG. 9 shows the measurement result of the leakage rate of the biological material 61 when the liquid 60 is filtered by the filtration device 100A. In FIG. 9, the vertical axis indicates the leakage rate (%) of the biological substance 61, and the horizontal axis indicates the concentration (cell / ml) of the biological substance 61. FIG. 10 shows the measurement result of the leakage rate of the biological material 61 when the liquid 60 is filtered by the filtration device of the reference example. The measurement conditions for the leakage rate of biological substances in FIGS. 9 and 10 are the same as the measurement conditions for filtration in FIGS. 7 and 8 described above. Leakage rate means the proportion of biological material that has passed through the membrane. The leak rate is calculated by (number of biological substances passing through the membrane part) / (number of biological substances contained in the liquid before filtration) × 100.

  As shown in FIG. 9, in the filtering device 100A, when the liquid 60 was filtered to extract an amount of 80% and discarded, the upper limit of the leakage rate of the biological material 61 was about 7%. That is, the recovery rate of the biological material 61 in the filtration device 100A was about 93%.

  As shown in FIG. 10, in the filtration device of the reference example, when the liquid 60 is filtered to extract an amount of 80% and discarded, the upper limit of the leakage rate of the biological material 61 is about 15%. It was. That is, the recovery rate of the biological material 61 in the filtration device 100A was about 85%.

  Thus, the filtering device 100A can achieve a higher recovery rate than the filtering device of the reference example. More specifically, in the filtration device of the reference example, the pressure in the vicinity of the membrane part 120 increases, and the biological material having high deformability originally deforms and may pass through the through hole of the membrane part 120. . On the other hand, in the case of the filtering device 100A, the pressure in the vicinity of the membrane unit 20 is relatively low, and the filtration operation can be performed while keeping the deformation of the biological material small, so that it passes through the through-hole of the membrane unit 20. Few. Therefore, the filtering device 100A can recover the biological material 61 at a higher recovery rate than the filtering device of the reference example.

  According to the filtering device 100A according to the first embodiment, the following effects can be obtained.

  In the filtration device 100A, the membrane unit 20 allows the liquid 60 containing the biological substance 61 to pass from the first main surface VS1 to the second main surface VS2 positioned vertically above the first main surface VS1. In other words, in the filtration device 100, the liquid 60 is passed through the membrane portion 20 from the lower side in the vertical direction toward the upper side to perform filtration. With such a configuration, it is possible to separate the biological substance 61 from the liquid 60 while suppressing clogging of the film unit 20 due to the deposition of the biological substance 61. As a result, in the filtering device 100A, the liquid 60 having a higher concentration is filtered in a shorter time as compared with the filtering device of the reference example that allows the liquid 60 to pass through the membrane portion 120 from the upper side to the lower side in the vertical direction. Can do. Further, in the filtration device 100A, the recovery rate of the biological material 61 can be increased as compared with the filtration device of the reference example. In the first embodiment, the filtering device 100A separates the biological material 61 and the liquid 60, but is not limited to this. For example, the filtration device 100A may filter a foreign substance having a size larger than that of the biological substance 61 contained in the liquid 60 by allowing the solution in the liquid 60 and the biological substance 61 to pass therethrough. Or 100A of filtration apparatuses may filter and classify | categorize the inorganic substance or organic substance from which the magnitude | size contained in the solution differs.

  In the filtration device 100A, the membrane unit 20 uses a metal thin film as a porous membrane. With such a configuration, it is possible to prevent the membrane portion 20 from being damaged by applying a force to the membrane portion 20. Further, even when the liquid 60 passes through the membrane part 20, since the through-hole 21 of the membrane part 20 is not easily deformed, the biological substance 61 is prevented from passing through the membrane part 20 due to the deformation of the through-hole 21. can do. Furthermore, damage to the film part 20 due to the liquid 60 can also be suppressed.

  In the filtration device 100 </ b> A, a vent 31 is provided to release the pressure applied to the liquid 60 by forming a gap between the outer wall of the container 10 and the inner wall of the liquid container 30. With such a configuration, the liquid 60 in the liquid container 30 can be opened to the outside. Therefore, the pressure applied to the liquid 60 by suction can be released from the vent 31, and the pressure applied to the biological substance 61 in the liquid 60 can be reduced. As a result, it is possible to suppress the biological material 61 from being deformed, and to reduce clogging in the film unit 20. The gas passing through the vent 31 is preferably sterilized. This is to prevent the mixing of biological materials other than the biological material 61 originally contained in the liquid 60. Moreover, you may connect via the vent 31 with the gas bag which the biological substance containing the carbon dioxide moderately likes. Furthermore, when the capacity of the gas bag is large, the pressure applied to the liquid 60 by suction can be easily released.

  In the filtering device 100A, the suction part 40 sucks the liquid 60 held in the liquid container 30, thereby allowing the liquid 60 to pass from the first main surface VS1 to the second main surface VS2 of the film part 20. With such a configuration, the liquid 60 in the liquid container 30 can be passed through the membrane unit 20 and the biological material 61 can be separated from the liquid 60. Further, the suction can be performed in a shorter time by sucking the liquid 60 by the suction unit 40.

  In the filtration device 100 </ b> A, the moving unit 50 moves the container unit 10 toward the liquid 60 as the liquid 60 in the liquid container 30 decreases. With such a configuration, it is possible to perform filtration while maintaining the state in which the membrane portion 20 is disposed near the liquid surface where the concentration of the biological substance 61 is low. Further, by maintaining the state where the introduction port 11 of the container part 10 is arranged near the liquid surface of the liquid 60, it is possible to suppress the biological substance 61 from adhering to the outer wall of the container part 10.

  In addition, in Embodiment 1, although the container part 10 demonstrated the structure arrange | positioned so that the axial direction of the container part 10 may become the same as a perpendicular direction, it is not limited to this. For example, the container part 10 may be arrange | positioned so that the axial direction of the container part 10 may become diagonal with respect to a perpendicular direction. As described above, the filtering device 100A may be arranged in an oblique direction to perform filtration.

  In Embodiment 1, although the container part 10 demonstrated the structure which is a cylindrical body, it is not limited to this. The container unit 10 may be configured to introduce the liquid 60 therein, pass through the film unit 20 and discharge the liquid 60, and may have a polygonal column shape such as a square column.

  In the first embodiment, the film unit 20 uses a metal thin film, but is not limited thereto. The membrane unit 20 may be a porous membrane, and may be a membrane, a filter paper, a nonwoven fabric, or the like, for example.

  In Embodiment 1, the film part 20 is provided in the introduction port 11 of the container part 10, but it is not limited to this. The film part 20 is not limited as long as the liquid 60 passes from the first main surface VS1 to the second main surface VS2 positioned on the upper side in the vertical direction from the first main surface VS1. For example, the film part 20 may be provided between the inlet 11 and the outlet 12 of the container part 10. The film part 20 may be provided in the discharge port 12. In the first embodiment, the example in which one film unit 20 is provided in the introduction port 11 of the container unit 10 has been described. However, the present invention is not limited to this. A plurality of film parts 20 may be provided between the inlet 11 and the outlet 12 of the container part 10. For example, the first film part 20 may be provided at the inlet 11 of the container part 10 and the second film part 20 may be provided above the first film part 20 in the vertical direction. Thus, the recovery rate can be improved by configuring the multistage filtration device 100A using the plurality of membrane portions 20. In addition, by designing the size of the through hole of the first film unit 20 and the size of the through hole of the second film unit 20 to be different, cells having two different sizes can be filtered. Thereby, a cell can be classified.

  In the first embodiment, the film unit 20 is disposed so that the first main surface VS1 and the second main surface VS2 are perpendicular to the vertical direction, but the present invention is not limited to this. FIG. 11 shows a filtering device 100B according to a modification of the first embodiment. As in the filtration device 100B shown in FIG. 11, the membrane unit 20 may be arranged in an oblique direction with a predetermined angle θ with respect to the vertical direction. In other words, the film part 20 may be disposed to be inclined with respect to the horizontal direction. Moreover, a part of film | membrane part 20 may be arrange | positioned in the diagonal direction with respect to the perpendicular direction. With such a configuration, the allowable amount of the cake layer formed by the film part 20 is increased, so that the clogging of the film part 20 by the biological substance 61 can be further suppressed. That is, by disposing the membrane part 20 at an angle, the area where the membrane part 20 is in contact with the liquid 60 can be increased, and the filtration efficiency is improved.

  In the first embodiment, the liquid container 30 forms the air vent 31 by providing a gap between the outer wall of the container unit 10 and the inner wall of the liquid container 30, but the present invention is not limited to this. For example, the vent 31 may be formed by providing a hole in the side wall of the liquid container 30. Further, a ventilation filter may be provided instead of the ventilation port 31.

  In Embodiment 1, although the liquid container 30 demonstrated the structure provided with the vent 31 which releases the pressure concerning a liquid, it is not limited to this. For example, the liquid container 30 may be in a state where the vent 31 is not provided and the liquid 60 is not opened to the outside.

  In the first embodiment, the configuration in which the suction unit 40 sucks the liquid 60 in the liquid container 30 to allow the liquid 60 to pass through the film unit 20 has been described. However, the configuration is not limited thereto. For example, the liquid 60 may be passed from the first main surface VS1 to the second main surface VS2 of the film unit 20 by pressurizing the liquid 60 in the liquid container 30 from a position corresponding to the vent 31. Alternatively, the liquid 60 may be passed from the first main surface VS1 to the second main surface VS2 of the membrane unit 20 by applying a centrifugal force to the liquid 60 in the liquid container 30 using a centrifuge.

  In Embodiment 1, although the suction part 40 demonstrated the structure which is a syringe, it is not limited to this. For example, the suction unit 40 may be a pump or the like and may be any device that can suck the liquid 60.

  In the first embodiment, the liquid container 30, the suction unit 40, and the moving unit 50 are not essential components, and these elements may be omitted or replaced with other elements.

  In Embodiment 1, although 100 A of filtration apparatuses demonstrated the example used for filtration of the biological material 61, it is not limited to this. For example, the filtration device 100A may be used to replace the medium in the culture container in which the cells are cultured. Even when the medium is exchanged during the cell culture using the filtration device 100A, clogging of the membrane part 20 by the cells can be suppressed. For example, when exchanging the culture medium of adhesive cells, the adhesive cells themselves are attracted to the inner wall of the culture container, so that it is difficult to contact the membrane portion 20. For this reason, according to the filter device 100A, compared with the filter device of the reference example, the efficiency of exchanging the culture medium of the adhesive cells can be improved.

(Embodiment 2)
[overall structure]
A filtration device 100C according to the second embodiment of the present invention will be described with reference to FIG.
FIG. 12 shows a schematic configuration of a filtration device 100C according to the second embodiment. In the second embodiment, differences from the first embodiment will be mainly described. In the second embodiment, the same or similar components as those in the first embodiment will be described with the same or similar reference numerals. In the second embodiment, descriptions overlapping with those in the first embodiment are omitted.

  As shown in FIG. 12, in the filtering device 100C of the second embodiment, the first introduction port 11a for introducing the liquid 60 is more than the discharge port 12a for discharging the liquid 60, as compared with the filtering device 100A of the first embodiment. The difference is that the container portion 10a has a curved shape so as to be positioned on the upper side in the vertical direction. Further, the filtration device 100C does not include the liquid container 30, the suction unit 40, and the moving unit 50.

  The filtration device 100 </ b> C includes a container part 10 a that introduces a liquid 60 containing a biological substance 61 and a membrane part 20 a that separates the biological substance 61 from the liquid 60.

  The container part 10a has a first introduction port 11a for introducing the liquid 60 and a discharge port 12a for discharging the liquid 60, and is curved so that the first introduction port 11a is positioned above the discharge port 12a in the vertical direction. It has a shape. In the second embodiment, the container portion 10a has a U-shaped tube shape. Specifically, the bottoms of the two tubes are integrally formed by connecting them with a U-curved tube.

  In the second embodiment, the container section 10a has a first introduction port 11a for introducing the liquid 60 on one end side and a second introduction port 13 for introducing cleaning water, and a discharge port for discharging the liquid 60 on the other end side. 12a and an insertion port 14 into which a pipette 70 is inserted. Specifically, the 1st inlet 11a is provided in the end of the container part 10a. The 2nd inlet 13 is provided in the pipe | tube extended toward the upper direction provided in the side wall of the one end side of the container part 10a. The discharge port 12a is provided in a pipe extending in the horizontal direction provided on the side wall on the other end side of the container portion 10a. The insertion port 14 is provided at the other end of the container portion 10a. The first introduction port 11a and the second introduction port 13 on one end side of the container part 10a are provided at a position vertically above the discharge port 12a on the other end side.

  In the second embodiment, the film part 20a is a metallic thin film having a plurality of through holes 21, and is disposed between the first inlet 11a and the outlet 12a. Specifically, the membrane portion 20a is disposed at the bottom of the tube on the other end side of the container portion 10a, and is connected to a connection portion between the tube on the other end side and a tube curved in a U shape. The first main surface VS1 of the film unit 20a is located on the lower side in the vertical direction than the second main surface VS2.

[Operation of filtration device]
Operation | movement of 100 C of filtration apparatuses is demonstrated using FIG. 13A-FIG. 13D.
13A to 13C show the filtration operation in the filtration device 100C. FIG. 13D shows an operation of cleaning the biological substance 61 in the filtration device 100C.

  As shown to FIG. 13A, the liquid 60 containing the biological material 61 is introduce | transduced into the container part 10a from the 1st inlet 11a (arrow 83 shown to FIG. 13A). The liquid 60 introduced into the container portion 10a flows toward the discharge port 12a due to its own weight (arrow 85 shown in FIG. 13A). Specifically, since the liquid level of the liquid 60 located on one end side of the container portion 10a is higher than the liquid level of the liquid 60 located on the other end side by a predetermined distance h, the first introduction on the one end side is performed. The liquid 60 introduced from the mouth 11a flows in the direction of gravity by its own weight. The liquid 60 that flows in the direction of gravity flows through the curved portion in the container portion 10a while maintaining the momentum, and is discharged from the discharge port 12a. At this time, the liquid 60 flows from the first main surface VS1 of the film part 20a to the second main surface VS2 positioned on the upper side in the vertical direction from the first main surface VS1 (arrow 84 shown in FIG. 13A). For this reason, the biological material 61 can be captured in the first main surface VS1 of the film part 20a.

  As shown in FIG. 13B, when the trapping amount of the biological substance 61 increases on the first main surface VS1 of the film part 20a, a cake layer is formed by the trapped biological substance 61.

  As shown in FIG. 13C, when a cake layer is formed in the film part 20a, the pipette 70 is inserted from the insertion port. The liquid 60 is injected from the pipette 70 inserted into the insertion port 14 toward the membrane portion 20a (arrow 86 shown in FIG. 13C). The liquid 60 from the pipette 70 flows from the second main surface VS2 of the film unit 20 toward the first main surface VS1. For this reason, the liquid 60 that has passed through the film part 20a is pushed down from the second main surface VS2 of the film part 20a toward the first main surface VS1 (arrow 87 shown in FIG. 13C). The biological substance 61 captured by the first main surface VS1 of the film part 20a can be removed from the first main surface VS1 to remove the cake layer. After the cake layer is removed, the filtration device 100C can continue the filtration by removing the pipette 70 from the insertion port 14 and introducing the liquid 60 containing the biological substance 61 from the first introduction port 11a.

  In this way, the filtering device 100C filters the liquid 60 containing the biological material 61 by performing the operations shown in FIGS. 13A to 13C. Further, the filtration device 100C can also concentrate the liquid 60 by repeatedly performing the operations shown in FIGS. 13A to 13C.

  After filtration or concentration of the liquid 60, the filtration device 100C can wash the filtered biological material 61 by introducing wash water from the second introduction port 13, as shown in FIG. 13D. When the filtered biological material 61 is washed, the introduction of the liquid 60 from the first introduction port 11a is stopped, and washing water is introduced from the second introduction port 13 (arrow 88 shown in FIG. 13D). The washing water introduced from the second introduction port 13 passes through the inside of the container part 10 and is discharged from the discharge port 12a (arrow 85 shown in FIG. 13D). Further, when clogging due to the biological substance 61 occurs in the membrane part 20a, the pipette 70 is inserted into the insertion port 14, and washing water is injected from the pipette 70 toward the membrane part 20a (arrow 89 shown in FIG. 13D). . After the clogging is eliminated, the pipette 70 is taken out from the insertion port 14 and cleaning water is introduced from the second introduction port 13.

  Thus, the filtering device 100C can wash the filtered biological material 61 by performing the operation shown in FIG. 13D.

[effect]
According to the filter device 100C according to the second embodiment, the following effects can be obtained.

  In the filtering device 100C, the container portion 10a has a U-shaped tube shape in which the bottoms of two tubes are connected by a tube curved in a U shape. In the container part 10a, the 1st inlet 11a which introduce | transduces the liquid 60 provided in the one end side is located in the perpendicular direction upper side rather than the discharge port 12a which discharges | emits the liquid 60 provided in the other end side. Moreover, the film part 20a is arrange | positioned between the 1st inlet 11a of the container part 10a, and the discharge port 12, The 2nd main main body located in the perpendicular direction upper side from 1st main surface VS1 from 1st main surface VS1. The liquid 60 is allowed to pass through the surface VS2. With such a configuration, the liquid 60 is introduced into the first introduction port 11a by its own weight, so that the liquid 60 passes from the first main surface VS1 to the second main surface VS2 of the film portion 20a to the VS2. 61 can be separated.

  In the filtering device 100C, an insertion port 14 for inserting the pipette 70 is provided on the other end side of the container portion 10a. With such a configuration, when clogging occurs in the film portion 20a, the pipette 70 is inserted into the insertion port 14, and the liquid is directed from the pipette 70 toward the first main surface VS1 from the second main surface VS2 of the film portion 20a. 60 can be injected. The liquid 60 injected from the pipette 70 is formed on the first main surface VS1 of the film part 20a by pushing back the biological material 61 blocking the through hole 21 of the film part 20a to the first introduction port 11a side. The cake layer can be removed.

  Further, the pressure due to the injection of the liquid 60 from the pipette 70 does not become so great as to cause deformation of the biological material 61. Therefore, in the filtering device 100C, the clogging of the membrane portion 20a can be eliminated without damaging the biological material 61 using the pipette 70. Further, by repeatedly injecting (pipetting) the liquid 60 with the pipette 70, it is possible to maintain a state in which clogging does not occur in the film part 20a.

  In the filtration device 100C, a second introduction port 13 for introducing cleaning water is provided on one end side of the container portion 10a. With such a configuration, the biological material 61 captured by the membrane part 20a can be easily washed by introducing wash water from the second inlet 13 after the liquid 60 is filtered or concentrated.

  In addition, in Embodiment 2, although the structure which provided the 2nd inlet 13 which introduce | transduces washing water into one end side, and the insertion port 14 which inserts the pipette 70 in the other end side was demonstrated, it is not limited to this. For example, the structure which introduces washing water from the 1st inlet 11a, without providing the 2nd inlet 13 may be sufficient. Moreover, the structure which inserts the pipette 70 in the discharge port 12a, without providing the insertion port 14 may be sufficient. With such a configuration, the liquid 60 can be filtered with a simple configuration.

  In Embodiment 2, although the structure which introduce | transduces washing water from the 2nd inlet 13 was demonstrated, it is not limited to this. For example, a liquid (substitution liquid) different from the liquid 60 may be introduced from the second introduction port 13 and the liquid 60 in the container unit 10 may be replaced with another liquid.

  In the second embodiment, the pipette 70 inserted into the insertion port 14 is configured to inject the liquid 60 toward the film part 20a in order to remove the cake layer formed on the first main surface VS1 of the film part 20a. Although described, it is not limited to this. For example, the pipette 70 may be used for stirring the liquid 60 in the container part 10a. Further, the pipette 70 may introduce a replacement liquid toward the film part 20a and replace the liquid 60 in the container part 10 with another liquid. The pipette 70 may be pipetted in a closed system that does not allow the injection pressure of the liquid 60 from the pipette 70 to escape to the outside of the container portion 10a by being inserted so as to close the insertion port 14.

  In Embodiment 2, although the container part 10a demonstrated the U-shaped pipe | tube, it is not limited to this. For example, the curved U-shaped portion of the container portion 10a may be provided with a three-way branch for recovery using a rubber tube in order to provide flexibility and a difference in height between the left and right tubes. With such a configuration, the biological material 61 can be easily recovered.

  In Embodiment 2, although the structure which filters by the dead weight of the liquid 60 introduce | transduced from the 1st inlet 11a was demonstrated, it is not limited to this. For example, filtration may be performed by pressurizing the liquid 60 from the first introduction port 11a. With such a configuration, filtration can be performed in a short time.

  Although the example using the pipette 70 has been described in the second embodiment, the pipette 70 is not an essential configuration. For example, the pipette 70 may be omitted or may be replaced with other elements such as gas pressurization.

(Embodiment 3)
[overall structure]
A filtration device 100D according to Embodiment 3 of the present invention will be described with reference to FIG.
FIG. 14 shows a schematic configuration of the filtration device 100D of the third embodiment. In the third embodiment, differences from the first embodiment will be mainly described. In the third embodiment, the same or similar components as those in the first embodiment will be described with the same or similar reference numerals. In the third embodiment, descriptions overlapping with those in the first embodiment are omitted.

  As shown in FIG. 14, the filtering device 100D of the third embodiment has a configuration in which the container portion 10b can move on the inner wall of the liquid container 30b, compared to the filtering device 100A of the first embodiment. Different. Further, the filtering device 100D is different from the filtering device 100A in that the membrane portion 20b is provided obliquely with respect to the first side wall 10ba of the container portion 10b. The filtration device 100D does not include the suction unit 40.

  The filtration device 100D is disposed between a container portion 10b having an introduction port 11b for introducing a liquid 60 containing a biological substance 61 and a discharge port 12b for discharging the liquid 60, and the introduction port 11b and the discharge port 12b. A film part 20b having a plurality of through holes 21 and a liquid container 30b for holding the liquid 60 are provided. The container portion 10b is attached to the inside of the liquid container 30b and can move inside the liquid container 30b. The filtration device 100D moves the container part 10b downward, thereby causing the liquid 60 in the liquid container 30b to be positioned from the first main surface VS1 of the film part 20b to the upper side in the vertical direction from the first main surface VS1. It passes through VS2.

  In the third embodiment, the container portion 10b includes a first side wall 10ba disposed in the liquid container 30, a second side wall 10bb disposed outside the liquid container 30, a first side wall 10ba, and a second side wall 10bb. A third side wall 10bc to be connected is provided.

  The first side wall 10ba is an inner cylinder that is disposed in the liquid container 30 and is movable toward the liquid 60 held in the liquid container 30b. An inlet 11b through which the liquid 60 in the liquid container 30b is introduced is provided at one end of the first side wall 10ba, and an outlet 12b through which the liquid 60 is discharged is provided at the other end. The introduction port 11b is located on the lower side in the vertical direction than the discharge port 12b. A film portion 20b having a plurality of through holes 21 is disposed in the introduction port 11b.

  In the first side wall 10ba, the outer peripheral portion of the film part 20b is designed with a material and a dimension capable of sliding on the inner wall of the liquid container 30b. That is, the outer peripheral portion of the membrane portion 20b is designed so that the biological substance 61 does not pass between the outer peripheral portion of the membrane portion 20b and the liquid container 30b, and the membrane portion 20b faces the liquid 60 in the liquid container 30b. It is designed to be able to move.

  The second side wall 10 bb is an outer cylinder that is disposed outside the liquid container 30 and is slidable with respect to the outer wall of the liquid container 30. The second side wall 10bb includes a first moving unit 50a on the inner wall. The first moving part 50 a is engaged with the second moving part 50 b provided on the outer wall of the liquid container 30, and moves the container part 10 b toward the liquid 60. For example, the first moving part 50a is formed with an internal thread and is screwed with the second moving part 50b formed with an external thread.

  The third side wall 10bc is a ring-shaped member that connects the first side wall 10ba and the second side wall 10bb so as to form a space in which the side wall of the liquid container 30 enters between the first side wall 10ba and the second side wall 10bb. is there. Specifically, the third side wall 10bc connects the end of the first side wall 10ba on the discharge port 12b side and the upper end of the second side wall 10bb. The first side wall 10ba, the second side wall 10bb, and the third side wall 10bc may be integrally formed.

  The film portion 20b is disposed at the inlet 11b of the first side wall 10ba, and is disposed in an oblique direction with a predetermined angle θ with respect to the inner wall of the first side wall 10ba. In other words, the film part 20b is arranged to be inclined with respect to the horizontal direction. The diameter of the through-hole 21 of the membrane part 20b is designed to a size that allows the liquid 60 to pass through without passing the biological substance 61 to be filtered.

  The liquid container 30 b is a cylindrical container that holds the liquid 60 containing the biological substance 61. On the inner wall of the liquid container 30b, the first side wall 10ba of the container portion 10b is slidably disposed. The first side wall 10ba is movable downward toward the liquid 60 held in the liquid container 30b. The outer wall of the liquid container 30b includes a second moving unit 50b. The second moving part 50b engages with the first moving part 50a provided on the second side wall 10bb of the container part 10b. For example, the second moving part 50b is formed with a male screw as described above, and is screwed with the first moving part 50a formed with a female screw provided on the second side wall 10bb of the container part 10b.

[Operation of filtration device]
The operation of the filtration device 100D will be described with reference to FIGS. 15A and 15B.
15A and 15B show the filtering operation in the filtering device 100D.

  As shown in FIG. 15A, the container portion 10 b is removed from the liquid container 30 b, and the liquid 60 containing the biological substance 61 is introduced into the liquid container 30.

  As shown in FIG. 15B, the container portion 10b is attached to the liquid container 30b. Specifically, the first side wall 10ba of the container part 10b is arranged inside the liquid container 30b, and the first moving part 50a of the second side wall 10bb of the container part 10b and the second moving part 50b of the liquid container 30b are engaged. Combine. Then, by rotating the container part 10b in the circumferential direction 90, the container part 10b moves vertically downward toward the liquid 60 held in the liquid container 30b (arrow 91 shown in FIG. 15B). That is, the film part 20 b arranged at the introduction port 11 b of the container part 10 b moves vertically downward toward the liquid 60. For this reason, in the film part 20b, the liquid 60 in the liquid container 30b passes from the first main surface VS1 of the film part 20b to the second main surface VS2 (arrow 92 shown in FIG. 15B).

  In the third embodiment, the film part 20b provided obliquely with respect to the inner wall of the first side wall 10ba of the container part 10b moves toward the liquid 60 while rotating around the axis of the container part 10b. For this reason, the biological substance 61 adhering to the 1st main surface VS1 of the film | membrane part 20b can be peeled by the vibration by rotation.

  In the filtering device 100D, after the filtration is finished, for example, the liquid 60 is discharged from the discharge port 12b of the container portion 10b by turning the filtering device 100D upside down. Thereafter, a new liquid or a replacement liquid may be introduced. Alternatively, the liquid 60 may be discharged from the discharge port 12b by a method such as suction.

[effect]
According to the filtration device 100D according to Embodiment 3, the following effects can be obtained.

  In the filtration device 100D, the film part 20b is moved toward the liquid 60 held in the liquid container 30b by moving the container part 10b downward. Therefore, the liquid 60 in the liquid container 30b passes through the second main surface VS2 located on the upper side in the vertical direction from the first main surface VS1 of the film part 20b. With such a configuration, the biological substance 61 can be easily separated from the liquid 60 by gradually moving the film part 20 b toward the liquid 60.

  In the filtering device 100D, the liquid 60 extracted into the container portion 10b can be discharged from the discharge port 12b by turning the filtering device 100D upside down after the filtration is finished. Further, after discharging the liquid 60, by introducing a new liquid or a replacement liquid, it is possible to easily perform cleaning or liquid replacement. Thus, in the filtering device 100D, pipetting by a pipette or the like is not necessary, and user convenience is improved.

  In the filtering device 100D, the film part 20b is disposed obliquely with respect to the inner wall of the first side wall 10ba of the container part 10b. Therefore, when the film part 20b is moved toward the liquid 60 in the liquid container 30b, it is possible to suppress the biological substance 61 from adhering to the first main surface VS1 of the film part 20b. Thereby, clogging due to the adhesion of the biological substance 61 in the film part 20b can be suppressed.

  In the filtration device 100D, the membrane portion 20b moves downward while rotating. For this reason, the biological substance 61 adhering to the 1st main surface VS1 of the film | membrane part 20b can be peeled by the vibration produced by rotation of the film | membrane part 20b. Thereby, clogging due to the adhesion of the biological substance 61 in the film part 20b can be suppressed.

  In addition, in Embodiment 3, although the film | membrane part 20b demonstrated the structure provided diagonally with respect to the inner wall of 1st side wall 10ba of the container part 10b, it is not limited to this. For example, a part of the film part 20b may be provided obliquely with respect to the inner wall of the first side wall 10ba. The film part 20b may be provided perpendicular to the inner wall of the first side wall 10ba.

  In Embodiment 3, the configuration including the first moving part 50a provided on the inner wall of the second side wall 10bb of the container part 10b and the second moving part 50b provided on the outer wall of the liquid container 30 has been described. It is not limited to this. For example, the filtering device 100D is not provided with the first moving unit 50a and the second moving unit 50b, and is directed toward the liquid 60 held in the liquid container 30 by the weight of the film unit 20b and the container unit 10b. May be moved. Alternatively, the filtering device 100D may move the film part 20b toward the liquid 60 by pushing the third side wall 10bc downward.

  In the third embodiment, the second liquid is introduced inside the container portion 10b so that the liquid 60 can easily pass through the through hole 21 of the membrane portion 20b with the container portion 10b attached in the liquid container 30b. In the state, filtration may be started. That is, the filtration device 100D may start the filtration in a state where the second liquid is held on the second main surface VS2 of the film part 20b.

  In Embodiment 3, a stirring blade for stirring the liquid 60 may be provided inside the liquid container 30b. The stirring blade can suppress the biological substance 61 in the liquid 60 from adhering to the film part 20b.

(Embodiment 4)
[overall structure]
A filtration device 100E according to Embodiment 4 of the present invention will be described with reference to FIG.
FIG. 16 shows a schematic configuration of a filtration device 100E according to the fourth embodiment. In the fourth embodiment, differences from the first embodiment will be mainly described. In the fourth embodiment, the same or similar components as those in the first embodiment will be described with the same or similar reference numerals. In the fourth embodiment, descriptions overlapping with those in the first embodiment are omitted.

  As shown in FIG. 16, the filtration device 100E according to the fourth embodiment has a liquid 60 by applying a centrifugal force from the discharge port 12c of the container portion 10c to the introduction port 11c, as compared with the filtration device 100A according to the first embodiment. The difference is that it has a configuration capable of separating the biological material 61 from the biological material. Further, the filtration device 100E does not include the suction unit 40 and the moving unit 50.

  The filtration device 100E is disposed between a container portion 10c having an introduction port 11c for introducing the liquid 60 containing the biological substance 61 and a discharge port 12c for discharging the liquid 60, and the introduction port 11c and the discharge port 12c. A film part 20 c having a plurality of through holes 21 and a liquid container 30 c for holding the liquid 60 are provided. The container part 10c is attached inside the liquid container 30c. The filtering device 100E applies the centrifugal force in the direction from the discharge port 12c to the introduction port 11c of the container part 10c, thereby causing the liquid 60 in the liquid container 30c to flow from the first main surface VS1 to the first main surface VS1 of the film unit 20c. It passes through the second main surface VS2 located on the upper side in the vertical direction. That is, when a centrifugal force is applied, the liquid 60 flows in a direction opposite to the direction in which the centrifugal force is applied in the membrane portion 20c. The container portion 10c is provided with a deaeration hole.

  In Embodiment 4, the container part 10c is arrange | positioned in the liquid container 30c. In a state where the container portion 10c is disposed in the liquid container 30c, a lid 32 that covers the opening of the liquid container 30c is attached.

[Operation of filtration device]
Operation | movement of the filtration apparatus 100E is demonstrated using FIG. 17A-FIG. 17F.
17A to 17F show the filtration operation in the filtration device 100E.

  As shown in FIG. 17A, the container part 10c is removed from the liquid container 30c, and the liquid 60 containing the biological substance 61 is introduced into the liquid container 30c.

  As illustrated in FIG. 17B, the container portion 10 c is attached in the liquid container 30 c that holds the liquid 60. In the fourth embodiment, the lid 32 is attached in a state where the container portion 10c is held inside the liquid container 30c. That is, the inlet 11c of the container part 10c is disposed in the liquid 60 in the liquid container 30c. The lid 32 is attached by, for example, screwing a female screw provided inside the lid 32 and a male screw provided on the outer wall of the liquid container 30c.

  By attaching the container part 10c to the inside of the liquid container 30c, the liquid 60 held in the liquid container 30c is pushed up between the outer wall of the container part 10c and the inner wall of the liquid container 30c. In this state, the filtration device 100E is set in the centrifuge.

  As shown in FIG. 17C, when centrifugal force (arrow 93 shown in FIG. 17C) is applied in the direction from the discharge port 12c of the container part 10c to the introduction port 11c by a centrifuge (not shown), the outer wall of the container part 10c The liquid 60 pushed up between the inner wall of the liquid container 30c flows toward the bottom of the liquid container 30c (arrow 94 shown in FIG. 17C). At this time, the biological substance 61 collects at the bottom of the liquid container 30c. On the other hand, the liquid 60 passes from the first main surface VS1 of the film unit 20c to the second main surface VS2 positioned vertically above the first main surface VS1, and then from the introduction port 11c of the container unit 10c to the discharge port 12c. Flows toward (arrow 95 shown in FIG. 17C). And the height of the liquid level of the liquid 60 between the outer wall of the container part 10c and the inner wall of the liquid container 30c and the height of the liquid level of the liquid 60 which passed the film | membrane part 20c become the same. The height of the liquid surface of the liquid 60 between the outer wall of the container portion 10c and the inner wall of the liquid container 30c and the height of the liquid surface of the liquid 60 that has passed through the film portion 20c are the liquid container 30c at each location. This means the height of the liquid 60 from the bottom surface.

  As shown in FIG. 17D, the centrifuge is stopped and the lid 32 is removed from the liquid container 30c. After removing the lid 32, the liquid 60 that has passed through the membrane portion 20c is discharged. The liquid 60 is discharged by turning the liquid container 30c upside down with the container portion 10c attached to the liquid container 30c. At this time, the biological substance 61 accumulated at the bottom of the liquid container 30c cannot pass through the through hole 21 of the membrane part 20c. Therefore, the liquid 60 that does not contain the biological substance 61 is discharged from the discharge port 12c.

  As shown in FIG. 17E, a lid 32 is attached to the liquid container 30c, and centrifugal force from the outlet 12c to the inlet 11c is applied to the filtration device 100E by a centrifuge (arrow 93 shown in FIG. 17E). When centrifugal force is applied to the filtration device 100E, the liquid 60 between the outer wall of the container portion 10c and the inner wall of the liquid container 30c flows toward the bottom of the liquid container 30c, as in the operation shown in FIG. 17C (see FIG. 17E). Arrow 94). Then, the liquid 60 not containing the biological substance 61 flows from the bottom of the liquid container 30c to the introduction port 11c of the container 10c and passes through the membrane 20c (arrow 95 shown in FIG. 17E). And the height of the liquid level of the liquid 60 between the outer wall of the container part 10c and the inner wall of the liquid container 30c and the height of the liquid level of the liquid 60 which passed the film | membrane part 20c become the same.

  As shown in FIG. 17F, the centrifuge is stopped and the lid 32 is removed from the liquid container 30c. Thereafter, similarly to the operation shown in FIG. 17D, the liquid 60 that has passed through the film part 20c and accumulated inside the container part 10c is discharged from the discharge port 12c.

  As described above, the filtering device 100E separates the biological substance 61 from the liquid 60 by using the centrifugal force by performing the operations shown in FIGS. 17A to 17F. Furthermore, the filtration device 100E can concentrate the biological material 61 by repeating the operations shown in FIGS. 17A to 17F. Moreover, the filtration apparatus 100E can also wash | clean the biological material 61 by introduce | transducing washing water after concentration. In the filtration device 100E, after separating the biological material 61, the liquid 60 can be replaced with another liquid by introducing a replacement liquid.

[effect]
According to the filtration device 100E according to the fourth embodiment, the following effects can be obtained.

  In the filtration device 100E, when a centrifugal force is applied, the liquid 60 is passed through the membrane portion 20c in the direction opposite to the direction in which the centrifugal force is applied. Specifically, when a centrifugal force is applied to the filtering device 100C, the height of the liquid surface between the outer wall of the container part 10c and the inner wall of the liquid container 30c and the liquid 60 passing through the film part 20c. The liquid 60 is allowed to pass vertically upward through the film part 20c using the difference in height from the liquid level. With such a configuration, the biological substance 61 can be separated from the liquid 60 without clogging the membrane part 20 c with the biological substance 61. Further, in the filtration device 100E, the biological material 61 can be easily concentrated by repeatedly performing filtration by centrifugation.

  In the filtering device 100E, when the liquid 60 that has passed through the membrane portion 20c is taken out, for example, the liquid 60 can be easily discharged by turning the filtering device 100E upside down. Thus, in the filtering device 100E, pipetting by the operator is unnecessary, and the liquid 60 can be discharged without requiring a special skill from the operator. As a result, in the filtration device 100E, the recovery rate of the biological material 61 is not reduced by pipetting.

  In the filtration device 100E, after separating the biological material 61, the biological material 61 can be washed by introducing washing water and performing centrifugation. Further, in the filtration device 100E, after the biological material 61 is separated, the liquid can be easily replaced by introducing a replacement liquid.

  In addition, in Embodiment 4, although the structure provided with the lid | cover 32 was demonstrated, it is not limited to this. The lid 32 is not an essential component, and may be omitted or replaced with another element.

  Although the present invention has been fully described in connection with preferred embodiments with reference to the accompanying drawings, various variations and modifications will be apparent to those skilled in the art. Such changes and modifications are to be understood as included within the scope of the present invention as long as they do not depart from the scope of the present invention.

  The present invention relates to a filtration device and a filtration method, and is excellent in that a high-concentration liquid is filtered and in a short time. For example, it is useful in fields such as chemical analysis, charge / pharmaceuticals, clinical examination, public health management, and environmental measurement.

DESCRIPTION OF SYMBOLS 10 Container part 11 Inlet 12 Ejection port 20 Membrane part 21 Through-hole 30 Liquid container 31 Ventilation hole 32 Lid 40 Suction part 41 Tube 50 Moving part 60 Liquid 61 Biological substance 70 Pipette 100 Filtration apparatus

Claims (9)

A tubular container having an inlet for introducing a liquid containing a biological substance and an outlet for discharging the liquid;
A membrane part provided between the inlet and the outlet of the container part and having a plurality of through holes;
With
The container part is
A first pipe portion extending in a vertical direction and provided with the introduction port;
A second pipe portion extending in the vertical direction and provided with the discharge port;
A third pipe part extending in a direction different from the extending direction of the first pipe part and the second pipe part and connecting the bottom part of the first pipe part and the bottom part of the second pipe part;
Have
The film part is provided in the second pipe part,
The said inlet of the said container part is a filtration apparatus located in the perpendicular direction upper side rather than the said discharge outlet of the said container part. The third pipe part has a shape curved toward the lower side in the vertical direction.
The filtration device according to claim 1. The film part has a pair of main surfaces facing each other,
The pair of main surfaces of the film part is orthogonal to the vertical direction,
The filtration device according to claim 1 or 2. The second tube portion further has an insertion port for injecting a liquid toward the membrane portion.
The filtration apparatus as described in any one of Claims 1-3. The discharge port is provided on a side wall of the second pipe part,
The film portion is disposed to face the insertion port.
The filtration device according to claim 4.   The filtration device according to any one of claims 1 to 5, wherein the film unit is a metal thin film.   The filtration device according to any one of claims 1 to 6, wherein the container portion has a U-shaped tube shape. A method of filtering biological material from a liquid,
A tubular container part having an inlet for introducing a liquid containing a biological substance and an outlet for discharging the liquid, and a plurality of through holes provided between the inlet and the outlet of the container part A first pipe part extending in the vertical direction and provided with the introduction port; and a second pipe part extending in the vertical direction and provided with the discharge port. A third pipe part extending in a direction different from the extending direction of the first pipe part and the second pipe part and connecting the bottom part of the first pipe part and the bottom part of the second pipe part. The membrane part is provided in the second pipe part, and the inlet of the container part is positioned vertically above the outlet of the container part, the step of preparing a filtration device;
Introducing the liquid containing the biological material from the introduction port;
Capturing the biological substance in the membrane by passing the liquid through the membrane,
Discharging the liquid that has passed through the membrane from the outlet;
A filtration method comprising: In the filtration device, the second tube portion further has an insertion port for injecting a liquid toward the membrane portion,
The filtration method further comprises:
Injecting liquid from the insertion port toward the membrane part,
The filtration method of Claim 8 containing this.

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