WO2016208753A1 - Dispositif et procédé de filtrage - Google Patents

Dispositif et procédé de filtrage Download PDF

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Publication number
WO2016208753A1
WO2016208753A1 PCT/JP2016/068917 JP2016068917W WO2016208753A1 WO 2016208753 A1 WO2016208753 A1 WO 2016208753A1 JP 2016068917 W JP2016068917 W JP 2016068917W WO 2016208753 A1 WO2016208753 A1 WO 2016208753A1
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WIPO (PCT)
Prior art keywords
liquid
container
membrane
filtration device
filtration
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PCT/JP2016/068917
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English (en)
Japanese (ja)
Inventor
近藤　孝志
萬壽　優
順子 渡邉
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株式会社村田製作所
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Application filed by 株式会社村田製作所 filed Critical 株式会社村田製作所
Priority to JP2017525464A priority Critical patent/JP6516007B2/ja
Publication of WO2016208753A1 publication Critical patent/WO2016208753A1/fr

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D29/00—Filters with filtering elements stationary during filtration, e.g. pressure or suction filters, not covered by groups B01D24/00 - B01D27/00; Filtering elements therefor
    • B01D29/01—Filters with filtering elements stationary during filtration, e.g. pressure or suction filters, not covered by groups B01D24/00 - B01D27/00; Filtering elements therefor with flat filtering elements
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/02—Devices for withdrawing samples
    • G01N1/10—Devices for withdrawing samples in the liquid or fluent state

Definitions

  • the present invention relates to a filtration apparatus and a filtration method for filtering a biological substance in a liquid.
  • Patent Document 1 a cell trapping system for filtering biological substances in 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.
  • Patent Document 1 has a problem that clogging occurs due to deposition of a biological material on a filter, making it impossible to separate the biological material from a 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 due to a biological substance and separating the biological substance from a liquid.
  • the filtration device 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 biological substance is separated from the liquid by allowing the liquid to pass through the membrane portion in a horizontal direction.
  • 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 by passing the liquid in a horizontal direction to the membrane part; including.
  • a filtration device and a filtration method capable of suppressing clogging due to a biological substance and separating the biological substance from a liquid.
  • FIG. 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
  • 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
  • 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 filtration device 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 biological substance may be separated from the liquid by allowing the liquid to pass through the membrane portion in a horizontal direction.
  • the membrane part may be a metal thin film.
  • Such a configuration can suppress the deformation of the film portion even when a force is applied to the film portion.
  • At least a part of the membrane part may be provided obliquely with respect to the horizontal direction.
  • Such a configuration can further suppress clogging of the membrane part due to a biological substance.
  • the filtration device may include a suction unit that sucks the liquid from the introduction port of the container unit to the discharge port.
  • 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.
  • the filtration device comprising a liquid container for holding the liquid,
  • the container portion is arranged such that the introduction port and the discharge port are positioned in a horizontal direction,
  • the inlet of the container portion is disposed in the liquid container;
  • the membrane portion may allow the liquid in the liquid container to pass in a direction opposite to the centrifugal force when a centrifugal force is applied.
  • 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 by passing the liquid in a horizontal direction to the membrane part; May be included.
  • the liquid in the separation step, may be passed through the membrane part provided at least partially obliquely with respect to the horizontal direction.
  • Such a configuration can further suppress clogging of the membrane part due to a biological substance.
  • the separating step may include a step of sucking the liquid from the introduction port of the container part to the discharge port.
  • 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 separating step may include a step of releasing pressure applied to the liquid.
  • This configuration allows the pressure applied to the liquid to escape. 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.
  • the separating step includes Arranging the container part such that the inlet and the outlet of the container part are positioned in a horizontal direction; Disposing the inlet of the container in the liquid; A step of passing the liquid in a direction opposite to the centrifugal force in the membrane portion when a centrifugal force is applied to the liquid; May be included.
  • the liquid when a centrifugal force is applied to the membrane part, the liquid can be passed in the direction opposite to the centrifugal force, thereby further suppressing the occurrence of clogging due to the deposition of biological substances in the membrane part. Can do.
  • FIG. 1 is a schematic diagram of a filtration device 100A according to Embodiment 1 of the present invention.
  • 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 and a suction part 40 for sucking the liquid 60.
  • the “biological substance” means a substance derived from a living organism such as a cell (eukaryotic organism), a bacterium (eubacteria), or a virus.
  • cells eukaryotes
  • examples of cells 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.
  • sex cells nerve cells, leukocytes, lymphocytes, cells for regenerative medicine, autologous cells, cancer cells, circulating cancer cells (CTC), HL-60, HELA, and fungi.
  • bacteria examples include gram positive bacteria, gram negative bacteria, Escherichia coli, and tuberculosis bacteria.
  • virus examples include DNA virus, RNA virus, rotavirus, (bird) influenza virus, yellow fever virus, dengue fever virus, encephalitis virus, hemorrhagic fever virus, and immunodeficiency virus.
  • 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.
  • the biological substance may be a tissue in which cells are collected or an aggregated cell.
  • 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.
  • the container part 10 is arrange
  • a film part 20 is provided at the inlet 11 of the container part 10.
  • the introduction port 11 of the container unit 10 is inserted into an opening 32 provided on the side wall of the liquid container 30 and 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.
  • 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.
  • the membrane unit 20 is a porous membrane that separates the biological material 61 from the liquid 60.
  • the film part 20 is a metal thin film having a plurality of through holes 21.
  • 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.
  • the membrane unit 20 separates the biological material 61 from the liquid 60 by allowing the liquid 60 in the liquid container 30 to pass in the horizontal direction 80.
  • the main surface located on the liquid container 30 side is defined as a first main surface HS1
  • the main surface located on the discharge port 12 side is defined as a second main surface HS2.
  • the film part 20 is provided in the introduction port 11 of the container part 10. The film part 20 is disposed so that the first main surface HS1 and the second main surface HS2 are orthogonal to the horizontal direction.
  • first main surface HS1 and the second main surface HS2 of the film unit 20 are orthogonal 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.
  • the plurality of through holes 21 are periodically arranged over the first main surface HS1 and the second main surface HS2 of the film part 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 ⁇ m.
  • 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.
  • gold, nickel, stainless steel, and titanium are preferable.
  • the material of the film part 20 is nickel, the nickel surface may be plated with gold.
  • the material of the film part 20 is preferably a material capable of various sterilizations such as gamma ray irradiation, autoclave, ethylene oxide gas, and the like.
  • FIG. 2 shows a schematic configuration diagram of a part of the film part 20 which 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.
  • 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.
  • the through-hole 21 is not limited to a square, For example, a rectangle, a circle
  • 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 dimensions 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.
  • the liquid container 30 is a container that holds the liquid 60 containing the biological substance 61.
  • the upper wall of the liquid container 30 is provided with a vent 31 for releasing the pressure applied to the liquid 60.
  • the biological substance 61 is pressurized by a negative pressure.
  • the filtering device 100A since the liquid 60 can be opened to the outside by the vent 31, the pressure applied to the biological substance 61 in the liquid 60 can be released to the outside.
  • an opening 32 to which the inlet 11 of the container part 10 is attached is provided on the side wall of the liquid container 30.
  • the introduction port 11 of the container unit 10 is inserted into the opening 32 provided on the side wall of the liquid container 30 and is disposed in the liquid 60 held in the liquid container 30.
  • 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.
  • 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 moves in the horizontal direction from the first main surface HS1 to the second main surface HS2 through the film unit 20 from the inlet 11 to the outlet 12 of the container 10 (FIG. 1). Arrow 80).
  • FIG. 4 is a flowchart of the filtration method according to the first embodiment.
  • a filtration device 100A is prepared. Specifically, the inlet 11 of the container unit 10 is inserted into the opening 32 of the liquid container 30. A suction part 40 is attached to the discharge port 12 of the container part 10 via a tube 41.
  • step ST12 the liquid 60 containing the biological substance 61 is introduced into the liquid container 30.
  • step ST ⁇ b> 13 the biological material 61 is separated from the liquid 60 by allowing the liquid 60 to pass through the membrane unit 20.
  • Step ST13 includes step ST14 of sucking the liquid 60 in the liquid container 30 by the suction unit 40.
  • step ST14 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.
  • the liquid 60 passes in the horizontal direction from the first main surface HS1 of the film part 20 to the second main surface HS2.
  • the biological substance 61 cannot pass through the through hole 21 and remains in the liquid container 30.
  • Step ST13 includes step ST15 for releasing the pressure applied to the liquid 60 held in the liquid container 30.
  • 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.
  • the biological material 61 is separated from the liquid 60 by steps ST11 to ST15.
  • the liquid 60 that has passed through the membrane unit 20 can also be recovered.
  • FIGS. 5A to 5C show the operation of the filtration device 100A.
  • 5A to 5C omit the suction part 40 and the tube 41 for the sake of simplicity.
  • the liquid 60 is introduced into the liquid container 30 to which the container unit 10 is attached.
  • the liquid 60 is sucked from the inlet 11 to the outlet 12 of the container 10 by the suction part 40 (arrow 80 shown in FIG. 5B).
  • the liquid 60 in the liquid container 30 passes in the horizontal direction from the first main surface HS1 of the film unit 20 to the second main surface HS2.
  • 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 HS1 of the film unit 20.
  • the cake layer A1 is formed by further gathering the biological material 61 on the lower side in the vertical direction of the first main surface HS1 of the film unit 20.
  • the region A2 on the upper side in the vertical direction of the first main surface HS1 of the film part 20 the collection and separation of the biological material 61 are repeated. For this reason, in the region A2, clogging due to the cake layer does not occur, and the liquid 60 can pass through the film part 20 (arrow 82 shown in FIG. 5C).
  • the upward direction in the vertical direction is defined as the upper side
  • the downward direction in the vertical direction is defined as the lower side.
  • the biological substance 61 in the liquid 60 is a vertical force due to the suction force in the horizontal direction (arrow 80 shown in FIGS. 5B and 5C) from the introduction port 11 to the discharge port 12 of the container unit 10 by the suction unit 40 and gravity.
  • the downward force works.
  • the biological material 61 collects in the film unit 20 on the upper side in the vertical direction.
  • the biological substance 61 separates from the film part 20 on the upper side in the vertical direction and collects on the lower side in the vertical direction.
  • 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 vertically downward force due to gravity.
  • the biological substance 61 can be detached from the cake layer A1 by vibration of the filtration device 100A.
  • 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.
  • the biological material 61 repeats the collection and the separation, so that clogging is unlikely to occur.
  • the biological material 61 is likely to move downward in the vertical direction. Therefore, in the region A2, the biological material 61 is less likely to accumulate and clogging is less likely to occur.
  • the filtering device 100 ⁇ / b> A As described above, in the filtering device 100 ⁇ / b> A, clogging due to the deposition of the biological substance 61 can be suppressed in the region A ⁇ b> 2 on the upper side in the vertical direction of the membrane unit 20, and the biological substance 61 can be continuously separated from the liquid 60. it can.
  • 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.
  • the container part 110 is arranged such that the axial direction of the container part 110 is the same as the vertical direction, that is, the gravity direction.
  • the introduction port 111 of the container unit 110 is located above the discharge port 112 in the vertical direction, and the film unit 120 is provided at the discharge port 112 of the container unit 110.
  • 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 on the lower side in the vertical direction than the second main surface VS12. That is, the filtering device 100A of the first embodiment allows the liquid 60 to pass through the membrane part 20 in the horizontal direction, whereas the filtering device of the reference example causes the liquid 60 to flow from the upper side to the lower side in the vertical direction. To pass. 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.
  • the liquid 60 containing the biological substance 61 flows from the inlet 111 of the container 110 to 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.
  • the biological substance 61 is captured by the membrane part 120. For this reason, the biological substance 61 is deposited on the entire second main surface VS112 of the film part 120.
  • the 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.
  • the thickness of the cake layer A3 gradually increases as the capture of the biological substance 61 by the membrane part 120 increases.
  • 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.
  • the biological substance 61 captured by the membrane unit 120 is deposited on the entire second main surface VS12 of the membrane 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.
  • the container part 10 is arranged so that the axial direction of the container part 10 is horizontal, and the liquid 60 is allowed to pass through the film part 20 in the horizontal direction.
  • the filtering device 100A it is possible to suppress the occurrence of clogging due to the deposition of the biological material 61 in the region A2 in the vertical direction above the first main surface HS1 of the film unit 20. 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.
  • the liquid 60 containing the biological substance 61 is passed in the horizontal direction from the first main surface HS1 of the membrane unit 20 to the second main surface HS2.
  • the biological substance 61 can be efficiently separated from the liquid 60 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.
  • the filtering device 100A can suppress clogging of the membrane part 20 as compared with the filtering device of the reference example, it is possible to filter the liquid 60 having a higher concentration in a shorter period. Moreover, it can filter with high reproducibility compared with the filter apparatus of a reference example.
  • the filtering device 100A separates the biological material 61 and the liquid 60, but is not limited to this.
  • 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.
  • 100A of filtration apparatuses may filter and classify
  • 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.
  • a vent 31 for releasing the pressure applied to the liquid 60 is provided on the upper wall of the liquid container 30.
  • the liquid 60 in the liquid container 30 can be opened to the outside. Therefore, the pressure applied to the liquid 60 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.
  • 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 HS1 of the film part 20 to the second main surface HS2.
  • the liquid 60 in the liquid container 30 can be passed through the film unit 20 in the horizontal direction, and clogging of the film unit 20 can be suppressed.
  • the suction can be performed in a shorter time by sucking the liquid 60 by the suction unit 40.
  • the container part 10 demonstrated the structure arrange
  • the container part 10 may be arrange
  • the filtering device 100A may be arranged in an oblique direction to perform filtration.
  • 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.
  • 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.
  • membrane part 20 is provided in the inlet 11 of the container part 10, it is not limited to this.
  • the film part 20 is only required to allow the liquid 60 to pass in the horizontal direction from the first main surface HS1 to the second main surface HS2, and the position of the film part 20 is not limited.
  • 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.
  • a plurality of film parts 20 may be provided between the inlet 11 and the outlet 12 of the container part 10.
  • 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 closer to the discharge port 12 than the first film part 20.
  • the recovery rate can be improved by configuring the multistage filtration device 100A using the plurality of membrane portions 20.
  • 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.
  • the film part 20 demonstrated the example which passes a liquid in the horizontal direction 80 toward the discharge port 12 from the inlet 11 of the container part 10, it is not limited to this.
  • the “horizontal direction” may include not only a direction orthogonal to the vertical direction but also an oblique direction having a predetermined angle with respect to the vertical direction. That is, in the film part 20, the main direction through which the liquid 60 passes may be a horizontal direction, and the direction through which the liquid 60 passes may include an oblique direction with respect to the horizontal direction.
  • FIG. 7 shows a filtration device 100B according to a modification of the first embodiment.
  • the membrane unit 20 may be arranged in an oblique direction with a predetermined angle ⁇ with respect to the horizontal direction.
  • the film part 20 may be disposed to be inclined with respect to the vertical direction.
  • membrane part 20 may be arrange
  • the liquid container 30 is provided with the vent 31 on the upper wall of the liquid container 30, but the present invention is not limited to this.
  • the vent 31 may be formed by providing a hole in the side wall of the liquid container 30.
  • a ventilation filter may be provided instead of the ventilation port 31.
  • 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.
  • 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.
  • the present invention is not limited thereto.
  • the liquid 60 may be passed in the horizontal direction from the first main surface HS ⁇ b> 1 to the second main surface HS ⁇ b> 2 of the film unit 20.
  • the liquid 60 may be passed in the horizontal direction from the first main surface HS1 to the second main surface HS2 of the membrane unit 20.
  • the suction unit 40 may be any device that can suck the liquid 60, and may be, for example, a pump.
  • the liquid container 30 and the suction unit 40 are not essential components, and these elements may be omitted or replaced with other elements.
  • FIG. 8 shows a schematic configuration of a filtration device 100C according to the second embodiment.
  • differences from the first embodiment will be mainly described.
  • the same or similar components as those in the first embodiment will be described with the same or similar reference numerals.
  • descriptions overlapping with those in the first embodiment are omitted.
  • the filtration device 100C of the second embodiment is liquid by applying a centrifugal force in the direction from the discharge port 12a of the container part 10a to the introduction port 11a as compared with the filtration device 100A of the first embodiment.
  • the difference is that the biological material 61 can be separated from 60.
  • the filtration device 100C does not include the suction unit 40.
  • the filtration device 100C is disposed between a container portion 10a having an introduction port 11a for introducing the liquid 60 containing the biological substance 61 and a discharge port 12a for discharging the liquid 60, and the introduction port 11a and the discharge port 12a.
  • a film part 20 a having a plurality of through holes 21 and a liquid container 30 a for holding the liquid 60 are provided.
  • the container part 10a is arrange
  • the inlet 11a of the container part 10a is arranged in the liquid 60 in the liquid container 30a.
  • the membrane part 20a allows the liquid 60 in the liquid container 30a to pass in the direction opposite to the centrifugal force.
  • the filtering device 100C applies the centrifugal force in the direction from the discharge port 12a of the container part 10a to the introduction port 11a, thereby causing the liquid 60 in the liquid container 30a to flow from the first main surface HS1 of the film part 20a to the second main surface HS1. It passes through the surface HS2 in the horizontal direction.
  • the container portion 10a is provided with a deaeration hole.
  • a lid 50 that covers the opening of the liquid container 30a is attached in a state where the container portion 10a is disposed in the liquid container 30a.
  • FIGS. 9A to 9F show the filtration operation in the filtration device 100C.
  • the container portion 10a is removed from the liquid container 30a, and the liquid 60 containing the biological substance 61 is introduced into the liquid container 30a.
  • the container portion 10a is mounted in a liquid container 30a holding the liquid 60.
  • the lid 50 is attached to the liquid container 30a in a state where the container portion 10a is held inside the liquid container 30a. That is, the inlet 11a of the container part 10a is disposed in the liquid 60 in the liquid container 30a.
  • the lid 50 is attached by, for example, screwing a female screw provided inside the lid 50 and a male screw provided on the outer wall of the liquid container 30a.
  • the filtration device 100C is set in the centrifuge.
  • the filtration device 100C is set in the centrifuge so that the axial direction of the container portion 10a is horizontal. That is, the container part 10a is arranged in the centrifuge so that the inlet 11a and the outlet 12a of the container part 10a are positioned in the horizontal direction.
  • membrane part 20a become the same.
  • the height of the liquid surface of the liquid 60 between the outer wall of the container portion 10a and the inner wall of the liquid container 30a and the height of the liquid surface of the liquid 60 that has passed through the film portion 20a are the liquid container 30a at each location. This means the height of the liquid 60 from the bottom surface.
  • the centrifuge is stopped and the lid 50 is removed from the liquid container 30a.
  • the liquid 60 that has passed through the membrane portion 20a is discharged.
  • the liquid 60 is discharged by turning the liquid container 30a upside down with the container portion 10a attached to the liquid container 30a.
  • the biological substance 61 accumulated at the bottom of the liquid container 30a cannot pass through the through hole 21 of the membrane part 20a. Therefore, the liquid 60 not containing the biological substance 61 is discharged from the discharge port 12a.
  • a lid 50 is attached to the liquid container 30a, and centrifugal force from the outlet 12a to the inlet 11a is applied to the filtration device 100C by a centrifuge (arrow 83 shown in FIG. 9E).
  • a centrifuge arrow 83 shown in FIG. 9E.
  • the liquid 60 between the outer wall of the container 10a and the inner wall of the liquid container 30a flows to the bottom of the liquid container 30a (the arrow shown in FIG. 9E), similar to the operation shown in FIG. 9C.
  • the liquid 60 that does not contain the biological substance 61 passes through the membrane part 20a (arrow 85 shown in FIG. 9E).
  • membrane part 20a become the same.
  • the centrifuge is stopped and the lid 50 is removed from the liquid container 30a. Thereafter, similarly to the operation shown in FIG. 9D, the liquid 60 that has passed through the film part 20a and accumulated inside the container part 10a is discharged from the discharge port 12a.
  • the filtering device 100C separates the biological substance 61 from the liquid 60 by using the centrifugal force by performing the operations shown in FIGS. 9A to 9F. Furthermore, the filtration device 100C can concentrate the biological material 61 by repeating the operations shown in FIGS. 9A to 9F. Further, in the filtering device 100C, after concentration, the biological material 61 can be washed by introducing washing water. Further, in the filtering device 100C, after separating the biological material 61, the liquid 60 can be replaced with another liquid by introducing a replacement liquid.
  • the liquid 60 when a centrifugal force is applied, the liquid 60 is passed in the direction opposite to the direction in which the centrifugal force is applied in the membrane portion 20a. Specifically, when a centrifugal force is applied to the filtration device 100C, the height of the liquid surface between the outer wall of the container portion 10a and the inner wall of the liquid container 30a and the liquid 60 that has passed through the membrane portion 20a. The liquid 60 is allowed to pass through the film part 20a in the horizontal direction by utilizing 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 a with the biological substance 61. Further, in the filtration device 100C, the biological substance 61 can be easily concentrated by repeatedly performing filtration by centrifugation.
  • the liquid 60 that has passed through the membrane portion 20a when the liquid 60 that has passed through the membrane portion 20a is taken out, for example, the liquid 60 can be easily discharged by turning the filtering device 100C upside down.
  • the filtering device 100C pipetting by the operator is unnecessary, and the liquid 60 can be discharged without requiring a special skill from the operator.
  • the recovery rate of the biological material 61 is not reduced by pipetting.
  • the liquid 60 may be discharged by suction or the like.
  • the biological substance 61 can be easily washed by introducing washing water and performing centrifugation. Further, in the filtering device 100C, after the biological material 61 is separated, the liquid can be easily replaced by introducing the replacement liquid.
  • the filtration device 100C can be set with the axial direction of the container portion 10a being the same as the direction in which the centrifugal force is applied when it is attached to the centrifuge. For this reason, the centrifugal force is easily transmitted to the biological material 61, and the biological material 61 is easily separated from the liquid 60.
  • a centrifuge tube generally used for centrifugation is set obliquely with respect to the direction in which centrifugal force is applied when it is attached to a centrifuge.
  • the centrifuge tube if the axial direction of the centrifuge tube is set in the same direction as the centrifugal force, the separated biological material 61 is mixed with the liquid 60 again after centrifugation. For this reason, the centrifuge tube is disposed obliquely with respect to the direction in which the centrifugal force is applied in order to maintain the state where the centrifuged biological substance 61 is collected at the bottom of the centrifuge tube.
  • the centrifuge tube is disposed obliquely with respect to the direction in which the centrifugal force is applied, the centrifugal force is hardly transmitted to the biological material 61.
  • the axial direction of the container portion 10a can be set in the centrifuge so as to be the same as the direction in which the centrifugal force is applied, so that the centrifugal force is easily transmitted to the biological material 61. Therefore, the filtration device 100C can perform centrifugal separation under a rotation condition with a smaller number of rotations or a shorter time than a centrifuge tube by efficiently transmitting a centrifugal force to the biological material 61.
  • the filtering device 100C is set in the centrifuge so that the axial direction of the container portion 10a is the same as the direction in which the centrifugal force is applied has been described, but is not limited thereto.
  • the filtration device 100C may be set in the centrifuge so that the axial direction of the container portion 10a is inclined with respect to the direction in which the centrifugal force is applied.
  • FIG. 10 shows a schematic configuration of the filtration device 100D of the third embodiment.
  • FIG. 11 shows the filtration device 1 The figure which saw 00D from the top is shown. In order to simplify the description, the lid 10bb is omitted in FIG. A black arrow shown in FIG. 11 indicates the rotation direction of the filtration device 100D.
  • differences from the first embodiment will be mainly described.
  • the same or similar components as those in the first embodiment will be described with the same or similar reference numerals.
  • descriptions overlapping with those in the first embodiment are omitted.
  • the filtering device 100D of the third embodiment rotates the container portion 10b around the central axis CL of the container portion 10b as compared with the filtering device 100A of the first embodiment.
  • the difference is that the biological material 61 can be separated from the liquid 60 by the generated centrifugal force.
  • the filtration device 100D does not include the liquid container 30 and the suction unit 40.
  • the filtration device 100 ⁇ / b> D includes a container portion 10 b for introducing a liquid 60 containing a biological substance 61 and a membrane portion 20 b having a plurality of through holes 21.
  • the container part 10b includes a container body 10ba having an introduction port 11b for introducing the liquid 60, a lid part 10bb having a discharge port 12b for discharging the liquid 60, and a decompression port 70 for decompressing the inside of the container body 10ba.
  • the filtration device 100D forms a double cylinder structure by the container body 10ba and the membrane part 20b.
  • the inner cylinder is formed by a cylindrical film portion 20b
  • the outer cylinder is formed by a side wall of the container body 10ba.
  • a space for introducing the liquid 60 is formed between the membrane portion 20b and the side wall of the container body 10ba.
  • the bottom of the container body 10ba is inclined vertically downward toward the center of the container body 10ba.
  • the film part 20b is arranged between the inlet 11b and the outlet 12b of the container part 10b, and is arranged at a certain distance from the side wall of the container main body 10ba.
  • the filtration device 100D applies a centrifugal force from the central axis CL to the side wall of the container part 10b by rotating around the central axis CL of the container part 10b.
  • a centrifugal force is applied to the filtration device 100D, the liquid 60 in the container body 10ba moves in a direction opposite to the direction in which the centrifugal force is applied, and is horizontal from the first main surface HS1 to the second main surface HS2 of the film part 20a. Pass in the direction.
  • FIGS. 12A to 12C show the filtration operation in the filtration device 100D.
  • the lid portion 10bb is removed from the container body 10ba, and the liquid 60 containing the biological substance 61 is introduced into the container body 10ba from the introduction port 11b (arrow 86 shown in FIG. 12A).
  • a sealing lid 10bc is attached to the container body 10ba to seal the liquid 60 in the container body 10ba. Thereafter, the container portion 10b is rotated around the central axis CL of the container portion 10b (arrow 87 shown in FIG. 12B).
  • the rotation condition of the container part 10b may be set to a lower rotation than, for example, a condition for rotating a general centrifuge tube used for centrifugation.
  • the centrifugal force from the central axis CL to the side wall of the container body 10ba is loaded by rotating the container part 10b, the biological substance 61 gathers on the side wall of the container body 10ba. Therefore, the liquid located on the first main surface HS1 of the film part 20b is in a state where the concentration of the biological substance 61 is low.
  • the lid portion 10bc for sealing is removed and the lid portion 10bb is attached.
  • the inside of the container part 10b is made into a pressure-reduced state by reducing the pressure inside the container part 10b from the decompression port 70 provided in the upper part of the cover part 10bb.
  • the liquid 60 moves toward the central axis CL that is the rotation center of the container body 10ba. Therefore, the liquid 60 passes through the first main surface HS1 to the second main surface HS2 of the film part 20b in the horizontal direction and collects at the center of the bottom of the container body 10ba.
  • the liquid 60 collected at the center of the bottom of the container body 10ba is discharged to the outside by being sucked from the discharge port 12b (arrow 88 shown in FIG. 12C).
  • the biological material 61 is collected on the side wall of the container body 10ba by applying a centrifugal force, and the liquid 60 is moved in the direction opposite to the centrifugal force by reducing the pressure inside the container body 10ba. ing. Thereby, the liquid 60 and the biological material 61 are separated by collecting the liquid 60 in the center of the container body 10ba and discharging the liquid 60. Further, the filtration device 100D can perform the replacement, cleaning, and concentration processing of the liquid 60 by repeating the operations shown in FIGS. 12A to 12C.
  • the biological substance 61 can be separated from the liquid 60 by the centrifugal force from the central axis CL generated by rotating the container part 10b around the central axis CL of the container part 10b to the side wall of the container body 10ba. It has a configuration. With such a configuration, the filtration device 100D can collect the biological material 61 on the side wall of the container body 10ba by centrifugal force. Further, the liquid 60 having a low concentration of the biological substance 61 located on the first main surface HS1 of the film part 20b is moved in the direction opposite to the direction in which the centrifugal force is applied, thereby moving the first main part of the film part 20b. The liquid 60 can be passed in the horizontal direction from the surface HS1 to the second main surface HS2. As a result, clogging due to the biological material 61 can be suppressed in the film part 20b.
  • the biological material 61 collects on the side wall of the container body 10ba by the centrifugal action, the biological material 61 is unlikely to be deposited on the first main surface HS1 of the film part 20b. Therefore, the dimension of the through-hole 21 of the film part 20b can be made larger than the dimension of the through-hole of the filter used for filtration of Patent Document 1. As a result, in the filtering device 100D, it is possible to perform filtration under conditions superior to the extraction of the liquid 60.
  • the liquid 60 not containing the biological substance 61 can be extracted from the through-hole 21 of the membrane part 20b by reducing the pressure inside the container part 10b from the pressure reducing port 70. .
  • the filtering device 100D since the container portion 10b generates a centrifugal force by rotating around the central axis CL, the number of rotations can be reduced compared to a device that performs centrifugation using a centrifuge tube, Centrifugation time can be shortened. As a result, the number of organism-derived substances 61 that die due to centrifugation can be reduced.
  • the filtering device 100D when the liquid 60 that has passed through the membrane portion 20b is taken out, for example, the liquid 60 can be easily discharged by suction from the discharge port 12b. Thus, in the filtration device 100D, 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 100D, the recovery rate of the biological material 61 is not reduced by pipetting.
  • the sealing lid 10bc is used when rotating the container 10b.
  • the present invention is not limited to this.
  • the lid portion 10bb having the discharge port 12b may be used even when the container portion 10b is rotated. With such a configuration, the rotation of the container portion 10b and the discharge of the liquid 60 can be performed simultaneously.
  • the film part 20b was demonstrated as a metal thin film which has the some cylindrical through-hole 21, it is not limited to this.
  • the film part 20 b may be a metallic thin film having at least a part of the through hole 21.
  • the shape of the film part 20b may be a polygonal cylindrical shape.
  • FIG. 13 shows a schematic configuration of a filtration device 100E according to a modification.
  • the filtration device 100E may be provided with a discharge port 12c near the center of the bottom of the container body 10ba. With such a configuration, the liquid 60 can be discharged without sucking the liquid 60 (arrow 89 shown in FIG. 13).
  • Embodiment 3 the configuration in which the decompression port 70 is provided in the lid portion 10bb of the container portion 10b has been described, but the configuration is not limited thereto.
  • the decompression port 70 is provided to facilitate passage of the liquid 60 in the horizontal direction from the first main surface HS1 of the film part 20b to the second main surface HS2, and is not an essential configuration.
  • the present invention relates to a filtration device and a filtration method, and is excellent in terms of filtering a high concentration liquid and filtering in a short time. For example, it is useful in the fields of chemical analysis, charge / pharmaceuticals, clinical examination, public health management, environmental measurement, and the like.

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  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Filtration Of Liquid (AREA)
  • Sampling And Sample Adjustment (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Separation Using Semi-Permeable Membranes (AREA)

Abstract

L'invention fournit un dispositif et un procédé de filtrage qui permettent de supprimer l'obstruction par une substance biologique, et de séparer celle-ci d'un liquide. Le dispositif de filtrage de l'invention est équipé : d'une partie réceptacle qui possède un orifice d'introduction par lequel est introduit le liquide contenant la substance biologique, et un orifice de décharge par lequel est déchargé le liquide ; et d'une partie membrane qui est agencée entre l'orifice d'introduction et l'orifice de décharge de la partie réceptacle, et qui possède une pluralité de trous traversants. Le liquide est filtré horizontalement vers la partie membrane, et la substance biologique est ainsi séparée du liquide.
PCT/JP2016/068917 2015-06-26 2016-06-24 Dispositif et procédé de filtrage WO2016208753A1 (fr)

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