WO2021053896A1 - Filter, filter unit, and filter device - Google Patents

Filter, filter unit, and filter device Download PDF

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Publication number
WO2021053896A1
WO2021053896A1 PCT/JP2020/022478 JP2020022478W WO2021053896A1 WO 2021053896 A1 WO2021053896 A1 WO 2021053896A1 JP 2020022478 W JP2020022478 W JP 2020022478W WO 2021053896 A1 WO2021053896 A1 WO 2021053896A1
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WIPO (PCT)
Prior art keywords
filter
voltage
liquid
conductor
unit
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PCT/JP2020/022478
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French (fr)
Japanese (ja)
Inventor
洋昌 佐伯
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株式会社村田製作所
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Publication of WO2021053896A1 publication Critical patent/WO2021053896A1/en

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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D57/00Separation, other than separation of solids, not fully covered by a single other group or subclass, e.g. B03C
    • B01D57/02Separation, other than separation of solids, not fully covered by a single other group or subclass, e.g. B03C by electrophoresis
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B03SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03CMAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C5/00Separating dispersed particles from liquids by electrostatic effect
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M3/00Tissue, human, animal or plant cell, or virus culture apparatus
    • C12M3/06Tissue, human, animal or plant cell, or virus culture apparatus with filtration, ultrafiltration, inverse osmosis or dialysis means
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N1/00Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
    • C12N1/02Separating microorganisms from their culture media
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/10Processes for the isolation, preparation or purification of DNA or RNA

Definitions

  • the present invention relates to a filter that collects or separates.
  • Non-Patent Document 1 discloses a method for collecting exosomes in urine by utilizing a fixed charge on the surface of a substance.
  • urine is passed through zinc oxide nanowires fixed to a microfluidic substrate to collect exosomes in urine to a fixed charge of the nanowires.
  • Non-Patent Document 1 since the surface charge of the nanowire is fixed, the nanowire cannot release the captured exosome itself. Conventional techniques cannot capture or release target substances.
  • an object of the present invention is to provide a filter, a filter unit, and a filter device for collecting or separating a target substance.
  • the filter of the present invention is located on a conductor capable of flowing a liquid, an insulator film covering a portion of the conductor that the liquid contacts, and a portion of the surface of the conductor that the liquid does not contact. It is characterized by including a voltage application unit for applying a voltage from the outside.
  • the insulator film adsorbs the target substance in the liquid by the applied voltage. Since the part of the filter in contact with the liquid is covered with an insulator, no current flows due to the voltage. Since the insulator film adsorbs the substance by the voltage, the adsorption of the substance by the voltage can be released by stopping the application of the voltage. This allows the filter to collect or separate the target material.
  • the target substance can be collected or separated.
  • FIG. 1A is a schematic view showing the configuration of the filter device 100 according to the embodiment.
  • FIG. 1B is a schematic cross-sectional view of the filter unit 101.
  • FIG. 2A is a schematic perspective view showing the filter 20, and
  • FIG. 2B is a partially enlarged cross-sectional view of the filter 20.
  • FIG. 3 is a diagram for explaining one usage state of the filter 20.
  • 4 (A) to 4 (C) are diagrams for explaining a method for inspecting bacteria using the filter device 100.
  • 5 (A) to 5 (C) are diagrams for explaining medium exchange using the filter device 100.
  • FIG. 6 is a graph showing the results of Example 1.
  • FIG. 7 is a graph showing the results of Example 2.
  • FIG. 1A is a schematic view showing the configuration of the filter device 100 according to the embodiment.
  • FIG. 1B is a schematic cross-sectional view of the filter unit 101.
  • the filter 20 is represented by a broken line.
  • the axial direction of the filter unit 101 will be described as the Z direction.
  • the filter device 100 includes a filter unit 101, a DC power supply 102, and a control unit 103. Further, the filter device 100 includes a pump (not shown).
  • the filter unit 101 is connected to the DC power supply 102.
  • a DC voltage is applied to the filter unit 101 from the DC power supply 102.
  • the DC power supply 102 is connected to the control unit 103.
  • the control unit 103 controls the DC voltage of the DC power supply 102.
  • the control unit 103 switches the DC voltage of the DC power supply 102 between positive and negative.
  • the user can control the DC voltage applied to the filter unit 101 via the control unit 103.
  • the filter unit 101 includes a filter 20 and a fixture 10.
  • the fixture 10 fixes the filter 20.
  • the shape of the filter unit 101 is substantially tubular and has an internal space 13.
  • the filter 20 is arranged at the central portion of the filter unit 101 in the axial direction.
  • the fixture 10 includes two joints 11 and a socket 12.
  • the joint 11 and the socket 12 are tubular and have both ends open.
  • the joint 11 constitutes the internal space 13.
  • the two joints 11 are arranged so as to sandwich the filter 20 and their internal spaces 13 are continuous.
  • the socket 12 is arranged on the side surface of the two joints 11 and the filter 20 so as to cover the periphery of the two joints 11 and the filter 20.
  • the joint 11 is an example of the side wall portion of the flow path in the present invention.
  • FIG. 2A is a schematic perspective view showing the filter 20.
  • FIG. 2B is a partially enlarged cross-sectional view of the filter 20. Note that FIG. 2B is a view in which a part of the distribution section 21 is cut along a plane parallel to the Z direction.
  • the filter 20 includes a distribution unit 21, a frame unit 22, and a voltage application unit 16.
  • the frame portion 22 is formed so as to surround the circulation portion 21.
  • the frame portion 22 is a portion sandwiched by the joints 11, and the distribution portion 21 is a portion arranged in the internal space 13.
  • the distribution unit 21 has a mesh structure.
  • the distribution unit 21 is formed by arranging linear conductors 23 made of metal in a mesh pattern.
  • the distribution section 21 and the frame section 22 may be integrally formed of the same material of the conductor 23.
  • a flow path 25 capable of flowing a liquid is formed between the plurality of conductors 23.
  • the filter 20 can circulate the liquid through the flow path 25.
  • the conductor 23 is covered with an insulator film 24.
  • the insulator film 24 covers at least a portion of the conductor 23 that comes into contact with the liquid.
  • the insulator film 24 covers the distribution section 21 arranged in the flow path 25. Therefore, even if a voltage is applied to the conductor 23, no current flows.
  • the flow section 21 is at least a portion of the conductor 23 that comes into contact with the liquid, and is an example of the liquid passage section in the present invention.
  • the insulator film 24 is preferably formed by an atomic layer deposition method, that is, an ALD (Atomic layer deposition) method.
  • ALD atomic layer deposition
  • the insulator film 24 may be coated by a method other than the ALD method.
  • the insulator film 24 may be formed by anodization treatment.
  • the insulator film 24 is, for example, titanium (TiO 2 ), alumina (Al 2 O 3 ), silica (SiO 2 ), hafnia (HfO), zirconia (ZrO 2 ), zinc oxide (ZnO), or nickel oxide (NiO).
  • TiO 2 titanium
  • alumina Al 2 O 3
  • silica silica
  • hafnia HfO
  • zirconia zirconia
  • ZnO 2 zinc oxide
  • NiO nickel oxide
  • titania is preferably contained. Since titania is a material having excellent biocompatibility, it reduces the influence on the biological sample. Since silica is a substance that is easily negatively charged, it is difficult for a substance having a negative charge to be adsorbed when a positive voltage is not applied to the conductor 23.
  • the filter 20 can easily prevent clogging of a substance having a negative charge. Since zinc oxide, nickel oxide, and zirconia are substances that are easily charged positively, they are likely to adsorb substances that have a negative charge on the conductor 23 to which a positive voltage is applied. Further, since the isoelectric point of alumina and titania is near the neutral point, the surface charge in the neutral region is close to zero. Therefore, the user applies a positive voltage to the conductor 23 to adsorb a substance having a negative charge, or applies a negative voltage to the conductor 23 to adsorb a substance having a positive charge. It is easy to use regardless of whether the target substance is positively or negatively charged.
  • the voltage application unit 16 is located on the surface of the conductor 23 where the liquid does not come into contact.
  • the voltage application unit 16 is located, for example, on the side surface of the filter 20, that is, the side surface of the frame unit 22.
  • the voltage application unit 16 can be formed by forming an insulator film 24 on the entire conductor 23 by the ALD method and then scraping off a part of the insulator film 24. By scraping off the insulator film 24, the conductor 23 is exposed on the surface. As a result, the filter 20 forms a portion that is electrically connected to the outside.
  • the voltage applying portion 16 may be formed by patterning so that only the portion that becomes the voltage applying portion 16 is not formed.
  • the voltage application unit 16 comes into contact with the socket 12.
  • the voltage application unit 16 can be electrically connected to the external DC power supply 102 via the socket 12.
  • the voltage application unit 16 can apply a voltage to the conductor 23 from the outside via the socket 12.
  • the voltage application unit 16 may be electrically connected to the external DC power supply 102 via any location of the fixture 10.
  • the filter 20 may have a structure having a diameter larger than that of the two joints 11.
  • the filter 20 is arranged so as to be sandwiched between the two joints 11, and the outer peripheral portion is exposed to the outside.
  • the voltage application unit 16 formed on the side surface of the filter 20 can be directly connected to the DC power supply 102. Therefore, since the socket 12 is not required, the configuration of the filter unit 101 can be simplified.
  • FIG. 3 is a diagram for explaining one usage state of the filter 20.
  • the user first applies a positive voltage from the DC power supply 102 to the filter 20 via the control unit 103. As a result, a positive voltage is applied to the conductor 23 of the circulation unit 21. As shown in FIG. 3, a liquid containing the negatively charged substance 30 is flowed through the filter 20 along the direction of the arrow. At this time, since a positive voltage is applied to the conductor 23, the substance 30 is attracted to and adsorbed on the surface of the insulator film 24. Here, if the application of the positive voltage to the conductor 23 is stopped, the force for attracting the substance 30 on the surface of the insulator film 24 is weakened. As a result, the insulator film 24 can release the adsorption of the substance 30.
  • the user can also apply a negative voltage from the DC power supply 102 to the filter 20 via the control unit 103.
  • the insulator film 24 generates a repulsive force with the substance 30 adsorbed by the applied negative voltage. Therefore, the insulator film 24 can positively desorb the substance 30.
  • the filter 20 can collect or separate the negatively charged substance 30 which is the target substance.
  • the target substance 30, for example, includes bacteria, viruses, fungi, cells, DNA, RNA, extracellular vesicles, blood cells, some proteins, microbeads, and the like.
  • the user can also first apply a negative voltage from the DC power supply 102 to the filter 20 via the control unit 103.
  • the insulator film 24 can collect or separate a substance having a positive charge as a target substance.
  • Non-Patent Document 1 since the charge of the nanowire is fixed, the nanowire cannot release the captured exosome itself. In other words, exosomes cannot be recovered without being destroyed. For example, exosomes gathered on nanowires are exposed to a surfactant, which destroys the cell wall. As a result, the miRNA in the exosome is recovered from the cell fluid inside the exosome. Therefore, the invention described in Non-Patent Document 1 cannot be applied when culturing is assumed after collection such as immune cell capture.
  • the filter 20 adsorbs the target substance by the electric charge and releases the charge, or releases the adsorption by the charge of the opposite polarity, so that the target substance is not chemically affected. .. In this way, the filter 20 can be recovered as it is without destroying the target substance, and thus can be cultured after collection.
  • the filter 20 does not generate air bubbles, so that clogging can be prevented.
  • the filter 20 can generate an electric charge sufficient to adsorb the target substance on the insulator film 24 without electrolysis.
  • the distribution unit 21 has a mesh structure, but the present invention is not limited to this.
  • the distribution unit 21 may have a porous structure, for example, as long as the liquid can circulate.
  • the structure of the conductor 23 is complicated and the contact area with the liquid increases, so that the target substance is more likely to come into contact with the filter 20 than the mesh structure. Therefore, in the case of a porous structure, the collection efficiency of the target substance is improved.
  • the size of the opening of the flow path 25 of the mesh structure in the filter 20 can be made larger than the target substance 30 as shown in FIG. 3, for example.
  • the filter 20 does not collect by filtering the substance 30 with the size of the opening of the flow path 25 smaller than the size of the substance 30, but collects by the force of attracting the substance 30 of the filter 20. Since the substance 30 is smaller than the size of the opening of the flow path 25 having a mesh structure, the filter 20 can prevent clogging. Further, the larger the size of the opening of the flow path 25, the easier it is to manufacture the filter 20.
  • the size of the opening of the flow path 25 can be adjusted according to conditions such as the size of the target substance to be collected.
  • the voltage applied to the filter 20, the flow velocity of the liquid passing through the filter 20, the flow rate, the thickness of the insulator film 24, and the like can also be appropriately adjusted according to conditions such as the size of the target substance to be collected. Further, the filter device 100 can control the selectivity of the target substance to be collected according to the flow velocity of the liquid passing through the filter 20, the voltage applied to the filter 20, or the zeta potential of the target substance.
  • the filter device 100 is provided with one filter 20 in the present embodiment, it may be provided with a plurality of filters 20.
  • the filter device 100 includes a plurality of filters 20, the portion where the liquid comes into contact with the insulator film 24 of the filter 20 increases. Therefore, the filter device 100 can collect more target substances.
  • the filter device 100 was used to collect the target substance in the present embodiment, it can also be used for other purposes.
  • the filter device 100 can be used, for example, for separation, concentration, medium exchange in culture, bacterial inspection, and the like.
  • the concentration method using the filter device 100 will be described. For example, a case where 100 mL (concentration: 10 cells / mL) of a liquid containing 1000 bacteria is concentrated 10 times will be described. First, 100 mL of a liquid containing bacteria is passed through a filter 20 to which a positive voltage is applied, and the bacteria are adsorbed on the filter 20. After adsorbing all the bacteria in 100 mL of the liquid on the filter 20, 10 mL of the eluate is passed through the filter 20 to which a negative voltage is applied. As a result, bacteria are desorbed from the filter 20 and flow out together with the eluate to the outside of the filter device 100.
  • the filter device 100 By collecting the 10 mL eluate flowing out of the filter device 100, 10 mL of a liquid containing 1000 bacteria (concentration: 100 cells / mL) can be obtained. That is, the filter device 100 can also be used for concentrating the target substance.
  • the separation using the filter device 100 is almost the same as the bacterial inspection method described below, and thus the description thereof will be omitted.
  • 4 (A) to 4 (C) are diagrams for explaining a method for inspecting bacteria using the filter device 100.
  • the liquid to be tested contains, for example, two bacteria A41 and a bacterium B42 with different zeta potentials.
  • the user first applies a positive voltage (V1) to the conductor 23 of the filter 20.
  • V1 positive voltage
  • bacteria A41 and bacteria B42 are adsorbed on the surface of the insulator film 24 of the filter 20.
  • the user applies a positive voltage (V2) smaller than V1 to the conductor 23.
  • V2 a positive voltage
  • V3 a positive voltage
  • the user applies a positive voltage (V3) smaller than V2 to the conductor 23.
  • V3 a positive voltage
  • the bacterium A41 is eliminated from the surface of the insulator film 24. Therefore, the user can collect and inspect only the bacterium A41 downstream.
  • the user can separate and inspect each bacterium having a different zeta potential using the filter device 100.
  • the filter device 100 contains three or more types of bacteria, it can be similarly separated. It is also possible to set V3 to 0V or a negative voltage. It is also possible to gradually separate bacteria having different zeta potentials by gradually changing the voltage from V1 toward a negative voltage.
  • FIGS. 5A to 5C are diagrams for explaining medium exchange using the filter device 100. Note that FIGS. 5A to 5C show only the filter 20 of the filter unit 101 in the filter device 100, and the rest will be omitted.
  • the user uses the medium exchange unit 70 including the filter device 100.
  • the medium exchange unit 70 includes a filter unit 101, a container 51, a container 52, a tube 57, a container 53, a valve 54, a valve 55, a valve 56, a tube 57, and a tube 58.
  • the filter unit 101 is connected to one end of each of the pipe 57 and the pipe 58.
  • a pump (not shown) circulates the liquid through the pipe 57 and the pipe 58 to the filter 20 of the filter unit 101.
  • the pipe 57 has a first end 61 on the side that is not connected to the filter unit 101.
  • the tube 58 has a second end 62 and a third end 63 that are bifurcated on the side not connected to the filter unit 101.
  • the first end 61 is arranged inside the container 51
  • the second end 62 is arranged inside the container 52
  • the third end 63 is arranged inside the container 53, respectively.
  • the valve 54 is arranged between the filter unit 101 and the first end 61 of the pipe 57.
  • the valve 55 is arranged between the filter unit 101 and the second end 62 of the pipe 58.
  • the valve 56 is arranged between the filter unit 101 in the pipe 58 and the third end 63.
  • the valve 54, the valve 55, and the valve 56 open and close the pipe 57 and the pipe 58, respectively.
  • the culture solution is filled in the container 51.
  • the culture medium contains old medium and cells.
  • the new medium is filled in container 53. Further, the container 52 is in an empty state where nothing is filled.
  • the user first opens the valve 54 and the valve 55 and closes the valve 56.
  • the user drives a pump (not shown) to circulate the liquid in the direction of the arrow in FIG. 5 (B).
  • the culture solution in the container 51 is sucked up from the first end 61 and moves from the second end 62 to the container 52 via the filter 20.
  • a positive voltage is applied to the filter 20.
  • the cells in the culture medium are adsorbed on the filter 20, and the other old culture medium is moved to the container 52.
  • the user first sets the valve 54 and the valve 56 in the open state and the valve 54 in the closed state. Subsequently, the user drives a pump (not shown) to circulate the liquid in the direction of the arrow in FIG. 5 (C).
  • the medium in the container 53 is sucked up from the third end 63 and moves from the first end 61 to the container 51 through the filter 20.
  • no voltage is applied to the filter 20, or a negative voltage is applied to the filter 20.
  • the cells adsorbed on the filter 20 are detached from the filter 20 and moved to the container 51 together with the new medium. Therefore, the cells do not remain in the filter 20, and the recovery rate of the cells is improved.
  • the flow path 25 of the filter 20 can be designed to be large for cells. Therefore, it is possible to prevent cells from clogging the filter 20. Therefore, the user can smoothly change the medium.
  • the user can exchange the medium by using the filter device 100.
  • the operator When exchanging the medium using a pipette and a centrifuge as in the conventional case, the operator precipitates the cells by centrifuging the culture solution put in the centrifuge tube, and sucks up the supernatant culture solution with the pipette. In this case, the operation of transferring to a plurality of centrifuge tubes may occur and the cells may be exposed to air, and there is a problem that the yield is lowered due to the transfer. Furthermore, in the conventional medium exchange, there are cases where cells cannot be sufficiently separated by centrifugation, and the yield may decrease due to an erroneous operation of the pipette. For this reason, in the conventional medium exchange, it is necessary for the operator to become accustomed to the medium and to perform careful operation.
  • the medium exchange unit 70 can be used for, for example, anaerobic bacteria by making all the spaces closed. Further, since the operation of transferring to a plurality of centrifuge tubes can be omitted, the yield and efficiency are improved. Further, since the operator does not operate the pipette, the burden and time of the operator can be saved. Therefore, the method for exchanging the medium using the filter device 100 is excellent in yield and efficiency, and can exchange the medium in a stable state without being exposed to the outside air.
  • Example 1 Collection example using a mesh filter First, a stainless steel mesh filter with a mesh opening of 77 ⁇ m was prepared and stacked in three layers. An alumina (Al 2 O 3 ) film was formed on the laminated mesh filter by the ALD method. The thickness of the alumina film was about 30 nm. As a result, a mesh filter coated with an insulator film was obtained. The obtained mesh filter was set in the filter device.
  • a test solution containing yeast was prepared by adding 0.5 g of dry yeast to 1 L of pure water and stirring the mixture. By driving the pump, the test solution was flowed through the mesh filter at a flow velocity of 1.8 ml / min. At this time, a voltage of ⁇ 10 V was applied to the mesh filter. The liquid that had passed through the mesh filter was recovered, and 0.1 mL of the recovered liquid was sandwiched between two slide glasses and observed at a magnification of 200 times using a microscope (VHX-5000, manufactured by KEYENCE). In the observation, the number of yeasts present in the field of view 1.6 ⁇ 1.2 mm was counted. Next, a similar test was performed with a voltage of + 20 V applied to the mesh filter.
  • FIG. 6 is a graph showing the results of Example 1. As shown in FIG. 6, when a voltage of ⁇ 10 V was applied to the mesh filter, the number of yeasts counted was 1083. On the other hand, when a voltage of + 20 V was applied to the mesh filter, the number of yeasts counted was 79. That is, when a negative voltage was applied to the mesh filter, yeast was desorbed from the mesh filter and flowed out, and conversely, when a positive voltage was applied, yeast was adsorbed on the mesh filter. As described above, it was confirmed that a certain amount of yeast can be collected by applying a positive voltage to the mesh filter using the stainless steel mesh filter formed by the ALD method. The collection efficiency using the mesh filter was 93%.
  • Example 2 Collection example using a porous body
  • a stainless steel porous body having a filtration diameter of 10 ⁇ m and a thickness of 3 mm was prepared.
  • An alumina (Al 2 O 3 ) film was formed on the stainless steel porous body by the ALD method.
  • the thickness of the alumina film was about 30 nm.
  • a stainless steel porous body coated with an insulator film was obtained.
  • the obtained stainless steel porous body was set in a filter device.
  • a test solution containing yeast was prepared by adding 0.5 g of dry yeast to 1 L of pure water and stirring the mixture. By driving the pump, the test solution was flowed through the stainless steel porous body at a flow velocity of 0.5 ml / min.
  • a voltage of ⁇ 10 V was applied to the stainless steel porous body.
  • the test liquid was allowed to flow through the stainless steel porous body, and the liquid that passed through the stainless steel porous body was allowed to flow while being observed with a microscope (VHX-5000, manufactured by KEYENCE) at a magnification of 200 times. In the observation, the number of yeasts passing through the range of 1.6 ⁇ 1.2 mm in the field of view was counted in 10 seconds.
  • the same test was performed with a voltage of + 20 V applied to the stainless steel porous body for about 120 seconds. Subsequently, the same test was carried out with a voltage of ⁇ 10 V applied to the stainless steel porous body again.
  • FIG. 7 is a graph showing the results of Example 2. As shown in FIG. 7, when a voltage of ⁇ 10 V was first applied to the stainless steel porous body, the number of yeasts counted was about 200. Subsequently, when a voltage of + 20 V was applied to the stainless steel porous body, the number of yeasts counted was two. Furthermore, when a voltage of ⁇ 10 V was applied to the stainless steel porous body again, the number of yeasts counted was about 20000.

Abstract

Provided are a filter that collects or separates a target substance, a filter unit, and a filter device. The filter comprises an electric conductor capable of circulating a liquid, an insulator film that covers a portion of the electric conductor that the liquid comes into contact with, and a voltage application unit for applying voltage from the exterior, the voltage application unit being positioned in a portion of the surface of the electric conductor that the liquid does not come into contact with.

Description

フィルタ、フィルタユニット、及びフィルタ装置Filters, filter units, and filter devices
 本発明は、捕集又は分離するフィルタに関する。 The present invention relates to a filter that collects or separates.
 近年、病気を診断する方法としてバイオマーカーとなる特定の物質を体液等から捕集して検査する手法が開示されている。例えば、非特許文献1には、物質表面の固定電荷を利用して尿中のエクソソームを捕集する方法が開示されている。非特許文献1に記載の発明においては、マイクロ流体基板に固定された酸化亜鉛のナノワイヤに尿を通すことにより、尿中のエクソソームをナノワイヤの固定電荷に寄せ集める。 In recent years, as a method of diagnosing a disease, a method of collecting and inspecting a specific substance as a biomarker from a body fluid or the like has been disclosed. For example, Non-Patent Document 1 discloses a method for collecting exosomes in urine by utilizing a fixed charge on the surface of a substance. In the invention described in Non-Patent Document 1, urine is passed through zinc oxide nanowires fixed to a microfluidic substrate to collect exosomes in urine to a fixed charge of the nanowires.
 非特許文献1に記載の発明においては、ナノワイヤの表面電荷は固定的であるため、ナノワイヤは捕獲したエクソソーム自体を放出できない。従来技術では、ターゲット物質を捕獲したり放出したりできない。 In the invention described in Non-Patent Document 1, since the surface charge of the nanowire is fixed, the nanowire cannot release the captured exosome itself. Conventional techniques cannot capture or release target substances.
 そこで、本発明の目的は、ターゲット物質を捕集又は分離するフィルタ、フィルタユニット、及びフィルタ装置を提供することにある。 Therefore, an object of the present invention is to provide a filter, a filter unit, and a filter device for collecting or separating a target substance.
 この発明のフィルタは、液体を流通可能な導電体と、前記導電体のうち前記液体が接触する部分を覆う絶縁体膜と、前記導電体の表面のうち前記液体が接触しない部分に位置し、外部から電圧を印加するための電圧印加部と、を備えることを特徴とする。 The filter of the present invention is located on a conductor capable of flowing a liquid, an insulator film covering a portion of the conductor that the liquid contacts, and a portion of the surface of the conductor that the liquid does not contact. It is characterized by including a voltage application unit for applying a voltage from the outside.
 この構成において、絶縁体膜は、印加された電圧により液体中のターゲットとする物質を吸着する。フィルタの液体に接する部分は絶縁体で覆われているため、電圧により電流が流れることはない。絶縁体膜は、電圧により物質を吸着しているため、電圧の印加を停止すれば、電圧による物質の吸着を解除することができる。このため、フィルタは、ターゲット物質を捕集又は分離できる。 In this configuration, the insulator film adsorbs the target substance in the liquid by the applied voltage. Since the part of the filter in contact with the liquid is covered with an insulator, no current flows due to the voltage. Since the insulator film adsorbs the substance by the voltage, the adsorption of the substance by the voltage can be released by stopping the application of the voltage. This allows the filter to collect or separate the target material.
 この発明によれば、ターゲット物質を捕集又は分離できる。 According to the present invention, the target substance can be collected or separated.
図1(A)は、実施形態に係るフィルタ装置100の構成を示す模式図である。図1(B)は、フィルタユニット101の模式的な断面図である。FIG. 1A is a schematic view showing the configuration of the filter device 100 according to the embodiment. FIG. 1B is a schematic cross-sectional view of the filter unit 101. 図2(A)はフィルタ20を示す模式的な斜視図であり、図2(B)はフィルタ20の一部拡大断面図である。FIG. 2A is a schematic perspective view showing the filter 20, and FIG. 2B is a partially enlarged cross-sectional view of the filter 20. 図3は、フィルタ20の一使用状態を説明するための図である。FIG. 3 is a diagram for explaining one usage state of the filter 20. 図4(A)~(C)は、フィルタ装置100を用いた細菌の検査方法について説明するための図である。4 (A) to 4 (C) are diagrams for explaining a method for inspecting bacteria using the filter device 100. 図5(A)~(C)は、フィルタ装置100を用いた培地交換について説明するための図である。5 (A) to 5 (C) are diagrams for explaining medium exchange using the filter device 100. 図6は、実施例1の結果を示すグラフである。FIG. 6 is a graph showing the results of Example 1. 図7は、実施例2の結果を示すグラフである。FIG. 7 is a graph showing the results of Example 2.
 図1(A)は、実施形態に係るフィルタ装置100の構成を示す模式図である。図1(B)は、フィルタユニット101の模式的な断面図である。なお、図1(A)において、フィルタ20は破線で表している。以下、フィルタユニット101の軸線方向をZ方向として説明する。 FIG. 1A is a schematic view showing the configuration of the filter device 100 according to the embodiment. FIG. 1B is a schematic cross-sectional view of the filter unit 101. In FIG. 1A, the filter 20 is represented by a broken line. Hereinafter, the axial direction of the filter unit 101 will be described as the Z direction.
 図1(A)に示すように、本実施形態に係るフィルタ装置100は、フィルタユニット101、直流電源102、及び制御部103を備える。また、フィルタ装置100は、不図示のポンプを備える。 As shown in FIG. 1A, the filter device 100 according to the present embodiment includes a filter unit 101, a DC power supply 102, and a control unit 103. Further, the filter device 100 includes a pump (not shown).
 フィルタユニット101は、直流電源102と接続されている。フィルタユニット101は、直流電源102から直流電圧を印加される。直流電源102は、制御部103と接続されている。制御部103は、直流電源102の直流電圧を制御する。例えば、制御部103は、直流電源102の直流電圧を正又は負に切り替える。これにより、ユーザは、制御部103を介して、フィルタユニット101に印加する直流電圧を制御することができる。 The filter unit 101 is connected to the DC power supply 102. A DC voltage is applied to the filter unit 101 from the DC power supply 102. The DC power supply 102 is connected to the control unit 103. The control unit 103 controls the DC voltage of the DC power supply 102. For example, the control unit 103 switches the DC voltage of the DC power supply 102 between positive and negative. As a result, the user can control the DC voltage applied to the filter unit 101 via the control unit 103.
 図1(B)に示すように、フィルタユニット101は、フィルタ20及び固定具10を備える。固定具10は、フィルタ20を固定する。フィルタユニット101の形状は、概ね筒状であり、内部空間13を有する。フィルタ20は、フィルタユニット101の軸方向における中央部分に配置されている。 As shown in FIG. 1 (B), the filter unit 101 includes a filter 20 and a fixture 10. The fixture 10 fixes the filter 20. The shape of the filter unit 101 is substantially tubular and has an internal space 13. The filter 20 is arranged at the central portion of the filter unit 101 in the axial direction.
 固定具10は、二つの接手11及びソケット12を備える。接手11及びソケット12は、筒状であり両端が開口している。接手11は、内部空間13を構成している。二つの接手11はフィルタ20を挟んで、かつそれぞれの内部空間13が連続するように配置されている。ソケット12は、二つの接手11及びフィルタ20の周囲を覆うように二つの接手11及びフィルタ20の側面に配置されている。これにより、図1(B)に示す矢印で示すように、不図示のポンプで一方の内部空間13へ液体を流入させると、液体はフィルタ20を介して他方の内部空間13から流出する。なお、接手11は、本発明における流路側壁部の一例である。 The fixture 10 includes two joints 11 and a socket 12. The joint 11 and the socket 12 are tubular and have both ends open. The joint 11 constitutes the internal space 13. The two joints 11 are arranged so as to sandwich the filter 20 and their internal spaces 13 are continuous. The socket 12 is arranged on the side surface of the two joints 11 and the filter 20 so as to cover the periphery of the two joints 11 and the filter 20. As a result, as shown by the arrow shown in FIG. 1 (B), when the liquid is made to flow into one internal space 13 by a pump (not shown), the liquid flows out from the other internal space 13 through the filter 20. The joint 11 is an example of the side wall portion of the flow path in the present invention.
 図2(A)は、フィルタ20を示す模式的な斜視図である。図2(B)は、フィルタ20の一部拡大断面図である。なお、図2(B)は、流通部21の一部をZ方向に平行な面で切断した図である。 FIG. 2A is a schematic perspective view showing the filter 20. FIG. 2B is a partially enlarged cross-sectional view of the filter 20. Note that FIG. 2B is a view in which a part of the distribution section 21 is cut along a plane parallel to the Z direction.
 図2(A)に示すように、フィルタ20は、流通部21、枠部22、及び電圧印加部16を備える。枠部22は、流通部21の周囲を囲むように形成されている。枠部22は接手11によって挟まれる箇所であり、流通部21は、内部空間13に配置される箇所である。 As shown in FIG. 2A, the filter 20 includes a distribution unit 21, a frame unit 22, and a voltage application unit 16. The frame portion 22 is formed so as to surround the circulation portion 21. The frame portion 22 is a portion sandwiched by the joints 11, and the distribution portion 21 is a portion arranged in the internal space 13.
 流通部21は、メッシュ構造である。流通部21は、金属からなる線状の導電体23を網状に配置したものである。流通部21及び枠部22は同一の導電体23の素材で一体として形成されていてもよい。導電体23は、例えば、ステンレス、鉄、銅、アルミニウム、銀などが使用できる。図2(B)に示すように、複数の導電体23の間には液体を流通可能な流路25が形成されている。フィルタ20は、流路25を介して液体を流通させることができる。 The distribution unit 21 has a mesh structure. The distribution unit 21 is formed by arranging linear conductors 23 made of metal in a mesh pattern. The distribution section 21 and the frame section 22 may be integrally formed of the same material of the conductor 23. As the conductor 23, for example, stainless steel, iron, copper, aluminum, silver and the like can be used. As shown in FIG. 2B, a flow path 25 capable of flowing a liquid is formed between the plurality of conductors 23. The filter 20 can circulate the liquid through the flow path 25.
 導電体23は、絶縁体膜24によって被覆されている。絶縁体膜24は、導電体23のうち少なくとも液体と接触する部分を覆っている。言い換えると、絶縁体膜24は、流路25に配置されている流通部21を覆っている。このため、導電体23に電圧が印加されても、電流が流れることはない。なお、本実施形態において、流通部21は、導電体23のうち少なくとも液体と接触する部分であり、かつ本発明における液体通過部の一例である。 The conductor 23 is covered with an insulator film 24. The insulator film 24 covers at least a portion of the conductor 23 that comes into contact with the liquid. In other words, the insulator film 24 covers the distribution section 21 arranged in the flow path 25. Therefore, even if a voltage is applied to the conductor 23, no current flows. In the present embodiment, the flow section 21 is at least a portion of the conductor 23 that comes into contact with the liquid, and is an example of the liquid passage section in the present invention.
 絶縁体膜24は、原子層堆積法すなわちALD(Atomic layer deposition)法で形成されることが好ましい。ALD法では、複雑な形状の表面でも均一に被覆することができる。このため、メッシュ構造の導電体23であっても均一に被覆することができる。なお、絶縁体膜24は、ALD法以外の方法で被覆されていてもよい。例えば、絶縁体膜24は、陽極酸化処理で形成されてもよい。 The insulator film 24 is preferably formed by an atomic layer deposition method, that is, an ALD (Atomic layer deposition) method. In the ALD method, even a surface having a complicated shape can be uniformly covered. Therefore, even the conductor 23 having a mesh structure can be uniformly coated. The insulator film 24 may be coated by a method other than the ALD method. For example, the insulator film 24 may be formed by anodization treatment.
 絶縁体膜24は、例えばチタニア(TiO)、アルミナ(Al)、シリカ(SiO)、ハフニア(HfO)、ジルコニア(ZrO)、酸化亜鉛(ZnO)、又は酸化ニッケル(NiO)を含むことが好ましく、特に、チタニアを含むことが好ましい。チタニアは、生体親和性に優れる材料であるため、生体試料への影響を低減する。シリカは負に帯電し易い物質であるため、導電体23に正の電圧が印加されていない場合、負の電荷を有する物質が吸着しにくい。このため、シリカを絶縁体膜24に用いると、フィルタ20は、負の電荷を有する物質に対する目詰まりを防止し易い。酸化亜鉛、酸化ニッケル、及びジルコニアは正に帯電し易い物質であるため、正の電圧が印加された導電体23に対して負の電荷を有する物質を吸着し易い。また、アルミナ及びチタニアは等電点が中性近傍にあるために中性領域での表面電荷がゼロに近い。このため、ユーザは、導電体23に正の電圧を印加して負の電荷を有する物質を吸着したり、導電体23に負の電圧を印加して正の電荷を有する物質を吸着したりすることができ、ターゲット物質が正又は負のどちらに帯電していても用い易い。 The insulator film 24 is, for example, titanium (TiO 2 ), alumina (Al 2 O 3 ), silica (SiO 2 ), hafnia (HfO), zirconia (ZrO 2 ), zinc oxide (ZnO), or nickel oxide (NiO). Is preferably contained, and in particular, titania is preferably contained. Since titania is a material having excellent biocompatibility, it reduces the influence on the biological sample. Since silica is a substance that is easily negatively charged, it is difficult for a substance having a negative charge to be adsorbed when a positive voltage is not applied to the conductor 23. Therefore, when silica is used for the insulator film 24, the filter 20 can easily prevent clogging of a substance having a negative charge. Since zinc oxide, nickel oxide, and zirconia are substances that are easily charged positively, they are likely to adsorb substances that have a negative charge on the conductor 23 to which a positive voltage is applied. Further, since the isoelectric point of alumina and titania is near the neutral point, the surface charge in the neutral region is close to zero. Therefore, the user applies a positive voltage to the conductor 23 to adsorb a substance having a negative charge, or applies a negative voltage to the conductor 23 to adsorb a substance having a positive charge. It is easy to use regardless of whether the target substance is positively or negatively charged.
 電圧印加部16は、導電体23の表面のうち液体が接触しない部分に位置する。電圧印加部16は、例えばフィルタ20の側面、すなわち枠部22の側面に位置する。また、電圧印加部16は、導電体23の全体をALD法で絶縁体膜24を成膜し、その後、絶縁体膜24の一部をそぎ落とすことにより形成できる。絶縁体膜24をそぎ落とすことにより、導電体23が表面に露出する。これにより、フィルタ20は、外部と電気的に接続する部分を形成する。無論、電圧印加部16は、絶縁体膜24を成膜する際に、電圧印加部16となる箇所だけ成膜されないようにパターニングして形成してもよい。 The voltage application unit 16 is located on the surface of the conductor 23 where the liquid does not come into contact. The voltage application unit 16 is located, for example, on the side surface of the filter 20, that is, the side surface of the frame unit 22. Further, the voltage application unit 16 can be formed by forming an insulator film 24 on the entire conductor 23 by the ALD method and then scraping off a part of the insulator film 24. By scraping off the insulator film 24, the conductor 23 is exposed on the surface. As a result, the filter 20 forms a portion that is electrically connected to the outside. Of course, when the insulator film 24 is formed, the voltage applying portion 16 may be formed by patterning so that only the portion that becomes the voltage applying portion 16 is not formed.
 電圧印加部16は、ソケット12と接触する。電圧印加部16は、ソケット12を介して外部の直流電源102と電気的に接続することができる。これにより、電圧印加部16は、ソケット12を介して外部から導電体23に電圧を印加することができる。なお、電圧印加部16は、固定具10のいずれかの場所を介して外部の直流電源102と電気的に接続できればよい。 The voltage application unit 16 comes into contact with the socket 12. The voltage application unit 16 can be electrically connected to the external DC power supply 102 via the socket 12. As a result, the voltage application unit 16 can apply a voltage to the conductor 23 from the outside via the socket 12. The voltage application unit 16 may be electrically connected to the external DC power supply 102 via any location of the fixture 10.
 なお、フィルタユニット101において、フィルタ20は、二つの接手11より径の太い構造であってもよい。フィルタ20は、二つの接手11により挟み込まれるように配置され、外周部分が外部に露出している。この場合、フィルタ20の側面に形成された電圧印加部16は、直流電源102と直接接続することができる。従って、ソケット12が不要であるため、フィルタユニット101の構成を簡単なものにすることができる。 In the filter unit 101, the filter 20 may have a structure having a diameter larger than that of the two joints 11. The filter 20 is arranged so as to be sandwiched between the two joints 11, and the outer peripheral portion is exposed to the outside. In this case, the voltage application unit 16 formed on the side surface of the filter 20 can be directly connected to the DC power supply 102. Therefore, since the socket 12 is not required, the configuration of the filter unit 101 can be simplified.
 次に、フィルタ装置100の使用方法について説明する。図3は、フィルタ20の一使用状態を説明するための図である。ユーザは、初めに制御部103を介して直流電源102からフィルタ20に、正の電圧を印加する。これにより、正の電圧が流通部21の導電体23に印加される。図3に示すように、負の電荷を有する物質30を含む液体が、フィルタ20に矢印の方向に沿って流される。このとき、導電体23に正の電圧が印加されているため、物質30は、絶縁体膜24の表面に引き寄せられ、吸着する。ここで、導電体23に対する正の電圧の印加を停止すれば、絶縁体膜24表面における物質30を引き寄せる力が弱まる。これにより、絶縁体膜24は、物質30の吸着を解除することができる。 Next, how to use the filter device 100 will be described. FIG. 3 is a diagram for explaining one usage state of the filter 20. The user first applies a positive voltage from the DC power supply 102 to the filter 20 via the control unit 103. As a result, a positive voltage is applied to the conductor 23 of the circulation unit 21. As shown in FIG. 3, a liquid containing the negatively charged substance 30 is flowed through the filter 20 along the direction of the arrow. At this time, since a positive voltage is applied to the conductor 23, the substance 30 is attracted to and adsorbed on the surface of the insulator film 24. Here, if the application of the positive voltage to the conductor 23 is stopped, the force for attracting the substance 30 on the surface of the insulator film 24 is weakened. As a result, the insulator film 24 can release the adsorption of the substance 30.
 さらに、この時ユーザは、制御部103を介して直流電源102からフィルタ20に、負の電圧を印加することも可能である。この場合、絶縁体膜24は、印加された負の電圧により吸着している物質30との間に反発力を生じる。このため、絶縁体膜24は、積極的に物質30を脱離することができる。このように、フィルタ20は、ターゲット物質である負の電荷を有する物質30を捕集又は分離できる。なお、ターゲット物質である物質30としては、例えば、細菌、ウィルス、真菌、細胞、DNA、RNA、細胞外小胞、血球、一部のタンパク質、又はマイクロビーズ等がある。 Further, at this time, the user can also apply a negative voltage from the DC power supply 102 to the filter 20 via the control unit 103. In this case, the insulator film 24 generates a repulsive force with the substance 30 adsorbed by the applied negative voltage. Therefore, the insulator film 24 can positively desorb the substance 30. In this way, the filter 20 can collect or separate the negatively charged substance 30 which is the target substance. The target substance 30, for example, includes bacteria, viruses, fungi, cells, DNA, RNA, extracellular vesicles, blood cells, some proteins, microbeads, and the like.
 また、ユーザは、初めに制御部103を介して直流電源102からフィルタ20に、負の電圧を印加することも可能である。この場合、絶縁体膜24は、ターゲット物質として正の電荷を有する物質を捕集又は分離できる。 The user can also first apply a negative voltage from the DC power supply 102 to the filter 20 via the control unit 103. In this case, the insulator film 24 can collect or separate a substance having a positive charge as a target substance.
 ここで、非特許文献1に記載の発明においては、ナノワイヤの電荷は固定であるため、ナノワイヤは捕獲したエクソソーム自体を放出できない。言い換えると、エクソソームは、破壊されることなく回収することはできない。例えば、ナノワイヤに寄せ集めたエクソソームは、界面活性剤に晒されることで細胞壁を破壊される。これにより、エクソソーム中のmiRNAは、エクソソーム内部の細胞液から回収する。このため、非特許文献1に記載の発明は、免疫細胞捕獲のような捕集の後に培養を想定する場合には対応できない。 Here, in the invention described in Non-Patent Document 1, since the charge of the nanowire is fixed, the nanowire cannot release the captured exosome itself. In other words, exosomes cannot be recovered without being destroyed. For example, exosomes gathered on nanowires are exposed to a surfactant, which destroys the cell wall. As a result, the miRNA in the exosome is recovered from the cell fluid inside the exosome. Therefore, the invention described in Non-Patent Document 1 cannot be applied when culturing is assumed after collection such as immune cell capture.
 これに対して、本実施形態に係るフィルタ20は、電荷によりターゲット物質を吸着し、電荷を解除、又は逆極性の電荷により吸着を解除するため、ターゲット物質に化学的な影響を及ぼすことはない。このように、フィルタ20は、ターゲット物質を破壊することなく、そのまま回収することができるため、捕集の後に培養することができる。 On the other hand, the filter 20 according to the present embodiment adsorbs the target substance by the electric charge and releases the charge, or releases the adsorption by the charge of the opposite polarity, so that the target substance is not chemically affected. .. In this way, the filter 20 can be recovered as it is without destroying the target substance, and thus can be cultured after collection.
 また、仮に導電体23のうち液体に接触する部分に絶縁体膜24が無いと、ターゲット物質を導電体23に吸着できたとしても、液体が電気分解して気泡が発生する。発生した気泡は、フィルタ20を目詰まりさせる。これにより、液体がフィルタ20の流路を流れにくくなるため、フィルタ20の捕集及び分離する効率が低下する。 Further, if there is no insulator film 24 in the portion of the conductor 23 that comes into contact with the liquid, even if the target substance can be adsorbed on the conductor 23, the liquid is electrolyzed and bubbles are generated. The generated bubbles clog the filter 20. This makes it difficult for the liquid to flow through the flow path of the filter 20, and thus reduces the efficiency of collecting and separating the filter 20.
 これに対して、導電体23のうち液体に接触する部分を絶縁体膜24で覆うと、直流電圧を印加しても、フィルタ20と液体との間で電荷の移動は生じない。従って、液体の電気分解が起こらない。このため、フィルタ20は、気泡を発生させることがないため、目詰まりを防止できる。特に、ALD法のような均一な薄膜を形成できるプロセスを用いることで、フィルタ20は、電気分解をせず、かつ絶縁体膜24にターゲット物質を吸着できるほどの電荷を生じさせることもできる。 On the other hand, if the portion of the conductor 23 that comes into contact with the liquid is covered with the insulator film 24, no electric charge is transferred between the filter 20 and the liquid even if a DC voltage is applied. Therefore, electrolysis of the liquid does not occur. Therefore, the filter 20 does not generate air bubbles, so that clogging can be prevented. In particular, by using a process capable of forming a uniform thin film such as the ALD method, the filter 20 can generate an electric charge sufficient to adsorb the target substance on the insulator film 24 without electrolysis.
 なお、本実施形態において、流通部21は、メッシュ構造であったが、これには限定されない。流通部21は、液体が流通するものであればよく、例えば、多孔体構造であってもよい。多孔体構造の場合、導電体23の構造が複雑であり、液体との接触面積が増えるため、ターゲット物質は、メッシュ構造と比べてよりフィルタ20に接触し易い。従って、多孔体構造の場合、ターゲット物質の捕集効率が向上する。 In the present embodiment, the distribution unit 21 has a mesh structure, but the present invention is not limited to this. The distribution unit 21 may have a porous structure, for example, as long as the liquid can circulate. In the case of the porous structure, the structure of the conductor 23 is complicated and the contact area with the liquid increases, so that the target substance is more likely to come into contact with the filter 20 than the mesh structure. Therefore, in the case of a porous structure, the collection efficiency of the target substance is improved.
 また、フィルタ20におけるメッシュ構造の流路25の目開きの大きさは、例えば図3に示すように、ターゲット物質である物質30より大きなサイズとすることができる。フィルタ20は、流路25の目開きの大きさを物質30の大きさより小さくしてろ過することにより捕集するのではなく、フィルタ20の物質30を引き寄せる力により捕集することによる。物質30はメッシュ構造の流路25の目開きの大きさより小さいため、フィルタ20は目詰まりを防止できる。また、流路25の目開きのサイズが大きいほど、フィルタ20の製造も容易となる。なお、流路25の目開きの大きさは、捕集するターゲット物質の大きさ等の条件に応じて調節できる。 Further, the size of the opening of the flow path 25 of the mesh structure in the filter 20 can be made larger than the target substance 30 as shown in FIG. 3, for example. The filter 20 does not collect by filtering the substance 30 with the size of the opening of the flow path 25 smaller than the size of the substance 30, but collects by the force of attracting the substance 30 of the filter 20. Since the substance 30 is smaller than the size of the opening of the flow path 25 having a mesh structure, the filter 20 can prevent clogging. Further, the larger the size of the opening of the flow path 25, the easier it is to manufacture the filter 20. The size of the opening of the flow path 25 can be adjusted according to conditions such as the size of the target substance to be collected.
 なお、フィルタ20に対する印加電圧、フィルタ20を通す液体の流速、流量、又は絶縁体膜24の厚さ等も、適宜捕集するターゲット物質の大きさ等の条件に応じて調節できる。また、フィルタ装置100は、フィルタ20を通す液体の流速、フィルタ20に対する印加電圧、又はターゲット物質のゼータ電位に応じて、捕集するターゲット物質の選択性を制御することができる。 The voltage applied to the filter 20, the flow velocity of the liquid passing through the filter 20, the flow rate, the thickness of the insulator film 24, and the like can also be appropriately adjusted according to conditions such as the size of the target substance to be collected. Further, the filter device 100 can control the selectivity of the target substance to be collected according to the flow velocity of the liquid passing through the filter 20, the voltage applied to the filter 20, or the zeta potential of the target substance.
 なお、本実施形態において、フィルタ装置100は、一つのフィルタ20を備えていたが、複数のフィルタ20を備えていてもよい。フィルタ装置100が複数のフィルタ20を備える場合、液体がフィルタ20の絶縁体膜24と接する部分が増える。このため、フィルタ装置100は、より多くのターゲット物質を捕集することができる。 Although the filter device 100 is provided with one filter 20 in the present embodiment, it may be provided with a plurality of filters 20. When the filter device 100 includes a plurality of filters 20, the portion where the liquid comes into contact with the insulator film 24 of the filter 20 increases. Therefore, the filter device 100 can collect more target substances.
 なお、本実施形態において、フィルタ装置100は、ターゲット物質を捕集するために用いられたが、その他の用途にも用いることができる。フィルタ装置100は、例えば、分離、濃縮、培養における培地交換、細菌の検査等に用いることができる。 Although the filter device 100 was used to collect the target substance in the present embodiment, it can also be used for other purposes. The filter device 100 can be used, for example, for separation, concentration, medium exchange in culture, bacterial inspection, and the like.
 フィルタ装置100を用いた濃縮方法について説明する。例えば、細菌1000個を含む液体100mL(濃度:10個/mL)を10倍に濃縮する場合について説明する。初めに細菌を含む液体100mLを正の電圧を印加したフィルタ20に流して、細菌をフィルタ20に吸着させる。液体100mL中の全ての細菌をフィルタ20に吸着させた後に、負の電圧を印加したフィルタ20に、溶出液10mLを流す。これにより、フィルタ20から細菌が脱離し、溶出液と共にフィルタ装置100の外部へと流出する。フィルタ装置100から流出した10mLの溶出液を回収することにより、細菌1000個を含む液体10mL(濃度:100個/mL)が得られる。すなわち、フィルタ装置100は、ターゲット物質の濃縮にも利用できる。なお、フィルタ装置100を用いた分離については、以下に説明する細菌の検査方法と概ね同じであるため説明を省略する。 The concentration method using the filter device 100 will be described. For example, a case where 100 mL (concentration: 10 cells / mL) of a liquid containing 1000 bacteria is concentrated 10 times will be described. First, 100 mL of a liquid containing bacteria is passed through a filter 20 to which a positive voltage is applied, and the bacteria are adsorbed on the filter 20. After adsorbing all the bacteria in 100 mL of the liquid on the filter 20, 10 mL of the eluate is passed through the filter 20 to which a negative voltage is applied. As a result, bacteria are desorbed from the filter 20 and flow out together with the eluate to the outside of the filter device 100. By collecting the 10 mL eluate flowing out of the filter device 100, 10 mL of a liquid containing 1000 bacteria (concentration: 100 cells / mL) can be obtained. That is, the filter device 100 can also be used for concentrating the target substance. The separation using the filter device 100 is almost the same as the bacterial inspection method described below, and thus the description thereof will be omitted.
 次に、フィルタ装置100を用いた細菌の検査方法について説明する。図4(A)~(C)は、フィルタ装置100を用いた細菌の検査方法について説明するための図である。 Next, a method for inspecting bacteria using the filter device 100 will be described. 4 (A) to 4 (C) are diagrams for explaining a method for inspecting bacteria using the filter device 100.
 フィルタ装置100を用いて複数の細菌を含む液体を検査する方法について説明する。検査する液体は、例えばゼータ電位の異なる2つの細菌A41及び細菌B42を含む。ユーザは初めにフィルタ20の導電体23に正の電圧(V1)を印加する。図4(A)に示すように、フィルタ20の絶縁体膜24の表面に細菌A41及び細菌B42を吸着する。 A method of inspecting a liquid containing a plurality of bacteria using the filter device 100 will be described. The liquid to be tested contains, for example, two bacteria A41 and a bacterium B42 with different zeta potentials. The user first applies a positive voltage (V1) to the conductor 23 of the filter 20. As shown in FIG. 4A, bacteria A41 and bacteria B42 are adsorbed on the surface of the insulator film 24 of the filter 20.
 次に、ユーザは、導電体23にV1より小さい正の電圧(V2)を印加する。これにより、図4(B)に示すように絶縁体膜24の表面から細菌B42が脱離する。従って、ユーザは下流で細菌B42のみを回収して検査することができる。また、ユーザは、導電体23にV2よりさらに小さい正の電圧(V3)を印加する。これにより、図4(C)に示すように絶縁体膜24の表面から細菌A41が脱離する。従って、ユーザは下流で細菌A41のみを回収して検査することができる。 Next, the user applies a positive voltage (V2) smaller than V1 to the conductor 23. As a result, the bacterium B42 is eliminated from the surface of the insulator film 24 as shown in FIG. 4 (B). Therefore, the user can collect and inspect only the bacterium B42 downstream. Further, the user applies a positive voltage (V3) smaller than V2 to the conductor 23. As a result, as shown in FIG. 4C, the bacterium A41 is eliminated from the surface of the insulator film 24. Therefore, the user can collect and inspect only the bacterium A41 downstream.
 このように、ユーザはフィルタ装置100を用いてゼータ電位の異なる細菌毎に分離して、検査することができる。フィルタ装置100は、3種類以上の細菌を含む場合も、同様に分離することができる。なお、V3を0V、又は負の電圧とすることも可能である。また、電圧をV1から徐々に負の電圧へ向けて変化させることにより、徐々にゼータ電位の異なる細菌を分離することも可能である。 In this way, the user can separate and inspect each bacterium having a different zeta potential using the filter device 100. When the filter device 100 contains three or more types of bacteria, it can be similarly separated. It is also possible to set V3 to 0V or a negative voltage. It is also possible to gradually separate bacteria having different zeta potentials by gradually changing the voltage from V1 toward a negative voltage.
 次に、フィルタ装置100を用いた培地交換について説明する。図5(A)~(C)は、フィルタ装置100を用いた培地交換について説明するための図である。なお、図5(A)~(C)は、フィルタ装置100のうち、フィルタユニット101のフィルタ20のみを表し、後は省略する。 Next, the medium exchange using the filter device 100 will be described. 5 (A) to 5 (C) are diagrams for explaining medium exchange using the filter device 100. Note that FIGS. 5A to 5C show only the filter 20 of the filter unit 101 in the filter device 100, and the rest will be omitted.
 フィルタ装置100を用いた培地交換においては、ユーザは、フィルタ装置100を含む培地交換ユニット70を使用する。図5(A)に示すように、培地交換ユニット70は、フィルタユニット101、容器51、容器52、管57、容器53、バルブ54、バルブ55、バルブ56、管57、及び管58を備える。フィルタユニット101は、管57及び管58のそれぞれ一端に接続されている。不図示のポンプは、管57及び管58を介して液体をフィルタユニット101のフィルタ20に流通させる。 In the medium exchange using the filter device 100, the user uses the medium exchange unit 70 including the filter device 100. As shown in FIG. 5A, the medium exchange unit 70 includes a filter unit 101, a container 51, a container 52, a tube 57, a container 53, a valve 54, a valve 55, a valve 56, a tube 57, and a tube 58. The filter unit 101 is connected to one end of each of the pipe 57 and the pipe 58. A pump (not shown) circulates the liquid through the pipe 57 and the pipe 58 to the filter 20 of the filter unit 101.
 管57は、フィルタユニット101と接続されていない側の第1端61を有する。管58は、フィルタユニット101と接続されていない側において二股に分離した第2端62及び第3端63を有する。第1端61は容器51の内部に配置され、第2端62は容器52の内部に配置され、第3端63は容器53の内部にそれぞれ配置されている。バルブ54は、管57におけるフィルタユニット101と第1端61との間に配置されている。バルブ55は、管58におけるフィルタユニット101と第2端62との間に配置されている。バルブ56は、管58におけるフィルタユニット101と第3端63との間に配置されている。バルブ54、バルブ55、及びバルブ56は、それぞれ管57及び管58を開閉する。 The pipe 57 has a first end 61 on the side that is not connected to the filter unit 101. The tube 58 has a second end 62 and a third end 63 that are bifurcated on the side not connected to the filter unit 101. The first end 61 is arranged inside the container 51, the second end 62 is arranged inside the container 52, and the third end 63 is arranged inside the container 53, respectively. The valve 54 is arranged between the filter unit 101 and the first end 61 of the pipe 57. The valve 55 is arranged between the filter unit 101 and the second end 62 of the pipe 58. The valve 56 is arranged between the filter unit 101 in the pipe 58 and the third end 63. The valve 54, the valve 55, and the valve 56 open and close the pipe 57 and the pipe 58, respectively.
 培養液は、容器51に充填されている。培養液は、古い培地と細胞を含む。新しい培地は、容器53に充填されている。また、容器52は、なにも充填されていない空の状態である。 The culture solution is filled in the container 51. The culture medium contains old medium and cells. The new medium is filled in container 53. Further, the container 52 is in an empty state where nothing is filled.
 ユーザは、初めにバルブ54及びバルブ55を開いた状態、バルブ56を閉じた状態とする。次にユーザは、不図示のポンプを駆動し、図5(B)の矢印方向へ液体を流通させる。容器51の培養液は、第1端61から吸い上げられ、フィルタ20を介して第2端62から容器52へと移動する。この時、フィルタ20は、正の電圧が印加されている。これにより、培養液中の細胞は、フィルタ20に吸着し、その他の古い培養液は容器52へと移動する。 The user first opens the valve 54 and the valve 55 and closes the valve 56. Next, the user drives a pump (not shown) to circulate the liquid in the direction of the arrow in FIG. 5 (B). The culture solution in the container 51 is sucked up from the first end 61 and moves from the second end 62 to the container 52 via the filter 20. At this time, a positive voltage is applied to the filter 20. As a result, the cells in the culture medium are adsorbed on the filter 20, and the other old culture medium is moved to the container 52.
 次に、ユーザは、初めにバルブ54及びバルブ56を開いた状態、バルブ54を閉じた状態とする。続いて、ユーザは、不図示のポンプを駆動し、図5(C)の矢印方向へ液体を流通させる。容器53の培地は、第3端63から吸い上げられ、フィルタ20を通って第1端61から容器51へと移動する。このとき、フィルタ20は、電圧が印加されていない、又は負の電圧が印加されている。これにより、フィルタ20に吸着した細胞は、フィルタ20から脱離し、新しい培地とともに容器51へと移動する。このため細胞はフィルタ20へ残留することなく、細胞の回収率が向上する。また、フィルタ20の流路25は細胞に対して大きく設計することができる。このため、細胞がフィルタ20に目詰まりすることが防げる。従って、ユーザはスムーズに培地の交換をすることができる。以上のように、ユーザは、フィルタ装置100を用いて培地の交換を行うことができる。 Next, the user first sets the valve 54 and the valve 56 in the open state and the valve 54 in the closed state. Subsequently, the user drives a pump (not shown) to circulate the liquid in the direction of the arrow in FIG. 5 (C). The medium in the container 53 is sucked up from the third end 63 and moves from the first end 61 to the container 51 through the filter 20. At this time, no voltage is applied to the filter 20, or a negative voltage is applied to the filter 20. As a result, the cells adsorbed on the filter 20 are detached from the filter 20 and moved to the container 51 together with the new medium. Therefore, the cells do not remain in the filter 20, and the recovery rate of the cells is improved. Further, the flow path 25 of the filter 20 can be designed to be large for cells. Therefore, it is possible to prevent cells from clogging the filter 20. Therefore, the user can smoothly change the medium. As described above, the user can exchange the medium by using the filter device 100.
 従来のようにピペット及び遠心分離機を使用して培地交換する場合、作業者は、遠沈管に入れた培養液を遠心分離することにより細胞を沈殿させて、上澄みの培養液をピペットで吸い上げる。この場合、複数の遠沈管に移し替える操作が生じ細胞が空気に晒されるおそれがあり、また移し替えることによる収率の低下の問題があった。さらに、従来の培地交換においては、遠心分離によって十分に細胞を分離できない場合、及びピペットの誤操作によって収率が低下する場合があった。このため、従来の培地交換においては、作業者の慣れ及び慎重な操作が必要とされていた。 When exchanging the medium using a pipette and a centrifuge as in the conventional case, the operator precipitates the cells by centrifuging the culture solution put in the centrifuge tube, and sucks up the supernatant culture solution with the pipette. In this case, the operation of transferring to a plurality of centrifuge tubes may occur and the cells may be exposed to air, and there is a problem that the yield is lowered due to the transfer. Furthermore, in the conventional medium exchange, there are cases where cells cannot be sufficiently separated by centrifugation, and the yield may decrease due to an erroneous operation of the pipette. For this reason, in the conventional medium exchange, it is necessary for the operator to become accustomed to the medium and to perform careful operation.
 これに対して、培地交換ユニット70は、全て密閉した空間とすることで、例えば嫌気性の細菌にも利用することができる。また、複数の遠沈管に移し替える操作も省くことができるため、収率及び効率が向上する。さらに、作業者がピペットを操作することもないため、作業者の負担及び時間が省ける。従って、フィルタ装置100を用いた培地の交換方法は、収率及び効率に優れ、かつ外気に接することなく安定した状態で培地交換を行うことができる。 On the other hand, the medium exchange unit 70 can be used for, for example, anaerobic bacteria by making all the spaces closed. Further, since the operation of transferring to a plurality of centrifuge tubes can be omitted, the yield and efficiency are improved. Further, since the operator does not operate the pipette, the burden and time of the operator can be saved. Therefore, the method for exchanging the medium using the filter device 100 is excellent in yield and efficiency, and can exchange the medium in a stable state without being exposed to the outside air.
 以下、本発明に係るフィルタ20を用いた実施例1及び実施例2について説明する。 Hereinafter, Examples 1 and 2 using the filter 20 according to the present invention will be described.
 (実施例1)メッシュフィルタを用いた捕集例
 初めに、目開き77μmのステンレス製のメッシュフィルタを作成し、三層に重ねた。積層したメッシュフィルタに対し、ALD法でアルミナ(Al)膜を成膜した。アルミナ膜の厚みは約30nmであった。これにより、絶縁体膜で被覆されたメッシュフィルタを得た。得られたメッシュフィルタを、フィルタ装置にセットした。
(Example 1) Collection example using a mesh filter First, a stainless steel mesh filter with a mesh opening of 77 μm was prepared and stacked in three layers. An alumina (Al 2 O 3 ) film was formed on the laminated mesh filter by the ALD method. The thickness of the alumina film was about 30 nm. As a result, a mesh filter coated with an insulator film was obtained. The obtained mesh filter was set in the filter device.
 次に、ドライイースト0.5gを純水1Lに入れて攪拌したイースト菌を含む試験液を調製した。ポンプを駆動させることにより、流速1.8ml/minでメッシュフィルタに試験液を流した。この時、メッシュフィルタには、-10Vの電圧を印加した。メッシュフィルタを通過した液を回収し、回収液0.1mLを2枚のスライドガラスで挟んだ状態で顕微鏡(VHX-5000、KEYENCE社製)を用いて200倍に拡大して観察した。観察においては、視野1.6×1.2mmの範囲に存在するイースト菌の数をカウントした。次に、メッシュフィルタに+20Vの電圧を印加した状態で同様の試験を行った。 Next, a test solution containing yeast was prepared by adding 0.5 g of dry yeast to 1 L of pure water and stirring the mixture. By driving the pump, the test solution was flowed through the mesh filter at a flow velocity of 1.8 ml / min. At this time, a voltage of −10 V was applied to the mesh filter. The liquid that had passed through the mesh filter was recovered, and 0.1 mL of the recovered liquid was sandwiched between two slide glasses and observed at a magnification of 200 times using a microscope (VHX-5000, manufactured by KEYENCE). In the observation, the number of yeasts present in the field of view 1.6 × 1.2 mm was counted. Next, a similar test was performed with a voltage of + 20 V applied to the mesh filter.
 図6は、実施例1の結果を示すグラフである。図6に示すように、メッシュフィルタに-10Vの電圧を印加したとき、カウントしたイースト菌の数は、1083個であった。一方、メッシュフィルタに+20Vの電圧を印加したとき、カウントしたイースト菌の数は、79個であった。すなわち、メッシュフィルタに負の電圧を印加するとイースト菌はメッシュフィルタから脱離することにより流出し、逆に正の電圧を印加するとイースト菌はメッシュフィルタに吸着した。このように、ALD法で成膜したステンレス製のメッシュフィルタを用いて、メッシュフィルタに正の電圧を印加することによって一定程度のイースト菌が捕集できることが確認された。また、メッシュフィルタを用いた捕集効率は、93%であった。 FIG. 6 is a graph showing the results of Example 1. As shown in FIG. 6, when a voltage of −10 V was applied to the mesh filter, the number of yeasts counted was 1083. On the other hand, when a voltage of + 20 V was applied to the mesh filter, the number of yeasts counted was 79. That is, when a negative voltage was applied to the mesh filter, yeast was desorbed from the mesh filter and flowed out, and conversely, when a positive voltage was applied, yeast was adsorbed on the mesh filter. As described above, it was confirmed that a certain amount of yeast can be collected by applying a positive voltage to the mesh filter using the stainless steel mesh filter formed by the ALD method. The collection efficiency using the mesh filter was 93%.
 (実施例2)多孔体を用いた捕集例
 初めに、直径10μmのろ過径を持つ厚さ3mmのステンレス多孔体を用意した。ステンレス多孔体に対し、ALD法でアルミナ(Al)膜を成膜した。アルミナ膜の厚みは約30nmであった。これにより、絶縁体膜で被覆されたステンレス多孔体を得た。得られたステンレス多孔体を、フィルタ装置にセットした。
(Example 2) Collection example using a porous body First, a stainless steel porous body having a filtration diameter of 10 μm and a thickness of 3 mm was prepared. An alumina (Al 2 O 3 ) film was formed on the stainless steel porous body by the ALD method. The thickness of the alumina film was about 30 nm. As a result, a stainless steel porous body coated with an insulator film was obtained. The obtained stainless steel porous body was set in a filter device.
 次に、ドライイースト0.5gを純水1Lに入れて攪拌したイースト菌を含む試験液を調製した。ポンプを駆動させることにより、流速0.5ml/minでステンレス多孔体に試験液を流した。初めに、ステンレス多孔体には、-10Vの電圧を印加した。実施例2においては、ステンレス多孔体に試験液を流しながら、ステンレス多孔体を通過した液を流動させたまま顕微鏡(VHX-5000、KEYENCE社製)を用いて200倍に拡大して観察した。観察においては、10秒間に視野1.6×1.2mmの範囲を通過するイースト菌の数をカウントした。次に、ステンレス多孔体に+20Vの電圧を約120秒間印加した状態で同様の試験を行った。また引き続き、ステンレス多孔体に再度-10Vの電圧を印加した状態で同様の試験を行った。 Next, a test solution containing yeast was prepared by adding 0.5 g of dry yeast to 1 L of pure water and stirring the mixture. By driving the pump, the test solution was flowed through the stainless steel porous body at a flow velocity of 0.5 ml / min. First, a voltage of −10 V was applied to the stainless steel porous body. In Example 2, the test liquid was allowed to flow through the stainless steel porous body, and the liquid that passed through the stainless steel porous body was allowed to flow while being observed with a microscope (VHX-5000, manufactured by KEYENCE) at a magnification of 200 times. In the observation, the number of yeasts passing through the range of 1.6 × 1.2 mm in the field of view was counted in 10 seconds. Next, the same test was performed with a voltage of + 20 V applied to the stainless steel porous body for about 120 seconds. Subsequently, the same test was carried out with a voltage of −10 V applied to the stainless steel porous body again.
 図7は、実施例2の結果を示すグラフである。図7に示すように、ステンレス多孔体に初めに-10Vの電圧を印加したとき、カウントしたイースト菌の数は、約200個であった。続いて、ステンレス多孔体に+20Vの電圧を印加したとき、カウントしたイースト菌の数は、2個であった。さらに、再びステンレス多孔体に-10Vの電圧を印加したとき、カウントしたイースト菌の数は、約20000個であった。 FIG. 7 is a graph showing the results of Example 2. As shown in FIG. 7, when a voltage of −10 V was first applied to the stainless steel porous body, the number of yeasts counted was about 200. Subsequently, when a voltage of + 20 V was applied to the stainless steel porous body, the number of yeasts counted was two. Furthermore, when a voltage of −10 V was applied to the stainless steel porous body again, the number of yeasts counted was about 20000.
 このように、メッシュフィルタを用いた時と同様に、ステンレス多孔体に負の電圧を印加すると、ステンレス多孔体に吸着されることなく流出し、逆に正の電圧を印加するとイースト菌はステンレス多孔体に吸着した。イースト菌はこのように、ALD法で成膜したAlで被覆されたステンレス多孔体を用いても、ステンレス多孔体に正の電圧を印加することによって一定程度のイースト菌が捕集できることが確認された。また、ステンレス多孔体を用いた捕集効率は、99%であった。これから、実施例1のメッシュフィルタと比べて、ステンレス多孔体をフィルタとして用いた方が、捕集効率が高いことが確認された。 In this way, as in the case of using the mesh filter, when a negative voltage is applied to the stainless steel porous body, it flows out without being adsorbed by the stainless steel porous body, and conversely, when a positive voltage is applied, yeast bacteria become the stainless steel porous body. Adsorbed to. It has been confirmed that yeast can collect a certain amount of yeast by applying a positive voltage to the stainless porous body even if the stainless porous body coated with Al 2 O 3 formed by the ALD method is used. Was done. The collection efficiency using the stainless steel porous body was 99%. From this, it was confirmed that the collection efficiency was higher when the stainless steel porous body was used as the filter as compared with the mesh filter of Example 1.
 また、所定時間(ここでは約120秒間である。)ステンレス多孔体に正の電圧を印加した状態で試験液を流してイースト菌をステンレス多孔体に吸着させた後に、負の電圧を印加することで、吸着したイースト菌がステンレス多孔体から一斉に脱離することにより一度に流出する。これにより、イースト菌が濃縮された流出液が得られる。従って、イースト菌を捕集する時間に応じた濃度のイースト菌濃縮液が得られることが確認された。 Further, by applying a negative voltage to the stainless steel porous body after adsorbing yeast on the stainless steel porous body by flowing a test solution in a state where a positive voltage is applied to the stainless steel porous body for a predetermined time (here, about 120 seconds). , The adsorbed yeast is desorbed from the stainless steel porous body all at once and flows out at once. As a result, a effluent in which yeast is concentrated is obtained. Therefore, it was confirmed that a yeast concentrate having a concentration corresponding to the time for collecting yeast can be obtained.
 上述の実施形態の説明は、すべての点で例示であって、制限的なものではないと考えられるべきである。本発明の範囲は、上述の実施形態ではなく、特許請求の範囲によって示される。さらに、本発明の範囲には、特許請求の範囲と均等の意味及び範囲内でのすべての変更が含まれることが意図される。 The above description of the embodiment should be considered to be exemplary in all respects and not restrictive. The scope of the present invention is shown not by the above-described embodiment but by the scope of claims. Furthermore, the scope of the present invention is intended to include all modifications within the meaning and scope equivalent to the claims.
10…固定具
11…接手(流路側壁部)
12…ソケット
13…内部空間
16…電圧印加部
20…フィルタ
21…流通部(液体通過部)
22…枠部
23…導電体
24…絶縁体膜
25…流路
100…フィルタ装置
101…フィルタユニット
102…直流電源
103…制御部
10 ... Fixture 11 ... Joint (side wall of flow path)
12 ... Socket 13 ... Internal space 16 ... Voltage application part 20 ... Filter 21 ... Distribution part (liquid passing part)
22 ... Frame part 23 ... Conductor 24 ... Insulator film 25 ... Flow path 100 ... Filter device 101 ... Filter unit 102 ... DC power supply 103 ... Control unit

Claims (10)

  1.  液体を流通可能な導電体と、
     前記導電体のうち前記液体が接触する部分を覆う絶縁体膜と、
     前記導電体の表面のうち前記液体が接触しない部分に位置し、外部から電圧を印加するための電圧印加部と、を備える、
     フィルタ。
    Conductors that can flow liquids and
    An insulator film that covers a portion of the conductor that comes into contact with the liquid,
    It is located on a portion of the surface of the conductor that the liquid does not come into contact with, and includes a voltage applying portion for applying a voltage from the outside.
    filter.
  2.  前記導電体は、メッシュ構造、又は多孔体構造である部分を有する、
     請求項1に記載のフィルタ。
    The conductor has a portion having a mesh structure or a porous structure.
    The filter according to claim 1.
  3.  前記絶縁体膜は、チタニア、アルミナ、シリカ、ハフニア、酸化亜鉛又はジルコニアを含む、
     請求項1又は2に記載のフィルタ。
    The insulator film contains titanium, alumina, silica, hafnia, zinc oxide or zirconia.
    The filter according to claim 1 or 2.
  4.  前記絶縁体膜は、原子層堆積法又は陽極酸化処理で形成される、
     請求項1乃至請求項3のいずれかに記載のフィルタ。
    The insulator film is formed by an atomic layer deposition method or an anodization treatment.
    The filter according to any one of claims 1 to 3.
  5.  前記電圧印加部は、前記絶縁体膜の一部を削除することにより形成される、
     請求項1乃至請求項4のいずれかに記載のフィルタ。
    The voltage application portion is formed by removing a part of the insulator film.
    The filter according to any one of claims 1 to 4.
  6.  液体を流すための流路を構成する流路側壁部と、
     液体を流通可能な導電体と、を備え、
     前記導電体は、前記流路側壁部に固定される固定具と、前記流路に配置される液体通過部と、前記液体通過部を覆う絶縁体膜と、前記固定具に外部から電圧を印加するための電圧印加部と、を備える、
     フィルタユニット。
    The side wall of the flow path that constitutes the flow path for flowing the liquid,
    With a conductor capable of flowing liquid,
    The conductor is a fixture fixed to the side wall of the flow path, a liquid passage portion arranged in the flow path, an insulator film covering the liquid passage portion, and an external voltage applied to the fixture. A voltage application unit for
    Filter unit.
  7.  前記電圧印加部は、前記固定具を介して外部から電圧を印加する、
     請求項6に記載のフィルタユニット。
    The voltage applying unit applies a voltage from the outside through the fixture.
    The filter unit according to claim 6.
  8.  請求項6又は7に記載のフィルタユニットと、
     前記固定具に電圧を印加する直流電源と、を備える、
     フィルタ装置。
    With the filter unit according to claim 6 or 7.
    A DC power supply that applies a voltage to the fixture.
    Filter device.
  9.  前記直流電源の直流電圧を制御する制御部をさらに備える、
     請求項8に記載のフィルタ装置。
    A control unit for controlling the DC voltage of the DC power supply is further provided.
    The filter device according to claim 8.
  10.  前記制御部は、前記直流電圧を正又は負に切り替える、
     請求項9に記載のフィルタ装置。
    The control unit switches the DC voltage between positive and negative.
    The filter device according to claim 9.
PCT/JP2020/022478 2019-09-20 2020-06-08 Filter, filter unit, and filter device WO2021053896A1 (en)

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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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US20030159932A1 (en) * 2000-05-03 2003-08-28 Betts Walter Bernard Method and apparatus for analysing low concentrations of particles
JP2004301549A (en) * 2003-03-28 2004-10-28 Fujitsu Ltd Molecule adsorbing and discharging device and molecule adsorbing and discharging method
JP2005254118A (en) * 2004-03-11 2005-09-22 Sanyo Electric Co Ltd Device and method for collecting microorganism
JP2008516215A (en) * 2004-10-04 2008-05-15 コミツサリア タ レネルジー アトミーク Device for electrophoretic separation of particles contained in a fluid
JP2012511156A (en) * 2008-12-05 2012-05-17 ナノアイヴイディー,インコーポレイテッド Microfluidic lab-on-test card for point-of-care analyzers

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2000350574A (en) * 1999-06-11 2000-12-19 Canon Inc Electric concentration of cell-containing liquid and cell concentrating apparatus
US20030159932A1 (en) * 2000-05-03 2003-08-28 Betts Walter Bernard Method and apparatus for analysing low concentrations of particles
JP2004301549A (en) * 2003-03-28 2004-10-28 Fujitsu Ltd Molecule adsorbing and discharging device and molecule adsorbing and discharging method
JP2005254118A (en) * 2004-03-11 2005-09-22 Sanyo Electric Co Ltd Device and method for collecting microorganism
JP2008516215A (en) * 2004-10-04 2008-05-15 コミツサリア タ レネルジー アトミーク Device for electrophoretic separation of particles contained in a fluid
JP2012511156A (en) * 2008-12-05 2012-05-17 ナノアイヴイディー,インコーポレイテッド Microfluidic lab-on-test card for point-of-care analyzers

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