Liquid sample processing device

Abstract

To make it possible to miniaturize a device, and furthermore, efficiently to pretreat trace samples, or to remove or separate impurities that interfere with measurement in systems that collect body fluid, such as blood, and a trace amount of other fluid and perform pretreatment for its examination.SOLUTION: A device for collecting liquid includes: a flow path member 110 having a flow path capable of acquiring liquid from one end and containing the acquired liquid; a tank 120 that contains processing solution in an internal space 121 and is configured to accept at least one end of the flow path member and start mixing, in the internal space, the processing solution contained in the tank with the liquid contained in the flow path; a pump that discharges mixed solution from the tank; and a filter 160 that separates some of components contained in the mixed solution.SELECTED DRAWING: Figure 1G

Description

Technical Field

[0001] The present disclosure relates to an apparatus for processing a liquid sample, for example, an apparatus for mixing a liquid sample with a processing liquid and obtaining a processed liquid.

Background Art

[0002] In a system for collecting body fluids such as blood and other trace amounts of liquid and performing pretreatment for their inspection, miniaturization of the apparatus is required. They are also effective in point-of-care testing. They are also desired for testing trace amounts of specimens. In an apparatus with limited size, further performance such as efficiently pretreating trace amounts of specimens or removing or separating impurities that interfere with measurement is required.

Summary of the Invention

[0003] Here, for example, without limitation, the need for efficiently collecting, pretreating, and efficiently extracting the pretreated liquid is recognized.

[0004] In some embodiments of this disclosure, a liquid sampling device is provided. In some embodiments, the liquid sampling device samples or collects a liquid. In some embodiments, the liquid sampling device comprises a flow path member. The flow path member may comprise a flow path. In some embodiments, the liquid sampling device comprises a flow path. In some embodiments, the flow path is configured to take liquid from one end thereof. In some embodiments, the flow path can contain the taken liquid. In some embodiments, the liquid sampling device comprises a tank. In some embodiments, the tank contains a processing solution inside it. In some embodiments, the tank is configured to receive a flow path member at part or one end thereof. In some embodiments, the tank is configured so that the processing solution contained in the tank and the liquid contained in the flow path are mixed in its internal space. Mixing may begin at least in the internal space. In some embodiments, the liquid sampling device comprises a pump for discharging the mixed liquid (hereinafter sometimes also referred to as the mixed solution) from the tank. In some embodiments, the liquid sampling device comprises a filter. The filter may be configured to separate some components contained in the mixed solution.

[0005] According to the above embodiment, for example, a series of processes that involve collecting a relatively small amount of liquid and performing pretreatment on the collected liquid can be made more efficient.

[0006] Further aspects and advantages of the present disclosure will be readily apparent to those skilled in the art from the following detailed description, which shows and describes only exemplary embodiments of the present disclosure. As will be understood, other different embodiments are possible, and some of their details can be modified in various obvious ways without departing from the present disclosure. Accordingly, the drawings and description should be considered illustrative and not limiting in nature. [Brief explanation of the drawing]

[0007] [Figure 1A]This is a cross-sectional view showing the process of using a liquid sampling device according to one embodiment. [Figure 1B] This is a cross-sectional view showing the process of using a liquid sampling device according to one embodiment. [Figure 1C] This is a cross-sectional view showing the process of using a liquid sampling device according to one embodiment. [Figure 1D] This is a cross-sectional view showing the process of using a liquid sampling device according to one embodiment. [Figure 1E] This is a cross-sectional view showing the process of using a liquid sampling device according to one embodiment. [Figure 1F] This is a cross-sectional view showing the process of using a liquid sampling device according to one embodiment. [Figure 1G] This is a cross-sectional view showing the process of using a liquid sampling device according to one embodiment. [Figure 2A] This is a cross-sectional view showing the process of using a liquid sampling device according to one embodiment. [Figure 2B] This is a cross-sectional view showing the process of using a liquid sampling device according to one embodiment. [Figure 2C] This is a cross-sectional view showing the process of using a liquid sampling device according to one embodiment. [Figure 2D] This is a cross-sectional view showing the process of using a liquid sampling device according to one embodiment. [Figure 2E] This is a cross-sectional view showing the process of using a liquid sampling device according to one embodiment. [Figure 3] This is a cross-sectional view showing a filter channel according to a certain embodiment. [Figure 4] This is a cross-sectional view showing a filter channel according to a certain embodiment. [Modes for carrying out the invention]

[0008] In some embodiments, the liquid may be a bodily fluid secreted by the subject, or it may be a liquid other than a bodily fluid. The liquid other than a bodily fluid may be a liquid adhering to the object, or it may not be a liquid adhering to the object. The liquid not adhering to the object may be a liquid contained within the object.

[0009] The liquid to be collected may be a solution. The liquid may be a body fluid, a solution derived from a body fluid, or a dilution of a body fluid. The liquid may be a non-body fluid solution, or a mixed solution of a body fluid or a solution derived from a body fluid and a solution derived from a non-body fluid. The solution may be a solution used for sample measurement, or a solution used for calibration measurement. For example, the solution may be a standard solution or a calibration solution. The sample to be measured may be a specimen.

[0010] Body fluid may be lymph, interstitial fluid such as interstitial fluid, intracellular fluid, or interstitial fluid, or it may be coelomic fluid, serosal fluid, pleural fluid, ascites, pericardial fluid, cerebrospinal fluid, synovial fluid, or aqueous humor. Body fluid may be digestive fluid such as saliva, gastric juice, bile, pancreatic juice, or intestinal juice, or it may be sweat, tears, nasal mucus, urine, semen, vaginal fluid, amniotic fluid, or breast milk. Body fluid may be animal body fluid or human body fluid. "Body fluid" may also be a solution. The solution may contain the substance to be measured and may include physiological buffers such as phosphate-buffered saline (PBS) or N-tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid buffer (TES). The solution is not particularly limited as long as it contains the substance to be measured.

[0011] In some embodiments, the body fluid may be blood. In some embodiments, blood may be collected. For example, blood may be collected at the same time as bleeding caused by puncture. For example, blood may be aspirated by inserting a needle. In some embodiments, the puncture device (e.g., a needle, an injection needle, etc.; the same applies hereinafter) may be placed at the tip of the capillary tube. In some embodiments, the capillary tube may be formed as the puncture device.

[0012] In some embodiments, the subjects may include humans, or may be humans. In some embodiments, the subjects may include non-human animals, or may be non-human animals. Non-human animals may include mammals, or may be mammals. Non-human animals may, for example, not limited to, working animals, domesticated animals, pets, or wild animals.

[0013] In some embodiments, the liquid sampling device includes a flow channel member. In some embodiments, the flow channel member may have a flow channel connecting one end to the other. In some embodiments, the flow channel member may have multiple flow channels. In some embodiments, it may have only one flow channel. In some embodiments, if the flow channel member has multiple flow channels, the multiple flow channels extend in the direction of the axial direction of the pipe connecting one end to the other. In some embodiments, the multiple flow channels may or may not be arranged substantially parallel to each other.

[0014] In some embodiments, the flow path may include capillaries (also called capillary channels). In some embodiments, at least a portion of the flow path may consist of capillaries. In some embodiments, the flow path may include capillaries at least at the one end that takes in the liquid. In some embodiments, the capillaries may comprise a plurality of capillaries.

[0015] As used herein, the term "pipe axis direction" refers to the direction connecting one end and the other end of a flow channel member.

[0016] In some embodiments, the flow path member may be columnar and extend in the pipe axis direction connecting one end and the other end. In some embodiments, the columnar flow path member may have a plurality of grooves extending in the pipe axis direction on the outer peripheral surface, or may have only one groove. In some embodiments, the grooves constitute the flow path of the liquid. The cross-section of the groove may be formed, for example, without limitation, in a U shape (the corners may be substantially right angles, obtuse angles or acute angles, and may be rounded), or in a V shape (the corners may be substantially acute angles and may be rounded), or may generally be formed in a valley shape. In some embodiments, the flow path may be formed in a slit shape. The slit or the groove open to the outside is easily accessible from the outside. For example, it becomes easier to bring a treatment liquid (hereinafter sometimes also referred to as a treatment solution) into contact with the liquid in the flow path. For example, mixing becomes easier thereby.

[0017] In some embodiments, the flow path member may be columnar and extend in the pipe axis direction. In some embodiments, the cross-sectional shape of the columnar flow path member viewed from the pipe axis direction may be circular or elliptical. In some embodiments, the flow path member may have a cross-sectional shape of a polygon such as a triangle, a quadrilateral, a pentagon, a hexagon, an octagon, etc. In some embodiments, the flow path member may have a plurality of flow paths extending in the pipe axis direction inside thereof and communicating one end and the other end. In some embodiments, the cross-section of the flow path member may be constant in the pipe axis direction (such as a cylindrical shape), or may change in the pipe axis direction (such as the cross-section becoming smaller towards one end).

[0018] In some embodiments, the flow path member may be formed by bundling a plurality of single tubes extending in the tube axis direction. In some embodiments, the single tube may be cylindrical and extend in the tube axis direction, and may have a flow path connecting one end and the other end. In some embodiments, the plurality of single tubes may be integrally joined by adhesion, welding, or the like. In some embodiments, the plurality of single tubes may be integrally bundled with a band or the like. In some embodiments, they may be integrally molded with a resin material. For example, by bundling a plurality of single tubes, the holes of the plurality of single tubes and the gaps between the plurality of single tubes form a flow path for the liquid.

[0019] In some embodiments, the flow path may be configured to acquire and hold a predetermined amount or a quantified amount of liquid. In some embodiments, the liquid can be sucked into the flow path by capillary action. At least the tip of the flow path may include a capillary (channel). In some embodiments, the capillary of the flow path may have a predetermined length. The volume of the liquid collected by the flow path may be defined by the length of the capillary. In some embodiments, the capillary may have a lateral hole provided in a part thereof. In some embodiments, capillary action occurs from one end (the tip) of the capillary to the lateral hole. The volume may define the amount of the liquid to be collected. The cross-sectional area of the capillary may increase at the other end or a part thereof. Thereby, capillary action does not substantially occur any more. In some embodiments, the portion of the flow path downstream of the capillary, that is, in the direction away from one end (from the tip) or toward the other end, may be configured to inhibit the occurrence of capillary action.

[0020] The portion where capillary action occurs from one end (the tip) may define the amount of the liquid to be collected. The cross-sectional area and length of the capillary may define the amount of the liquid to be collected. In some embodiments, the capillary may be provided with a mark indicating a certain collection amount or a scale from which the collection amount can be known.

[0021] In some embodiments, the flow path may collect liquid using a suction mechanism other than a capillary. For example, a mechanism such as a pump connected to the flow path may be provided. Using these suction mechanisms, a certain amount of liquid can be collected with relative accuracy.

[0022] <tank> In some embodiments, the tank may be configured to contain a processing solution. The processing solution may be filled into the tank for use. In some embodiments, the tank may contain the processing solution. In some embodiments, the tank may be sealed to contain the processing solution. The tank may not be sealed to contain the processing solution. For example, the tank may have an opening.

[0023] In some embodiments, the tank may have a tank body. The inner wall of this tank body may define the interior or internal space of the tank. In some embodiments, the tank may have a tank body and a sealing member. These may define the interior of the tank.

[0024] At least a portion of the sealing member is configured to receive the flow path member. The flow path member may push the sealing member that seals the tank body into the tank, release the tank's seal, and enter the tank. The sealing member may comprise at least two sealing members. The first sealing member may be configured to receive the flow path member. The second sealing member may be configured to discharge the mixed solution from the tank.

[0025] The first and second sealing members are each sealed and fixed to the tank body, and may be removed by external force. For example, the sealing member may be a bead, or may include a bead. The bead may be mechanically removable and fixed to the inner wall of the tank body. The bead may be fixed to the tank body so that it can be removed from its fixed position by being pressed. For example, the sealing member may be a breakable film, or may include a breakable film. The film may be configured to tear when pressed by a pointed member.

[0026] In some embodiments, the flow channel member may be inserted inside a tank containing the treatment solution. In this case, the liquid obtained from the flow channel of the flow channel member comes into contact with the treatment solution. The obtained liquid and the treatment solution begin to mix. This liquid and treatment solution may mix naturally or by diffusion. The user may shake the liquid sampling device to promote mixing. The liquid sampling device may be inverted, rotated around the tube axis, or vibrated using machinery such as a stirrer or a shaker. This may promote mixing. Beads acting as sealing members may move within the tank to promote mixing.

[0027] In some embodiments, the tank may be configured to seal the acquired liquid and processing solution inside after the flow channel member has been inserted into the tank. The tank may be configured to seal its interior at least while the liquid and processing solution are mixing. The tank may be configured to seal the mixed solution produced by the mixing of the acquired liquid and processing solution. For example, the tank may have a lid. This lid may be closed to seal the mixed solution inside the tank. For example, the internal space of the tank may be sealed by the inserted flow channel member and the tank.

[0028] In some embodiments, a storage container may be provided to receive the mixed solution discharged from the apparatus. The mixed solution can be transported or stored by sealing it in the tank's internal space or in the storage container.

[0029] The volume of the capillary (or the channel portion that acquires the liquid, hereinafter the same) may be the same as or greater than values ​​such as 1 μL, 2 μL, 3 μL, 4 μL, 5 μL, 6 μL, 7 μL, 8 μL, 9 μL, 10 μL, 15 μL, 20 μL, 25 μL, etc. The volume of the capillary may be the same as or less than values ​​such as 100 μL, 90 μL, 80 μL, 70 μL, 60 μL, 50 μL, 40 μL, 35 μL, 30 μL, 25 μL, 20 μL, 15 μL, 10 μL, etc. The volume of the capillary may be between 5 μL and 30 μL. The volume of the capillary may be between 10 μL and 20 μL.

[0030] The volume of the tank (or the volume of the liquid (processing solution) contained in the tank, hereinafter the same) may be the same as or less than values ​​such as 10 μL, 20 μL, 25 μL, 30 μL, 35 μL, 40 μL, 45 μL, 50 μL, etc. The volume of the tank may be the same as or less than values ​​such as 5 mL, 3 mL, 2 mL, 1 mL, 500 μL, 400 μL, 300 μL, 250 μL, 200 μL, 150 μL, 100 μL, 50 μL, etc. The volume of the tank may be between 2 and 50 times the volume of the capillary tube, or between 2 and 20 times. The dilution ratio may be between 2 and 20 times, or between 2 and 50 times. The volume of the tank may, for example, be substantially 25 μL, or substantially 250 μL, for example, not limited to these values.

[0031] <Processing solution> In some embodiments, the processing solution may be a diluent. The diluent may be used to dilute the acquired liquid. The processing solution may also be a liquid (pretreatment solution) used to perform a predetermined treatment (pretreatment) on the acquired liquid before any measurements are taken. The treatment solution may be water or an aqueous solution. The treatment solution may be a buffer solution. The treatment solution may be, for example, Good's buffer. The treatment solution may be physiological saline. The treatment solution may be an organic solvent.

[0032] For example, if the substance being measured is sensitive to pH or salt concentration, such as a protein, a buffer solution such as physiological saline or Good's Buffer may be used. For example, if the substance being processed is a small molecule such as an amino acid, buffering capacity is not necessarily required. In that case, water or other aqueous solutions, or organic solvents, may be used. The processing solution may contain additives such as stabilizers and preservatives. Additives to maintain the structure of proteins may also be used.

[0033] In some embodiments, the osmotic pressure of the treatment solution may be adjusted. For example, when the purpose is serum separation, the osmotic pressure of the treatment solution may be the same as that of human body fluids (285 ± 5 mOsm / L) (isotonic solution). If the osmotic pressure is low (hypotonic solution), red blood cells may rupture and hemolysis may occur. Conversely, if the osmotic pressure is high (hypertonic solution), it may affect the separation performance of the blood cell separation filter. Also, the measurement results may be affected by the excess release of the target substance from the blood cells.

[0034] In some embodiments, the treatment solution may contain a stabilizer for the target substance. For example, a protein structure stabilizer may be used. The protein may be, for example, albumin, not limited to that example. For example, the structure of albumin can be stabilized using a stabilizer. By using a stabilizer, an indicator molecule such as BCP can be specifically bound to a predetermined site. If the charge at or near the binding site and the environment of the amino acid side chain are suitable, it becomes easier to bind the indicator to the protein and specificity is maintained. Protein stabilizers include, for example, sugars, polysaccharides, salts, etc., not limited to that example.

[0035] The treatment solution may contain, for example, a substance that solubilizes or decomposes mucin in saliva. This can reduce the viscosity of bodily fluids such as saliva.

[0036] The treatment solution may contain a substance (inhibitor) that inhibits the reaction related to the target substance. For example, saliva contains digestive enzymes such as amylase. Substances that inhibit the action of these digestive enzymes may be used.

[0037] The treatment solution may contain a substance (coagulant) that coagulates substances contained in the target liquid. For example, the target liquid may contain a coagulant that coagulates specific substances such as fine dust, blood cells, mucin, membrane proteins, and oils. These substances may be formed into larger clumps. The clumps formed by coagulation are easier to remove in subsequent filtering.

[0038] The treatment solution may contain substances that decompose, solubilize, coagulate, or inhibit or promote the reaction of substances.

[0039] The components of the treatment solution may be selected from the group consisting of physiological saline, HEPES, TES, MES, tricine, and PBS. The components of the treatment solution may also include Good Buffer (e.g., HEPES, TES, MES, tricine). The treatment solution may also contain standard substances to be used in subsequent measurements.

[0040] <pump> In some embodiments, the pump may include a syringe. The syringe generally consists of a piston and a cylinder. The syringe may be manually driven. The syringe may be mechanically driven. The form of the pump is not limited to a syringe. The pump may include an electric pump.

[0041] In some embodiments, the pump can pressurize the inside of the tank. In some embodiments, the pump can introduce air into the tank from the outside.

[0042] In some embodiments, the pump may be equipped with a pipette valve. In some embodiments, a pipette valve may be further provided on the syringe. In addition to the syringe, the pipette valve can be used to pressurize the tank.

[0043] The pump may be configured to apply pressure to a flow path or the interior of a flow path. It may also be configured to apply pressure to the flow path from either end of the flow path. The pump pressure may be applied directly to the flow path. The pump pressure may be applied inside a tank, and as a result, to the interior of the flow path.

[0044] The pressure from the pump may be positive or negative. The pressure may be varied over time. Positive and negative pressure may be applied alternately over time.

[0045] <Discharge Channel> In some embodiments, the apparatus may include a discharge channel (also called a discharge channel or discharge path) for discharging the mixed solution to the outside. The apparatus may also include a discharge channel member having a discharge channel. Hereafter, unless otherwise specified, the term "discharge channel" may mean "discharge channel member."

[0046] In some embodiments, the discharge channel may be located in a tank. The tank may have a discharge channel. The discharge channel may be attached to the tank. The discharge channel may be detachably attached to the tank. The discharge channel may be fluidly connected to the tank. The discharge channel may be fixed to the tank. The discharge channel may be formed as part of the tank by integral molding.

[0047] In some embodiments, the pump may be configured to apply pressure to the other end of the flow path, causing at least some or substantially all of the mixed solution, treatment solution, or liquid in the flow path to be discharged from the flow path. If the tank is sealed, the pressure will also be applied inside the tank. The mixed solution inside the tank may be discharged to the outside through the discharge channel due to the pressure.

[0048] In some embodiments, the discharge channel may be located at the other end of the flow path (the end opposite to the end from which the liquid is taken in). The discharge channel may be fluid-coupled to the other end of the flow path. The discharge channel may be configured to be detachably attached to the flow path member. The discharge channel may be fixed to the flow path member. The discharge channel may be formed as part of the flow path member by integral molding. This allows the mixed solution to flow through the flow path and be discharged through the discharge channel. This allows, for example, residual liquid in the flow path to be flushed out as it is discharged. The mixed solution may also flush out any capillary portions.

[0049] In some embodiments, a second internal space may be located in the discharge path of the mixed solution. This space may be used to further mix the mixed solution. This allows the mixed solution, temporarily discharged from the first internal space, to be further mixed in the second internal space. Mixing in the first internal space may not be sufficient. The acquired liquid and the processing solution can be thoroughly mixed by flow in the discharge path, flow or diffusion in the second internal space, etc. The acquired liquid and the processing solution can be thoroughly mixed in the second internal space. The second internal space may be fluidly connected to the outlet of the device. This allows the mixed solution to exit the second internal space and be discharged from the outlet. In some embodiments, the second internal space may be located in the discharge channel between the first internal space and the filter.

[0050] <filter> In some embodiments, a filter may be placed in the discharge path of the mixed solution. In some embodiments, the filter may have the ability to separate a certain substance (separation filter).

[0051] In some embodiments, the filter may comprise a plasma or serum separation filter. The filter may comprise a plasma separation filter (or membrane) that receives blood, captures cellular components, and allows plasma to pass through. The filter may comprise a serum separation filter (or membrane) that receives blood, captures blood clots, and allows serum to pass through.

[0052] The filter may be equipped with filters for separating other substances. For example, the filter may be able to remove small debris. For example, the filter may be able to remove high molecular weight substances such as mucin. For example, the filter may be able to remove proteins that have aggregated due to the action of the treatment solution. For example, the filter may carry a substance that has the ability to react with substances passing through it. For example, an antibody may be carried on the filter. For example, a substance that has the ability to bind to proteins may be carried on the filter. For example, the surface of the filter (for example, the surface of the filter fibers) may be composed of a substance that has a high affinity for a particular substance. As a result, the particular substance may be adsorbed onto the filter surface.

[0053] In some embodiments, the filter may be made of a fibrous material. The filter may be a woven fabric or a nonwoven fabric. In some embodiments, the filter may be made of a porous material.

[0054] The filter may be made of fibrous material such as cellulose, glass, or polymer. The filter material may be selected from the group consisting of cellulose, glass, and polymer.

[0055] <Embodiment 1> Figures 1A to 1F illustrate the structure of a liquid sampling device according to one embodiment, step by step. The liquid device shown in Figures 1A to 1F extends in the direction of the pipe axis, and each component is assembled in the direction of the pipe axis.

[0056] As shown in Figure 1A, the flow channel member 110 has a flow channel 111 that penetrates in the direction of the pipe axis, and liquid can be obtained from one end (tip) of it. The flow channel 111 extends in the longitudinal direction of the flow channel member 110. The tip of the flow channel 111 is a capillary tube. A lateral hole 112 is made in the flow channel 111. The tip 113 of the flow channel is brought close to or into contact with the liquid 102 present on the object 101. The liquid 102 rises up the capillary tube 111 from the tip by capillary action, stops at the position of the lateral hole 112, and is not drawn up any further (see Figure 1B).

[0057] As shown in Figure 1B, the tank 120 has an internal space 121 in which the processing solution 131 is contained. The internal space 121 is sealed from both sides in the direction of the pipe axis by two sealing members (beads in the figure) 122 and 123. In the upper part of the drawing, bead 122 is fitted into the upper opening. In the lower part of the drawing, fastener 124 is fitted into the tank 120. Bead 123 is fitted into the opening of fastener 124. These beads 122 and 123 seal the processing solution 131 inside the internal space 121 of the tank 120.

[0058] Next, as shown in Figure 1C, the flow channel member 110, which acquires and contains the liquid 102 in the capillary tube 111, is inserted into the tank 120. The flow channel member 110 is inserted into the tank 120 from the tip 113 of the capillary tube 111. The tip of the flow channel member 110 pushes the sealing member 122 and drops it into the internal space 121 of the tank.

[0059] The liquid 102 that was acquired and contained in the flow path comes into contact with the pretreatment solution 131 that was in the tank's internal space 121. As a result, the two mix, and a mixed solution 132 is produced (Figure 1D). The liquid 102 and the pretreatment solution 131 may mix by diffusion. Mixing may also be facilitated by the movement of the beads 122.

[0060] As shown in Figure 1D, a discharge channel member 140 is provided. The discharge channel member 140 shown in Figure 1D has a first discharge channel member 141 which is inserted into the tank internal space 121 and has a discharge channel 143 for discharging the mixed solution 132, and a second discharge channel member 142 which has an outlet 144. The first discharge channel member 141 and the second discharge channel member 142 are combined with a filter 160 in the middle of the discharge channel 143. One end of the discharge channel 143 of the first discharge channel member 141 of this discharge channel member 140 is inserted into the tank internal space 121 via a lower fastener 124 of the tank 120.

[0061] As a result, the discharge channel member 140 is assembled to the tank 120, as shown in Figure 1E. The beads 123 are pushed into the internal space 121 of the tank.

[0062] The liquid 102 that was acquired and contained in the flow path comes into contact with the pretreatment solution 131 that was in the tank's internal space 121. As a result, the two mix, and a mixed solution 132 is produced. The liquid 102 and the pretreatment solution 131 may mix by diffusion. Mixing may also be facilitated by the movement of the beads 122.

[0063] In this state, the flow channel member 110 is sealed and fitted into the tank 120. The discharge channel member 140 is sealed and fitted into the tank 120. The internal space 121 of the tank 120 is sealed by the flow channel member 110 and the discharge channel member 140. The mixed solution 132 is contained in this sealed internal space 121.

[0064] As shown in Figure 1F, a cylinder 152 is formed on the upper side of the flow channel member 110 (opposite the capillary tube 120). A piston 151 is fitted into this cylinder 152. The piston 151 and cylinder 152 form a syringe 150. This syringe 150 functions as a pump and can apply pressure to the fluid-connected capillary tube 120 and the sealed internal space 121 through it.

[0065] As shown in Figure 1G, by pushing the piston 151, the mixed solution in the sealed internal space 121 of the tank 120 flows from the discharge channel 143 to the filter 160. The mixed solution 132 is filtered by the filter 160. The filtered discharged solution 133 is discharged to the outside from the outlet 144 of the discharge channel 143.

[0066] <Embodiment 2> Figures 2A to 2D illustrate the structure of a liquid sampling device according to one embodiment, step by step. The liquid device shown in Figures 2A to 2D extends in the direction of the pipe axis, and its parts are assembled in the direction of the pipe axis.

[0067] As shown in Figure 2A, the flow channel member 210 has a flow channel 211 that penetrates in the direction of the pipe axis, and one end of the flow channel member 210 forms a capillary tube with a lateral hole 212. The capillary tube can collect a specified amount of liquid 202 between its tip and the lateral hole 212. In Figure 2, the flow channel member 210 has already collected the target liquid 202.

[0068] In the embodiment shown in Figures 2A to 2D, a discharge channel member 240 is connected to a flow channel member 210. The flow channel 211 of the flow channel member 210 is fluidly connected to the discharge channel 243 of the discharge channel member 240 at its other end (the end opposite to the end from which the target liquid 202 is acquired).

[0069] The discharge channel member 240 shown in Figure 2A has a first discharge channel member 241 which is fitted with the flow channel member 210 and has a discharge channel 243 for discharging the mixed solution 232 (see Figure 2C, etc.), and a second discharge channel member 242 which has an outlet 244. The first discharge channel member 241 and the second discharge channel member 242 are combined with a filter 260 in the middle of the discharge channel 243.

[0070] As shown in Figure 2A, the tank 220 has an internal space 221 in which the processing solution 231 is contained. The internal space 221 of the tank 220 is sealed from both sides in the direction of the pipe axis by two sealing members (beads in the figure) 222 and 223. In the upper part of the drawing, bead 222 is fitted into the upper opening. In the lower part of the drawing, bead 223 is fitted into the lower opening. These beads 222 and 223 seal the processing solution 231 inside the internal space 221 of the tank 220.

[0071] Next, as shown in Figures 2A and 2B, the flow channel member 210, which acquires and contains the liquid 202 in the capillary tube 211, is inserted into the tank 220. The flow channel member 210 is inserted into the tank 220 from the tip of the capillary tube 211. The tip of the flow channel member 210 pushes the sealing member (bead) 222, causing it to fall into the internal space 221 of the tank.

[0072] The liquid 202 acquired and contained in the flow path comes into contact with the pretreatment solution 231 that was in the internal space 221 of the tank. As a result, the two mix and a mixed solution 232 is produced (Figure 2B). The liquid 202 and the pretreatment solution 231 may mix by diffusion. Mixing may be facilitated by the movement of the beads 222. The tank 220 may be shaken or rotated, or the flow path member 210 may be moved relative to the tank 220. For example, the flow path member 210 may be removed from the tank 220 and reinserted, or this may be repeated. The flow path member 210 may be rotated relative to the tank 220.

[0073] As shown in Figure 2C, the tank 220, the flow path member 210, and the discharge channel member 240, which are fitted together, are inverted vertically.

[0074] In this state, the flow channel member 210 is sealed and fitted into the tank 220. The discharge channel member 240 is fitted into the tank 220. The internal space 221 of the tank 220 is defined by the flow channel member 210 and the second bead 223. The mixed solution 232 is contained in this internal space 221.

[0075] As shown in Figure 2C, a cylinder 252 is formed on the upper side of the tank 220 (opposite the insertion opening for the capillary tube 211). A piston 251 is fitted into this cylinder 252. The piston 251 and cylinder 252 form a syringe 250. This syringe 250 has a pump function and can apply pressure to the inside of the syringe 250 and to the sealed internal space 221.

[0076] As shown in Figure 2D, when the piston 251 is pushed axially against the tank 220, the resulting pressure pushes the beads 223. The beads 223 fall into the internal space 221 of the tank.

[0077] As shown in Figure 2E, by further pushing the piston 251, the mixed solution 232 that was in the sealed internal space 221 of the tank 220 flows from the discharge channel 243 to the filter 260. The mixed solution 232 is filtered by the filter 260. The filtered discharged solution 233 is discharged to the outside from the outlet 244 of the discharge channel 243.

[0078] <filter> This disclosure provides a flow channel having a filter (also referred to as a filter flow channel, filter flow channel member, filter flow channel device, etc.; names are not limited thereto). The filter flow channel may be incorporated into the liquid sampling device of this disclosure. The filter flow channel may be incorporated into other flow channel devices. This disclosure provides a flow channel device having a filter.

[0079] In some embodiments, the filter is placed within the flow path. Generally, the filter receives the liquid flowing through the flow path and filters or removes a predetermined substance. The filtered liquid is discharged into the flow path. The liquid inside the filter may seep to the circumferential surface (hereinafter sometimes referred to as the outer surface) perpendicular to the flow path direction of the filter. The filter or filter flow path may be configured so that the liquid passing through and permeating the filter does not reach the outer surface of the filter. Liquid that reaches the outer surface of the filter may flow along the inner wall of the flow path. Liquid flowing along the inner wall of the filter is substantially unaffected by the filter's action. Therefore, it is important to prevent the liquid from reaching the outer surface of the filter and to allow the liquid to pass through the filter.

[0080] <Filter Type 1> Figure 3 shows a filter flow path (device) 1100 according to one embodiment. The filter flow path 1100 comprises a first flow path member 1101, a second flow path member 1102, and a filter 1110 fixed between them. Both the first flow path member 1101 and the second flow path member 1102 are formed in a cylindrical shape. The second flow path member 1102 is inserted inside the first flow path member 1101 and fitted axially to it. The first flow path member 1101 and the second flow path member 1102 are combined coaxially in the flow direction (arrow in the figure).

[0081] The first flow channel member 1101 and the second flow channel member 1102 define the flow channel 1120 and define the space in which the filter 1110, which has a radial size larger than the cross-section of the flow channel 1120, is arranged. The end of the second flow channel member 1102 is formed in a circular or concentric shape when viewed from the axial direction. This end face is formed perpendicular to the axial direction. This circular end is in contact with the outer circumference of the surface of the filter 1110 that is perpendicular to the axial direction.

[0082] The liquid 1131 before filtration flows through the channel 1120 and is absorbed by the filter 1110. The liquid 1131 flows through the filter and is filtered. The filtered liquid 1132 is discharged into the channel 1120. As shown in Figure 3, in some embodiments, the diameter of the channel portion where the filter is located may be larger than the diameter of the other parts of the channel. A filter wider than the channel diameter may be placed in that portion.

[0083] The diameter of the flow path 1120 is sufficiently smaller than that of the filter 1110. Therefore, the liquid permeating the filter 1110 does not reach its outer surface. The liquid 1131 before filtering is absorbed by the upstream surface of the filter 1110 and flows through the filter 1110 while being filtered. At this time, the filter flow path 1100 is designed so that the liquid 1133 inside the filter does not reach the outer circumference of the filter 1110 (the inner surface of the first flow path member 1101 in Figure 3).

[0084] In some embodiments, the second flow channel member 1102 may be pressed against the first flow channel member 1101. In some embodiments, the outer periphery of the filter 1110 may be crushed in the flow direction. This can prevent or reduce the outward penetration of the liquid into the filter.

[0085] <Filter Type 2> In some embodiments, the circumferential end faces of the filter may be substantially non-contacting the inner wall of the flow path in at least a portion of the flow direction. The filter may be non-contacting the inner wall of the flow path over its entire circumference. In some embodiments, the circumferential end faces of the filter may be substantially non-contacting the inner wall of the flow path in at least a portion of the flow direction.

[0086] Figure 4 shows a filter flow path (device) 1200 according to one embodiment. The filter flow path 1200 comprises a first flow path member 1201, a second flow path member 1202, and three filters 1210a, 1210b, and 1210c. The filters 1210a, 1210b, and 1210c do not necessarily have to be sandwiched or fixed between the first flow path member 1201 and the second flow path member 1202. Both the first flow path member 1201 and the second flow path member 1202 are formed in a cylindrical shape. The second flow path member 1202 is inserted inside the first flow path member 1201 and fitted axially to it. The first flow path member 1201 and the second flow path member 1202 are combined coaxially in the flow direction.

[0087] The first flow channel member 1201 and the second flow channel member 1202 define the flow channel 1220 and define the space in which filters 1210b and 1210c, which have a radial size larger than the cross-section of the flow channel 1220, are arranged. The end of the second flow channel member 1202 is formed in a circular or concentric shape when viewed from the axial direction. This end face is formed perpendicular to the axial direction. This circular end is in contact with the outer circumference of the surface of the second filter 1210b that is perpendicular to the axial direction.

[0088] The first filter 1210a is positioned within the first flow channel member 1201 and is configured to absorb substantially all of the liquid 1231 flowing through the flow channel 1220. The first filter 1210a is also in contact with the second filter 1210b. As a result, substantially all of the liquid that flows out of the first filter 1210a is absorbed by the second filter 1210b.

[0089] The outer surface of the second filter 1210b is not in contact with the inner wall of the flow path 1220. Therefore, the liquid 1233 that reaches the outer surface of the second filter 1210b can be prevented from moving to the inner wall of the flow path 1220 and flowing through it.

[0090] In some embodiments, the filter 1210 may not have a first filter 1210a, but instead consist of a second filter 1210b and a third filter 1210c.

[0091] The second filter 1210b is positioned so as to be in contact with the third filter 1210c from the outside. The outside of the second filter 1210b is in contact with the third filter 1210c from the inside, from the outside of the third filter 1210c. Viewed from the axial upstream side, the second filter 1210b is positioned sufficiently inside the third filter 1210c without completely extending beyond its outer circumference. This makes it possible to avoid or reduce, for example, the liquid reaching the outer surface of the third filter 1210c. The liquid 1231 that reaches the filter flows inside the filter without contacting the inner wall of the flow path 1220. The liquid 1233 inside the filter undergoes a predetermined filtering process. The filtered liquid 1232 is then discharged to the outside from the filter 1210c.

[0092] As seen in filter types 1 and 2, it is important that the filter absorbs all the liquid flowing through it and that the liquid does not pass through the filter area before it has undergone the predetermined filtering action. For this purpose, for example, the filter may have a constriction relative to the inner wall of the flow path in a portion of the flow direction.

[0093] For filtering large quantities of liquid, filters with a large surface area may be used. On the other hand, for filtering small amounts of liquid, it is necessary to reduce the cross-sectional area and / or volume of the flow path and filter. The filter flow paths provided in some embodiments of this disclosure can reduce the flow path and filter volume. This makes it possible, for example, to maintain sufficient filtering performance while minimizing the amount of liquid remaining in the filter.

[0094] This disclosure also provides the following embodiments. A001 A device for collecting liquids, A flow channel member having a channel capable of acquiring liquid from one end and containing the acquired liquid, A tank containing a processing solution in its internal space, wherein at least one end of the flow channel member is received, and the tank is configured such that mixing begins in the internal space between the processing solution contained in the tank and the liquid contained in the flow channel, A pump for discharging the mixed solution from the aforementioned tank, A filter for separating some of the components contained in the mixed solution, A device equipped with the following features. A011 The aforementioned liquid is a body fluid. The apparatus described in Embodiment A001. A012 The aforementioned liquid is blood. The apparatus described in Embodiment A001 or A011. A021 The flow path includes a capillary tube at least at one end for acquiring the liquid. The apparatus according to any one of embodiments A001 to A012. A022 The capillary tube comprises a plurality of capillaries. The apparatus described in Embodiment A021. A023 The capillary tube is formed in a slit shape. The apparatus described in Embodiment A021 or A022. A024 The aforementioned flow path is configured to acquire and contain a predetermined amount of liquid. The apparatus according to any one of embodiments A001 to A023. A025 The capillary in the flow path has a predetermined length. The apparatus according to any one of embodiments A021 to A023. A026 The portion of the flow path downstream from the capillary (away from one end) is configured to inhibit the occurrence of capillary action. The apparatus described in Embodiment A025. A031 The tank seals the processing solution. The apparatus according to any one of embodiments A001 to A026. A032 The tank comprises a tank body and a sealing member, which define the interior of the tank. The apparatus described in Embodiment A031. A033 At least a portion of the sealing member is configured to receive the flow path member. The apparatus described in Embodiment A032. A034 The sealing member comprises at least two sealing members, The first sealing member is configured to receive the flow path member, The second sealing member is configured to discharge the mixed solution from the tank. The apparatus described in Embodiment A033. A035 The sealing member includes beads and is mechanically and detachably fixed to the inner wall of the tank body. The apparatus according to any one of embodiments A032 to A034. A036 The sealing member includes a breakable film, The apparatus according to any one of embodiments A032 to A035. A037 The tank is configured to seal the mixed solution. The apparatus according to any one of embodiments A001 to A036. A041 The aforementioned treatment solution is a diluent. The apparatus according to any one of embodiments A001 to A037. A051 The pump is equipped with a syringe. The apparatus according to any one of embodiments A001 to A041. A052 The pump is equipped with a pipette valve. The apparatus according to any one of embodiments A001 to A051. A055 The pump is configured to apply pressure to the flow path from either end of the flow path. The apparatus described in Embodiment A051 or A052. A056 Applying pressure to the aforementioned flow path means applying positive or negative pressure to the aforementioned flow path. The apparatus described in Embodiment A055. A061 The tank is equipped with a discharge channel for discharging the mixed solution. The apparatus according to any one of embodiments A001 to A056. A062 The pump is configured to apply pressure to the other end of the flow path and to discharge the mixed solution in the flow path and the tank to the outside through the discharge channel. The apparatus described in Embodiment A061. A065 The other end of the aforementioned flow path is further equipped with a discharge channel that is fluid-connected to it. The apparatus according to any one of embodiments A001 to A056. A066 The filter is located in the discharge channel. The apparatus described in Embodiment A065. A071 The discharge channel is fluidly connected to the internal space and comprises a second internal space arranged in the path through which the liquid is discharged. The apparatus according to any one of embodiments A061 to A065. A072 The second internal space is fluidly connected to the outlet of the apparatus, and the mixed solution is discharged from the outlet. The apparatus described in Embodiment A071. A081 The filter comprises a plasma or serum separation filter. The apparatus according to any one of embodiments A001 to A072. A082 The filter contains cellulose or glass fibers. The apparatus according to any one of embodiments A001 to A081. A091 The filter receives the mixed solution and is configured such that the mixed solution does not seep out of the radial periphery in at least a portion of the direction in which the mixed solution is discharged. The apparatus according to any one of embodiments A001 to A082. A092 The filter is positioned in the discharge channel and is configured to receive the mixed solution in a region substantially including the center, and to prevent the mixed solution from seeping out from its periphery. The apparatus according to any one of embodiments A061 to A082. A093 The filter is placed in the discharge channel, The discharge channel is configured to guide the mixed solution to an area inward from the periphery of the filter. The apparatus according to any one of embodiments A061 to A092. A095 A portion of the discharge channel has a cylindrical end, The cylindrical end is positioned so as to be in close contact with the inside of the peripheral portion of the filter. The apparatus according to any one of embodiments A091 to A093. A096 The aforementioned filter is Separation filter, The discharge channel includes a guide filter positioned upstream of the separation filter and in contact with the separation filter, the guide filter being configured to receive the mixed solution and guide the mixed solution to the separation filter, The apparatus according to any one of embodiments A091 to A093. A097 The guide filter is positioned inside the discharge channel and is arranged to be non-contact with the inner wall of the discharge channel in the circumferential direction for at least a portion of the discharge direction. The apparatus described in Embodiment A096. A098 The guide filter is positioned such that it contacts the inner wall of the discharge channel in the direction from upstream to downstream of the discharge channel, and then does not contact the inner wall of the discharge channel in the circumferential direction. The apparatus according to any one of embodiments A001 to A082. A101 The aforementioned filter comprises a plurality of filters, The apparatus according to any one of embodiments A001 to A098. A102 The plurality of filters are arranged in a stacked manner in the direction of flow through the discharge channel. The apparatus described in Embodiment A101. A103 The filter comprises a plurality of filters stacked in the flow direction of the discharge channel. The apparatus according to any one of embodiments A001 to A102. A104 The aforementioned plurality of filters include at least, A first filter is provided which is in contact with the inner wall of the discharge channel in the circumferential direction and is configured to receive substantially all of the mixed solution that has flowed through it. A second filter is disposed downstream of the first filter in contact with the first filter, and is disposed non-contact with the inner wall of the discharge channel in the circumferential direction for at least a portion of the flow direction of the discharge channel, A third filter is positioned downstream of the second filter and in contact with the second filter, having a larger diameter than the second filter, and configured to receive substantially all of the mixed solution that has come out of the second filter, and to prevent the received mixed solution from reaching its peripheral surface. Equipped with, The apparatus according to any one of embodiments A101 to A103. A201 A device for collecting liquids, A flow channel member having a channel capable of acquiring liquid from one end and containing the acquired liquid, A tank containing a processing solution in its internal space, wherein at least one end of the flow channel member is received, and the tank is configured such that mixing begins in the internal space between the processing solution contained in the tank and the liquid contained in the flow channel, A pump for discharging the mixed solution from the tank, A device equipped with the following features. A255 The pump is configured to apply pressure to the flow path from either end of the flow path. The apparatus described in Embodiment A201. A261 The tank is equipped with a discharge channel for discharging the mixed solution. The apparatus described in Embodiment A201 or A255. A262 The pump is configured to apply pressure to the other end of the flow path and to discharge the mixed solution in the flow path and the tank to the outside through the discharge channel. The apparatus described in Embodiment A261. A265 The other end of the aforementioned flow path is further equipped with a discharge channel that is fluid-connected to it. The apparatus described in Embodiment A261. A266 The filter is located in the discharge channel. The apparatus described in Embodiment A265.

[0095] While several embodiments and examples of the present disclosure have been described above, these embodiments and examples are illustrative in nature. For example, each of the above embodiments has been described in detail to make the present disclosure easier to understand, and dimensions, configurations, materials, and circuits may be added or modified as needed. Embodiments that arbitrarily combine one or more of the features of the present disclosure listed above are also included in the scope of the present disclosure. The claims encompass a number of variations on the embodiments, without departing from the technical idea of ​​the present disclosure. Therefore, the embodiments and examples disclosed herein are provided for illustrative purposes only and should not be considered as limiting the scope of the present disclosure. [Explanation of symbols]

[0096] 101 Target 102,202 liquid 110,210 Flow channel members 111,211 Flow channels / capillaries 112,212 horizontal cave 113,213 Tip 120,220 tanks 121,221 Interior space 122,123,222,223 Sealing material / beads 124 Fasteners 131,231 Treatment solutions 132,232 mixed solution 133,233 Drainage solution 140,240 Discharge channel member 141,241 First discharge channel member 142,242 Second discharge channel member 143,243 emission channels 144,244 outlet 150,250 syringes 151,251 pistons 152,252 cylinders 160,260 filters 1100, 1200 filter channels (devices) 1101,1201 First flow channel member 1102,1202 Second flow channel member 1110, 1210a~c filters 1120,1220 flow path 1131,1231 Liquid before filtering 1132,1232 Filtered liquid 1133,1233 Liquid in the filter

Claims

1. A flow channel device, The device comprises a filter positioned within the flow path of the flow channel device, which receives the fluid flowing through the flow path in a region substantially including the center, and is configured to prevent the fluid from seeping out from its periphery. The aforementioned filter is Separation filter, The system includes a guide filter positioned upstream of the separation filter and in contact with the separation filter, The outer circumference of the guide filter is compressed in the direction of flow in the flow path by the flow path member. The guide filter is positioned inside the flow path and is arranged so as to be non-contact with the inner wall of the flow path in the circumferential direction for at least a portion of the flow path direction. The outer periphery of the guide filter is compressed, and the guide filter is not in contact with the inner wall, thereby suppressing the movement of liquid from the guide filter to the inner wall of the flow path. Fluid flow device.

2. A flow channel device according to claim 1, The aforementioned filter is A first filter is provided, which is configured to contact a portion of the inner wall of the flow path in the circumferential direction and to receive substantially all of the fluid that flows through it. A second filter is disposed downstream of the first filter in contact with the first filter, and the second filter is disposed non-contact with the inner wall of the flow path in the circumferential direction in at least a portion of the flow direction of the flow path, A third filter is positioned downstream of the second filter and in contact with the second filter, having a larger diameter than the second filter, and configured to substantially receive all of the fluid that flows out of the second filter, and to prevent the received fluid from reaching its peripheral end surface. Equipped with, Fluid flow device.

3. A flow channel device according to claim 1, The fluid is blood or saliva in the fluid channel device.

4. A flow channel device according to claim 1, The filter comprises a plasma or serum separation filter. Fluid flow device.

5. A flow channel device according to claim 1, The aforementioned filter includes a filter for separating mucin contained in saliva. Fluid flow device.

6. A flow channel device according to claim 5, The filter is located in the discharge channel of the flow channel device. Fluid flow device.

7. A flow channel device according to claim 6, A flow path device further comprising a pump that applies pressure inside the flow path and discharges the contents from the flow path through the discharge channel and the filter to the outside.

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