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 for mixing a liquid sample with a processing liquid and obtaining a processed liquid. [Background technology]

[0002] There is a demand for miniaturized devices in systems that collect small amounts of body fluids such as blood and other liquids and perform pretreatment for testing. These are also effective for point-of-care testing. They are also desirable for testing small amounts of samples. In devices with limited size, there is also a demand for performance such as efficient pretreatment of small amounts of samples, or removal or separation of impurities that interfere with measurement. Summary of the Invention

[0003] By way of example and not limitation, there is recognized a need herein for efficiently collecting and pre-treating liquids and efficiently removing the pre-treated liquids.

[0004] In some embodiments of the present disclosure, a liquid collector (apparatus or device) is provided. In some embodiments, the liquid collector collects or collects a liquid. In some embodiments, the liquid collector includes a flow path member. The flow path member may include a flow path. In some embodiments, the liquid collector includes a flow path. In some embodiments, the flow path is configured to acquire liquid from one end thereof. In some embodiments, the flow path can accommodate the acquired liquid. In some embodiments, the liquid collector includes a tank. In some embodiments, the tank contains a processing solution therein. In some embodiments, the tank is configured to receive a flow path member at a portion or one end thereof. In some embodiments, the tank is configured to mix the processing solution contained in the tank and the liquid contained in the flow path in an interior space thereof. The mixing may at least be initiated in the interior space. In some embodiments, the liquid collector includes a pump that discharges the mixed liquid (hereinafter, also referred to as the mixed solution) from the tank. In some embodiments, the liquid collector includes a filter. The filter may be configured to separate some components contained in the mixed solution.

[0005] According to the above embodiment, for example, it is possible to efficiently carry out a series of processes in which a relatively small amount of liquid is collected and the collected liquid is subjected to pretreatment.

[0006] Further aspects and advantages of the present disclosure will become readily apparent to those skilled in the art from the following detailed description, in which only illustrative embodiments of the present disclosure are shown and described. As will be understood, the present disclosure is capable of other and different embodiments, and its several details are capable of modification in various obvious respects, without departing from the present disclosure. Accordingly, the drawings and description are to be regarded as illustrative in nature, and not as restrictive. [Brief description of the drawings]

[0007] [Figure 1A]1A-1D are cross-sectional views illustrating a process of using a liquid collection device according to an embodiment. [Figure 1B] 1A-1D are cross-sectional views illustrating a process of using a liquid collection device according to an embodiment. [Figure 1C] 1A-1D are cross-sectional views illustrating a process of using a liquid collection device according to an embodiment. [Figure 1D] 1A-1D are cross-sectional views illustrating a process of using a liquid collection device according to an embodiment. [Figure 1E] 1A-1D are cross-sectional views illustrating a process of using a liquid collection device according to an embodiment. [Figure 1F] 1A-1D are cross-sectional views illustrating a process of using a liquid collection device according to an embodiment. [Figure 1G] 1A-1D are cross-sectional views illustrating a process of using a liquid collection device according to an embodiment. [Figure 2A] 1A-1D are cross-sectional views illustrating a process of using a liquid collection device according to an embodiment. [Figure 2B] 1A-1D are cross-sectional views illustrating a process of using a liquid collection device according to an embodiment. [Figure 2C] 1A-1D are cross-sectional views illustrating a process of using a liquid collection device according to an embodiment. [Figure 2D] 1A-1D are cross-sectional views illustrating a process of using a liquid collection device according to an embodiment. [Figure 2E] 1A-1D are cross-sectional views illustrating a process of using a liquid collection device according to an embodiment. [Diagram 3] FIG. 2 is a cross-sectional view showing a filter flow path according to an embodiment. [Figure 4] FIG. 2 is a cross-sectional view showing a filter flow path according to an embodiment. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0008] In some embodiments, the liquid may be a bodily fluid secreted by a subject, or a liquid other than a bodily fluid. The liquid other than a bodily fluid may be a liquid attached to an object, or a liquid not attached to an object. The liquid not attached to an object may be a liquid contained in an 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 solution that is not a body fluid (non-body fluid-derived), 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] The body fluid may be lymphatic fluid, tissue fluid such as interstitial fluid, intercellular fluid, or interstitial fluid, body cavity fluid, serous cavity fluid, pleural fluid, peritoneal fluid, pericardial fluid, cerebrospinal fluid, synovial fluid, or aqueous humor. The body fluid may be digestive fluid such as saliva, gastric juice, bile, pancreatic juice, or intestinal fluid, or may be sweat, tears, nasal mucus, urine, semen, vaginal fluid, amniotic fluid, or milk. The body fluid may be an animal body fluid or a human body fluid. The "body fluid" may be a solution. The solution may contain a physiological buffer solution such as phosphate buffered saline (PBS) or N-tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid buffer (TES) containing the substance to be measured. The solution is not particularly limited as long as it contains the substance to be measured.

[0011] In some embodiments, the bodily fluid may be blood. In some embodiments, blood may be collected. For example, blood may be collected simultaneously with bleeding from a puncture. For example, blood may be aspirated by inserting a needle. In some embodiments, a puncture device (e.g., a needle, a syringe needle, etc., same below) may be disposed at the tip of a capillary tube. In some embodiments, a capillary tube may be formed as a puncture device.

[0012] In some embodiments, the subject may include or be a human. In some embodiments, the subject may include or be a non-human animal. The non-human animal may include or be a mammal. The non-human animal may be, for example, but not limited to, a working animal, a livestock animal, a pet animal, or a wild animal.

[0013] In some embodiments, the liquid collection device includes a flow path member. In some embodiments, the flow path member may have a flow path connecting one end and the other end. In some embodiments, the flow path member may have a plurality of flow paths. In some embodiments, the flow path member may have only one flow path. In some embodiments, when the flow path member has a plurality of flow paths, the plurality of flow paths extend in the tube axis direction connecting one end and the other end. In some embodiments, the plurality of flow paths may be arranged substantially parallel to each other, or may not be arranged parallel to each other.

[0014] In some embodiments, the flow path may include a capillary (also referred to as a capillary channel). In some embodiments, at least a portion of the flow path may consist of a capillary. In some embodiments, the flow path may include a capillary at at least one end that obtains the liquid. In some embodiments, the capillary may comprise multiple capillaries.

[0015] The term "pipe axis direction" as used herein refers to a direction connecting one end and the other end of the flow path member.

[0016] In some embodiments, the flow path member may be a columnar shape extending in the tube 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 tube axis direction on the outer circumferential surface, or may have only one groove. In some embodiments, the groove constitutes a liquid flow path. The cross section of the groove may be formed, for example, but not limited to, 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 be generally formed in a valley shape. In some embodiments, the flow path may be formed in a slit shape. A slit or a groove that is open to the outside is easily accessible from the outside. For example, it is easy to bring a processing liquid (hereinafter, also referred to as a processing solution) into contact with the liquid in the flow path. For example, it is easy to mix them.

[0017] In some embodiments, the flow path member may be columnar extending in the tube axis direction. In some embodiments, the columnar flow path member may have a cross-sectional shape viewed from the tube axis direction that is circular or elliptical. In some embodiments, the flow path member may have a polygonal cross-sectional shape, such as a triangle, a rectangle, a pentagon, a hexagon, or an octagon. In some embodiments, the flow path member may have a plurality of flow paths extending in the tube axis direction and communicating one end with the other end. In some embodiments, the cross section of the flow path member may be constant in the tube axis direction (e.g., cylindrical) or may change in the tube axis direction (e.g., the cross section becomes smaller toward 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 extending in the tube axis direction and have a flow path connecting one end and the other end. In some embodiments, the plurality of single tubes may be joined together by adhesion, welding, or the like. In some embodiments, the plurality of single tubes may be bound together by a band or the like. In some embodiments, the plurality of single tubes may be molded together from 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 liquid.

[0019] In some embodiments, the flow path may be configured to capture and contain a predetermined or metered amount of liquid. In some embodiments, liquid may be drawn up into the flow path by capillary action. At least the tip of the flow path may comprise a capillary (channel). In some embodiments, the capillary of the flow path may have a predetermined length. The length of the capillary may define the volume of liquid that the flow path collects. In some aspects, the capillary may have a side hole in a portion thereof. In some aspects, capillary action occurs from one end (the tip) of the capillary to the side hole. The volume may define the amount of liquid that is collected. The capillary may have a larger cross-sectional area at the other end or a portion thereof. This prevents substantial capillary action from occurring further. In some aspects, the portion of the flow path downstream of the capillary, i.e., away from the one end (from the tip) or toward the other end, may be configured to inhibit capillary action from occurring.

[0020] The portion of the capillary tube where the capillary action occurs may define the amount of liquid that is collected. The cross-sectional area and length of the capillary tube may define the amount of liquid that is collected. In some embodiments, the capillary tube may be provided with markings or graduations to indicate a certain amount of liquid that has been collected.

[0021] In some embodiments, the flow path may have a suction mechanism other than a capillary to pick up liquid, such as a pump or other mechanism coupled to the flow path, which can be used to pick up a relatively precise amount of liquid.

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

[0023] In some embodiments, the tank may have a tank body. An inner wall of the tank body may define an interior or interior space of the tank. In some embodiments, the tank may have a tank body and a sealing member, which 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 inside of the tank, unseal the tank, and enter the inside of the tank. The sealing member may include at least two sealing members. A first sealing member may be configured to receive the flow path member. A second sealing member may be configured to discharge the mixed solution from the tank.

[0025] The first sealing member and the second sealing member are each sealingly fixed to the tank body and may be removed by an external force. For example, the sealing members may be or may comprise beads. The beads may be mechanically removably fixed to the inner wall of the tank body. The beads may be fixed to the tank body such that they can be pushed to remove them from their fixed position. For example, the sealing members may be or may comprise a destructible film. The film may be configured to be broken by being pushed by a sharp member.

[0026] In some embodiments, the flow path member may be inserted into a tank containing the processing solution. At that time, the acquired liquid in the flow path of the flow path member comes into contact with the processing solution. The acquired liquid and the processing solution start to mix. The liquid and the processing solution may mix naturally or by diffusion. The user may shake the liquid collection device to promote mixing. The liquid collection device may be turned upside down, rotated around the tube axis, or vibrated using a machine such as a stirring device or a shaking device. This may promote mixing. Beads 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 the processing solution therein after the flow path member is inserted into the tank. The tank may be configured to seal the interior thereof at least during mixing of the liquid and the processing solution. The tank may be configured to seal a mixed solution produced by mixing the acquired liquid and the processing solution. For example, the tank may have a lid. The lid may be closed to seal the mixed solution in the tank. For example, the inserted flow path member and the tank may seal the tank interior space.

[0028] In some embodiments, a storage vessel may be provided to receive the mixed solution discharged from the apparatus. The mixed solution may be sealed in the tank interior space or in the storage vessel for transport or storage.

[0029] The volume of the capillary (or the flow path portion that acquires the liquid, hereinafter the same) may be equal to or greater than 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 equal to or smaller than 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 equal to or smaller than 10 μL, 20 μL, 25 μL, 30 μL, 35 μL, 40 μL, 45 μL, 50 μL, etc. The volume of the tank may be equal to or smaller than 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 volume of the capillary tube. The dilution ratio may be 2 to 20 times, or 2 to 50 times. The volume of the tank may be, for example, but not limited to, substantially 25 μL, or substantially 250 μL.

[0031] <Processing solution> In some embodiments, the processing solution may be a diluting solution. The diluting solution may be used to dilute the acquired liquid. The processing solution may be a liquid (pre-processing solution) for performing a predetermined process (pre-processing) on ​​the acquired liquid prior to measurement. The processing solution may be water or an aqueous solution. The processing solution may be a buffer solution. The processing solution may be, for example, Good's buffer. The processing solution may be a saline solution. The processing solution may be an organic solvent.

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

[0033] In some embodiments, the osmotic pressure of the processing solution may be adjusted. For example, when the purpose is serum separation, the osmotic pressure of the processing solution may be the same as the osmotic pressure of human body fluids (285±5 mOsm / L) (isotonic solution). If the osmotic pressure is low (hypotonic solution), red blood cells may burst and hemolyze. Conversely, if the osmotic pressure is high (hypertonic solution), the separation ability of the blood cell separation filter may be affected. In addition, the target substance may be released in excess from the blood cells, affecting the measurement results.

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

[0035] The treatment solution may, for example, include substances that solubilize or degrade mucins in saliva, thereby reducing the viscosity of bodily fluids such as saliva.

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

[0037] The treatment solution may contain a substance (a flocculant) that flocculates substances contained in the target liquid. For example, the target liquid may contain a flocculant that flocculates specific substances, such as fine dust, blood cells, mucin, membrane proteins, and oils. These substances may be broken into larger clumps. The clumps generated by flocculation are easier to remove in a subsequent filter process.

[0038] The processing solution may contain substances that degrade, solubilize, aggregate, or inhibit or promote the reaction of the substance.

[0039] The components of the processing solution may be selected from the group consisting of saline, HEPES, TES, MES, Tricine and PBS. The components of the processing solution may include Good's buffer (e.g., HEPES, TES, MES, Tricine). The processing solution may include a standard used in subsequent measurements.

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

[0041] In some embodiments, the pump can apply pressure to the interior of the tank. In some embodiments, the pump can draw air from the outside into the interior of the tank.

[0042] In some embodiments, the pump may include a pipette valve. In some embodiments, a pipette valve may be disposed on the syringe. In addition to the syringe, the pipette valve may apply pressure to the reservoir.

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

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

[0045] <Exhaust Channel> In some embodiments, the device may include a discharge channel (also referred to as a discharge flow path or a discharge path) for discharging the mixed solution to the outside. The device may include a discharge channel member having the discharge channel. Hereinafter, the discharge channel may refer to the discharge channel member unless otherwise stated.

[0046] In some embodiments, the exhaust channel may be disposed in the tank. The tank may include the exhaust channel. The exhaust channel may be attached to the tank. The exhaust channel may be removably attached to the tank. The exhaust channel may be fluidly connected to the tank. The exhaust channel may be fixed to the tank. The exhaust channel may be formed as part of the tank by being molded integrally therewith.

[0047] In some embodiments, the pump may be configured to apply pressure to the other end of the flow path to expel at least a portion or substantially all of the mixed solution, processing solution, or liquid in the flow path from the flow path. If the tank is sealed, the pressure may also be applied to the tank. The mixed solution in the tank may be expelled to the outside through an outlet channel due to the pressure.

[0048] In some embodiments, the discharge channel may be disposed at the other end of the flow path (the end opposite to the end where the liquid is acquired). The discharge channel may be fluidly connected to the other end of the flow path. The discharge channel may be configured to be removably attached to the flow path member. The discharge channel may be fixed to the flow path member. The discharge channel may be formed as a part of the flow path member by integral molding. In this way, the mixed solution flows through the flow path and is discharged from the discharge channel. In this way, for example, residual liquid in the flow path can be washed away when it is discharged. The mixed solution may wash away a portion of the capillary tube.

[0049] In some embodiments, a second internal space may be disposed 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. It is possible that the mixing in the first internal space is insufficient. The acquired liquid and the processing solution can be mixed well by flow in the discharge path, flow or diffusion in the second internal space, etc. The acquired liquid and the processing solution can be mixed well in the second internal space. The second internal space may be fluidly connected to an outlet of the device. This allows the mixed solution to exit the second internal space and be discharged through the outlet. In some embodiments, the second internal space may be disposed in the discharge channel between the first internal space and the filter.

[0050] <filter> In some embodiments, a filter may be disposed in the discharge path of the mixed solution. In some embodiments, the filter may have the ability to separate a predetermined 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, traps cellular components, and allows plasma to pass through. The filter may comprise a serum separation filter (or membrane) that receives blood, traps blood clots, and allows serum to pass through.

[0052] The filter may include a filter that separates other substances. For example, the filter may be capable of removing small debris. For example, the filter may be capable of removing high molecular weight substances such as mucin. For example, the filter may be capable of removing proteins that have aggregated due to the action of a treatment solution. For example, the filter may carry a substance that has the ability to react with a substance that passes through the filter. For example, the filter may carry an antibody. For example, the filter may carry a substance that has the ability to bind to a protein. For example, the surface of the filter (for example, the surface of the filter fiber) may be composed of a substance that has a high affinity for a predetermined substance. Thereby, the predetermined substance can be adsorbed onto the filter surface.

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

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

[0055] <Embodiment 1> 1A to 1F show an example of a structure of a liquid collection device according to an embodiment for each step of use. The liquid device shown in Fig. 1A to 1F extends in the axial direction of the tube, and each member is combined in the axial direction of the tube.

[0056] As shown in FIG. 1A, a flow path member 110 has a flow path 111 penetrating in the axial direction of the tube, and liquid can be obtained from one end (tip) of the flow path member 110. The flow path 111 extends in the longitudinal direction of the flow path member 110. The tip of the flow path 111 is a capillary tube. A side hole 112 is formed in the flow path 111. The tip 113 of the flow path is brought close to or into contact with the liquid 102 present on the object 101. The liquid 102 moves up the capillary tube 111 from the tip by capillary action and stops at the position of the side hole 112, and is not sucked up above it (see FIG. 1B).

[0057] As shown in Fig. 1B, the tank 120 has an internal space 121 in which a processing solution 131 is contained. The internal space 121 is sealed from both sides in the tube axial direction by two sealing members (beads in the figure) 122, 123. At the upper side of the figure, the bead 122 is fitted into the upper opening. At the lower side of the figure, a fastener 124 is fitted into the tank 120. A bead 123 is fitted into the opening of the fastener 124. These beads 122, 123 allow the internal space 121 of the tank 120 to seal the processing solution 131 therein.

[0058] 1C, the flow path member 110 that has acquired and contained the liquid 102 in the capillary tube 111 is inserted into the tank 120. The flow path member 110 is inserted into the tank 120 from the tip 113 of the capillary tube 111. The tip of the flow path member 110 pushes the sealing member 122 and drops into the tank internal space 121.

[0059] The liquid 102 that has been acquired and stored in the flow path comes into contact with the pretreatment solution 131 that has been in the tank internal space 121. As a result, the two are mixed to generate a mixed solution 132 (FIG. 1D). The liquid 102 and the pretreatment solution 131 may be mixed by diffusion. The mixing may be promoted by the movement of the beads 122.

[0060] As shown in FIG. 1D, a discharge channel member 140 is provided. The discharge channel member 140 shown in FIG. 1D includes a first discharge channel member 141 having a discharge channel 143 for discharging the mixed solution 132, which is inserted into the tank inner space 121, and a second discharge channel member 142 having a discharge port 144. The first discharge channel member 141 and the second discharge channel member 142 are combined with a filter 160 sandwiched 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 inner space 121 through the lower fastener 124 of the tank 120.

[0061] As a result, the exhaust channel member 140 is assembled to the tank 120, as shown in Figure IE. The beads 123 are pushed into the tank interior space 121.

[0062] The liquid 102 that has been acquired and stored in the flow path comes into contact with the pretreatment solution 131 that has been in the tank internal space 121. As a result, the two are mixed to generate a mixed solution 132. The liquid 102 and the pretreatment solution 131 may be mixed by diffusion. The mixing may be promoted by the movement of the beads 122.

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

[0064] 1F, a cylinder 152 is formed on the upper side (opposite side to the capillary tube 120) of the flow path member 110. A piston 151 is fitted into this cylinder 152. The piston 151 and the cylinder 152 form a syringe 150. This syringe 150 has a pump function and can apply pressure to the capillary tube 120, which is fluidly connected thereto, and the sealed internal space 121 via the capillary tube 120.

[0065] 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 discharge port 144 of the discharge channel 143.

[0066] <Embodiment 2> 2A to 2D exemplarily show the structure of a liquid collection device according to an embodiment for each step of use. The liquid device shown in Fig. 2A to 2D extends in the axial direction of the tube, and each part is assembled in the axial direction of the tube.

[0067] As shown in Fig. 2A, the flow path member 210 has a flow path 211 penetrating in the tube axial direction, one end of which forms a capillary tube with a side hole 212. The capillary tube can collect a specified amount of liquid 202 between the tip and the side hole 212. In Fig. 2, the flow path member 210 has already collected the target liquid 202.

[0068] 2A-2D, a discharge channel member 240 is connected to a flow path member 210. The flow path 211 of the flow path member 210 is in fluid communication with a discharge channel 243 of the discharge channel member 240 at its other end (the end opposite the tip that captures the target liquid 202).

[0069] 2A includes a first discharge channel member 241 having a discharge channel 243 that fits into the flow path member 210 and discharges the mixed solution 232 (see FIG. 2C, etc.), and a second discharge channel member 242 having a discharge port 244. The first discharge channel member 241 and the second discharge channel member 242 are combined with a filter 260 sandwiched in the middle of the discharge channel 243.

[0070] As shown in Fig. 2A, the tank 220 has an internal space 221 in which a processing solution 231 is contained. The internal space 221 of the tank 220 is sealed from both sides in the tube axis direction by two sealing members (beads in the figure) 222, 223. At the upper side of the figure, the bead 222 is fitted into the upper opening. At the lower side of the figure, the bead 223 is fitted into the lower opening. These beads 222, 223 allow the internal space 221 of the tank 220 to seal the processing solution 231 therein.

[0071] 2A and 2B, the flow path member 210 that has acquired and stored the liquid 202 in the capillary tube 211 is inserted into the tank 220. The flow path member 210 is inserted into the tank 220 from the tip of the capillary tube 211. The tip of the flow path member 210 pushes the sealing members (beads) 222, causing them to drop into the tank internal space 221.

[0072] The liquid 202 that has been acquired and stored in the flow path comes into contact with the pretreatment solution 231 that was in the tank internal space 221. As a result, the two are mixed to generate a mixed solution 232 (FIG. 2B). The liquid 202 and the pretreatment solution 231 may be mixed by diffusion. The mixing may be promoted by the movement of the beads 222. The tank 220 may be rocked 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 FIG. 2C, the tank 220, the flow path member 210, and the discharge channel member 240, which are fitted together, are turned upside down.

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

[0075] 2C, a cylinder 252 is formed on the upper side of tank 220 (the side opposite to the insertion opening of 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 syringe 250 and to the sealed internal space 221.

[0076] 2D, by pushing the piston 251 axially against the tank 220, the pressure pushes the beads 223. The beads 223 fall into the tank interior space 221.

[0077] 2E, by further pushing the piston 251, the mixed solution 232 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 discharge port 244 of the discharge channel 243.

[0078] <filter> The present disclosure provides a flow path having a filter (also referred to as a filter flow path, a filter flow path member, a filter flow path device, etc., but the names are not limited to these). The filter flow path may be incorporated into the liquid collection device of the present disclosure. The filter flow path may be incorporated into other flow path devices. The present disclosure provides a flow path device having a filter.

[0079] In some embodiments, the filter is disposed in the flow path. The filter generally receives 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 permeate a circumferential surface (hereinafter, sometimes referred to as an outer surface) perpendicular to the flow path direction of the filter. The filter or the filter flow path may be configured so that the liquid that passes through and permeates the filter does not reach the outer surface of the filter. The liquid that reaches the outer surface of the filter may flow down the inner wall of the flow path. The liquid that runs down the inner wall of the filter is substantially not affected by the action of the filter. 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> 3 shows a filter flow path (device) 1100 according to an embodiment. The filter flow path 1100 includes a first flow path member 1101, a second flow path member 1102, and a filter 1110 sandwiched and 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 thereto in the axial direction. 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 path member 1101 and the second flow path member 1102 define a flow path 1120 and a space in which a filter 1110 having a radial size larger than the cross section of the flow path 1120 is disposed. The end of the second flow path 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 periphery of the surface of the filter 1110 perpendicular to the axial direction.

[0082] Pre-filter liquid 1131 flows through flow path 1120 and is absorbed by filter 1110. Liquid 1131 flows through the filter and is filtered. Filtered liquid 1132 is discharged into flow path 1120. As shown in Figure 3, in some embodiments, the diameter of the portion of the flow path where the filter is located may be larger than the diameter of the remaining portions of the flow path. A filter wider than the flow path diameter may be located in that portion.

[0083] The diameter of the flow path 1120 is sufficiently smaller than that of the filter 1110. Therefore, the liquid penetrating the filter 1110 does not reach its outer surface. The liquid 1131 before the filter 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 periphery of the filter 1110 (the inner circumferential surface of the first flow path member 1101 in FIG. 3).

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

[0085] <Filter type 2> In some embodiments, the circumferential end surface of the filter may be substantially out of contact with the inner wall of the flow path over at least a portion of the flow direction of the flow path. The filter may be out of contact with the inner wall of the flow path over the entire circumferential direction. In some embodiments, the circumferential end surface of the filter may be substantially out of contact with the inner wall of the flow path over at least a portion of the flow direction of the flow path.

[0086] 4 shows a filter flow path (device) 1200 according to an embodiment. The filter flow path 1200 includes 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 is fitted thereto in the axial direction. The first flow path member 1201 and the second flow path member 1202 are combined coaxially in the flow direction.

[0087] The first flow path member 1201 and the second flow path member 1202 define a flow path 1220 and a space in which filters 1210b and 1210c having a radial size larger than the cross section of the flow path 1220 are disposed. The end of the second flow path 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 periphery of the surface perpendicular to the axial direction of the second filter 1210b.

[0088] The first filter 1210a is disposed in the first flow path member 1201 and is configured to absorb substantially all of the liquid 1231 flowing through the flow path 1220. The first filter 1210a is further 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 second filter 1210b is not in contact with the inner wall of flow path 1220. Therefore, it is possible to prevent liquid 1233 that has reached the outer surface of second filter 1210b from moving to the inner wall of flow path 1220 and flowing therethrough.

[0090] In some embodiments, the filter 1210 may be composed of a second filter 1210b and a third filter 1210c, without a first filter 1210a.

[0091] The second filter 1210b is disposed so as to contact the third filter 1210c from the inside of its outer periphery. The outer periphery of the second filter 1210b is disposed so as to contact the third filter 1210c from the inside of its outer periphery. When viewed from the upstream side in the axial direction, the second filter 1210b is disposed sufficiently inside the third filter 1210c without completely going outside the outer periphery. 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 filter process. Then, the filtered liquid 1232 is 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 prevents the liquid from passing through the filter area before it has been subjected to a predetermined filtering action. For this purpose, for example, the filter may have a constriction with respect to the inner wall of the flow path in a part of the flow direction of the filter.

[0093] For filtering a large amount of liquid, a filter having a large area may be used. On the other hand, for filtering a small amount of liquid, a small cross-sectional area and / or volume of the flow path and the filter is required. The filter flow path provided in some embodiments of the present disclosure allows for a small flow path and a small filter volume. This allows, for example, to maintain sufficient filtering performance and minimize the amount of liquid remaining in the filter.

[0094] The present disclosure also provides the following embodiments. A001 An apparatus for collecting a liquid, comprising: A flow path member having a flow path capable of receiving a liquid from one end and storing the received liquid; a tank containing a processing solution in an internal space, the tank being configured to receive at least one end of the flow path member so that mixing of the processing solution contained in the tank and the liquid contained in the flow path is initiated in the internal space; a pump for discharging the mixed solution from the tank; A filter for separating a portion of components contained in the mixed solution; An apparatus comprising: A011 The liquid is a body fluid. An apparatus as described in embodiment A001. A012 The liquid is blood. An apparatus described in embodiment A001 or A011. A021 the flow path includes a capillary at at least one end that receives the liquid; An apparatus described in any one of embodiments A001 to A012. A022 The capillary tube comprises a plurality of capillaries. An apparatus as described in embodiment A021. A023 The capillary tube is formed in a slit shape. An apparatus described in embodiment A021 or A022. A024 The flow path is configured to acquire and contain a volume of liquid. An apparatus described in any one of embodiments A001 to A023. A025 The capillary of the flow path has a predetermined length. An apparatus described in any one of embodiments A021 to A023. A026 A portion of the flow path downstream (away from one end) of the capillary is configured to inhibit capillary action from occurring. An apparatus as described in embodiment A025. A031 The tank contains the processing solution. An apparatus described in any one of embodiments A001 to A026. A032 The tank has a tank body and a sealing member, which define an interior of the tank. An apparatus as described in embodiment A031. A033 At least a portion of the sealing member is configured to receive the flow path member. An apparatus as described in embodiment A032. A034 The sealing member comprises at least two sealing members; a first sealing member configured to receive the flow path member; a second sealing member configured to evacuate the mixed solution from the tank; An apparatus as described in embodiment A033. A035 The sealing member includes beads and is mechanically and removably fixed to the inner wall of the tank body. An apparatus described in any one of embodiments A032 to A034. A036 The sealing member comprises a rupturable film. An apparatus described in any one of embodiments A032 to A035. A037 The tank is configured to seal the mixed solution. An apparatus described in any one of embodiments A001 to A036. A041 The processing solution is a dilute solution. An apparatus described in any one of embodiments A001 to A037. A051 The pump comprises a syringe. An apparatus described in any one of embodiments A001 to A041. A052 The pump includes a pipette valve. An apparatus described in any one of embodiments A001 to A051. A055 The pump is configured to apply pressure to the flow path from either one of both ends of the flow path. An apparatus described in embodiment A051 or A052. A056 Applying pressure to the flow path is applying a positive pressure or a negative pressure to the flow path. An apparatus as described in embodiment A055. A061 The tank is provided with a discharge channel for discharging the mixed solution. An apparatus described in any one of embodiments A001 to A056. A062 The pump is configured to apply pressure to the other end of the flow path 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 a drain channel fluidly connected to the other end of the flow path; An apparatus described in any one of embodiments A001 to A056. A066 The filter is disposed in the exhaust channel. The apparatus described in embodiment A065. A071 the exhaust channel comprises a second interior space in fluid communication with the interior space and disposed in a path through which the liquid exhausts; An apparatus described in any one of embodiments A061 to A065. A072 the second interior space is fluidly connected to an outlet of the device, and the mixed solution is discharged through the outlet; An apparatus as described in embodiment A071. A081 The filter comprises a plasma or serum separation filter. An apparatus described in any one of embodiments A001 to A072. A082 The filter comprises cellulose or glass fibers. An apparatus described in any one of embodiments A001 to A081. A091 The filter is configured to receive the mixed solution and prevent the mixed solution from seeping out to a radially peripheral portion in at least a portion of a direction in which the mixed solution is discharged. An apparatus described in any one of embodiments A001 to A082. A092 The filter is disposed in the discharge channel and configured to receive the mixed solution in a region including a substantial center and prevent the mixed solution from seeping out from a peripheral portion thereof. An apparatus described in any one of embodiments A061 to A082. A093 the filter is disposed in the exhaust channel; The outlet channel is configured to guide the mixed solution to a region inside the periphery of the filter. An apparatus described in any one of embodiments A061 to A092. A095 a portion of the exhaust channel having a cylindrical end; The cylindrical end is disposed in intimate contact with the inside of the periphery of the filter. An apparatus described in any one of embodiments A091 to A093. A096 The filter comprises: A separation filter; a guide filter disposed upstream of the separation filter in the discharge channel 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. An apparatus described in any one of embodiments A091 to A093. A097 The guide filter is disposed inside the discharge channel and is disposed so as to be out of contact with an inner wall of the discharge channel over at least a portion of a discharge direction and a circumferential direction. The apparatus described in embodiment A096. A098 The guide filter is arranged so as to contact the inner wall of the discharge channel in a direction from the upstream to the downstream of the discharge channel, and then not to contact the inner wall of the discharge channel in a circumferential direction. An apparatus described in any one of embodiments A001 to A082. A101 The filter comprises a plurality of filters. An apparatus described in any one of embodiments A001 to A098. A102 The plurality of filters are stacked and arranged in the flow direction of the exhaust channel. An apparatus as described in embodiment A101. A103 The filter comprises a plurality of filters stacked in a flow direction of the exhaust channel. An apparatus described in any one of embodiments A001 to A102. A104 The plurality of filters include at least A first filter configured to contact an inner wall of the discharge channel in a circumferential direction and to receive substantially all of the mixed solution flowing therethrough; A second filter is disposed downstream of the first filter in contact with the first filter, and the second filter is disposed in a non-contact manner with an inner wall of the discharge channel in a circumferential direction in at least a portion of the flow direction of the discharge channel; a third filter disposed downstream of the second filter in contact with the second filter, the third filter having a larger diameter than the second filter and configured to receive substantially all of the mixed solution discharged from the second filter and to prevent the received mixed solution from reaching a peripheral end surface of the third filter; Equipped with An apparatus described in any one of embodiments A101 to A103. A201 An apparatus for collecting a liquid, comprising: A flow path member having a flow path capable of receiving a liquid from one end and storing the received liquid; a tank containing a processing solution in an internal space, the tank being configured to receive at least one end of the flow path member so that mixing of the processing solution contained in the tank and the liquid contained in the flow path is initiated in the internal space; A pump for discharging the mixed solution from the tank; An apparatus comprising: A255 The pump is configured to apply pressure to the flow path from either one of both ends of the flow path. The apparatus described in embodiment A201. A261 The tank is provided with a discharge channel for discharging the mixed solution. An apparatus described in embodiment A201 or A255. A262 The pump is configured to apply pressure to the other end of the flow path 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 a drain channel fluidly connected to the other end of the flow path. The apparatus described in embodiment A261. A266 The filter is disposed in the exhaust channel. The apparatus described in embodiment A265.

[0095] Although some embodiments and examples of the present disclosure have been described above, these embodiments and examples are illustrative of the present disclosure. For example, the above-mentioned embodiments have been described in detail to clearly explain the present disclosure, and dimensions, configurations, materials, and circuits may be added and changed as necessary. In addition, embodiments in which one or more features of the present disclosure listed above are arbitrarily combined are also included in the scope of the present disclosure. The claims encompass many modifications to the embodiments without departing from the technical idea of ​​the present disclosure. Therefore, the embodiments and examples disclosed in this specification are presented for illustrative purposes 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 path member 111,211 Channels / Capillaries 112,212 Side Cave 113,213 Tip 120,220 Tank 121,221 Interior space 122,123,222,223 Sealing materials / beads 124 Fasteners 131,231 Processing solution 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 Discharge Channel 144,244 outlet 150,250 Syringe 151,251 Piston 152,252 cylinders 160,260 Filters 1100,1200 Filter flow path (device) 1101, 1201 First flow path member 1102, 1202 Second flow path member 1110,1210a~c Filter 1120,1220 Channel 1131,1231 Liquid before filter 1132,1232 Filtered liquid 1133,1233 Liquid in the filter

Claims

1. An apparatus for collecting a liquid, comprising: A flow path member having a flow path capable of receiving a liquid from one end and storing the received liquid; a tank containing a processing solution in an internal space, the tank being configured to receive at least one end of the flow path member, so that the processing solution contained in the tank comes into contact with the liquid contained in the flow path in the internal space and mixing of the processing solution and the liquid is initiated; a discharge channel disposed in the tank for discharging the mixed solution of the processing solution and the liquid; A pump for discharging the mixed liquid from the tank; A filter disposed in the discharge channel and configured to separate a portion of components contained in the mixed solution; An apparatus comprising:

2. The liquid is blood or saliva.

2. The apparatus of claim 1.

3. the flow path includes a capillary at at least one end that receives the liquid; 2. The apparatus of claim 1.

4. The capillary tube is formed in a slit shape.

4. The apparatus of claim 3.

5. The flow path is configured to acquire and contain a volume of liquid.

2. The apparatus of claim 1.

6. The tank includes a tank body and a sealing member that define an interior of the tank; The processing solution is sealed in the tank.

2. The apparatus of claim 1.

7. The sealing member comprises at least two sealing members; a first sealing member configured to receive the flow path member; a second sealing member configured to evacuate the mixed solution from the tank; 7. The apparatus of claim 6.

8. The sealing member includes beads and is mechanically and removably fixed to the inner wall of the tank body.

8. Apparatus according to claim 6 or 7.

9. The sealing member comprises a rupturable film.

8. Apparatus according to claim 6 or 7.

10. The pump is configured to apply pressure to discharge the mixed solution in the flow path and the tank to the outside through the discharge channel.

2. The apparatus of claim 1.

11. The outlet channel is fluidly connected to the flow path.

2. The apparatus of claim 1.

12. The filter comprises a plasma or serum separation filter.

2. The apparatus of claim 1.

13. The filter is disposed in the discharge channel and configured to receive the mixed solution in a region including a substantial center and prevent the mixed solution from seeping out from a peripheral portion thereof.

2. The apparatus of claim 1.

14. a portion of the exhaust channel having a cylindrical end; The cylindrical end is disposed so as to be in intimate contact with the inside of the peripheral portion of the filter.

14. The apparatus of claim 13.

15. The filter comprises: A separation filter; a guide filter disposed upstream of the separation filter in the discharge channel and in contact with the separation filter, configured to receive the mixed solution and guide the mixed solution to the separation filter; The guide filter is disposed inside the discharge channel and is disposed so as to be out of contact with an inner wall of the discharge channel over a circumferential direction in at least a portion of a discharge direction.

2. The apparatus of claim 1.

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